Disse a ion p esen ed o ob ain he Ph.D deg ee in Enginee ing
Sciences and Technology, Chemical Enginee ing
Ins i u o de Tecnologia Química e Biológica An ónio Xa ie | Uni e sidade No a de Lisboa
Oei as,
Sep embe , 2019
A sus ainable pa h owa ds wa e pu i ica ion - an
insigh based on hyd ophobic Deep Eu ec ic Sol en s
Ca a ina Flo indo
Ca a ina Isabel San os Flo indo
Oei as, Sep embe , 2019
A sus ainable pa h owa ds
wa e pu i ica ion - an insigh
based on hyd ophobic Deep
Eu ec ic Sol en s
II
III
Ca a ina Isabel San os Flo indo
Disse a ion p esen ed o ob ain he Ph.D deg ee
in Enginee ing and Technology Sciences,
Chemical Enginee ing
Ins i u o de Tecnologia Química e Biológica An ónio Xa ie |
Uni e sidade No a de Lisboa
Oei as, Sep embe , 2019
A sus ainable pa h owa ds
wa e pu i ica ion - an insigh
based on hyd ophobic Deep
Eu ec ic Sol en s
IV

V
Ti le
A sus ainable pa h owa ds wa e pu i ica ion - an insigh based on
hyd ophobic Deep Eu ec ic Sol en s
Disse a ion p esen ed o ob ain he Ph.D deg ee in Enginee ing
Sciences and Technology, Chemical Enginee ing
Au ho
Ca a ina Isabel San os Flo indo
Sepa a ion and Ex ac ion Technologies Labo a o y
Ins i u o de Tecnologia Química e Biológica An ónio Xa ie
Uni e sidade No a de Lisboa
A . da República Es ação Ag onómica Nacional
2780-157 Oei as
Po ugal
Sep embe 2019
Copy igh © 2019 by Ca a ina Flo indo
All igh s ese ed
P in ed in Po ugal
VI
VII
I decla e ha he wo k p esen ed in his hesis, excep whe e o he wise
s a ed, is based on my own esea ch. The wo k was mainly pe o med in
he Sepa a ion and Ex ac ion Technologies Labo a o y o he Ins i u o de
Tecnologia Química e Biológica An ónio Xa ie , Uni e sidade No a de
Lisboa be ween Janua y 2015 and June 2016 and Ins i u o Supe io
Técnico, Uni e sidade de Lisboa be ween July 2016 and Janua y 2019,
and supe ised by P o esso Doc o Isabel Ma ucho (IST-UL and ITQB)
and Doc o Luís C. B anco (REQUIMTE - FCT). Pa o he esul s was also
a ained du ing isi ing pe iods o Pho ochemis y and Sup amolecula
Chemis y G oup, LAQV-REQUIMTE, Depa amen o de Química,
Faculdade de Ciências e Tecnologia, Uni e sidade No a de Lisboa, and
o he Tom Wel on’s g oup, Depa men o Chemis y, Impe ial college o
London, Uni ed Kingdom.
Financial suppo was p o ided by Fundação pa a a Ciência e a Tecnologia
h ough he doc o al ellowship SFRH/BD/102313/2014.
VIII
XV
CONTENTS
A sus ainable pa h owa ds wa e pu i ica ion - an insigh based
on hyd ophobic Deep Eu ec ic Sol en s
Abs ac ..................................................................................... XVII
Resumo ..................................................................................... XIX
Publica ions ...............................................................................XXIII
Thesis Layou .......................................................................... XXVII
CHAPTER 1 - DEVELOPMENT OF SUSTAINABLE ALTERNATIVE
GREEN SOLVENTS
Chap e 1.1
In oduc ion: s a e-o - he-a and hesis mo i a ion ...................................4
CHAPTER 2 - A STEP TOWARDS HYDROPHOBIC DEEP EUTECTIC
SOLVENTS
Chap e 2.1
No el men hol-based eu ec ic mix u es: hyd ophobic low iscosi y
sol en s .................................................................................................. 46
Chap e 2.2
F om Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low
Viscous Fa y Acid-based Deep Eu ec ic Sol en s .................................. 92
CHAPTER 3 - FROM CHARACTERIZATION TO WATER APPLICATION
OF DEEP EUTECTIC SOLVENTS
Chap e 3.1
De elopmen o Hyd ophobic Deep Eu ec ic Sol en s o Ex ac ion o
Pes icides om Aqueous En i onmen s ............................................... 140

XVI
Chap e 3.2
Task speci ic sus ainable hyd ophobic deep eu ec ic sol en s o
pu i ica ion o wa e con amina ed wi h Bisphenol-A ............................. 178
Chap e 3.3
Remo al o cip o loxacin om wa e en i onmen s using ask-speci ic
hyd ophobic deep eu ec ic sol en s ...................................................... 216
Chap e 3.4
Hyd ophobic deep eu ec ic sol en s as adso ben ma e ials o emo al o
mic opollu an s om wa e sou ces ...................................................... 248
CHAPTER 4 - HYDROPHILIC VS. HYDROPHOBIC DEEP EUTECTIC
SOLVENTS
Chap e 4.1
A close look in o Deep Eu ec ic Sol en s: explo ing in e molecula
in e ac ions using sol a och omic p obes ............................................. 290
Chap e 4.2
Sup amolecula hyd ogel based on a sodium deep eu ec ic
sol en ........................................................................................... ……322
CHAPTER 5 – FINAL REMARKS
Chap e 5.1
Concluding Rema ks and Ou look ........................................................ 358
XVII
ABSTRACT
One o he main conce ns o mode n socie y is o p o ide clean wa e o
e e yone. The occu ence o a wide di e si y o mic opollu an s in aqua ic
ecosys ems leads o se ious public heal h and en i onmen al p oblems.
Thus, he de elopmen o sus ainable and cos -e ec i e al e na i es o
wa e pu i ica ion echnologies is nowadays an impo an challenge. Deep
eu ec ic sol en s (DESs) ha e been p oposed as new al e na i es o
con en ional sol en s and e en ionic liquids. The choice o low cos ,
na u ally occu ing compounds and he s aigh o wa d p epa a ion a e
among he key ea u es o hese sol en s.
This hesis ocuses he de elopmen o no el designe sol en s, and hei
he mophysical cha ac e iza ion, a ge ing he implemen a ion o wa e
pu i ica ion echnologies. The wo k s a s wi h he de elopmen o new
sus ainable hyd ophobic DESs, composed exclusi ely o na u al
compounds, including men hol and se e al a y acids (Chap e 2.1 and
2.2). The applica ion o hyd ophobic DES o wa e pu i ica ion was
explo ed using wo di e en app oaches, liquid-liquid ex ac ion (LLE) and
suppo ed DES as adso ben ma e ials, o he emo al o h ee classes o
majo con aminan s in aqua ic en i onmen s: pes icides, plas ic addi i e
and pha maceu ical compounds (Chap e 3.1, 3.2 and 3.3).
The de ailed knowledge o he p ope ies o Hyd ophobic DES is c ucial o
hei implemen a ion. In pa icula , pola i y is a p ope y ha plays an
impo an ole in he ex ac ion o mul i unc ional molecules. DES’s pola i y
using sol a och omic p obes we e measu ed and hyd ophilic and
hyd ophobic amilies o DES we e compa ed o he i s ime (Chap e 4.1).
Finally, no el hyd ophobic DESs de i ed om a sodium sal o long chain
a y acids we e also p epa ed and cha ac e ized and hei wa e beha iou
s udied. Me alo DES-based hyd ogels we e obse ed in he p esence o
wa e (Chap e 4.2).
XVIII
XIX
RESUMO
Uma das p incipais p eocupações da sociedade mode na é desen ol e
p ocessos e icien es de a amen o de água de modo a o nece água
po á el pa a odos. No en an o, a exis ência de uma g ande di e sidade
de mic opoluen es em ambien es aquá icos ocasiona g a es p oblemas
ambien ais e de saúde pública. Assim, o desen ol imen o de al e na i as
sus en á eis pa a p ocessos de pu i icação de água cons i ui um dos
maio es desa ios a uais. Os sol en es eu éc icos (SE) su gem como
al e na i as aos sol en es con encionais e mesmo líquidos iónicos. A
possibilidade da seleção de compos os na u ais e de baixo cus o, assim
como a sua p epa ação ácil e ápida des acam-se como as p incipais
an agens des es sol en es ino ado es.
A p esen e ese ap esen a o desen ol imen o de no os sol en es
sus en á eis, e a sua ca ac e ização e mo ísica, isando a implemen ação
de ecnologias sus en á eis de pu i icação de água. O abalho
ap esen ado inicia-se com o desen ol imen o de no os SE hid o óbicos,
exclusi amen e cons i uídos po compos os na u ais como o men ol e
á ios ácidos go dos (Capí ulos 2.1 e 2.2). A aplicação de SE hid o óbicos
pa a a pu i icação de água oi ambém explo ada, usando duas
abo dagens dis in as; a ex ação líquido-líquido e a adso ção, pa a a
emoção de ês classes de con aminan es ele an es em ambien es
aquá icos: pes icidas, adi i os e compos os a macêu icos (Capí ulos 3.1,
3.2 e 3.3).
O conhecimen o de alhado das p op iedades de SE hid o óbicos é c ucial
pa a ga an i o sucesso das ex ações. Em pa icula , a pola idade é uma
p op iedade que desempenha um papel impo an e na ex ação de
moléculas mul i uncionais. A pola idade de á ios SE usando sondas
sol a oc ómicas oi medida, e o am e e uadas compa ações en e SE
hid o ílicos e hid o óbicos (Capí ulo 4.1). Finalmen e, o am ambém
XX
desenhados e ca ac e izados no os SE hid o óbicos de i ados de um sal
de sódio de di e sos ácidos go dos de cadeia longa. O es udo do seu
compo amen o em água e idenciou a o mação de me alo hid ogéis
(Capí ulo 4.2).

XXI
KEYWORDS
 Hyd ophobic Deep Eu ec ic Sol en s  Eu ec ic Mix u es 
 G een Sol en s  G een Chemis y  Wa e Pu i ica ion 
 Mic opollu an s 
PALAVRAS-CHAVE
 Sol en es Eu éc icos P o undos Hid o óbicos  Mis u as
Eu éc icas  Sol en es Ve des  Química Ve de 
 Pu i icação de água  Mic opoluen es 
XXII
XXIII
PUBLICATIONS
Thesis publica ions (9)
C. Flo indo, Leona do Miakawa, Luís C. B anco, and Isabel M. Ma ucho,
Hyd ophobic deep eu ec ic sol en s as adso ben ma e ials o emo al o
mic opollu an s om wa e sou ces, pending pa en (2019).
C. Flo indo, Na halie V. Mon ei o, Be na do D. Ribei o, Luís C. B anco and
Isabel M. Ma ucho, Hyd ophobic deep eu ec ic sol en s o pu i ica ion o
wa e con amina ed wi h bisphenol-A, Jou nal o Molecula Liquids, in
p ess, (2019).
C. Flo indo, F ancine Lima, Luís C. B anco and Isabel M. Ma ucho,
Hyd ophobic deep eu ec ic sol en s: a ci cula app oach o pu i y wa e
con amina ed wi h cip o loxacin, ACS Sus ainable Chem. Eng. (2019), 7,
14739-14746.
C. Flo indo, Luís C. B anco, and Isabel M. Ma ucho, In he ques o g een
sol en s design: om hyd ophilic o hyd ophobic (deep) eu ec ic sol en s,
ChemSusChem (2019), 12, 1549.
C. Flo indo, Lucas G. Celia-Sil a, Luís F. G. Ma ins, Luís C. B anco, and
Isabel M. Ma ucho, Sup amolecula hyd ogel based on a sodium deep
eu ec ic sol en , Chem. Commun. (2018), 54, 7527-7530.
C. Flo indo, Leila Rome o, Ignacio Rin oul, Luis B anco, and Isabel M.
Ma ucho, F om Phase Change Ma e ials o G een Sol en s: Hyd ophobic
Low Viscous Fa y Acid-based Deep Eu ec ic Sol en s, ACS Sus ainable
Chem. Eng. (2018), 6, 3888–3895.
C. Flo indo, A. J. S. McIn osh, T. Wel on, L. C. B anco, I. M. Ma ucho, A
close look in o deep eu ec ic sol en s: explo ing in e molecula
XXIV
in e ac ions using sol a och omic p obes, Phys. Chem. Chem. Phys.
(2018), 20, 206-213.
C. Flo indo, L. C. B anco, I.M. Ma ucho, De elopmen o hyd ophobic
deep eu ec ic sol en s o ex ac ion o pes icides om aqueous
en i onmen s, Fluid Phase Equilib ia (2017), 448,135-142.
B. D. Ribei o, C. Flo indo, L. I , M. A. Coelho, I. M. Ma ucho, No el
Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s,
ACS Sus ainable Chem. Eng., (2015), 3 (10), 2469–2477.
O he publica ions (11)
C. Flo indo, Lucas G. Celia-Sil a, Luís F. G. Ma ins, Luís C. B anco and
Isabel M. Ma ucho, No el Sodium sal -based Deep Eu ec ic Sol en s:
p epa a ion and he mophysical cha ac e iza ion, in p epa a ion (2019).
C. Flo indo,* Filipa Lima,* Be na do Dias Ribei o, Isabel M. Ma ucho, Deep
Eu ec ic Sol en s: O e coming XXI Cen u y Challenges, Cu en Opinion in
G een and Sus ainable Chemis y (2019), 31-36 (*equally con ibu ing
au ho s).
C. Flo indo, M. Ma ga ida Oli ei a, L. C. B anco, I. M. Ma ucho,
Ca bohyd a es-based deep eu ec ic sol en s: The mophysical p ope ies and
ice s aw dissolu ion, Jou nal o Molecula Liquids (2017), 247, 441-447.
C. Flo indo, L. C. Tomé, I. M. Ma ucho, The modynamic s udy o agg ega ion
o Cholinium-based Pe luo oalkanoa e Ionic Liquids, J. Chem. Eng. (2016),
61, 3979-3988.
D. Pa inha, L. C. Tomé, C. Flo indo, H. R. Soa es, A. S. Co oadinha, I. M.
Ma ucho, New low- oxici y cholinium-based ionic liquids wi h
pe luo oalkanoa e anions o Aqueous Biphasic Sys em implemen a ion, ACS
Sus ainable Chem. Eng. (2016), 4 (5), 2670-2679.
XXXI
Chap e 4.2
Sup amolecula hyd ogel based on a sodium deep eu ec ic sol en
The in oduc ion o me al
con aining componen s in
hyd ophobic DESs makes a
game change in hei
hyd ophilici y and allows o
he o ma ion o
sup amolecula hyd ogel.
CHAPTER 5 – FINAL REMARKS
Chap e 5.1
Concluding Rema ks and Ou look
The majo conclusions,
di ec ions and u u e wo k in
he DESs ield a e he e
highligh ed.
A doo o new possibili ies and
challenges o u u e esea ch
will be opened.

XXXII
XXXIII
Thesis Guidelines
I decided o p esen he esea ch de eloped du ing he ime o my PhD
p ojec in an a icle-based hesis o m, di ided in o i e chap e s,
de elopmen o sus ainable al e na i e g een sol en s, a s ep owa ds
hyd ophobic deep eu ec ic sol en s, om cha ac e iza ion o wa e
applica ion o deep eu ec ic sol en s, hyd ophilic s. hyd ophobic deep
eu ec ic sol en s and inal ema ks, which a e he main a eas o which
hese hesis con ibu es. Each chap e is di ided in o se e al sub-chap e s
which con ain he published a icles. Chap e 1 in oduces he gene al
con ex o deep eu ec ic sol en s as a new gene a ion o sus ainable
sol en s, and he main objec i es o he hesis. All da a p esen ed in he
ollowing chap e s (2 o 4) a e en i ely based on published (o submi ed)
scien i ic a icles in pee e iewed jou nals, bea ing in mind ha hey a e
no by hei ch onological o de o publica ion, bu a he build a
comp ehensi e p og ess o he ield. The hesis kick-o consis ed o he
de elopmen o no el hyd ophobic DES, explo ing and ga he ing
e idences o he unde s anding hei p ope ies as well as hei applica ion
as immiscible sol en o pu i ica ion o wa e con amina ed wi h se e al
mic opollu an s. Finally, a compa ison be ween hyd ophilic and
hyd ophobic DES is p esen ed, pu ing in e idence he design o DES
con aining bo h hyd ophilic and hyd ophobic pa s and hei beha iou in
wa e .
Fu he mo e, in each a icle-based chap e is possible o ind a b ie e iew
o he s a e o he a , ma e ials and me hods, esul s as well as hei
discussion and he main conclusions o he pa icula wo k. Mo eo e ,
since in each chap e o hesis, he igu es, ables, symbols and
abb e ia ions a e p ope ly iden i ied and ca e ully desc ibed, a gene al lis
o hem we e no included in his hesis.
CHAPTER 1
DEVELOPMENT OF
SUSTAINABLE ALTERNATIVE
GREEN SOLVENTS
F om solid o liquid s a e
In oduc ion: s a e-o - he-a and hesis mo i a ion

CHAPTER 1.1
In oduc ion: s a e-o - he-a and hesis
mo i a ion
In oduc ion: s a e-o - he-a and hesis mo i a ion
This chap e was adap ed om an in i ed mini- e iew: C. Flo indo,
L. C. B anco, I. M. Ma ucho, In he ques o g een sol en s design:
om hyd ophilic o hyd ophobic (deep) eu ec ic sol en s,
ChemSusChem, 2019, 12, 1549 (in i ed o be a co e o he issue).
The au ho was in ol ed in he li e a u e e iew conce ning he
e olu ion o hyd ophobic DES ield as well as in he discussion and
in e p e a ion o esul s and he p epa a ion o he e iew.
Chap e 1.1
CONTENT
1. GENERAL CONTEXT ........................................................................ 8
2. HYDROPHOBIC (DEEP) EUTECTIC SOLVENTS .......................... 13
2.1. DEVELOPMENT AND PREPARATION OF HYDROPHOBIC
(D)ESS ......................................................................................................... 18
2.2. PHYSICOCHEMICAL PROPERTIES OF HYDROPHOBIC
(D)ESS .......................................................................................................... 24
2.2.1. Mel ing empe a u e o hyd ophobic (D)ESs ........................ 25
2.2.2. Densi y and Viscosi y o Hyd ophobic (D)ESs ..................... 27
2.2.3. Solubili y o wa e in Hyd ophobic (D)ESs ........................... 29
2.3. VERSATILE APPLICATIONS OF HYDROPHOBIC (D)ESS – FROM
NATURE TO GREEN CHEMISTRY ................................................................... 31
3. ECONOMIC ASSESSMENT OF DESS ........................................... 35
4. FRAMEWORK AND OBJECTIVES ................................................ 36
5. THESIS OUTLINE ............................................................................ 37
6. REFERENCES ................................................................................. 38
In oduc ion: s a e-o - he-a and hesis mo i a ion
7
Chap e 1.1
14
Figu e 4. E olu ion o he numbe o publica ions in he ield o Deep
Eu ec ic Sol en s in gene al (blue) and Hyd ophobic Deep Eu ec ic
Sol en s (g een) du ing he las yea s, ha con ained “deep eu ec ic
sol en s” o “hyd ophobic deep eu ec ic sol en s” in hei i les, keywo ds
and abs ac s as ob ained om ISI web o knowledge. Da a o 2018
include up o Decembe .
As i can be obse ed om Figu e 4, despi e he in e es o his no el class
o DESs, a e y limi ed numbe o hyd ophobic (D)ESs has been p oposed
so a . The mos epo ed hyd ophobic (D)ESs a e essen ially composed
o qua e na y ammonium sal s wi h long alkyl chains o hyd ophobic na u al
compounds as HBA, combined wi h se e al hyd ophobic HBD as
ca boxylic acids o alcohols wi h long alkyl chains, in con as wi h
hyd ophilic DES, whe e combina ions o choline chlo ide sal and o he
ammonium sal s possessing small alkyl chains wi h se e al acids, amines,
alcohols, aminoacids, among o he s, a e he mos s udied. Figu e 5
summa izes he mos used HBDs and HBAs in he p epa a ion o
hyd ophobic deep eu ec ic sol en s. As i was men ioned be o e, he majo
di e ence in e ms o chemical s uc u es o he pa en compounds, ei he

In oduc ion: s a e-o - he-a and hesis mo i a ion
15
ionic o neu al, lays in he p esence o long alkyl chains and hus in he
dec easing o he impo ance o he hyd ophilic domains, such as cha ges
o he sal s, and hyd ophilic g oups, such as ca boxyla e and hyd oxyl
g oups.
Figu e 5. Typical HBDs and HBAs used in hyd ophobic (D)ESs
p epa a ion.
Te abu ylammonium chlo ide,
[N4444]Cl
Me hyl ioc ylammonium
b omide, [N8881]B
QUATERNARY AMMONIUM SALTS NATURAL
COMPOUNDS
FATTY ACIDS
Lau ic acid
Decanoic acid
Te ahep ylammoniumchlo ide,
[N7777]Cl
Te aoc ylammoniumchlo ide,
[N8888]Cl
Dodecanoa e sodium
Men holThymol
CARBOXYLIC ACIDS NATURAL
COMPOUNDS
ALCOHOLS
Men hol
Oleic acid
Ibup o en
THERAPEUTICAL
COMPOUNDS
Ca boxylic acids Pe luo odecanoic acid
lidocaine
Cyclohexanol
Campho
Undecylenicacid
Long alkyl chain alcohols
Chap e 1.1
16
The di e ence in he chemical s uc u es o he pa en compounds is
esponsible o he magni ude o he mel ing poin dep ession. One o he
di e ences be ween hyd ophilic and hyd ophobic (D)ESs is he ac ha in
he i s class a deep dep ession in he mel ing poin is ypically ob ained,
unlike hyd ophobic (D)ES whe e la ge and small dep essions can be
ob ained. This di e ence in mel ing poin dep ession beha iou is due o
he p esence o cha ged and pola moie ies leading o ex ensi e hyd ogen
bond in e ac ions in hyd ophilic DESs, whe eas in hyd ophobic (D)ES a
la ge dep ession is only ob ained in he p esence o sal s, e en i hei
cha ges sc eened by he long hyd oca bon alkyl chains. Neu al
hyd ophobic (D)ESs a e essen ially eu ec ic mix u es, showing small
dep essions in he mel ing poin s, leading o highly luid sol en s, a e y
appealing p ope y o some applica ions. Figu e 6 shows a di ec
compa ison o phase diag ams o wo hyd ophobic (D)ESs, one composed
o dodecanoa e sodium sal and decanoic acid7 and he o he con aining
L(-)-Men hol and decanoic acid.
In oduc ion: s a e-o - he-a and hesis mo i a ion
17
Figu e 6. Compa ison o solid-liquid phase diag am be ween a deep
eu ec ic sol en composed o dodecanoa e sodium sal and decanoic acid
(⚫ NaC12: C10)18 and an eu ec ic sol en composed o a na u al compound,
L-Men hol and decanoic acid (◼ L(-)-Men hol: C10)19.
Two dis inc beha io s a e depic ed in Figu e 6: hyd ophobic deep eu ec ic
sol en , due o he p esence o dodecanoa e sodium sal , o a hyd ophobic
eu ec ic sol en , when only neu al componen s a e used. Since solid-liquid
phase diag ams a e no a ailable o mos DESs, i is di icul o disce n
when a deep dep ession o he mel ing poin s occu s. Al hough in li e a u e
all hese compounds a e designa ed by hyd ophobic DESs, in his e iew
we adop he e minology hyd ophobic (D)ESs in gene al, while DESs and
ESs will be used when o hose composed o sal s o composed o neu al
compounds, espec i ely.
Ano he impo an poin ha comes up om he obse a ion o he phase
diag ams in Figu e 6 is he liquid egion ha is in ac a ailable om he
(D)ESs o ma ion. The new empe a u e-composi ion su ace whe e a
liquid is a ained due o (D)ESs o ma ion depends on lowe mel ing
Tempe a u e
Mole F ac ion
A (Tm)
B (Tm)
Chap e 1.1
18
empe a u e o (D)ESs componen s and he empe a u e o he eu ec ic
poin . Fo example, o NaC12: C10, bo h hese empe a u es a e close and
hus a small liquid su ace is ob ained, while o L(-)-Men hol: C10, since he
di e ence in hese empe a u es is highe , a la ge su ace is a ailable, as
indica ed in shadow in he ex .
2.1. De elopmen and p epa a ion o Hyd ophobic (D)ESs
Unlike hyd ophilic DESs, he numbe o hyd ophobic (D)ESs and ESs is
qui e limi ed. This is mainly due o he es ic ed numbe o cheap, eadily
a ailable hyd ophobic sal s and o he hyd ophobic o ganic na u al
compounds ha o m eu ec ic sol en s close o bellow oom empe a u e.
Jus like hyd ophilic DESs, hyd ophobic DESs and ESs ha e also s a ed
o be s udied om he applica ion poin o iew, lea ing simila undamen al
ques ions unanswe ed.
A summa y o he hyd ophobic DESs and ESs epo ed in he li e a u e is
shown in Tables 1 (ammonium sal s) and 2 (na u al compounds).
In oduc ion: s a e-o - he-a and hesis mo i a ion
19
Table 1. Summa y o hyd ophobic DESs epo ed in li e a u e, composed
o ammonium sal s.
HYDROPHOBIC DESs
Mola
Ra io
s udied
(HBA:HBD)
Tempe a u e
o Eu ec ic
Poin (ºC)
Re e ence
HBA
HBD
QUATERNARY AMMONIUM SALTS
Te abu ylammonium
Chlo ide
[N4444]Cl
Ace ic acid*
1:1
▬
20
Le ulinic acid*
1:2
▬
20
Hexanoic acid*
1:2
▬
20
Oc anoic acid*
1:1, 1:2
▬
20-22
Decanoic acid*
1:1, 1:2
-11.95
20-25
Lau ic acid*
1:1, 1:2
▬
20, 22
Te abu ylammonium
B omide
[N4444]B
Ace ic acid*
1:2
▬
26
P opionic acid*
1:2
▬
26
Ac ylic acid*
1:2
▬
26
Bu y ic acid*
1:2
▬
26
Oc anoic acid*
1:1, 1:2
0.58
22, 26
Decanoic acid*
1:1, 1:2
16-17
22, 26
Lau ic acid*
1:1
22
Oleic acid*
1:2
1.86
26
Me hyl ioc ylammonium
Chlo ide
[N8881]Cl
Hexanoic acid*
1:2
▬
27
Oc anoic acid
1:2
▬
21, 27
Decanoic acid
1:2
-0.05
21, 23, 25, 27
Lau ic acid
1:2
▬
27
My is ic acid
1:1
▬
27
Palmi ic acid
1:1
▬
27
cis-9-oc adecenoic
acid
1:2
▬
27
Ricinoleic acid
1:2
▬
27
E hylene glycol*
1:2
▬
28
1-P opanol*
1:2
▬
27-28
1,3-P opanediol*
1:2
▬
28
Glyce ol*
1:2
▬
28
1-Bu anol*
1:2
▬
27-28
1,2-Bu anediol*
1:2
▬
28
Hexyl alcohol*
1:2
▬
27-28
Cap yl alcohol
1:2
▬
27-28
Decyl alcohol
1:2
▬
27-28
Dodecyl alcohol
1:2, 1:1
▬
27-28
1-Te adecanol
1:2
▬
27-28
Hexadecanol
1:2
▬
27
Cyclohexanol*
1:2
▬
27-28
DL-Men hol
1:2
▬
27-28

Chap e 1.1
20
Me hyl ioc ylammonium
B omide
[N8881]B
Decanoic acid
1:2
8.95
23, 25
Te ahep ylammonium
Chlo ide
[N7777]Cl
Decanoic acid
1:2
-16.65
23, 29
Lau ic acid
1:2
▬
29
Oleic acid
1:2
▬
29
Ibup o en
7:3
▬
29
Te aoc ylammonium
Chlo ide
[N8888]Cl
Decanoic acid
1:2, 1:1.5
1.95
23-25
Pe Fluo odecanoic
acid
1:2
24
Te aoc ylammonium
B omide
[N8888]B
Decanoic Acid
1:2
8.95
23-25, 30
Dodecanoa e sodium
sal , NaC12
Decanoic Acid **
All ange
23
18
*uns able upon con ac wi h wa e ** o ms a hyd ogel in con ac wi h wa e
In oduc ion: s a e-o - he-a and hesis mo i a ion
21
Table 2. Summa y o hyd ophobic ESs epo ed in li e a u e, composed o
neu al compounds.
HYDROPHOBIC ESs
Mola Ra io
s udied
(HBA:HBD)
Tempe a u e o
Eu ec ic Poin
(ºC)
Re e ence
HBA
HBD
NATURAL OR NEUTRAL COMPOUNDS
DL-Men hol
Ace ic acid*
1:1
▬
20, 31-32
Bu y ic acid*
1:1
▬
20, 32
Py u ic acid*
1:2
▬
20, 31
Lac ic acid*
1:1, 1:2
▬
31-32
Le ulinic acid*
1:1
▬
20
P opionic acid*
1:1
▬
32
Hexanoic acid*
1:1
▬
20, 32
Oc anoic acid
2:1, 1:1, 1:2
-1.82
19-20, 22, 32
Decanoic acid
2:1, 1:1, 1:2
8.86
19-20, 22, 29-30
Lau ic acid
2:1, 1:1, 1:2
21.23
19-20, 22, 29,
31-33
Ibup o en acid
3:1
▬
16
Phenylace ic acid*
1:1
▬
32
Mandelic acid*
1:1
▬
32
L(-)-Men hol
Oc anoic acid
All ange
-1.82
34, 29
Decanoic acid
All ange
8.86
Lau ic acid
All ange
21.23
My is ic acid
All ange
26.62
Palmi ic acid
All ange
33.18
S ea ic Acid
All ange
37.88
Thymol
Oc anoic Acid
All ange
6.68
19
Decanoic Acid
All ange
18.86
19, 30, 35
Lau ic Acid
All ange
24.83
19
My is ic Acid
All ange
38.16
19
Palmi ic Acid
All ange
41.22
19
S ea ic Acid
All ange
46.22
19
Lidocaine
2:1
▬
30
Campho
7:3, 3:2, 1:1
-44
35
Undecylenic Acid
7:3, 3:2, 1:1,
1:2, 1:3, 1:4
7.5
35
Chap e 1.1
22
FATTY ACIDS
Decanoic acid
Lidocaine
2:1, 3:1, 4:1
No mel ing,
Tg = -66.15
36-37
Lau ic acid
Oc anoic Acid
All ange
9
38
Nonanoic acid
All ange
9
38
Decanoic Acid
All ange
18
38
*uns able upon con ac wi h wa e ** o ms a hyd ogel in con ac wi h wa e
The i s epo ed hyd ophobic DES was based on qua e na y ammonium
sal s wi h long alkyl chains and decanoic acid, whe e he hyd ophobic
cha ac e was con i med by he s udy o he leaching o DES componen s
o he wa e phase as well as hei wa e up ake.23 Following he same idea,
se e al wo ks using qua e na y ammonium sal s wi h long alkyl chains
we e hen p oposed, changing he HBD using di e en chemical s uc u es,
such as ca boxylic acids and alcohols wi h di e en alkyl chains (C2 o C18)
and wi h double bonds. Rega ding he use o [N4444]Cl and [N4444]B o
p epa e hyd ophobic DESs, i is only highligh ed he ac ha hyd ophobic
DESs could be p epa ed using hese compounds and ha wo phases a e
ob ained when in con ac wi h wa e . Thei chemical s abili y will be
discussed u he ahead, and conclusions wi hd awn.
As o wha conce ns hyd ophobic ESs, Ma ucho´s g oup31 p oposed he
i s hyd ophobic ES based on na u al enewable esou ces by combining
DL-men hol and se e al na u al ca boxylic acids. In he same ein,
Cou inho´s g oup19 also con ibu ed o inc ease he ield o neu al
hyd ophobic sol en s, p oposing no el na u al hyd ophobic eu ec ic
sol en s based on e penoids, L(-)-men hol and hymol combined wi h
se e al ca boxylic acids. O he hyd ophobic ESs based on lidocaine and
decanoic acid a se e al mola a ios we e also p oposed.36 O he
sus ainable hyd ophobic ESs composed o wo compounds om he same
amily, long chain a y acids, ha e also been p oposed.38 In hese
hyd ophobic ESs, bo h acids can wo k as HBA and as HBD, and we e
inspi ed in phase change ma e ials, bu choosing he componen s ca e ully
In oduc ion: s a e-o - he-a and hesis mo i a ion
23
so ha eu ec ic poin s lowe han oom empe a u e we e ob ained. In a
subsequen wo k, Flo indo e al.18 p esen ed a no el amily o hyd ophobic
DES con aining a sodium sal o a a y acid, which ac s as HBA, combined
wi h ano he a y acid, as HBD. Mo eo e , he au ho s ound he o ma ion
o a hyd ogel when con ac ing he sodium-based DES wi h wa e . The
p esence o he cha ged sodium a oms seems o be c ucial o he
o ma ion o he hyd ogel, since in he p e ious wo k whe e he epo ed
DES was composed by wo ca boxylic acids wi h a long alkyl chain and he
comple e DES immiscibili y wi h wa e was obse ed wi hou gel o ma ion.
In he p esen case, ins ead o wo mu ually immiscible liquid phases, a
hyd ogel was ob ained. The mo e wa e added, he mo e iscous he gel
became.
Conce ning he cha ac e iza ion o hese hyd ophobic sys ems, e y ew
solid-liquid phase diag ams a e a ailable o hyd ophobic DESs and ESs.
In Tables 1 and 2, i is possible o see ha phase diag ams a e only
a ailable in he cases whe e he “all ange” label is.
Rega ding he de elopmen o hyd ophobic (D)ESs, he selec ion o
app op ia e HBA and HBD is a key ac o . Bo h K oon's23 and Ma ucho’s20
eams poin ed ou he ele ance o he hyd ophobici y o bo h componen s.
A comp ehensi e s udy on he chemical and wa e s abili y o se e al
hyd ophobic (D)ESs, composed o ei he neu al o ionic compounds, was
pe o med h ough hei NMR analysis o he wa e phase. I was clea ha
he hyd ophobici y o (D)ESs depends on he hyd ophobici y o he
indi idual componen s and ha (D)ESs o med by one hyd ophilic and one
hyd ophobic compound a e no s able in wa e , since he hyd ophilic
componen will leach o he wa e phase acco ding o i s wa e solubili y.20
Figu e 7 illus a es he 1H NMR spec a o ES- ich and wa e - ich phases
o wo di e en hyd ophobic ESs, DL-men hol: ace ic acid (1:1) and DL-
men hol: lau ic acid (2:1). Mo eo e , a ma ix wi h he wa e s abili y o he
s udied hyd ophobic (D)ESs, whe e ✓ indica es s able (D)ES and Χ
uns able (D)ES in con ac wi h wa e , is also p esen ed.
Chap e 1.1
30
Figu e 11. Compa ison o wa e solubili y (w %) and iscosi y o se e al
hyd ophobic (D)ESs a 25 ºC. Da a aken om li e a u e 19, 23, 31, 34, 38.
Ba s co espond o solubili y o wa e in hyd ophobic (D)ESs and poin s o
iscosi y da a o pu e hyd ophobic (D)ESs.
I can be obse ed ha hyd ophobic (D)ESs ha e low wa e solubili ies,
lowe han 7 w %. The la ges wa e solubili y (6.94 w %) was ob ained o
[N4444]Cl: C10 (1:2), closely ollowed by [N8881]Cl: C10 (1:2) (6.22 w %).
Again, his is p obably due o he mo e a ailable cha ge on he ni ogen
a om o he ammonium ca ion owing o he p esence o a leas one sho
alkyl chain. This obse a ion is in line wi h he ecen ly epo ed hyd ogel
o ma ion when NaC12: C10 (1:4) is con ac ed wi h wa e , which was
explained by he p esence o he cha ged sodium a oms.18 O e all, he
wa e solubili y can be anked by amily o hyd ophobic (D)ESs acco ding
o ollowing o de : a y acids < men hol < hymol < qua e na y ammonium
Viscosi y
C12: C8 (1:3)
C12: C10 (1:2)
L(-)-Men hol: C8 (1.5:1)
L(-)-Men hol: C10 (1.5:1)
L(-)-Men hol: C12 (3:1)
Thymol: C8 (1:1.4)
Thymol: C10 (1:1)
[N4444]Cl: C10 (1:2)
[N8881]Cl: C10 (1:2)
[N7777]Cl: C10 (1:2)
[N8888]Cl: C10 (1:2)
Viscosi y a 25 ºC (mPa.s)
0
3
6
9
12
15
Solubili y o wa e in DESs (w %)
0
10
20
30
250
500
750
1000

In oduc ion: s a e-o - he-a and hesis mo i a ion
31
sal s, whe e a y acid-based ESs solubilize ≤ 5 w % o wa e , men hol-
based ESs less han 2.5 w % o wa e , hymol-based DESs less han 3.7
w % o wa e and inally long alkyl chains ammonium sal s-based DESs
solubilize be ween 2 o 7 w % o wa e . Also, o all he amilies o
hyd ophobic (D)ESs, wa e solubili y dec eases wi h he inc ease o he
HBD alkyl chain.
Cu iously, he wa e solubili y o de o he 3 di e en selec ed amilies o
hyd ophobic (D)ESs ma ches he iscosi y o de , whe e, he
e alkylammonium sal s-based DESs ( he mos iscous amily o
hyd ophobic DES) is also he one wi h he highes wa e solubili y, and he
a y-acids ESs amily show he lowes wa e solubili y and iscosi y.
Al hough hyd ophobic (D)ESs he wa e solubili y is small, he iscosi y is
less a ec ed by his small wa e p esence, p obably because he hyd ogen
bonding ne wo k is no as impo an he e as i is o hyd ophilic DESs. In
he case o ionic hyd ophobic DESs, hei high wa e solubili y he o ma ion
o in e molecula c osslinked s uc u es, usually in ol ing he pa icipa ion
o wa e molecules, hus inc easing he iscosi y, some imes o ming
hyd ogels.42
2.3. Ve sa ile applica ions o hyd ophobic (D)ESs – F om
na u e o g een chemis y
Al hough some impo an in o ma ion on hyd ophobic (D)ESs om he
undamen al poin s o iew is s ill missing, he de elopmen o applica ions
using hese sol en s is al eady a lou ishing ield. One ad an age o
hyd ophobic (D)ESs is hei wa e immiscibili y, allowing hei use in
ex ac ions and sepa a ions o compounds om aqueous phases. Al hough
he ield o hyd ophobic (D)ESs is new, a ai amoun o publica ions on
hei possible applica ions has been published. In Figu e 12, main a eas o
applica ion o hyd ophobic (D)ESs, ex ac ion o na u al componen s om
Chap e 1.1
32
plan s, CO2 cap u e, o ganic syn hesis and ma e ials, and wa e
pu i ica ion, a e ep esen ed.
Figu e 12. A eas o signi ican impac and use o hyd ophobic (D)ESs.
The i s applica ions o be p oposed o hyd ophobic DESs ocused on he
use o long chain e aalkylammonium b omide sal s combined wi h long
chain o ganic acids o ex ac ola ile acids om aqueous solu ions.23 The
po en ial o hese hyd ophobic DESs was p o en and compa ed o he
indus ial s anda d compound ( ioc ylamine, TOA), wi h hyd ophobic DESs
showing supe io ex ac ion e iciencies. Ribei o e al.31 used all na u al
hyd ophobic ESs, composed o men hol and na u ally occu ing acids
(py u ic acid, ace ic acid, L-lac ic acid and lau ic acid), o illus a e hei
abili y o ex ac ou model biomolecules (ca eine, yp ophan, isoph halic
acid and anillin) om aqueous solu ions. Van Osch e al.36 p oposed a
hyd ophobic ESs based on decanoic acid and lidocaine, o he emo al o
a wide ange o me al ions om aqueous solu ions. I was shown ha all
ansi ion me al ions could be ex ac ed wi h high dis ibu ion coe icien s
wi hin 5 seconds, allowing he egene a ion o he used ESs. O he
In oduc ion: s a e-o - he-a and hesis mo i a ion
33
au ho s19 also epo ed he selec i e ex ac ion and sepa a ion o Cu(II)
om o he ansi ion me als in mildly acidic aqueous solu ions using all
na u al hyd ophobic ESs based on low-p ice and biodeg adable e penes
and a y acids. Fu he mo e, he used hyd ophobic ESs could be
success ully eco e ed and ecycled using selec ed hyd ophilic DESs.
Pe sis en mic opollu an s, such as pes icides om neonico inoids amily,20
Bisphenol-A,38 a plas icize p esen in wa e bo les and simul aneously
ac ing as an endoc ine dis up o , was success ully ex ac ed using all
na u al hyd ophobic ES, wi h ex ac ion e iciencies a ound 70% and mo e
han 90%, espec i ely. Recen ly, Die z e al.30 epo ed he selec i e
sepa a ion o u u al and hyd oxyme hyl u u al om an aqueous solu ion
using suppo ed hyd ophobic (D)ESs liquid memb ane. Fou di e en
hyd ophobic (D)ESs ([N8888]B : C10 acid, hymol: C10 acid, men hol: C10 acid
and hymol: lidocaine) and he au ho s concluded ha by ailo ing
hyd ophobic DESs iscosi y and po e size o he suppo , he eco e y and
sepa a ion o he compounds could be achie ed. Makoś e al.35 de eloped
hyd ophobic ESs based on hymol and (±)-campho , decanoic and 10-
undecylenic acids o isola e and en ich polycyclic a oma ic hyd oca bons
om aqueous samples using ul asound-assis ed dispe si e liquid-liquid
mic oex ac ion.
Ano he applica ion wi h g ea po en ial is he use o hyd ophobic (D)ESs
o CO2 cap u e. Die z e al.24 epo ed he use o PC-SAFT equa ion o
s a e o modelling he CO2 solubili ies in se e al hyd ophobic DESs.
A e wa ds, Zubei al.25 measu ed he solubili y o CO2 in hyd ophobic
DESs, whe e decanoic acid was combined wi h i e di e en hyd ophilic
and hyd ophobic qua e na y ammonium sal s, in he empe a u e ange
om 25 o 50 ºC and a CO2 p essu es up o 2 MPa. I was ound ha he
CO2 solubili y was much highe in hyd ophobic han in hyd ophilic DES, bu
bo h could be epea edly used as abso bing agen s wi hou losing
abso p ion capaci y.
Chap e 1.1
34
Finally, ano he a ea in conside able expansion is ex ac ion o seconda y
me aboli es om plan s using hyd ophobic (D)ESs h ough mic oex ac ion
echniques. Cao e al.27 demons a ed he e iciency o hyd ophobic DESs
as designe sol en s o ex ac polyp enyl ace a es om Ginkgo biloba
lea es. The au ho s p oposed a e na y hyd ophobic DESs, composed o
me hyl ioc ylammonium chlo ide, cap yl alcohol and oc ylic acid a a mola
a io o 1:2:3, as he mos e icien ex ac an . The same eam28 also s udied
he ex ac ion o a emisinin om A emisia annua lea es. The hyd ophobic
DES based on me hyl ioc ylammonium chlo ide and 1-bu anol a a mola
a io o 1:4 showed he highes ex ac ion yield, and also highe e iciency
han con en ional o ganic sol en , pe oleum e he . These s udies illus a e
he e sa ili y and he p ope ies’ unabili y o hyd ophobic (D)ESs as g een
and sa e ex ac ion sol en s o pha maceu ical applica ions. Finally,
Křížeke al.32 de eloped se e al hyd ophobic ESs based on e penes and
na u al o ganic acids o ex ac phy ocannabinoids om aw cannabis plan
ma e ial. The au ho s also p o ed ha hyd ophobic DES ha e supe io
pe o mance in ex ac ion e iciencies o e o he con en ional sol en s. Fo
example, ini ial sc eening showed ha ESs composed o a men hol: ace ic
acid (1:1) mix u e had he g ea es ex ac ion e iciency wi h yields anging
om 118.6% o 132.6% compa ed o a me hanol/chlo o o m mix u e.
Finally, ano he a ea whe e hese compounds ha e been widely applied is
in o ganic syn hesis and also in he de elopmen o no el ma e ials.
Bold ini e al., 28 epo ed he use o a hyd ophobic eu ec ic sol en based
on men hol and a na u ally occu ing ca boxylic acid as an eco- iendly
elec oly e medium in dye-sensi ized sola cells. They concluded ha he
good pe o mances, he highe ol age and he lowe ecombina ion
esis ances all sugges ha hyd ophobic eu ec ic mix u es can play an
impo an ole in imp o ing he eco-compa ible and sus ainable cha ac e
o liquid dye-sensi ized sola cells.
In oduc ion: s a e-o - he-a and hesis mo i a ion
35
3. Economic assessmen o DESs
Since he p ice o sol en s is a key issue o indus y, whene e a new class
o al e na i e sol en s is p oposed one o he mos asked ques ions is how
much will i cos ? Up o his poin , i can be a i med ha he success o
DESs lays on i s simplici y o p epa a ion when compa ed wi h hei pa en
compounds, o ganic sal s and ionic liquids. Typically, qua e na y
ammonium and phosphonium sal s a e used o p epa e DESs, which a e
cheape han he iconic imidazolium-based ionic liquids. The simplici y o
DESs p epa a ion, ypically jus mixing and hea ing, and he absence o
pu i ica ion s eps is a eal ad an age no only om he syn he ic poin o
iew bu also om an economic poin o iew. The in oduc ion o all neu al
DESs, b ough o he a ena blue (g een and cheap) DES, since he aw
ma e ials, a y acids, e pene, alcohols e c., a e now mo e en i onmen ally
iendly and cos -e ec i e compounds. Howe e , i should be kep in mind
ha hese compounds will possibly ha e non-negligible apou p essu e,
leading o e apo a i e losses.
The inal compa ison ha needs o be made is wi h adi ionally used
o ganic sol en s. In ac , sol en s like oluene, me hanol and chlo o o m
a e s ill cheape han e penes and o ganic acids. This is he eason why
euse and egene a ion s eps o al e na i e sol en s always need o be
s udied, e alua ed and included in he p ocesses. I ci cula p ocesses a e
de eloped, and g een sol en s egene a ed, he p ocess as a whole will be
mo e economically and en i onmen ally sus ainable.

Chap e 1.1
36
4. F amewo k and Objec i es
The con inuous p esence o se e al mic opollu an s in he wa e sou ces
o public wa e sys ems can be linked o a ange o human and
en i onmen al heal h e ec s including cance , bi h de ec s, neu ological
and ep oduc i e diseases, while dec easing he biodi e si y. Al hough
d inking and was ewa e ea men plan s use ad anced echnologies o
mic opollu an s emo al, none o hese p ocesses we e speci ically
designed o emo e all o ms o pollu ion.
The main objec i e o his wo k is o s udy and de elop new DES o be
used in emo al o se e al classes o mic opollu an s, namely pes icides,
plas ic addi i e and pha maceu ical compounds, om wa e en i onmen s.
DESs p esen excellen sol a ing quali ies, which can be ailo ed o
gua an ee he success o he p oposed echnologies. To achie e he goal,
his hesis explo es i s he p epa a ion and cha ac e iza ion o no el
hyd ophobic deep eu ec ic sol en s, wi h he aim o making hem a ac i e
sol en s o wa e applica ions. Fu he mo e, he wo k p esen ed in his
hesis also add esses he de elopmen o wo di e en echnologies,
namely liquid-liquid ex ac ion (LLE) and adso p ion. In o de o imp o e
hese echnologies, al eady implemen ed in wa e ea men plan s, and
seeking a comple e and e icien emo al o mic opollu an s om aqueous
s eams, wi hou con amina ing he wa e bodies, p ope ies unabili y,
mic opollu an s a ini y and ex ac ion pe o mance o se e al amilies o
hyd ophobic DES we e explo ed. Finally, o assu e he comple e
sus ainabili y o p ocess using p oposed echnologies, he euse and
ecycling o he hyd ophobic DESs we e in es iga ed.
The esul s achie ed in his hesis as well as he de elopmen and
applica ion o hese inno a i e sol en s a e expec ed o open new doo s o
sus ainabili y, pushing g een chemis y o he dese ed place in sepa a ion
and pu i ica ion p ocesses.
In oduc ion: s a e-o - he-a and hesis mo i a ion
37
5. Thesis ou line
This hesis is o ganized in i e blocks sepa a ed by sub-chap e s. A e a
b ie in oduc ion on he e olu ion o he DES ield and he de elopmen o
hyd ophobic DES, Chap e 2 is composed o sub-chap e s 2.1 and 2.2,
which desc ibe he p epa a ion and cha ac e iza ion o no el and
sus ainable hyd ophobic eu ec ic sol en s based on na u al compounds.
Fo he i s ime, sol en s composed o DL-Men hol combining ca boxylic
acids and composed exclusi ely by a y acids, possessing p omising
p ope ies, such as e y low iscosi y and low wa e con en , compa ed o
he adi ional sol en s, we e in oduced in he ield.
In Chap e 3, which includes sub-chap e s 3.1, 3.2, 3.3 and 3.4, p esen s
he de elopmen and applica ion o echniques o cleaning aqueous
solu ions con amina ed wi h se e al mic opollu an s anging om
pes icides, o plas ic addi i e as well as ac i e pha maceu ical ing edien s.
Pa icula ly, liquid-liquid ex ac ion (LLE) and adso p ion p ocesses we e
es ed as well-known echnologies combining se e al hyd ophobic DESs
we e employed o he single-s ep ex ac ion and concen a ion o ou
pes icides (ace amip id, imidaclop id, hiame hoxam and ni enpy am), a
plas ic addi i e (Bisphenol-A), a nons e oidal an i-in lamma o y d ugs
(diclo enac) and inally a luo oquinolone (cip o loxacin). Fi s , liquid-liquid
ex ac ion, an al eady well-exploi ed echnique, was applied in o de o
unde s and he a ini y o mic opollu an s, wi h di e en chemical s uc u es
and unc ionali ies, o hyd ophobic DES in e ms o ex ac ion e iciencies
(chap e s 3.1, 3.2 and 3.3). Following he excellen esul s and
pe o mances o hyd ophobic DES and using he p e ious know-how
acqui ed, a no el adso p ion echnique was also employed. I was shown
ha hyd ophobic DESs can be suppo ed in a po ous il e and be used as
adso p ion ma e ial o success ully emo e mic opollu an s om wa e
(chap e 3.4). Mo eo e , he adso p ion p ocess he e de eloped is a e y
in e es ing app oach, since i is e icien and sus ainable, due o he low
Chap e 1.1
38
quan i y o sol en used, and he possible euse o se e al cycles wi hou
losing e iciency.
Chap e 4 is di ided in sub-chap e s 4.1 and 4.2 and p esen s a
compa ison be ween hyd ophilic and hyd ophobic amilies o DES. Since
hese sol en s a e equen ly p oposed as g een al e na i es o adi ional
sol en s, i is impo an o unde s and he di e ences be ween hei
physical p ope ies. Fo example, pola i y plays an impo an ole in
sol a ion phenomena and i is impo an o unde s and a ini y o
ex ac ions. The e o e, s udies h ough sol a och omic esponses o UV-
is abso p ion p obes o di e en amilies o DESs we e conduc ed. On
he o he hand, Chap e 4.2 explo es he design o no el DES composed
o a sodium sal based on a y acids which can be di ec ly compa ed wi h
hose composed exclusi ely by a y acids. The in oduc ion o ino ganic
ca ions in DES b ings some pa ial wa e solubili y beha iou wi hou
comp omising he DES chemical s abili y.
Finally, in Chap e 5, all esul s epo ed and discussed du ing he hesis
a e compiled and main conclusions a e e ea ed. No el di ec ions and
pe spec i es a e p esen ed, and u u e wo k highligh ed. A doo o new
possibili ies and challenges o u u e esea ch is widely opened.
6. Re e ences
1. Polle , P.; Da ey, E. A.; U eña-Bena ides, E. E.; Ecke , C. A.; Lio a, C.
L., Sol en s o sus ainable chemical p ocesses. G een Chemis y 2014,
16 (3), 1034-1055.
2. Cal o-Flo es, F. G.; Mon eagudo-A ebola, M. J.; Dobado, J. A.; Isac-
Ga cía, J., G een and Bio-Based Sol en s. Topics in Cu en Chemis y
2018, 376 (3), 18.
3. Cla ke, C. J.; Tu, W.-C.; Le e s, O.; B öhl, A.; Halle , J. P., G een and
Sus ainable Sol en s in Chemical P ocesses. Chemical Re iews 2018,
118 (2), 747-800.
In oduc ion: s a e-o - he-a and hesis mo i a ion
39
4. Wa ne , J. C.; Cannon, A. S.; Dye, K. M., G een chemis y.
En i onmen al Impac Assessmen Re iew 2004, 24 (7), 775-799.
5. Anas as, P.; Eghbali, N., G een Chemis y: P inciples and P ac ice.
Chemical Socie y Re iews 2010, 39 (1), 301-312.
6. Vanda, H.; Dai, Y.; Wilson, E. G.; Ve poo e, R.; Choi, Y. H., G een
sol en s om ionic liquids and deep eu ec ic sol en s o na u al deep
eu ec ic sol en s. Comp es Rendus Chimie 2018, 21 (6), 628-638.
7. CHAPTER 1 In oduc ion o Sol en s and Sus ainable Chemis y. In
Sus ainable Sol en s: Pe spec i es om Resea ch, Business and
In e na ional Policy, The Royal Socie y o Chemis y: 2017; pp 1-34.
8. Cla k, J. H.; Ta ene , S. J., Al e na i e Sol en s:  Shades o G een.
O ganic P ocess Resea ch & De elopmen 2007, 11 (1), 149-155.
9. Abbo , A. P.; Cappe , G.; Da ies, D. L.; Rasheed, R. K.; Tamby ajah,
V., No el sol en p ope ies o choline chlo ide/u ea mix u es. Chemical
Communica ions 2003, (1), 70-71.
10. Abbo , A. P.; Boo hby, D.; Cappe , G.; Da ies, D. L.; Rasheed, R. K.,
Deep Eu ec ic Sol en s Fo med be ween Choline Chlo ide and Ca boxylic
Acids:  Ve sa ile Al e na i es o Ionic Liquids. Jou nal o he Ame ican
Chemical Socie y 2004, 126 (29), 9142-9147.
11. Smi h, E. L.; Abbo , A. P.; Ryde , K. S., Deep Eu ec ic Sol en s (DESs)
and Thei Applica ions. Chemical Re iews 2014, 114 (21), 11060-11082.
12. Choi, Y. H.; an Sp onsen, J.; Dai, Y.; Ve be ne, M.; Hollmann, F.;
A ends, I. W. C. E.; Wi kamp, G.-J.; Ve poo e, R., A e Na u al Deep
Eu ec ic Sol en s he Missing Link in Unde s anding Cellula Me abolism
and Physiology? Plan Physiology 2011, 156 (4), 1701-1705.
13. Flo indo, C.; Oli ei a, F. S.; Rebelo, L. P. N.; Fe nandes, A. M.;
Ma ucho, I. M., Insigh s in o he Syn hesis and P ope ies o Deep Eu ec ic
Sol en s Based on Cholinium Chlo ide and Ca boxylic Acids. ACS
Sus ainable Chemis y & Enginee ing 2014, 2 (10), 2416-2425.
14. Lima, F.; Gou enaux, J.; B anco, L. C.; Sil es e, A. J. D.; Ma ucho, I.
M., Towa ds a sul u clean uel: Deep ex ac ion o hiophene and
dibenzo hiophene using polye hylene glycol-based deep eu ec ic sol en s.
Fuel 2018, 234, 414-421.
15. G udniewska, A.; de Melo, E. M.; Chan, A.; Gniłka, R.; Bo a yński, F.;
Ma ha u, A. S., Enhanced P o ein Ex ac ion om Oilseed Cakes Using
CHAPTER 2.1
No el Men hol-based Eu ec ic Mix u es:
Hyd ophobic Low Viscosi y Sol en s

No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
3
Adap ed om: Be na do D. Ribei o, C. Flo indo, Lucas C. I ,
Ma ia A. Z. Coelho, I. M. Ma ucho, No el Men hol-based Eu ec ic
Mix u es: Hyd ophobic Low Viscosi y Sol en s, ACS Sus ainable
Chemis y (2015), 3, 2469-2477.
Be na do d. Ribei o and Lucas C. I we e in ol ed in he syn hesis
o he new compounds as well as pe o med he biomolecules
ex ac ion expe imen s. The au ho con ibu ed o he execu ion o
he he mophysical p ope ies and cha ac e iza ion expe imen s
desc ibed in his chap e , as well as in ol ed in he discussion and
in e p e a ion o esul s and he p epa a ion o he manusc ip .
Chap e 2.1.
48
CONTENT
ABSTRACT ........................................................................................................ 50
1. INTRODUCTION .............................................................................. 50
2. EXPERIMENTAL SECTION ............................................................ 54
2.1. MATERIALS…………………………………………………… 54
2.2. METHODOLOGIES……………………………………………...54
2.2.1. P epa a ion Me hodology o DESs…………………… 54
2.2.2. NMR Measu emen s………………………………………. 55
2.2.3. FTIR Measu emen s………………………………………. 55
2.2.4. The mophysical P ope ies……………………………... 56
2.2.5. Biomolecules Ex ac ion………………………………… 57
3. RESULTS AND DISCUSSION ........................................................ 57
3.1. THERMAL PROPERTIES………………………………………. 58
3.2. FTIR ANALYSIS……………………………………………….. 59
3.3. THERMOPHYSICAL PROPERTIES……………………………... 61
3.4. BIOMOLECULES PARTITION…………………………………... 70
4. CONCLUSIONS ............................................................................... 74
5. ACKNOWLEDGEMENTS ................................................................ 74
6. SUPPLEMENTARY INFORMATION ............................................... 75
6.1. CHARACTERIZATION OF EUTECTIC MIXTURES………………. 75
7. REFERENCES ................................................................................. 88
No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
49
Chap e 2.1.
50
Abs ac
Inspi ed by one o he majo p oblems in pha maceu ical indus y, we
ad an ageously used he o ma ion o eu ec ic mix u es o syn hesize new
sol en s. The aim o his wo k is o iden i y low iscosi y, cheap,
biodeg adable and hyd ophobic eu ec ic sol en s om na u al esou ces.
Consequen ly, no el eu ec ic mix u es based on DL-men hol and na u ally
occu ing acids, namely py u ic acid, ace ic acid, L-lac ic acid and lau ic acid,
we e syn hesized and a e he e epo ed o he i s ime. The ob ained DL-
men hol-based eu ec ic mix u es we e analysed using NMR and FTIR
spec oscopy in o de o check hei s uc u es and pu i ies and o con i m he
in e ac ion o he wo compounds leading o he eu ec ic o ma ion. Impo an
sol en he mophysical p ope ies, such as densi y and iscosi y, o he
p epa ed eu ec ic sol en s wi h di e en wa e con en s (d ied and wa e -
sa u a ed) we e measu ed. Finally, and aking ad an age o hei hyd ophobic
cha ac e , namely he o ma ion o wo phases wi h wa e a oom
empe a u e, ou di e en biomolecules, ca eine, yp ophan, isoph halic
acid and anillin, we e ex ac ed and he ex ac ion e iciencies o he
p epa ed eu ec ic sol en s compa ed.
1. In oduc ion
One o he majo challenges in mode n chemis y and chemical enginee ing
is he o mula ion o new sol en s, which simul aneously mee he G een
Chemis y c i e ia and ha e he abili y o dissol e as la ge as possible
spec um o solu es. Cu en ly wo majo classes o sol en s, ionic liquids
(ILs) and eu ec ic mix u es,1,2 a e being de eloped and used by academia
and indus y. Rega ding ILs, hei comme cial a ailabili y p omo ed he
p oduc ion o a la ge body o in o ma ion conce ning hei he mophysical and
anspo p ope ies, oxici y and phase equilib ia, and consequen ly, new
applica ions can now be p ope ly e alua ed. Con e sely, eu ec ic mix u es,
No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
51
and in pa icula deep eu ec ic sol en s, p epa ed om he combina ion o a
sal o an ionic liquid wi h a neu al compound, a e s ill in he in ancy, lacking
o ganiza ion and p ope ies sys ema iza ion. Mos o he eu ec ic mix u es
p oposed so a a e based on ma e ials om enewable esou ces, such as
ca boxylic acids, suga s, amines, polyols, e c, and al hough hey a e cheap
and usually conside ed non oxic and biodeg adable, hei inhe en oxici y
and biodeg adabili y needs o be e alua ed case by case. Fo example, i has
been showed ha choline chlo ide: glucose and choline chlo ide: glyce ol
deep eu ec ic sol en s display low cy o oxici y, while choline chlo ide: oxalic
acid possesses mode a e cy o oxici y. Ne e heless, hese h ee deep
eu ec ic sol en s we e classi ied as ′ eadily biodeg adable′ based on hei
high le els o mine aliza ion. I has been showed ha some deep eu ec ic
sol en s can be a good eplacemen o analogous ILs, due o he simila i y
be ween hei p ope ies and he ac ha hey can be ad an ageously
p epa ed in a cheape , quicke and easie way.3 The p epa a ion o deep
eu ec ic sol en s depends usually on he es ablishmen o hyd ogen bonds
be ween he wo compounds, one ac ing as hyd ogen bond dono and he
o he as hyd ogen bond accep o . Howe e , as in o he luids whe e
hyd ogen bonds a e he dominan in e ac ions, one o he majo d awbacks o
his class o sol en s is hei gene al high iscosi y when compa ed o o ganic
sol en s and e en some imes o ILs o e en hei solid/pas y/gel-like s a e.
The main pu pose o his wo k is o iden i y cheap and biodeg adable
sol en s based on eu ec ic mix u es, which can be p epa ed om na u al
esou ces. A quick look in o he eu ec ic sol en s om na u al esou ces ha
ha e been p oposed in he li e a u e, ells us ha he as majo i y, i no all,
a e hyd ophilic o e y hyd ophilic. Consequen ly, he eu ec ic mix u es om
enewable esou ces wi h a ce ain hyd ophobic cha ac e , which displayed
liquid-liquid equilib ia wi h wa e , a e in need. Due o i s e y small solubili y in
wa e (0.46 mg/ml a 25ºC),4 men hol is a good candida e o p epa e
sus ainable, cheap and hyd ophobic sol en s using he o ma ion o eu ec ic
mix u es app oach. Men hol can be ex ac ed om Men ha species, i is

Chap e 2.1.
52
abundan and cheap (~€60/kg). Eu ec ic mix u es con aining men hol ha e
been epo ed in he pha maceu ical ield. Fo example, men hol and
bo neol5,6 and campho 7 and N-E hyl-5-me hyl-2-(1-
me hyle hyl)cyclohexaneca boxamide8 eu ec ic mix u es ha e been p epa ed
and used as ehicles o ansde mal d ug deli e y, while eu ec ic mix u es o
men hol and es os e one9, ibup o en10,11, lidocaine12, ubiquinone13, cap op il7,
daidzein5, luconazole6 ha e been used as analgesic, an imic obial,
an ip u i ic, an i-in lamma o y and an i ussi e14,15 compounds. The mal
p ope ies o some o hese eu ec ic mix u es ha e been esea ched: o
example while L-men hol/ es os e one 80:20 mola a io and L-
men hol/ubiquinone 70:30 mola a io display a mel ing empe a u e (Tm) o
39.3 ºC9 and 38.5 ºC13, espec i ely, L-men hol/lidocaine 70:30 mola a io
has a lowe Tm o 26 ºC12, and L-men hol/ibup o en 70:30 mola a io e en
lowe , 19 ºC10. These examples clea ly illus a e he ole o he second
componen on he mel ing empe a u e o hese eu ec ics.
In his wo k, ou eu ec ic mix u es composed o DL-men hol and di e en
acids we e p epa ed jus by hea ing and mixing he pu e compounds and
s udied, as lis ed in Table 1.
Table 1. Summa y o di e en eu ec ic mix u es s udied in his wo k using DL-
men hol as hyd ogen bond accep o and di e en hyd ogen bond dono s.
Hyd ogen
Bond Dono
Mola
a io
Aspec
Ace ic acid
1:1
T anspa en liquid
Py u ic acid
1:2
T anspa en yellow liquid
Lac ic acid
1:2
T anspa en liquid
Lau ic acid
2:1
T anspa en liquid
No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
53
The chemical s uc u es o DL-men hol and he used o ganic acids a e
depic ed in Figu e 1.
Figu e 1. Chemical s uc u e o he compounds used o he DL-men hol-
based eu ec ic mix u es s udied in his wo k.
In o de o e alua e he eal echnological alue o he p epa ed eu ec ic
mix u es as sol en s, ele an he mophysical p ope ies, such as densi y and
iscosi y, we e measu ed, wi hin he empe a u e ange indica ed by he DSC
and TGA s udies and a di e en wa e con en s, d ied and wa e -sa u a ed.
Finally, and aking ad an age o he hyd ophobic cha ac e o hese eu ec ics,
and hus hei wo liquid phase o ma ion in he p esence o wa e a oom
empe a u e, he ex ac ion e iciency o ou di e en biomolecules, ca eine,
yp ophan isoph halic acid and anillin om he wa e phase o he eu ec ic
mix u e phase was e alua ed in e ms o hei pa i ion coe icien s.
Lau ic acid
Ace ic acid
Py u ic acid
L-Lac icacid
DL-Men hol
Chap e 2.1.
54
2. Expe imen al Sec ion
2.1. Ma e ials
DL-men hol ( 95% mass ac ion pu i y), py u ic acid (pu i y > 98%), ace ic
acid (pu i y ≥ 99.7%), lau ic acid (pu i y > 98%), ca eine (pu i y 99%), anillic
acid (pu i y  97%, e acycline (pu i y  98%) and yp ophan (pu i y  98%)
we e pu chased om Sigma-Ald ich and used as ecei ed. L-lac ic acid
solu ion (81 w % in wa e ) was supplied by Fluka. The wa e used was
ul apu e, double dis illed, passed h ough a e e se osmosis sys em and
u he ea ed wi h a Milli-Q plus 185 wa e pu i ica ion appa a us.
2.2. Me hodologies
2.2.1. P epa a ion Me hodology o DESs
DL-men hol-based eu ec ic mix u es we e p epa ed by adding di e en
hyd ogen bond dono s (polye hylene glycol, monoe hylene glycol,
choles e ol, py u ic acid, ace ic acid, L-lac ic acid, bu y ic acid, hexanoic acid
and lau ic acid) o DL-men hol in di e en mola a ios. The mix u e o he wo
compounds was hen hea ed up o 50 ºC o 15 min and hen cooled down
slowly un il i eaches he oom empe a u e. Some o hese eu ec ic mix u es
yielded ei he pas y compounds o liquids wi h mel ing poin s highe han ha
o DL-men hol. O he s also did no yield an eu ec ic mix u e (such as in he
case when glycols we e used) and hus o he a ios we e a emp ed wi hou
success. Consequen ly, hese eu ec ic mix u es we e disca ded. Only ou
eu ec ic mix u es o DL-men hol and di e en acids we e s udied in his wo k,
as lis ed in Table 1. Fo he p epa a ion o he d ied samples, he DL-
men hol-based eu ec ic mix u es we e main ained o a leas ou days in a
schlenk unde high acuum (ci ca 10-1 Pa) a oom empe a u e. Fo he
wa e sa u a ed samples, bina y mix u es con aining wa e and he eu ec ic
No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
55
mix u e we e p epa ed, igo ously shaken and le o equilib a e o a day.
Samples o he eu ec ic mix u e phase we e ca e ully aken wi h a sy inge.
The amoun o wa e p esen in each d ied and sa u a ed sample was
measu ed, in o de o in e hei ela i e hyg oscopici y, and hus
hyd ophobici y. The wa e con en was de e mined by Ka l Fishe i a ion
(model Me ohm 831 Ka l Fishe coulome e ). A e p epa a ion o eu ec ic
mix u es, p o on and ca bon Nuclea Magne ic Resonance (1H and 13C NMR)
and Fou ie T ans o m In a ed Spec oscopy (FTIR) we e used o check he
eu ec ic mix u es s uc u es and pu i ies and o con i m he in e ac ion
be ween wo compounds leading o he eu ec ic o ma ion.
2.2.2. NMR Measu emen s
All he expe imen s we e ca ied ou on a B uke AVANCE 400 spec ome e
ope a ed a oom empe a u e wi h 16 and 500 scans o he 1H NMR and 13C
NMR spec a, espec i ely. The eu ec ic mix u es samples we e p epa ed on
5 mm NMR ubes by weigh app oxima ely 30 mg o eu ec ic mix u e and hen
adding 0.5 mL o deu e a ed chlo o o m (CDCl3). The homogenei y o he
sample was assu ed by o ex mixing.
2.2.3. FTIR Measu emen s
FTIR measu emen s we e ca ied ou using a B üke IFS66/S FTIR
spec ome e (B üke Dal onics, MA, USA) wi h a single e lec ion ATR cell
(Du aDisk, equipped wi h a diamond c ys al). The da a ela i e o spec al
egion we e eco ded be ween 4000 cm-1 and 600 cm-1 a oom empe a u e.
Fo each sample, 290 scans we e eco ded a a spec al esolu ion o 4 cm-1
and i e eplica spec a we e collec ed in o de o e alua e ep oducibili y
(OPUS 5.0).
Chap e 2.1.
62
Table 2. Molecula weigh (MW) and wa e con en , in mass pe cen age (w
%), o he d ied and wa e -sa u a ed DL-men hol-based eu ec ic mix u es
s udied in his wo k.
Eu ec ic Mix u es
MW
Wa e con en
(w %)
(g.mol-1)
D ied
Sa u a ed
DL-men hol: ace ic acid
108.16
0.429
1.567
DL-men hol: py u ic acid
110.79
1.023
1.268
DL-men hol: lac ic acid
112.14
0.153
1.634
DL-men hol: lau ic acid
170.95
0.276
1.237
Fo example, Flo indo e al.3 epo ed he wa e con en o wa e sa u a ed
deep eu ec ic sol en s composed o a sal , cholinium chlo ide, and se e al
o ganic di-acids, wi h alues be ween 14-19 w %, and monoacids, such as
le ulinic acid wi h wa e con en nea 10 w %. Consequen ly, he
hyd ophobici y o he DL-men hol-based eu ec ic mix u es is much highe
han hose p oduced om sal s, p obably also due o he p esence o cha ges
in hese las ones.
The expe imen al densi y esul s o he d ied and wa e -sa u a ed (Table 2)
samples o he ou p epa ed eu ec ic mix u es as a unc ion o empe a u e
a e plo ed in Figu e 4.

No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
63
Figu e 4. Expe imen al densi ies (ρ) o he d ied and wa e -sa u a ed eu ec ic
mix u es as unc ion o empe a u e: DL-men hol: ace ic acid (●), DL-men hol:
py u ic acid (), DL-men hol: lac ic acid (), DL-men hol: lau ic acid (▲).
The illed symbols co espond o he d ied samples and he emp y symbols
co espond o he wa e -sa u a ed samples. The lines ep esen he i ed
da a calcula ed using equa ion (1).
The densi y da a a e p esen ed in Tables S2 in he Supplemen a y
In o ma ion. I is e y di icul o ex ac conclusions ega ding he ela ionship
be ween he chemical s uc u e o he acids p esen in he eu ec ic mix u es
and he espec i e he mophysical p ope ies since di e en mola a ios we e
used. Only in he case o he eu ec ic mix u es con aining py u ic and L-lac ic
acids, bo h de i ed om p opanoic acid, he same mola a io (1:2) was used.
Howe e , e en hen o hese DES, a s aigh o wa d compa ison canno be
clea ly es ablished. Se e al explana ions can be pu o wa d, such as he
possibili y o dime s o ma ion in L-lac ic acid and he con o ma ional e ec s
D ied
T (K)
280 300 320 340 360

(g.cm-3)
0.85
0.90
0.95
1.00
1.05
Col 2 s Col 3
Col 2 s Col 4
Col 2 s Col 5
Col 2 s Col 6
Col 8 s Col 9
Col 8 s Col 10
Col 8 s Col 11
Col 8 s Col 12
x column s y column
x column 1 s y column 1
x column 2 s y column 2
x column 3 s y column 3
x column 4 s y column 4
x column 5 s y column 5
x column 6 s y column 6
x column 7 s y column 7
Chap e 2.1.
64
be ween he wo ca boxyl g oups in he py u ic acid, o accoun o his
beha iou .20
I can be obse ed ha gene ally he p esence o wa e inc eases he densi y
o he eu ec ic mix u es. The only excep ion is he DL-men hol: lac ic acid
whe e a small dec ease was obse ed. Howe e , he e ec o wa e in much
mo e p onounced o he eu ec ic mix u es con aining py u ic and lac ic
acids, which can be p obably linked o p esence o subs i uen g oups which
a e able o in e ac wi h wa e ia hyd ogen bonding. The densi ies o he
eu ec ic mix u es con aining he linea acids, ace ic and lau ic acids a e less
a ec ed by he wa e p esence. In ac , d ied and sa u a ed DL-men hol:
py u ic acid p esen a e y small di e ence in he wa e con en which is
howe e e lec ed in he densi y o he wo mix u es.
The densi y dec eases linea ly wi h empe a u e o all d ied and wa e
sa u a ed samples, in he whole empe a u e ange s udied. A linea equa ion
was used o exp ess he co ela ion wi h he empe a u e:
ρ =a + bT
(eq. 1)
whe e ρ co esponds o densi y in g·cm-3, T is he empe a u e in K and a and
b a e he i ing pa ame e s. The adjus able pa ame e s (a and b) we e
de e mined om he i ing o he expe imen al densi y da a, om he
equa ion 1 and a e p esen ed in Table 3, as well as he he mal expansion
coe icien s (αp) we e de e mined and a e p esen ed in Table S4 in he
Supplemen a y in o ma ion.
No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
65
Table 3. Fi ed alues o pa ame e s, a and b, by equa ion (1) and s anda d
de ia ion σ, o he densi y o d ied and wa e -sa u a ed eu ec ic mix u es as
a unc ion o empe a u e.
The he mal expansion coe icien alues ob ained o he eu ec ic mix u es
a y be ween 7.891 o 8.998 x 104 K-1 in he case o he d ied samples, and in
gene al a e up o 2 – 6 % highe o he wa e -sa u a ed samples. The
highes he mal expansion coe icien s we e obse ed o he DL-men hol:
ace ic acid, whe eas he DL-men hol: lac ic acid displayed he lowes ones.
The mola olumes (Vm) o d ied and wa e -sa u a ed eu ec ic mix u es
s udied in his wo k we e calcula ed om he densi y esul s and a e
p esen ed in Table S5 in he Supplemen a y In o ma ion. Mola olumes we e
de e mined o a ange o empe a u es om 293.15 K and 353.15 K, and
we e ob ained om he ollowing equa ion:
Vm = M
ρ
(eq. 2)
Eu ec ic
Mix u es
a
(g·cm-3)
b (10-4)
(g·cm-3·K)
σ*
D ied
Sa .
D ied
Sa .
D ied
Sa .
DL-men hol:
ace ic acid
1.183
1.147
-0.8418
-0.7901
4.7 E-04
4.2E-04
DL-men hol:
py u ic acid
1.246
1.194
-0.8407
-0.8341
4.1 E-04
2.8E-04
DL-men hol:
lac ic acid
1.278
1.149
-0.8187
-0.7749
3.2 E -
04
2.5E-04
DL-men hol:
lau ic acid
1.112
1.118
-0.7308
-0.7442
3.3 E -
04
3.3 E -04
*𝜎=(∑(𝜌𝑖𝑒𝑥𝑝− 𝜌𝑖𝑐𝑎𝑙)2
𝑛−𝑣 )0.5 whe e n is he numbe o expe imen al poin s, he numbe
o adjus able pa ame e s.
Chap e 2.1.
66
whe e M co esponds o he mola mass in g·mol-1 and ρ is he densi y in
g·cm-3. The mola olumes o he wa e -sa u a ed eu ec ic mix u es
con aining py u ic and lac ic acid a e highe han hose o he d ied mix u es,
p obably due o he wa e p esen . The mola olumes inc ease in he
ollowing o de : DL-men hol: lac ic acid < DL-men hol: py u ic acid < DL-
men hol: ace ic acid < DL-men hol: lau ic acid. Usually, he mola olumes
a e in ag eemen wi h he mola mass o each compound, which does no
happen in his s udy, since he eu ec ic mix u e wi h he highes mola mass
does no exhibi he highes mola olume. This can be p obably be explained
by chemical and s uc u al di e ences in hyd ogen bond dono s (he e he
p esence o dimme s migh play an impo an ole), he di e en p opo ions
be ween DL-men hol and hyd ogen bond dono s and he di e en amoun s o
wa e . The mola olume o he d ied and sa u a ed DL-men hol: lau ic acid
eu ec ic mix u e do no signi ican ly di e om each o he , due o minimal
di e ence in hei wa e con en . As o he d ied and sa u a ed DL-men hol:
ace ic acid mix u e he mola olumes, hey a e also e y simila in
ag eemen o wha was obse ed o hei densi y alues.
The expe imen al iscosi y da a o he d ied and he wa e -sa u a ed
samples o eu ec ic mix u es, as a unc ion o empe a u e, a e depic ed in
Figu e 5 and epo ed in Table S3 in Supplemen a y In o ma ion.
No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
67
Figu e 5. Expe imen al iscosi ies (ƞ) o he d ied and wa e -sa u a ed
eu ec ic mix u es as unc ion o empe a u e: DL-men hol: ace ic acid (●), DL-
men hol: py u ic acid (), DL-men hol: lac ic acid (), DL-men hol: lau ic
acid (▲). The illed symbols co espond o he d ied samples and he emp y
symbols co espond o he wa e -sa u a ed samples. The lines ep esen he
i ed da a calcula ed using equa ion (2).
The iscosi ies o he d ied samples o he eu ec ic mix u es inc ease in he
ollowing o de : DL-men hol: ace ic acid < DL-men hol: lau ic acid < DL-
men hol: py u ic acid < DL-men hol: lac ic acid. I can be obse ed ha
despi e he simila chemical s uc u e o he py u ic and lac ic acids and he
ac ha hey a e in same p opo ion in he eu ec ic mix u es hey display e y
di e en iscosi y alues. In ac , DL-men hol: lac ic acid mix u es iscosi y is
one o de o magni ude highe han ha o he o he h ee eu ec ic mix u es
s udied in his wo k. Rega ding he wa e con en , wo dis inc ypes o
beha iou s can be obse ed, independen ly o he DL-men hol: ca boxylic
acid p opo ions: o he eu ec ic mix u es con aining lau ic and ace ic acids,
T (K)
290 300 310 320 330 340 350 360

(mPA.s)
0
100
200
300
400
Col 2 s Col 3
Col 2 s Col 4
Col 2 s Col 5
Col 2 s Col 6
Col 2 s Col 9
Col 2 s Col 10
Col 2 s Col 11
Col 2 s Col 12

Chap e 2.1.
68
he p esence o wa e inc eases he iscosi y, while o he o he wo
mix u es, he opposi e beha iou is obse ed, in he whole empe a u e
ange. These ac s clea ly illus a e he g ea a ie y o beha iou s ha hese
eu ec ic mix u es in pa icula display, which canno be a p io i p edic ed. The
lack o sys ema iza ion o he eu ec ic mix u es and deep eu ec ic mix u es
he mophysical p ope ies is p obably due o he la ge a ie y o compounds
ha a e possible o p epa e, leading o compounds which p ope ies a e no
possible o compa e.
The expe imen al iscosi y alues we e i ed as a unc ion o empe a u e,
using he Vogel-Fulche -Tammann (VFT) model using he ollowing equa ion:
lnƞ= A𝜂+B𝜂
(T−C𝜂) (eq. 3)
whe e η is he iscosi y in mPa·s, T is he empe a u e in K, and Aη, Bη, and
Cη a e adjus able pa ame e s. The adjus able pa ame e s we e de e mined
om he i ing o he expe imen al alues and a e lis ed in Table 4.
Table 4. Fi ed pa ame e s o VFT model gi en by Equa ion 3 and espec i e
co ela ion coe icien (R2) o d ied and wa e -sa u a ed eu ec ic mix u es.
Aƞ
(mPa.s)
Bƞ
(K)
Cƞ
(K)
R2
DL-men hol:
ace ic acid
D ied
-3.213
595.666
187.422
1
Sa u a ed
-3.689
677.581
196.432
0.9999
DL-men hol:
py u ic acid
D ied
-2.423
464.436
218.436
0.9999
Sa u a ed
-2.782
476.198
215.341
1
DL-men hol:
lac ic acid
D ied
-3.381
745.522
213.049
1
Sa u a ed
-3.902
725.375
203.865
1
DL-men hol:
lau ic acid
D ied
-3.599
815.874
178.123
0.9999
Sa u a ed
-3.883
887.449
171.033
0.9999
No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
69
The ac i a ion ene gy was calcula ed based on he iscosi y dependence wi h
empe a u e as ollows:
Ea=R.∂(lnη)
∂(1
T)=R.( Bη
(Cη
2
T2−2Cη
T+1)) (eq. 4)
whe e η is he iscosi y, T is he empe a u e, Bη and Cη a e he adjus able
pa ame e s ob ained om equa ion 3 and R is he uni e sal gas cons an .
The alues o he ac i a ion ene gies o he ou p epa ed eu ec ic mix u es
a e p esen ed in Table 5.
Table 5. Ac i a ion ene gy alues (Ea (KJ/mol)) o d ied and wa e -sa u a ed
eu ec ic mix u es as a unc ion o empe a u e, de e mined by equa ion 4.
T (K)
DL-men hol:
ace ic acid
DL-men hol:
py u ic acid
DL-men hol:
lac ic acid
DL-men hol:
lau ic acid
D ied
Sa .
D ied
Sa .
D ied
Sa .
D ied
Sa .
293.15
38.1
51.7
59.5
56.2
83.0
65.0
44.1
42.5
298.15
35.9
48.4
54.0
51.3
76.1
60.3
41.9
40.6
303.15
33.9
45.5
49.5
47.2
70.2
56.3
39.9
38.8
308.15
32.3
42.9
45.6
43.6
65.0
52.7
38.1
37.3
313.15
30.7
40.6
42.2
40.6
60.7
49.5
36.5
35.8
318.15
29.3
38.5
39.3
37.9
56.8
46.7
35.1
34.6
323.15
28.1
36.6
36.8
35.6
53.4
44.3
33.7
33.3
328.15
26.9
34.9
34.5
33.5
50.4
42.0
32.5
32.2
333.15
25.9
33.4
32.6
31.7
47.7
40.1
31.3
31.2
338.15
24.9
32.1
30.8
30.1
45.3
38.2
30.3
30.2
343.15
24.1
30.8
29.2
28.5
43.1
36.6
29.3
29.3
348.15
23.2
29.7
27.8
27.2
41.2
35.1
28.4
28.5
353.15
22.5
28.6
26.5
26.0
39.4
33.8
27.6
27.8
Chap e 2.1.
70
The use o equa ion 4 o desc ibe he empe a u e beha iou o iscosi y
allows he discussion o he ene gy ba ie o a luid o shea s ess, Ea,
alues. The highe he Ea, he mo e di icul i is o he molecules/agg ega es
o mo e pas each o he . This can be a di ec consequence o he size o
en anglemen o he molecules/agg ega es and/o he p esence o s onge
in e ac ions wi hin he luid. Rega ding he size o he hyd ogen bond dono s
and using he calcula ed mola olume calcula ed in Table S6, i can be
obse ed ha his pa ame e does no g ea ly in luence he iscosi y, since
DL-men hol: lau ic acid has a la ge Vm and i is no he mos iscous mix u e.
On he o he hand, i can be obse ed ha he mix u es con aining lac ic acid
a e he mos iscous, which clea ly indica es he ele an ole o he hyd oxyl
subs i uen g oup in he es ablishmen o hyd ogen bonds, hus inc easing he
iscosi y. In he case o he py u ic acid, he ca boxyl g oup is no as good
hyd ogen bond dono as he hyd oxyl, and hus i s capaci y o es ablish
hyd ogen bonds in much smalle han ha o lac ic acid. Bo h he wo eu ec ic
mix u es con aining linea non subs i u ed ca boxylic acids, lau ic and ace ic
acids, ha e he smalles Ea alues, in ag eemen wi h hei small iscosi y.
Only in his case, he di e ences in Vm accoun s o he di e ences in Ea and
hus, in iscosi y.
The Ea alues ob ained o wa e sa u a ed samples a e simila o each o he ,
indica ing ha he p esence o wa e , e en in di e en amoun s, and in
mix u es wi h di e en mola a ios, leads an easie and simila lux o he
di e en molecules/agg ega es.
3.4. Biomolecules Pa i ion
Fou model biomolecules, namely ca eine, e acycline, yp ophan and
anillic acid, we e used o illus a e he usage o he p oposed eu ec ic
mix u es as ex ac ion sol en s o biomolecules om aqueous solu ions.
Since he p oposed eu ec ic mix u es a e all pa ially miscible wi h wa e , no
addi ion o sal ing ou agen s, such as sal s, polyme s e c, is necessa y o
No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
71
achie e a wo-phase sys em. The pa i ion coe icien o each biomolecule i,
Ki, was calcula ed as he a io o hei concen a ion in bo h he eu ec ic
mix u e- ich phase (Ci,EM) and in he wa e - ich phase (Ci,AQ), acco ding o he
ollowing equa ion:
𝐾𝑖= 𝐶𝑖𝐸𝑀
𝐶𝑖𝐴𝑄
(eq. 5)
The esul s ob ained o he ou biomolecules es ed a e p esen ed in Table
6.
Table 6. Pa i ion coe icien s, Ki, o he di e en biomolecules be ween DL-
men hol-based eu ec ic mix u es and aqueous solu ions. The pKa o he
biomolecules and hei wa e solubili y is also shown.
Eu ec ic Mix u es
pH
Ca eine
T yp ophan
Vanillin
Isoph halic
Acid
DL-men hol: ace ic
acid
1.91
1.81 ± 0.01
9.05 ± 0.33
4.74 ± 0.03
8.52 ± 0.23
DL-men hol: lac ic
acid
1.18
37.3 ± 0.09
14.76 ± 0.17
3.03 ± 0.15
3.31 ± 0.12
DL-men hol: lac ic
acid
1.47
1.16 ± 0.01
2.85 ± 0.04
6.65 ± 0.04
12.94 ±
0.10
DL-men hol: lau ic
acid
3.74
1.09 ± 0.01
5.23 ± 0.12
7.02 ± 0.01
1.96 ± 0.03
pKa*
14.0
2.38; 9.39
7.4
3.7; 4.6
Wa e Solubili y*
(mg/mL) a 25 ºC
16
11.4
10
0.13
*h p://pubchem.ncbi.nlm.nih.go /
Chap e 2.1.
78
Figu e S6. 13C NMR spec a o DL-men hol: py u ic acid eu ec ic mix u e
in CDCl3. The s uc u e and numbe ing o bo h compounds is also
depic ed.
Figu e S7. 13C NMR spec a o DL-men hol: lau ic acid eu ec ic mix u e in
CDCl3. The s uc u e and numbe ing o bo h compounds is also depic ed.
9
2
3
56
8
12
1, 4, 7, 10
1
CDCl3
11
1 1
3
2
4
510
8
9
6
7
12
11
10
1 1
3
2
4
5
8
9
6
7
9
2
35
68 4, 7, 11, 12
1
CDCl3
10
11
12
12
12
12
12 12
12 12
13 14
10

No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
79
Figu e S8. 13C NMR spec a o DL-men hol: lac ic acid eu ec ic mix u e in
CDCl3. The s uc u e and numbe ing o bo h compounds is also depic ed.
FTIR spec a o eu ec ic mix u es
Figu e S9. FTIR spec a o he pu e DL-men hol, py u ic acid and he
eu ec ic mix u e o DL-men hol and py u ic acid (1:2 mola a io).
1 1
3
2
4
5
8
9
6
7
11 92
3
5
6
8
12
1, 4, 7 1
CDCl3
10
12
11
10
C: Use s use Desk op Bolsa In es igação DES DES_men ol FTIR DL-men hol.3 DL-men hol SENSITIVITY TEST MIR, DTGS, Globa
C: Use s use Desk op Bolsa In es igação DES DES_men ol FTIR DES_men ol+py u ic acid.3 DES_men ol+py u ic acid SENSITIVITY TEST MIR, DTGS, Globa
C: Use s use Desk op Bolsa In es igação DES DES_men ol FTIR py u ic acid.2 py u ic acid SENSITIVITY TEST MIR, DTGS, Globa
2014/07/24
2014/07/24
2014/07/24
1000150020002500300035004000
Wa enumbe cm-1
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0
ATR Uni s
Page 1/1
DL-men hol1:2py u ic acid
Py u ic acid
DL-men hol
Chap e 2.1.
80
Figu e S10. FTIR spec a o he pu e DL-men hol, lau ic acid and he
eu ec ic mix u e o DL-men hol and lau ic acid (2:1 mola a io).
Figu e S11. FTIR spec a o he pu e DL-men hol, lac ic acid and he
eu ec ic mix u e o DL-men hol and lac ic acid (1:2 mola a io).
C: Use s use Desk op Bolsa In es igação DES DES_men ol FTIR DL-men hol.3 DL-men hol SENSITIVITY TEST MIR, DTGS, Globa
C: Use s use Desk op Bolsa In es igação DES DES_men ol FTIR DES_men ol+lau ic acid.0 DES_men ol+lau ic acid SENSITIVITY TEST MIR, DTGS, Globa
C: Use s use Desk op Bolsa In es igação DES DES_men ol FTIR lau ic acid.4 lau ic acid SENSITIVITY TEST MIR, DTGS, Globa
2014/07/24
2014/07/24
2014/07/24
1000150020002500300035004000
Wa enumbe cm-1
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0
ATR Uni s
Page 1/1
DL-men hol2:1Lau ic acid
Lau ic acid
DL-men hol
C: Use s use Desk op Bolsa In es igação DES DES_men ol FTIR DL-men hol.3 DL-men hol SENSITIVITY TEST MIR, DTGS, Globa
C: Use s use Desk op Bolsa In es igação DES DES_men ol FTIR2 DES_men ol_lac ic.0 DES_men ol_lac ic SENSITIVITY TEST MIR, DTGS, Globa
C: Use s use Desk op Bolsa In es igação DES DES_men ol FTIR2 acido_lac ico_des ilado3.0 acido_lac ico_des ilado3 SENSITIVITY TEST MIR, DTGS, Globa
2014/07/24
2014/10/14
2014/10/14
1000150020002500300035004000
Wa enumbe cm-1
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0
ATR Uni s
Page 1/1
DL-men hol1:2Lac ic acid
Lac ic acid
DL-men hol
No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
81
The mal p ope ies o eu ec ic mix u es
TGA analysis
Table S1. Decomposi ion empe a u es (Tdec) o he eu ec ic mix u es
s udied in his wo k.
Pu e compounds
Tdec (ºC)
DL-men hol
168.95
Ace ic acid
▬*
Py u ic acid
164.48
Lac ic acid
229.46
Lau ic acid
292.34
Eu ec ic Mix u es
Tdec (ºC)
DL-men hol: ace ic acid
200.79
DL-men hol: py u ic acid
218.50
DL-men hol: lac ic acid
228.89
DL-men hol: lau ic acid
231.49
*Ace ic acid has a boiling poin a 118 °C, hus was no possible o
de e mine i s decomposi ion empe a u e by TGA measu emen s.
Chap e 2.1.
82
DSC Analysis
Figu e S12. DL-men hol-based eu ec ic mix u es: (A) pu e DL-men hol;
(B) DL-men hol: Ace ic acid (50%); (C) DL-men hol: Py u ic Acid (50%);
(D) DL-men hol: Lac ic acid (66.7%); (E) DL-men hol: Lau ic Acid (66.7%).
No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
83
Figu e S13. E ec o men hol isome s in eu ec ic mix u es: (A) L-Men hol;
(B) D-Men hol; (C) L-Men hol: Lac ic acid; (D) D-Men hol: Lac ic acid; (E)
L-Men hol: Lau ic Acid; (F) D-Men hol: Lau ic Acid).

Chap e 2.1.
84
The mophysical p ope ies o eu ec ic mix u es
Table S2. Expe imen al densi ies (ρ (g·cm-3)) o d ied and wa e -sa u a ed samples o he eu ec ic mix u es as a unc ion
o empe a u e.
T (K)
DL-men hol:
ace ic acid
DL-men hol:
py u ic acid
DL-men hol:
lac ic acid
DL-men hol:
lau ic acid
D ied
Sa u a ed
D ied
Sa u a ed
D ied
Sa u a ed
D ied
Sa u a ed
293.15
0.935
0.915
0.999
0.949
1.038
0.921
0.897
0.8995
298.15
0.931
0.911
0.995
0.945
1.033
0.917
0.894
0.8959
303.15
0.927
0.907
0.991
0.941
1.029
0.914
0.890
0.8923
308.15
0.923
0.904
0.987
0.937
1.025
0.910
0.886
0.8887
313.15
0.919
0.900
0.983
0.933
1.021
0.906
0.883
0.8851
318.15
0.915
0.896
0.978
0.928
1.017
0.902
0.879
0.8815
323.15
0.911
0.892
0.974
0.924
1.013
0.899
0.876
0.8778
328.15
0.906
0.888
0.970
0.920
1.009
0.895
0.872
0.8740
333.15
0.902
0.884
0.966
0.916
1.005
0.891
0.868
0.8702
338.15
0.898
0.880
0.962
0.912
1.001
0.887
0.865
0.8665
343.15
0.894
0.876
0.958
0.908
0.997
0.883
0.861
0.8627
348.15
0.889
0.872
0.953
0.903
0.992
0.879
0.857
0.8588
353.15
0.884
0.867
0.948
0.899
0.988
0.874
0.853
0.8546
No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
85
Table S3. Expe imen al iscosi ies (ƞ (mPa·s)) o d ied and wa e -sa u a ed eu ec ic mix u es as a unc ion o
empe a u e.
T (K)
DL-men hol:
ace ic acid
DL-men hol:
py u ic acid
DL-men hol:
lac ic acid
DL-men hol:
lau ic acid
D ied
Sa u a ed
D ied
Sa u a ed
D ied
Sa u a ed
D ied
Sa u a ed
293.15
11.296
27.751
44.637
28.288
370.860
68.421
33.058
29.689
298.15
8.691
19.454
29.951
19.383
218.927
44.181
24.417
22.076
303.15
6.904
14.258
21.241
13.992
134.253
30.006
18.630
16.957
308.15
5.590
10.752
15.667
10.469
86.529
21.155
14.513
13.286
313.15
4.564
8.234
11.882
7.993
58.840
15.385
11.453
10.527
318.15
3.843
6.561
9.360
6.379
40.711
11.533
9.293
8.587
323.15
3.251
5.277
7.511
5.151
29.467
8.849
7.610
7.057
328.15
2.782
4.310
6.144
4.239
21.951
6.938
6.315
5.873
333.15
2.391
3.522
5.034
3.492
16.954
5.467
5.226
4.872
338.15
2.095
3.000
4.321
3.006
13.119
4.506
4.507
4.201
343.15
1.843
2.548
3.700
2.582
10.460
3.716
3.862
3.599
348.15
1.632
2.183
3.203
2.242
8.487
3.104
3.342
3.107
353.15
1.464
1.866
2.744
1.941
7.013
2.569
2.859
2.650
Chap e 2.1.
86
Table S4. The mal expansion coe icien s (αp) de e mined o d ied and wa e -sa u a ed men hol-based eu ec ic
mix u es. The isoba ic he mal expansion coe icien (αp) was calcula ed h ough 𝛼𝑝 = −1
𝜌(𝛿𝜌
𝛿𝑇)𝑝= −(𝛿ln𝜌
𝛿 𝑇 )𝑝, whe e ρ is
he densi y in g·cm-3, T is he empe a u e in K and p is he p essu e in MPa.
T (K)
αp × 104 (K-1)
DL-men hol:
ace ic acid
DL-men hol:
py u ic acid
DL-men hol:
lac ic acid
DL-men hol:
lau ic acid
D ied
Sa u a ed
D ied
Sa u a ed
D ied
Sa u a ed
D ied
Sa u a ed
293.15
8.998
8.631
8.412
8.787
7.891
8.410
8.144
8.270
298.15
9.039
8.669
8.448
8.825
7.922
8.445
8.177
8.305
303.15
9.080
8.706
8.484
8.865
7.954
8.481
8.211
8.339
308.15
9.121
8.744
8.520
8.904
7.986
8.517
8.245
8.374
313.15
9.163
8.783
8.556
8.944
8.018
8.554
8.279
8.409
318.15
9.205
8.822
8.593
8.984
8.050
8.590
8.313
8.445
323.15
9.248
8.861
8.630
9.025
8.082
8.627
8.348
8.481
328.15
9.291
8.900
8.668
9.065
8.115
8.665
8.383
8.517
333.15
9.334
8.940
8.705
9.107
8.148
8.702
8.418
8.553
338.15
9.378
8.980
8.743
9.148
8.182
8.740
8.454
8.590
343.15
9.422
9.021
8.782
9.190
8.215
8.779
8.490
8.627
348.15
9.467
9.061
8.821
9.233
8.249
8.818
8.526
8.665
353.15
9.512
9.103
8.860
9.276
8.283
8.857
8.562
8.702
No el Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s
87
Table S5. Values o Mola Volume (Vm) o eu ec ic mix u es as a unc ion o empe a u e.
T (K)
DL-men hol:
ace ic acid
DL-men hol:
py u ic acid
DL-men hol:
lac ic acid
DL-men hol:
lau ic acid
D ied
Sa u a ed
D ied
Sa u a ed
D ied
Sa u a ed
D ied
Sa u a ed
293.15
115.67
118.20
110.90
116.75
108.03
121.75
190.58
190.05
298.15
116.17
118.72
111.35
117.24
108.56
186.35
191.21
190.81
303.15
116.67
119.24
111.80
117.74
108.98
187.11
192.07
191.58
308.15
117.18
119.64
112.25
118.24
109.40
187.89
192.94
192.36
313.15
117.69
120.17
112.71
118.75
109.83
188.65
193.60
193.14
318.15
118.20
120.71
113.29
119.39
110.27
189.44
194.48
193.93
323.15
118.72
121.25
113.75
119.91
110.70
190.24
195.14
194.74
328.15
119.38
121.80
114.22
120.43
111.14
191.07
196.04
195.59
333.15
119.91
122.35
114.69
120.95
111.58
191.91
196.94
196.44
338.15
120.44
122.90
115.17
121.48
112.03
192.76
197.63
197.28
343.15
120.98
123.46
115.65
122.02
112.48
193.64
198.54
198.15
348.15
121.66
124.03
116.26
122.69
113.04
194.56
199.47
199.05
353.15
122.35
124.75
116.87
123.24
113.50
195.55
200.41
200.03
Chap e 2.2
94
CONTENT
ABSTRACT ........................................................................................................ 96
1. INTRODUCTION .............................................................................. 96
2. EXPERIMENTAL SECTION ............................................................ 99
2.1. MATERIALS…………………………………………………… 99
2.2. APPARATUSES AND PROCEDURES…………………………… 100
2.2.1. P epa a ion Me hodology .......................................................... 100
2.2.2. Solid-Liquid Phase diag ams de e mina ion.............................. 101
2.2.3. Hyd ophobici y analysis ............................................................. 101
2.2.4. Liquid-Liquid Ex ac ion o Bisphenol A ..................................... 102
2.2.5. The mophysical P ope ies........................................................ 103
2.2.6. NMR Measu emen s ................................................................. 103
3. RESULTS AND DISCUSSION ...................................................... 104
4. CONCLUSIONS ............................................................................. 117
5. ACKNOWLEDGEMENTS .............................................................. 118
6. SUPPLEMENTARY INFORMATION ............................................. 119
6.1. PHASE DIAGRAM DETERMINATION 119
6.2. THERMOPHYSICAL CHARACTERIZATION 120
6.3. LIQUID-LIQUID EXTRACTIONS 123
6.4. CHARACTERIZATION OF DES USING NMR SPECTROSCOPY 127
7. REFERENCES ............................................................................... 131

F om Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low Viscous Fa y Acid-based
Deep Eu ec ic Sol en s
95
Chap e 2.2
96
Abs ac
Inspi ed by he use o a y acids in de elopmen o low empe a u e la en
hea s o age ma e ials, no el low iscous and hyd ophobic deep eu ec ic
sol en s (DESs) based exclusi ely on a y acids a e he ein p oposed as
sus ainable sol en s. Th ee DESs we e p epa ed by exclusi ely combining
a y acids, namely oc anoic acid (C8), nonanoic acid (C9), decanoic acid (C10)
and dodecanoic acid (C12), which can simul aneously ac as hyd ogen bond
dono s and accep o s. The ob ained a y acid-based DESs we e analyzed in
o de o check hei s uc u es, pu i ies and p opo ions. Wa e s abili y was
also ca e ully e alua ed h ough 1H NMR. Fa y-acid DESs mel ing poin ’s
diag ams we e de e mined by isual obse a ion. Good ag eemen was
ob ained be ween he expe imen al eu ec ic poin and ha p edic ed by
conside ing an ideal sys em o wo indi idually mel ing compounds. Impo an
sol en he mophysical p ope ies, such as densi y and iscosi y o he d ied
and wa e -sa u a ed DESs we e measu ed. Finally, he emo al o bisphenol-
A, a pe sis en mic opollu an p esen in aqueous en i onmen s illus a es he
po en ial o bina y and e na y a y acid-based DESs as ex ac ion sol en s.
All p epa ed DESs showed good abili y o ex ac bisphenol-A om wa e wi h
ex ac ion e iciencies up o 92%.
1. In oduc ion
De eloping a cos e ec i e and en i onmen ally benign sol en is o i al
impo ance in chemical indus y. The demand o en i onmen ally benign,
less oxic, biodeg adable, na u al and low-cos sol en s has slowly
encou aged he de elopmen o no el al e na i e sol en s. O e he pas
decade, some g een sol en s ha e eme ged as ha mless sol en s, namely
supe c i ical luids, bio-based sol en s, ionic liquids (ILs) and mo e ecen ly
deep eu ec ic sol en s (DESs).1-3 Eu ec ic mix u es a e a well-known class o
mul icomponen solid sys ems, p esen ing mel ing poin empe a u e
F om Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low Viscous Fa y Acid-based
Deep Eu ec ic Sol en s
97
dep essions ela i e o hei pa en compounds. Howe e , he high mel ing
poin s o many eu ec ic mix u es hampe hei applica ion as g een sol en s
a oom empe a u e. Eu ec ics sol en s ha a e liquid a ound oom
empe a u e ha e been sca cely epo ed in he li e a u e un il he beginning
o he 21s cen u y.4 Only in 2003, Abbo e al. p oposed eu ec ic mix u es as
a e sa ile and sus ainable pla o m o unable sol en s. In ac , hese au ho s
showed ha i a sal o a solid ionic liquid is used in he mix u e, a la ge
mel ing poin dep ession can be ob ained, hus coining he designa ion Deep
Eu ec ic Sol en s (DESs). These sol en s ha e been eme ging as a new
gene a ion o sol en s wi h a g ea po en ial o a a ie y o applica ions, such
as in elec ochemis y and me al ex ac ion a ea,5 nano echnology,6
s abiliza ion o DNA,7 ma e ials chemis y,8 ca alysis,9 o ganic syn hesis,10
among o he s.
DESs ha e been in oduced as al e na i es o ionic liquids, o e coming hei
main disad an ages, such as high cos and oxici y, while keeping hei
negligible apou p essu e, easy unabili y and excellen sol a ion
p ope ies.11-12 Al hough less explo ed, mix u es o wo neu al na u al
compounds can also yield liquids a oom empe a u e. Despi e he ac ha
mel ing poin dep essions o neu al eu ec ic mix u es a e no as deep as
when ionic compounds a e used, hey ha e also adop ed he uni ying DESs
designa ion, since hey can also be used as sol en s. Choi and co-wo ke s13
ha e been epo ing a la ge numbe o s able na u al DESs, ei he based on
cha ged compounds o neu al na u al compounds, which a e liquid a oom
empe a u e. One o he main ad an ages o DESs is hei e y simple
syn he ic p ocess, which consis s on mixing di e en p opo ions o wo o
mo e componen s, un il a liquid wi h a mel ing poin lowe han he s a ing
ma e ials is ob ained.14 Gene ally, DESs a e o en simply p epa ed om
bina y mix u es o hyd ogen bond accep o s (HBA), such as qua e na y
ammonium sal s combined wi h a hyd ogen bond dono (HBD), such as an
aminoacid,15 a suga ,16 an alcohol17 o a ca boxylic acid.18 Recen ly, o he
Chap e 2.2
98
non-ionic DESs ha e been epo ed, o example eu ec ic mix u es composed
o dime hylu ea combined wi h ci ic acid, mannose o L- a a ic acid.19-20
This ield has g ea ly e ol ed in he las couple o yea s, showing a g ea
di e si y o s a ing compounds ha o m liquids a oom empe a u e when
combined in ce ain mola a io,21 hus p o iding a powe ul ool o con ol he
p ope ies o DESs. Recen ly, he lack o chemical s abili y o hyd ophilic
DESs based on hyd ophilic ammonium sal s when in con ac wi h wa e
mo i a ed he de elopmen o hyd ophobic DESs as g een subs i u es o
con en ional o ganic sol en s.22-23 Di e se s a ing compounds ha e been
used in hyd ophobic DESs p epa a ion, anging om long chain qua e na y
ammonium halides23 o hyd ophobic na u al compounds, such as men hol24
and long alkyl chain a y acids.22-23
In his wo k, new na u al hyd ophobic DESs, composed exclusi ely o a y
acids, a e de eloped. Long hyd oca bon chain a y acids eu ec ics ha e
been la gely explo ed as phase change ma e ials (PCMs), o low
empe a u e la en hea s o age.25 Thei impo ance is essen ially ela ed o
hei good chemical s abili y, smalle olume change du ing phase ansi ion
and high la en hea o usion and mel ing empe a u e in he desi ed
ope a ing ange.26 The phase change empe a u es o a y acids eu ec ics
can be easily adjus ed by mixing a y acids wi h di e se alkyl chain leng hs in
sui able p opo ions while keeping non- eac i i y, ecyclabili y, non-
co osi eness, low cos and he non- oxici y ad an ages o a y acids.27 To
he bes o ou knowledge, no s udy add essed ye he p epa a ion and use o
g een sol en s using a y acids PCMs s a ing ma e ials. In his pe spec i e,
he goal o he p esen con ibu ion is o use he same class o ma e ials ha
can be modula ed o hea s o age applica ions o de elop no el sus ainable
hyd ophobic DESs o be used in wa e pu i ica ion echnologies. Fo ha
pu pose, dodecanoic acid (C12 acid) was combined wi h oc anoic acid (C8
acid), nonanoic acid (C9 acid) and decanoic acid (C10 acid) o p epa e new
hyd ophobic sus ainable sol en s. The use o acids wi h hyd oca bon chains
F om Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low Viscous Fa y Acid-based
Deep Eu ec ic Sol en s
99
smalle han C8 was disca ded since i leads o chemically uns able DES
when in con ac wi h wa e , due o he leaching o he hyd ophilic acids o he
aqueous phase.23,25 Bisphenol A (BPA), a syn he ic o ganic chemical used as
a e icien plas icize in he p ocessing o a numbe o plas ics,28 was chosen
o illus a e he use o he p epa ed DES in wa e ea men . Despi e i s small
concen a ions in wa e s eams, BPA has been ecognized as a pe sis en
mic opollu an due o i s impo an e ec as an endoc ine dis up o , leading o
al e ed immune unc ions, imbalanced ho mone a ios, ep oduc i e
diso de s, diabe es, ca dio ascula disease and many al e a ions in
child en.29-30 Bina y and e na y a y acids based DESs we e e alua ed as
possible ex ac o s o BPA om wa e media.
2. Expe imen al Sec ion
2.1. Ma e ials
All a y acids, namely oc anoic acid (C8) (pu i y ≥ 98%), nonanoic acid (C9)
(pu i y ≥ 98%), decanoic acid (C10) (pu i y ≥ 98%) and dodecanoic acid (C12)
(pu i y ≥ 98%) we e pu chased om Sigma-Ald ich. All ma e ials we e used
wi hou u he pu i ica ion. In Figu e 1, he chemical s uc u es and
espec i e ac onyms o he eu ec ic sol en s used in his wo k a e p esen ed.
The wa e used was ul apu e; double dis illed, passed h ough a e e se
osmosis sys em and u he ea ed wi h Milli-Q plus wa e pu i ica ion
appa a us.

Chap e 2.2
100
Figu e 1. Chemical s uc u es o he compounds used o he a y acid-
based deep eu ec ic sol en s s udied in his wo k.
2.2. Appa a uses and p ocedu es
2.2.1. P epa a ion Me hodology
Mix u es o se e al ca boxylic acids wi h long alkyl chains we e p epa ed by
adding di e en a y acids, which can simul aneously ac as hyd ogen bond
dono s and accep o s, in a sealed glass ial a 40 °C un il a homogeneous
clea solu ion was o med. A e he de e mina ion o he solid-liquid phase
diag ams, p o on and ca bon Nuclea Magne ic Resonance (1H and 13C
NMR) we e used o check he eu ec ic mix u es s uc u es and pu i ies
(p esen ed in Suppo ing In o ma ion (SI)). As i can be seen, all he peaks
ha e been a ibu ed DES componen s, and no ex a peaks we e ound in he
1H and 13C NMR spec a indica ing ha no side eac ions occu ed and hese
DES a e pu e.
Hyd ogen Bond Accep o s & Hyd ogen Bond Dono s
Fa y acid-based Deep Eu ec ic Sol en s
Oc anoic acid, C8
Nonanoic acid, C9
Decanoic acid, C10
Dodecanoic acid, C12
F om Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low Viscous Fa y Acid-based
Deep Eu ec ic Sol en s
101
2.2.2. Solid-Liquid Phase diag ams de e mina ion
Mix u es o di e en a y acids (HBA and HBD) we e p epa ed in he whole
composi ion ange, allowing he measu emen o he solid-liquid phase
diag ams o hese new DESs. The (T, x) phase diag ams we e measu ed in a
glass lask using a isual me hodology, a a mosphe ic p essu e, unde
cons an s i ing. The eu ec ic sys ems composi ions we e de e mined by
weigh ing, a oom empe a u e, all componen s wi hin ± 10-4 g using an
analy ical balance model AX223 om Ohaus.
B ie ly, mix u es in a ying mola p opo ions o he HBD and HBA we e
p epa ed in o se e al glass lasks, as p e iously desc ibed. Then, he
p epa ed eu ec ic mix u es wi h di e en composi ions we e hea ed in an oil
ba h unde s i ing using a hea ing pla e un il he comple e mel ing o he
mix u es was obse ed. A e his i s hea ing cycle, he empe a u e was
u ned o and du ing he cooling cycle, empe a u es co esponding o he
i s c ys al appea ance we e eco ded. The empe a u e was measu ed wi h
a P 100 p obe wi h a p ecision o ± 0.1 ºC. Fo all he eu ec ic mix u es
composi ions, he mel ing occu s o e a ange o empe a u es in be ween
he mel ing empe a u es o he s a ing compounds. The abo e p ocedu e
was epea ed o ob ain su icien da a o cons uc he phase diag ams o
each eu ec ic sol en sys em.
2.2.3. Hyd ophobici y analysis
In o de o in e abou he DESs hyd ophobici y, and consequen ly quan i y
he wa e con en in d ied and sa u a ed new eu ec ic sol en s, mix u es
con aining bo h componen s (wa e and he eu ec ic mix u es) we e p epa ed,
igo ously shaken o 30min and le o se le o 24h. Samples o each phase
we e ca e ully aken wi h a sy inge and he amoun o wa e p esen in each
sample was quan i ied. The wa e con en p esen in bo h phases o he
in es iga ed eu ec ic sol en s was de e mined by Ka l Fische i a ion
(Me ohm 870 KF Ti ino Plus) and he esul s a e p esen ed in Table 1.
Chap e 2.2
102
Table 1. Summa y o composi ions, and wa e con en o d ied and wa e -
sa u a ed a y acid-based DESs.
Deep Eu ec ic Sol en s
(HBA + HBD)
Mole a io
Wa e con en
(w %)
D ied
Sa u a ed
Dodecanoic
acid (C12)
Oc anoic
acid, (C8)
1:3
0.004
1.353
Nonanoic
acid, (C9)
1:3
0.006
0.843
Decanoic
acid, (C10)
1:2
0.019
0.523
2.2.4. Liquid-Liquid Ex ac ion o Bisphenol A
Aqueous solu ions o he mic opollu an Bisphenol-A wi h a concen a ion o
0.05 g dm-3 o concen a ion was p epa ed. Al hough mic opollu an s a e
p esen in eal wa e samples in low concen a ions, anging om ng/L o
se e al μg/L, he highe concen a ion o bisphenol A in he s a ing aqueous
solu ion used in his wo k, allowed he use o a simple and di ec de ec ion
echnique, UV- is spec oscopic echnique. On he o he hand, he use o
concen a ed solu ions o BPA gua an ees ha he e is no sa u a ion o BPA
in he coexis ing phases when en isaging he use o he p oposed echnology
in eal wa e samples. A e wa ds, 2 mL o his solu ion was pu in o con ac
wi h equal amoun o each one o he eu ec ic mix u es and s i ed a 300
pm, a oom empe a u e and p essu e condi ions, o maximize mass
ans e . The lasks we e hen le o phase sepa a ion o 24h, so ha
comple e sepa a ion o he wo phases and consequen ly he equilib a ion o
pollu an be ween he wo phases we e achie ed. Samples o he aqueous
phase we e aken and he quan i ica ion o he pollu an was ca ied ou by
F om Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low Viscous Fa y Acid-based
Deep Eu ec ic Sol en s
103
UV- is spec oscopy using a SHIMADZU UV-1700, Pha ma-Spec
spec opho ome e , a wa eleng h o 276 nm o Bisphenol A, by means o a
calib a ion cu e p e iously es ablished. Each alue o he ex ac ion
e iciency is he a e age o h ee measu emen s.
2.2.5. The mophysical P ope ies
Measu emen s o iscosi y and densi y o he DESs we e ca ied ou in he
empe a u e ange om 20 up o 80 ºC and a a mosphe ic p essu e, using
an An on Paa (model SVM 3000) au oma ed o a ional S abinge
iscome e -densime e . The empe a u e unce ain y is ±0.01ºC. The ela i e
unce ain y o he dynamic iscosi y is ± 0.25 %, and he absolu e unce ain y
o he densi y is ± 0.0005 g·cm−3. DESs we e simul aneously sampled o he
wa e con en quan i ica ion and he densi y and iscosi y measu emen s.
2.2.6. NMR Measu emen s
All he expe imen s we e ca ied ou on a B uke AVANCE 400 spec ome e
ope a ed a oom empe a u e wi h 16 and 500 scans o he 1H NMR and 13C
NMR spec a, espec i ely. The eu ec ic mix u es samples we e p epa ed on
5 mm NMR ubes by weigh app oxima ely 30 mg o eu ec ic mix u e and hen
adding 0.5 mL o deu e a ed dime hylsul oxide (DMSO-d6). The homogenei y
o he sample was assu ed by o ex mixing.
Chap e 2.2
110
Figu e 4. Expe imen al densi ies o he s udied d ied ( illed) and wa e
sa u a ed (emp y) a y acid-based DESs (● C8 acid: C12 acid; ● C9 acid: C12
acid; ● C10 acid: C12 acid) as unc ion o empe a u e.
These alues a e lowe han he densi ies ound o mos hyd ophilic DESs
(a ound 1150 kg.m-3)38-39 and also o he epo ed hyd ophobic DESs (889 o
942 kg.m-3)22 and can be explained by he low densi ies o he s a ing a y
acids. As expec ed, he p esence o wa e inc eases he densi y o he a y
acids DESs. Howe e , due o he high hyd ophobici y o hese new DESs,
hei wa e con en is e y small, and hus only a e y small e ec o wa e
was obse ed in he DESs densi y. The same end was obse ed o he
densi y o d ied and wa e sa u a ed DESs: C8:C12 DES < C9:C12 DES <
C10:C12 DES. This end shows ha as he alkyl chain o acid inc eases, he
densi y o he DESs dec eases in a linea manne .
The expe imen al iscosi y alues we e i ed as a unc ion o empe a u e,
using he Vogel-Fulche -Tammann (VFT) model:
Tempe a u e (ºC)
20 40 60 80 100

(g.cm-3)
0.84
0.86
0.88
0.90
0.92

F om Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low Viscous Fa y Acid-based
Deep Eu ec ic Sol en s
111
ln ƞ= Aη+Bη
(T-Cη) (eq. 3)
whe e η is he iscosi y in mPa·s, T is he empe a u e in ºC, and Aη, Bη, and
Cη a e adjus able pa ame e s. The expe imen al iscosi y esul s o he d ied
and sa u a ed DESs as a unc ion o empe a u e a e p esen ed in Table S4
and plo ed in Figu e 5.
Figu e 5. Expe imen al iscosi ies o he new d ied ( illed) and wa e
sa u a ed (emp y) a y acid-based DESs (● C8 acid: C12 acid; ● C9 acid: C12
acid; ● C10 acid: C12 acid) as unc ion o empe a u e.
The adjus able pa ame e s o VFT model we e de e mined om he i ing o
he expe imen al alues wi h empe a u e and a e lis ed in Table S5. The
ob ained iscosi ies a e qui e low, be ween 7 and 11 mPa·s a 25 ⁰C, o a
e y low wa e con en , compa ed o o he hyd ophobic low iscous DESs
epo ed in he li e a u e, such as hose based on DL-men hol and o he s
Tempe a u e (ºC)
020 40 60 80 100

(mPa.s)
0
2
4
6
8
10
12
14
16
Chap e 2.2
112
con aining se e al qua e na y ammonium sal s, which ypically a y om 11
o 50 mPa.s24 and 173 o 783 mPa.s22, espec i ely.
As expec ed, an exponen ial dec ease o iscosi y wi h inc easing
empe a u e was obse ed o all samples o DESs. Again and due o he
high hyd ophobic cha ac e o hese DESs, he iscosi y alues o he d ied
and wa e sa u a ed a y acid-based DESs a e e y simila . Mo eo e , he
iscosi y is s ongly a ec ed by he HBD alkyl chain o a y acids since he
sho e he alkyl chains o he a y acid, he lowe he DES iscosi y,
acco ding o he ollowing he o de C8:C12 DES < C9:C12 DES < C10:C12 DES.
The ac i a ion ene gy was calcula ed based on he iscosi y dependence wi h
empe a u e as ollows:
Ea=R (Bη
(Cη
2
T2-2Cη
T+1)) (eq. 4)
whe e η is he iscosi y, T is he empe a u e, Bη and Cη a e he adjus able
pa ame e s ob ained om equa ion 4 and R is he uni e sal gas cons an .
The alues o he ac i a ion ene gies o he p epa ed eu ec ic sol en s a e
p esen ed in Table S6.
The use o equa ion 4 allows he discussion o he ene gy ba ie o a luid o
shea s ess, Ea, alues. The highe he Ea, he mo e di icul i is o he
molecules/agg ega es o mo e pas each o he . This can be a di ec
consequence o he size o en anglemen o he molecules/agg ega es and/o
he p esence o s onge in e ac ions wi hin he luid. The same end
obse ed in iscosi y alues was also obse ed o he Ea o d ied and wa e
sa u a ed DESs: C8:C12 DES < C9:C12 DES < C10:C12 DES. This end shows
ha as he alkyl chain o acid inc eases, he Ea o he DES inc eases in a
linea manne . All a y acid-based DESs con aining linea non subs i u ed
ca boxylic acids ha e low Ea alues (22 o 25 KJ/mol), in ag eemen wi h
hei small iscosi y. The Ea alues ob ained o wa e sa u a ed DESs a e
F om Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low Viscous Fa y Acid-based
Deep Eu ec ic Sol en s
113
simila o each o he , indica ing ha he p esence o wa e , e en in di e en
amoun s, and in mix u es wi h di e en mola a ios, leads an easie and
simila lux o he di e en molecules/agg ega es.
Taking in o accoun he esul s ob ained o he p epa ed a y acid-based
DESs, hei pe o mance in he ex ac ion o a pe sis en mic opollu an , BPA,
om wa e was s udied. The one s ep-ex ac ion efficiencies, EE, we e
calcula ed using equa ion 5, om he BPA concen a ion in he wa e phase
be o e, 𝐶𝐵𝑃𝐴,0
𝑎𝑞 , and a e he ex ac ion, 𝐶𝐵𝑃𝐴,1
𝑎𝑞 :
% EE= CBPA,0
aq -
CBPA,1
aq
CBPA,0
aq x 100
(eq. 5)
The one-s ep ex ac ion e iciencies o BPA using he p oposed bina y a y
acid-based DESs a e summa ized in Table 3 and plo ed in Figu e 6.
Chap e 2.2
114
Table 3. Ex ac ion e iciencies (% EE) o bisphenol-A using bina y and
e na y a y acid-based DESs (s i ing speed = 300 pm, a io DES/Wa e =
1:1, empe a u e = 25 ºC, mixing ime = 15 min).
Fa y acid-based DESs
Ex ac ion E iciencies
(EE%)
Bina y DESs
C8: C12 (3:1)
76.04 ± 1.13
C9: C12 (3:1)
88.32 ± 0.23
C10: C12 (2:1)
81.81 ± 0.34
Te na y DESs
C8:C9:C12 (1:1:1)
85.49 ± 0.86
C8:C9:C12 (1:2:1)
84.53 ± 0.43
C8:C9:C12 (2:1:1)
82.34 ± 1.10
C8:C9:C12 (3:1:1)
79.42 ± 0.54
C8:C9:C12 (3:2:1)
80.32 ± 0.78
C9:C10:C12 (1:1:1)
87.65 ± 1.06
C9:C10:C12 (1:2:1)
87.81 ± 0.67
C9:C10:C12 (2:1:1)
89.01 ± 0.72
C9:C10:C12 (2:2:1)
89.06 ± 0.34
C9:C10:C12 (3:1:1)
91.52 ± 0.41
C9:C10:C12 (3:2:1)
90.50 ± 0.57
C8:C10:C12 (1:1:1)
82.77 ± 1.03
C8:C10:C12 (2:1:1)
79.45 ± 0.46
C8:C10:C12 (3:1:1)
77.75 ± 0.72
C8:C10:C12 (3:2:1)
79.62 ± 0.58
F om Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low Viscous Fa y Acid-based
Deep Eu ec ic Sol en s
115
Figu e 6. One-s ep ex ac ion e iciencies (% EE) o Bisphenol A using he
a y acid-based DESs de eloped in his wo k (s i ing speed = 300 pm, a io
DES/Wa e = 1:1, empe a u e = 25 ºC, mixing ime = 15 min).
The s udied hyd ophobic DESs showed e y high 1-s ep ex ac ion
efficiencies (up o 92%) o BPA. Mo eo e , he ob ained ex ac ion
e iciencies can be o de ed acco ding o he ollowing sequence: C8:C12 DES
< C10:C12 DES < C9:C12 DES, showing no clea end be ween he % EE and
he hyd ophobici y o he DESs. Howe e , his migh be linked o he ac ha
C10:C12 DES has a di e en mola a io (2:1) han he o he wo DESs (3:1).
Since DESs can be p epa ed om wo o mo e componen s and
consequen ly hei p ope ies can be ailo ed by changing he numbe o
HBDs, e na y DESs we e also p epa ed by addi ion o a second HBD o
C8:C12, C9:C12 and C10:C12, aiming a achie ing highe ex ac ion e iciencies.
In his way, h ee amilies o e na y DESs we e p epa ed by he addi ion o a
hi d componen (oc anoic, nonanoic and decanoic acids) o he bina y DESs
s udied so a . The ex ac ion o BPA om aqueous media was ca ied ou
C8 acid : C12 acid (3:1)
C9 acid : C12 acid (3:1)
C10 acid : C12 acid (2:1)
% EE
0
20
40
60
80
100
76.04%
88.32%
81.81%

Chap e 2.2
116
and ob ained EE% a e also lis ed in Table 3 and p esen ed in Figu e S1 o
he SI. In Figu es S2, S3 and S4 a di ec compa ison o he EE% o BPA o
each bina y DESs wi h he co esponding e na y DESs is illus a ed. O e all,
he EE% ob ained o he e na y DESs a e be ween 79 and 91%, indica ing
ha addi ion o a hi d componen in he bina y DESs is indeed capable o
uning he ex ac ion e iciencies o BPA. Fu he mo e, he EE% ob ained o
he bina y DESs C8:C12 (76.04%) is he lowes , showing ha a highe
hyd ophobici y is a ou able in he ex ac ion o BPA. In o he wo ds, he
addi ion o ei he C9 o o m C8:C9:C12 o C10 o o m C8:C10:C12 enhance he
EE% o BPA. This can be seen om he EE% ob ained o he bina y DESs
C8:C12 and he e na y DES C8:C9:C12 (3:1:1) and C8:C9:C12 (3:2:1), wi h
alues o 79.42% and 80.32%, espec i ely, wi h hose ob ained o
C8:C10:C12 (3:1:1) and C8:C10:C12 (3:2:1) wi h alues o 77.75% and 79.62%,
espec i ely. On he o he hand, i can also obse ed ha a dec ease in he
p opo ion o C8 in he e na y DESs leads o highe ex ac ion e iciencies,
wi h EE% o 79.42%, 82.34% and 85.49% o C8:C9:C12 (3:1:1), C8:C9:C12
(2:1:1) and C8:C9:C12 (1:1:1), espec i ely. The same end can be obse ed
o he e na y DES C8:C10:C12 wi h EE% o 77.75%, 79.45% and 82.77% o
C8:C10:C12 (3:1:1), C8:C10:C12 (2:1:1) and C8:C10:C12 (1:1:1), espec i ely.
Mo eo e , compa ing he EE% o he C8:C9:C12 and C8:C10:C12 e na y DES
p epa ed in he same p opo ions, i can be concluded ha he addi ion o C9
as a hi d componen p o ides an highe inc ease o he EE% han he
addi ion o C10. Howe e , all hese ex ac ion e iciencies a e s ill lowe han
ha ob ained o he bina y DES C9:C12, wi h a alue o 88.32%.
Ne e heless, i is s ill possible o u he une his EE% by he addi ion o C10,
by he maximum EE% o 91.42% ob ained o C9:C10:C12 (3:1:1). In ac , all
he e na y DES C9:C10:C12 yield highe e iciencies han he wo o he e na y
DES amilies.
Passos, e al.29 also s udied he Bisphenol A ex ac ion om aqueous media
using in aqueous biphasic sys ems composed o 15 w % o K3PO4 + 25 w %
F om Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low Viscous Fa y Acid-based
Deep Eu ec ic Sol en s
117
o imidazolium o ammonium-based ionic liquid + 60 w % o aqueous phase,
ob aining ex ac ion e iciencies ha eached 100% o ex ac ion, in mos
sys ems, in one single s ep. Ne e heless, he c oss con amina ion o he
wa e phase is no negligible, since he composi ion o he sal ich phase in
equilib ium wi h he ionic liquid ich phase is 22.00 w % o K3PO4 and 25.00
w % o ionic liquid, hus leading o an addi ional en i onmen al p oblems. On
he o he hand, he a y acid-based DESs he e p oposed a e all immiscible
wi h wa e , no equi ing he addi ion o sal ing ou agen s, making hem mo e
economic and en i onmen ally iendly. Since he p oposed DESs p esen
e y low solubili y in wa e , minimal c oss con amina ion o he aqueous
phase occu s, as can be seen by NMR spec a. I should be ema ked ha in
his wo k he eco e y o BPA om DESs has no been add essed, howe e i
can be easily eco e ed om he DESs phase, by he addi ion o wa e as
an i-sol en and changes in pH, which lead o he pollu an p ecipi a ion and
allow he DES euse wi h minimal losses, as p e iously epo ed.40-41
I was demons a ed ha he al e na i e p ocess he ein p oposed is g eene ,
sa e , non oxic and mo e economical han ionic liquid-based aqueous
biphasic sys ems and i illus a es he po en ial o he a y acids DES
sol en s in he emo al o pe sis en pollu an s om wa e en i onmen s.
4. Conclusions
In his wo k, new low iscous hyd ophobic DES con aining only a y acids,
ha can ac as hyd ogen bond dono s and accep o s simul aneously, a e
p esen ed and s udied o he i s ime. These new sol en s a e eu ec ic
mix u es composed o se e al a y acids, namely oc anoic, nonanoic,
decanoic and dodecanoic acid, in di e en p opo ions. These hyd ophobic
sol en s we e designed o be chemically s able when in con ac wi h wa e
en i onmen s, which was p o ed using NMR spec oscopy.
Densi ies and iscosi ies we e s udied in he ange o empe a u es om 20
ºC o 80 ºC, o d ied and wa e sa u a ed DESs. Con a y o common deep
Chap e 2.2
118
eu ec ic sol en s, hese new eu ec ic sol en s p esen ed he lowes
iscosi ies e e ob ained (2 o 14 mPa.s) o his class o sol en s and
densi ies lowe han wa e , independen ly o he wa e con en .
These new a y acids based DESs ha e a p i ileged place among he g een
sol en s, since hey a e immiscible in wa e and s ill ha e low iscosi y. In
addi ion, aking ad an age o hei hyd ophobic cha ac e and he low
iscosi y, which allows quick and e icien mass ans e be ween he wo
phases in equilib ium, hese DESs we e used o ex ac one mic opollu an ,
Bisphenol-A, om wa e , illus a ing one o he majo conce n o ou socie y,
clean wa e . Ve y high 1-s ep ex ac ion e iciencies (a ound 92%) ob ained
o bina y and e na y a y acid-based DESs, showing ha i is possible o
une he ex ac ion e iciencies by in oducing new componen s in o he
DESs.
5. Acknowledgemen s
The au ho s, C. Flo indo, I.M. Ma ucho and L.C. B anco, g a e ully
acknowledge he inancial suppo o FCT/MCTES (Po ugal) o he PhD
ellowship SFRH/BD/102313/2014 and o he con ac unde P og ama
In es igado FCT 2012 and 2013 (IF/363/2012 and IF/0041/2013),
espec i ely. This wo k was inanced by CQE p ojec (UID/QUI/00100/2013)
and Resea ch Uni GREEN-i "Bio esou ces o Sus ainabili y"
(UID/Mul i/04551/2013).
F om Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low Viscous Fa y Acid-based
Deep Eu ec ic Sol en s
119
6. Supplemen a y In o ma ion
6.1. Phase Diag am De e mina ion
Table S1. Expe imen al solid-liquid equilib ia da a o a y acid-based DESs
a a mosphe ic p essu e.
xacid
Tm / ºC
xacid
Tm / ºC
xacid
Tm / ºC
Oc anoic acid
Nonanoic acid
Decanoic acid
0.000
16.50
0.000
12.60
0.000
31.60
0.100
12.00
0.143
12.00
0.147
25.00
0.143
11.00
0.250
9.00
0.200
22.00
0.200
10.00
0.333
12.00
0.270
20.00
0.250
9.00
0.435
15.00
0.333
18.00
0.333
12.00
0.500
21.00
0.435
20.00
0.435
17.00
0.565
26.00
0.500
23.00
0.500
21.00
0.667
29.00
0.565
25.00
0.600
26.00
0.750
32.00
0.667
30.00
0.667
28.00
0.857
37.00
0.750
35.00
0.750
34.00
1.000
43.20
0.857
40.00
0.833
37.00
1.000
43.20
0.875
40.00
1.000
43.20
Chap e 3.3
222
applied o emo al o me al ions om wa e , indium ex ac ion om
hyd ochlo ic and oxalic acids, emo al o pes icides and endoc ine dis up o
compounds om wa e , among o he s. 15-18 To he bes o ou knowledge, he
emo al o APIs om wa e using his class o sol en s is an almos non-
explo ed opic. Only one ecen s udy using hyd ophobic DES as ex ac an s
o pha maceu ical con aminan s om wa e phases has been published.19 In
ha wo k, he au ho s used a y acids/alcohols-based hyd ophobic deep
eu ec ic sol en s o ex ac wo an ibio ics (le o loxacin and cip o loxacin)
p esen in wa e using liquid-liquid mic oex ac ion. This s udy showed ha 1-
oc anol/ icap ylylme hylammonium chlo ide-based DES allowed he bes
ex ac ion e iciency wi h eco e ies abou 94.8%.
The main goal o his wo k is o e alua e he po en ial o hyd ophobic DES as
al e na i e ex ac an sol en s o cip o loxacin, one o he 10 high p io i y
compounds. Cip o loxacin is a common and widely used API, a b oad-
spec um luo oquinolone an ibio ic, used o ea mild o mode a e in ec ions
in he espi a o y and u ina y ac .20 Usually, i can be ound up o μg.L-1
le els in he aqua ic en i onmen . Two di e en amilies o hyd ophobic DES
we e used as ex ac an s: neu al DES, consis ing o all neu al and na u al
compounds, such as DL-men hol and a y acids as oc anoic (C8) and
decanoic (C10) acids; and cha ged DES, con aining qua e na y ammonium
sal s in hei cons i u ion, such as [N7777]B , [N8888]B and [N8881]B . F om he
sus ainabili y poin o iew, his las amily o compounds a e less appealing
han he i s one, since hey a e syn hesized om pe oleum-based
compounds and a e ecalci an . Al hough neu al DES do no p esen a deep
dep ession in he mel ing poin o he eu ec ic mix u es, hey a e he e
designa ed as DES o sake o simplici y.
Since cip o loxacin can exis in di e en o ms, ca ionic, anionic o
zwi e ionic, depending on pH in aqueous solu ions, i is impo an o es
neu al and ionic hyd ophobic DES o e alua e he e ec o DES cha ges on
he liquid-liquid ex ac ion o cip o loxacin. This wo k no only add esses he

Remo al o cip o loxacin om wa e en i onmen s using ask-speci ic hyd ophobic
deep eu ec ic sol en
223
emo al o cip o loxacin as mic opollu an in wa e s eams bu can also be o
in e es o he pha maceu ical indus y, which need o ea hei was es
be o e discha ge. Thus, om he indus ial applica ion poin o iew, i is e y
impo an o op imize he ex ac ion p ocess, namely educing associa ed
ene gy and cos s o he p ocess, leading a comple e en i onmen ally iendly
p ocess. Fo ha , he mos in luen ial expe imen al ex ac ion pa ame e s
we e op imized using a cen al composi e design (CCD). Mo eo e , he euse
and ecyclabili y o hyd ophobic DES we e also e alua ed. Adso p ion wi h
ac i a ed ca bon was chosen o emo e cip o loxacin om he hyd ophobic
DES since his echnology is al eady implemen ed and a ailable in wa e
ea men plan s and equi es a e y low mass o ob ain high emo al
e iciency. On op o ha , he use o ac i a ed ca bon o clean DES and no o
clean he wa e , a oids he con ac o wa e wi h ac i a ed ca bon and he
ecen heal h and en i onmen al p oblems associa ed wi h he p esence o
mic opa icles.
2. Expe imen al Sec ion
2.1. Ma e ials
DL-men hol (pu i y ≥ 95%), e ahep ylammonium b omide ([N7777]B ) (pu i y ≥
99%), e aoc ylammonium b omide ([N8888]B ) (pu i y ≥ 98%),
me hyl ioc ylammonium b omide ([N8881]B ) (pu i y ≥ 97%), oc anoic acid (C8)
(pu i y ≥ 98%), decanoic acid (C10) (pu i y ≥ 98%) and dodecanoic acid (C12)
(pu i y ≥ 98%) we e pu chased om Sigma-Ald ich and used as ecei ed.
Cip o loxacin mic opollu an was gene ously p o ided by Baye Heal hCa e
AG wi h high pu i y (>99.8%) and we e used as supplied. All aqueous
solu ions we e p epa ed by weigh ing he equi ed mass using an analy ic
labo a o y balance Ohaus Ad en u e ® Analy ical, h ough mixing high pu i y
wa e (Milli-Q wa e ). In o de o ob ain solu ions wi h di e en pH’s, aqueous
Chap e 3.3
224
solu ions o NaOH and HCl, o pH=11 and pH=4, espec i ely, we e
p epa ed.
2.2. Expe imen al Me hodologies
2.2.1. P epa a ion o DESs
DES we e p epa ed by mixing bo h componen s (HBD and HBA) in a glass
ial a a ce ain empe a u e and s i ing speed, un il a liquid homogeneous
mix u e is a ained. The wa e con en o each pu e hyd ophobic DESs was
de e mined by Ka l Fische i a ion (Me ohm 870 KF Ti ino Plus) and he
wa e con en ob ained was < 500 ppm. Based on p e ious s udies,16, 18, 21-23
he mola a io co esponding o he eu ec ic poin o each sys em was
selec ed o ca y ou he ex ac ion expe imen s. The a ios used o p epa e
he hyd ophobic DES used in his wo k a e shown in Table 1.
Table 1. Hyd ophobic DESs mola a ios s udied in his wo k.
Hyd ophobic DES s udied
Mola Ra io
C12: C8
1:3
C12: C10
1:2
DL-men hol: C8
1:1
DL-men hol: C10
1:1
DL-men hol: C12
2:1
[N7777]B : C10
1:2
[N8881]B : DL-men hol
1:2
[N8881]B :C8
1:2
[N8881]B :C10
1:2
[N8888]B :C10
1:2
Remo al o cip o loxacin om wa e en i onmen s using ask-speci ic hyd ophobic
deep eu ec ic sol en
225
2.2.2. Solubili y o cip o loxacin in di e en hyd ophobic DESs
To assess he solubili y o cip o loxacin in he s udied hyd ophobic DES,
small amoun s o pu e pha maceu ical ing edien (a ound 10 mg pe addi ion)
we e added o all p epa ed DES a oom empe a u e. The lasks we e s i ed
o a leas 12 hou s and obse ed a e wa ds. I all he solid added was
dissol ed (homogeneous mix u e was obse ed) ano he small amoun o
solid was added. This p ocedu e was epea ed un il he sa u a ion poin
(he e ogeneous mix u e) was isually de ec ed.
2.2.3. Miscibili y o wa e and DESs
In o de o de e mine he wa e con en p esen in hyd ophobic DES a oom
empe a u e, all p epa ed DES we e igo ously mixed wi h wa e in a 1:1
(DES: wa e ) mola p opo ion in a glass ial du ing he ime equi ed o each
equilib ium, which was p e iously de e mined. A e an e icien and comple e
sepa a ion o bo h phases, he DES phase was sampled wi h a needled
sy inge and injec ed in he Ka l Fische Coulome e Me ohm® o measu e
he wa e con en .
2.2.4. Liquid-liquid ex ac ion p ocedu e
The p epa ed hyd ophobic DES we e used as ex ac an sol en s o
cip o loxacin p esen in wa e a oom empe a u e. Fo ha pu pose, an
aqueous s ock solu ion o cip o loxacin o known concen a ion in wa e was
p e iously p epa ed and dilu ed o p epa e s anda ds so ha a calib a ion
cu e o he mic opollu an in Milli-Q wa e (cu e wi h R2 > 0.993) was
es ablished. Each p epa ed hyd ophobic DES and wa e con aining
cip o loxacin we e igo ously s i ed o adequa e ime o ensu e ha
equilib ium was eached, which was p e iously es ablished ough an
equilib ium cu e. All ex ac ions we e pe o med a oom empe a u e and
hen le o se le o a minimum o 12h o ensu e comple e phase sepa a ion.
Chap e 3.3
226
Using a needled sy inge, he wo phases we e ca e ully sampled and he
concen a ion o he emaining cip o loxacin in he wa e - ich phase was
measu ed using UV– is spec oscopy wi h a Shimadzu model UV-1800 –
Pha ma-Spec spec opho ome e . To elimina e possible in e e ences o DES
in he cip o loxacin quan i ica ion, he DES- ich phase was no quan i ied. Fo
each sample and expe imen , h ee eplica es we e pe o med.
2.2.5. Reuse and Recycling o DES
The po en ial euse o DES o se e al cycles o cip o loxacin ex ac ion was
also pe o med. A e comple e phase sepa a ion, he uppe phase (DES- ich
phase) was collec ed and hen exposed again o esh wa e con amina ed
wi h mic opollu an , a he same mass a io (1:1). This p ocedu e was
epea ed i e imes, yielding i e subsequen ex ac ion cycles.
In o de o ecycle he DES con aining cip o loxacin om i s e-use in se e al
consecu i e ex ac ions, adso p ion wi h ac i a ed ca bon (AC) was used o
emo e he cip o loxacin om DES. Fo ha pu pose, DES phase con aining
cip o loxacin was mixed wi h an amoun o AC in a glass ial a oom
empe a u e, and subsequen ly il e ed using a hyd ophobic
poly e a luo e hylene (PTFE) sy inge il e wi h a po e size o 0.22μm, o
ensu e he comple e emo al o he AC om DES phase. Finally, in o de o
quali a i ely check he absence o cip o loxacin om he egene a ed DES
phase, he ex ac an was dissol ed in ace oni ile and analyzed using an UV-
1800 Shimadzu® Spec opho ome e .
Remo al o cip o loxacin om wa e en i onmen s using ask-speci ic hyd ophobic
deep eu ec ic sol en
227
3. Resul s and discussion
3.1. Op imiza ion o Expe imen al Ex ac ion Condi ions
To assess he e iciency o he ex ac ion o cip o loxacin om wa e , he
concen a ions o cip o loxacin in he aqueous phase be o e (Co) and a e
ex ac ion (C) we e used h ough he ollowing exp ession:
𝐸𝐸 % = (𝐶𝑜−𝐶
𝐶𝑜 )x 100 (eq.1)
In o de o maximize he ex ac ion e iciency o cip o loxacin, se e al
expe imen al pa ame e s, such as con ac ime, s i ing speed, a io be ween
DES and wa e phases, ini ial concen a ion o mic opollu an and he e ec
o pH in wa e , we e op imized.
3.1.1. In luence o pH
Fluo oquinolones ha e wo p o onable g oups, meaning ha hey exis in
h ee dis inc o ms, depending on he pH, wi h di e en solubili y in wa e .24,
25 In Figu e 1, he specia ion p o ile o cip o loxacin as a unc ion o pH is
p esen ed. I can be seen ha he ca ionic specie is dominan a pH be ween
3 o 5, he zwi e ionic specie be ween 6 and 9 and he anionic specie a pH
highe han 10.

Chap e 3.3
228
Figu e 1. Dis inc o ms o cip o loxacin a di e en pH alues.26
In o de o s udy he e ec o pH in he ex ac ion o cip o loxacin om wa e ,
expe imen s we e ca ied ou a pH 3.3, 6.4 and 11.2 o a ain he ca ionic,
zwi e ionic and anionic o m, espec i ely. The ex ac ion e iciencies a
hese pH alues wi h he selec ed hyd ophobic DES a e p esen ed in Figu e
2.
Independen ly o he pH, i can be obse ed ha neu al hyd ophobic DES
display much highe cip o loxacin ex ac ion e iciencies ( om 40 o 90 %),
han ionic DES based on ammonium sal s ( om 0 - 20%, ypically a ound
0%).
Remo al o cip o loxacin om wa e en i onmen s using ask-speci ic hyd ophobic
deep eu ec ic sol en
229
Figu e 2. Ex ac ion e iciencies (EE %) o cip o loxacin a di e en pH alues
using di e en hyd ophobic DES (con ac ime = 10 min, DES/wa e a io =
1/1, s i ing speed = 300 pm, empe a u e = 25 ºC).
Gene ally, li e a u e shows ha ionic hyd ophobic DES a e mo e e icien
ex ac an s o a wide ange o compounds, om ola ile a y acids,14
pes icides15 o Bisphenol-A,18 han neu al hyd ophobic DES. Cu iously, such
beha io is no obse ed in his wo k, e en when cip o loxacin is in he ionic
o m. This ac ules ou ion exchange ex ac ion mechanism and e idences
he complex in e play o in e molecula o ces be ween DES and
cip o loxacin. Excellen ex ac ion e iciencies we e a ained when cheap,
neu al and all-na u al DES a e used, showing ha i is possible o implemen
sus ainable wa e cleaning p ocesses based on hese sol en s.23 Ionic
hyd ophobic DES, such as hose based on qua e na y ammonium sal s, a e
mo e oxic and expensi e han neu al all-na u al DES.
C12: C8 (1:3)
C12: C10 (1:2)
DL-Men hol: C8 (1:1)
DL-Men hol: C10 (1:1)
DL-Men hol: C12 (2:1)
[N7777]B : C10 (1:2)
[N8881]B : DL-Men hol (1:2)
[N8881]B : C8 (1:2)
[N8881]B : C10 (1:2)
[N8888]B : C10 (1:2)
EE %
0
20
40
60
80
100
pH = 3.3
pH = 6.4
pH = 11.2
Chap e 3.3
230
As i can be seen om Figu e 2, pH has a g ea in luence on he ex ac ion
e iciency, especially o neu al hyd ophobic DES, wi h highe ex ac ion
e iciencies ob ained a highe pH alues. I we conside ha a pH highe
han 4.9,25-27 he pKa o bo h acids, he acids a e dep o ona ed and
cip o loxacin is ei he in he zwi e ionic (pH = 6.4) o anionic (pH = 11.2) o m,
elec os a ic in e ac ions seem o be esponsible o he high ex ac ion
e iciencies o neu al hyd ophobic DES. No e ha he ionic DES he e s udied
also con ain acids bu he p obably he p esence o ammonium ca ion
in oduces s ong in e ac ions among he DES componen s, including
dep o ona ed acid, no lea ing su icien a ailable cha ges o he in e ac ion
wi h cip o loxacin. These esul s clea ly show he impo ance o DES
chemical design and he unde s anding o in e ac ions be ween DES and
di e en solu es a he molecula le el.
Conside ing hese esul s, C12: C10 DES was chosen o p oceed o he
op imiza ion o he o he expe imen al pa ame e s, since i p o ides a good
combina ion o e iciency (one o he bes ex ac an s o cip o loxacin om
wa e ) and sus ainabili y, as i is based on all na u al non- oxic compounds
DES. Ne e heless, he solubili y in wa e o some o hese DES ha e al eady
been epo ed be o e by us and some o he au ho s,15,16,18 using NMR, FTIR
and UV spec oscopies and i was concluded ha no aces o hese DESs
we e de ec ed in he aqueous phase up o he de ec ion limi o expe imen al
echniques used.
3.1.2. In luence o con ac ime
The in luence o he con ac ime in he ex ac ion o cip o loxacin using
C12:C10 hyd ophobic DES a di e en pH alues o he aqueous solu ion o
cip o loxacin is p esen ed in Figu e 3.
Remo al o cip o loxacin om wa e en i onmen s using ask-speci ic hyd ophobic
deep eu ec ic sol en
231
Figu e 3. E ec o he con ac ime in he ex ac ion e iciencies (EE %) o
cip o loxacin a di e en pHs using C12: C10 hyd ophobic DES (1:2) ([Cip] =
10ppm, s i ing speed = 300 pm, DES/wa e a io = 1/1, empe a u e = 25
ºC).
I can be obse ed ha he p ocess o he ex ac ion o cip o loxacin om
wa e is a he as , since he equilib a ion ime o all ex ac ions was ound
o be a ound 1 min o pH = 6.4 and 11.25 and 5 min o pH = 3.3. In o de o
ensu e ha all sys ems we e in equilib ium du ing he ex ac ion p ocess, 10
minu es was he pe iod o ime chosen o ca y ou he ollowing expe imen s.
3.1.3. In luence o s i ing speed
The in luence o s i ing speed a di e en pH condi ions was es ed o ou
di e en s i ing speeds, 100, 200, 300 and 500 pm. The esul s a e shown
in Figu e 4.
1 min
5 min
10 min
20 min
EE %
0
20
40
60
80
100
pH = 3.3
pH = 6.4
pH = 11.2
Chap e 3.3
238
can be concluded ha his pa ame e seems o consis en ly co ela ed wi h
he ex ac ion e iciencies o cip o loxacin, since he DES wi h he lowes
wa e solubili y, C12: C10, is also ha showing he highes ex ac ion e iciency
o cip o loxacin. Con e sely, DES wi h he poo es ex ac ion e iciencies,
[N8881]B : DL-Men hol and [N8881]B : C10, a e also hose wi h he highes wa e
solubili y. Hence, besides he in e ac ion be ween DES componen s and
cip o loxacin, DES wi h low wa e solubili y, hus a o ding a mo e
hyd ophobic phase, seem o be an essen ial ac o o he emo al o
cip o loxacin om wa e phases.
4.2. Solubili y o cip o loxacin in DES
Ano he impo an pa ame e ha needs o be e alua ed is solubili y o
cip o loxacin in he selec ed hyd ophobic DES. I solubili y ules he ex ac ion
mechanism o cip o loxacin om wa e , a high solubili y o his mic opollu an
in DES is desi able. The ob ained esul s o his pa ame e a e p esen ed in
Figu e 8.

Remo al o cip o loxacin om wa e en i onmen s using ask-speci ic hyd ophobic
deep eu ec ic sol en
239
Figu e 8. Compa ison o solubili y o cip o loxacin (symbols) in he
hyd ophobic DES s udied in his wo k and he espec i e ex ac ion
e iciencies in % (ba s) a 25 ºC.
As can be seen om he Figu e 8, solubili ies o cip o loxacin in he s udied
hyd ophobic DES show he same pa e n as ex ac ion e iciencies o
cip o loxacin om wa e using he same hyd ophobic DES. Ne e heless,
al hough C12: C8 is he DES ha can solubilize he highes amoun o
cip o loxacin (0.097g/g DES), i does no p esen he highes ex ac ion
e iciencies. This is p obably linked o he ac ha i does no exhibi he
smalles wa e solubili y (2 w %). C12: C10 displays he second highes
solubili y alue o cip o loxacin and he lowes wa e solubili y which leads o
he bes ex ac ion e iciency o cip o loxacin. Con e sely, ionic hyd ophobic
DES, wi h high wa e solubili ies in DES, p esen low solubili ies o
cip o loxacin, and hus low ex ac ion e iciencies o his mic opollu an . To
sum up, solubili y o bo h wa e and cip o loxacin in DES seem o be he
C12: C8 (1:3)
C12: C10 (1:2)
Men hol: C8 (1:1)
Men hol: C10 (1:1)
Men hol: C12 (2:1)
[N7777]B : C10 (1:2)
[N8881]B : Men hol (1:2)
[N8881]B : C8 (1:2)
[N8881]B : C10 (1:2)
[N8888]B : C10 (1:2)
Solubili y (g o Cip/g o DES)
0.00
0.02
0.04
0.06
0.08
0.10
0.12
EE %
0
20
40
60
80
100
Pa ially soluble
Insoluble
Chap e 3.3
240
uling pa ame e s o an e icien ex ac ion o his mic opollu an om wa e
phases.
5. Reuse and ecycle o DES
F om an economic and sus ainable poin -o - iew, he minimiza ion o he
amoun o sol en s used is e y impo an in he implemen a ion o he any
sepa a ion p ocess. In o de o es he e-use o C12: C10 hyd ophobic DES,
he DES- ich phase was collec ed a e each ex ac ion and eused in se e al
consecu i e ex ac ion cycles. The ob ained esul s a e p esen ed in Figu e 9.
Figu e 9. Re-use and ecycle o C12: C10 DES a e se e al cycles o
ex ac ion o cip o loxacin om wa e and a e cleaning using ac i a ed
ca bon ([Cip] = 10 ppm, pH= 6.4, con ac ime = 10 min, DES/wa e a io =
1/1, s i ing speed = 300 pm, empe a u e = 25 ºC).
I is possible o obse e ha C12: C10 hyd ophobic DES main ains i s capaci y
o emo e cip o loxacin om he wa e en i onmen , o a leas 4 cycles.
Only in he 5 h cycle, he ex ac ion capaci y o he DES s a ed o slowly
Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 REUSE
EE %
0
20
40
60
80
100
RECYCLED
Remo al o cip o loxacin om wa e en i onmen s using ask-speci ic hyd ophobic
deep eu ec ic sol en
241
dec ease, which is an indica ion ha hyd ophobic DES is almos eaching he
sa u a ion poin .
In o de o achie e ull sus ainabili y, he implemen a ion o a ci cula p ocess,
whe e DES can be cleaned and ecycled, is a manda o y. Fo ha pu pose,
adso p ion using ac i a ed ca bon (AC) was used o emo e cip o loxacin
om he eused DES, whe e cip o loxacin is concen a ed. The example o
he p ocedu e used o ecycle hyd ophobic DES is illus a ed in Figu e 10.
Figu e 10. Scheme o ci cula p ocess o ecycling o hyd ophobic DES
con amina ed wi h cip o loxacin.
As i was men ioned be o e, he use o AC in con ac wi h DES and no in
con ac wi h wa e p esen s he ad an age o non-con amina ion o he wa e
phase wi h ca bon pa icula e ma e . A e cleaning C12: C10 hyd ophobic
Hyd ophobic DES
LLE
Adding Ac i a ed
Ca bon as adso ben
Sepa a ing
wo phases
Fil a ion o
ac i a ed ca bon
om DES
Chap e 3.3
242
DES using AC, he DES was used again in he liquid-liquid ex ac ion o
cip o loxacin.
The esul s shown in Figu e 9 e eal sligh ly highe emo al ex ac ion
e iciencies o cip o loxacin (82%) han hose de e mined be o e using esh
DES (76%). Possible explana ion o his could be he ac ha some
impu i ies p esen in he componen s o he DES we e also emo ed du ing
he con ac wi h ac i a ed ca bon. Du ing he ecycle expe imen s i is
ele an o men ion ha DES phase was ca e ully analyzed in o de o a oid i
con aining AC, which can be seen in Figu e 10 whe e DES appea s clean.
The ecycle o DES using ac i a ed ca bon is hus iable and clean
hyd ophobic neu al DES can be used again o pe o m liquid-liquid
ex ac ion. The ac ha DES can be cleaned up and ecycles b ings posi i e
aspec s o he poin -o - iew o applica ion, since only a small amoun o DES
is needed.
6. Conclusions
Due o hei ad an ageous p ope ies, easy o p epa e, ypically composed o
na u al compounds wi h low oxici y and p ope ies can be adjus ed h ough
he use o di e en componen s, DES ha e been inc easingly a ac ing
a en ion as uly g een designe sol en s ha enable he de elopmen o
sus ainable p ocesses. In he p esen wo k, neu al and ionic hyd ophobic
DES we e p epa ed and hei pe o mance as ex ac an s o cip o loxacin, a
high p io i y pha maceu ical mic opollu an , om wa e es ed. The e ec o
se e al expe imen al a iables in he ex ac ion e iciencies was s udied and i
was concluded ha DES composed o na u al and neu al compounds o e ed
he bes ex ac ion e iciencies. In pa icula , C12: C10 p o ed o be he bes
ex ac an , displaying he second highes solubili y alue o cip o loxacin and
he lowes wa e solubili y which leads o he bes ex ac ion e iciency o
cip o loxacin.
Remo al o cip o loxacin om wa e en i onmen s using ask-speci ic hyd ophobic
deep eu ec ic sol en
243
Mo eo e , pH was ound o ha e a dominan ole in he ex ac ion e iciencies
since cip o loxacin is be e ex ac ed in he anionic o m, while empe a u e
and DES/wa e a io do no signi ican in luence he ex ac ion p ocess.
Cip o loxacin ex ac ion is clea ly linked o he hyd ophobici y o he DES, in
pa icula o he wa e solubili y in he DES. An economical and sus ainable
easible ci cula p ocess was de eloped using ac i a ed ca bon o ecycle he
DES phase, showing ha i is possible o wo k wi h sol en s composed
exclusi ely na u al compounds achie ing high ex ac ion e iciencies.
7. Acknowledgemen s
C. Flo indo and L.C. B anco, g a e ully acknowledge he inancial suppo o
FCT/MCTES (Po ugal) o he PhD ellowship SFRH/BD/102313/2014 and
o he con ac unde P og ama In es igado FCT 2013 (IF/0041/2013),
espec i ely. This wo k was inanced by CQE p ojec (UID/QUI/00100/2013)
and Resea ch Uni GREEN-i "Bio esou ces o Sus ainabili y"
(UID/Mul i/04551/2013).
8. Re e ences
1. Geissen, V.; Mol, H.; Klumpp, E.; Umlau , G.; Nadal, M.; an de Ploeg,
M.; an de Zee, S. E. A. T. M.; Ri sema, C. J., Eme ging pollu an s in he
en i onmen : A challenge o wa e esou ce managemen . In e na ional Soil
and Wa e Conse a ion Resea ch 2015, 3, (1), 57-65.
2. Jiang, J.-Q.; Zhou, Z.; Sha ma, V. K., Occu ence, anspo a ion,
moni o ing and ea men o eme ging mic o-pollu an s in was ewa e — A
e iew om global iews. Mic ochemical Jou nal 2013, 110, 292-300.
3. Kümme e , K., Pha maceu icals in he En i onmen : Sou ces, Fa e,
E ec s and Risks. Sp inge : 2001.
4. H. Jones, O. A.; Voul oulis, N.; Les e , J. N., Human Pha maceu icals in
Was ewa e T ea men P ocesses. C i ical Re iews in En i onmen al Science
and Technology 2005, 35, (4), 401-427.

Chap e 3.3
244
5. B odin, T.; Pio ano, S.; Fick, J.; Klaminde , J.; Heynen, M.; Jonsson, M.,
Ecological e ec s o pha maceu icals in aqua ic sys ems--impac s h ough
beha iou al al e a ions. Philosophical ansac ions o he Royal Socie y o
London. Se ies B, Biological sciences 2014, 369, (1656), 20130580.
6. Luo, Y.; Guo, W.; Ngo, H. H.; Nghiem, L. D.; Hai, F. I.; Zhang, J.; Liang,
S.; Wang, X. C., A e iew on he occu ence o mic opollu an s in he aqua ic
en i onmen and hei a e and emo al du ing was ewa e ea men .
Science o The To al En i onmen 2014, 473-474, 619-641.
7. de Voog , P.; Janex-Habibi, M. L.; Sache , F.; Puijke , L.; Mons, M.,
De elopmen o a common p io i y lis o pha maceu icals ele an o he
wa e cycle. Wa e Science and Technology 2009, 59, (1), 39-46.
8. Ali, I.; Gup a, V. K., Ad ances in wa e ea men by adso p ion
echnology. Na u e P o ocols 2007, 1, 2661.
9. López-Mon illa, J. C.; Pandey, S.; Shah, D. O.; C isalle, O. D., Remo al o
non-ionic o ganic pollu an s om wa e ia liquid–liquid ex ac ion. Wa e
Resea ch 2005, 39, (9), 1907-1913.
10. de los Ríos, A. P.; He nández-Fe nández, F. J.; Lozano, L. J.; Sánchez,
S.; Mo eno, J. I.; Godínez, C., Remo al o Me al Ions om Aqueous Solu ions
by Ex ac ion wi h Ionic Liquids. Jou nal o Chemical & Enginee ing Da a
2010, 55, (2), 605-608.
11. Smi h, E. L.; Abbo , A. P.; Ryde , K. S., Deep Eu ec ic Sol en s (DES)
and Thei Applica ions. Chemical Re iews 2014, 114, (21), 11060-11082.
12. Abbo , A. P.; Boo hby, D.; Cappe , G.; Da ies, D. L.; Rasheed, R. K.,
Deep Eu ec ic Sol en s Fo med be ween Choline Chlo ide and Ca boxylic
Acids:  Ve sa ile Al e na i es o Ionic Liquids. Jou nal o he Ame ican
Chemical Socie y 2004, 126, (29), 9142-9147.
13. Mbous, Y. P.; Hayyan, M.; Hayyan, A.; Wong, W. F.; Hashim, M. A.; Looi,
C. Y., Applica ions o deep eu ec ic sol en s in bio echnology and
bioenginee ing—P omises and challenges. Bio echnology Ad ances 2017,
35, (2), 105-134.
14. Shisho , A.; Bula o , A.; Loca elli, M.; Ca ado i, S.; And uch, V.,
Applica ion o deep eu ec ic sol en s in analy ical chemis y. A e iew.
Mic ochemical Jou nal 2017, 135, 33-38.
Remo al o cip o loxacin om wa e en i onmen s using ask-speci ic hyd ophobic
deep eu ec ic sol en
245
15. Flo indo, C.; B anco, L. C.; Ma ucho, I. M., De elopmen o hyd ophobic
deep eu ec ic sol en s o ex ac ion o pes icides om aqueous
en i onmen s. Fluid Phase Equilib ia 2017, 448, 135-142.
16. an Osch, D. J. G. P.; Zubei , L. F.; an den B uinho s , A.; Rocha, M. A.
A.; K oon, M. C., Hyd ophobic deep eu ec ic sol en s as wa e -immiscible
ex ac an s. G een Chemis y 2015, 17, (9), 4518-4521.
17. Te esha o , E. E.; Bol oe a, M. Y.; Folden, C. M., Fi s e idence o me al
ans e in o hyd ophobic deep eu ec ic and low- ansi ion- empe a u e
mix u es: indium ex ac ion om hyd ochlo ic and oxalic acids. G een
Chemis y 2016, 18, (17), 4616-4622.
18. Flo indo, C.; Rome o, L.; Rin oul, I.; B anco, L. C.; Ma ucho, I. M., F om
Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low Viscous Fa y
Acid–Based Deep Eu ec ic Sol en s. ACS Sus ainable Chemis y &
Enginee ing 2018, 6, (3), 3888-3895.
19. Kyung, T. W. D. Y. H. R., E alua ion o a y acid/alcohol-based
hyd ophobic deep eu ec ic sol en s as media o ex ac ing an ibio ics om
en i onmen al wa e . Analy ical and Bioanaly ical Chemis y 2018, 410,
7325–7336.
20. Flo indo, C.; Cos a, A.; Ma os, C.; Nunes, S. L.; Ma ias, A. N.; Dua e, C.
M. M.; Rebelo, L. P. N.; B anco, L. C.; Ma ucho, I. M., No el o ganic sal s
based on luo oquinolone d ugs: Syn hesis, bioa ailabili y and oxicological
p o iles. In e na ional Jou nal o Pha maceu ics 2014, 469, (1), 179-189.
21. Ribei o, B. D.; Flo indo, C.; I , L. C.; Coelho, M. A. Z.; Ma ucho, I. M.,
Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s. ACS
Sus ainable Chemis y & Enginee ing 2015, 3, (10), 2469-2477.
22. Ma ins, M. A. R., e al., Tunable Hyd ophobic Eu ec ic Sol en s Based on
Te penes and Monoca boxylic Acids. ACS Sus ainable Chemis y &
Enginee ing 2018, 6, (7), 8836-8846.
23. Pon es, P. V. A., e al., Measu emen and PC-SAFT modeling o solid-
liquid equilib ium o deep eu ec ic sol en s o qua e na y ammonium
chlo ides and ca boxylic acids. Fluid Phase Equilib ia 2017, 448, 69-80.
24. Roca Jalil, M. E.; Baschini, M.; Sapag, K., In luence o pH and an ibio ic
solubili y on he emo al o cip o loxacin om aqueous media using
mon mo illoni e. Applied Clay Science 2015, 114, 69-76.
Chap e 3.3
246
25. Jain, A.; Jain, S.; Pahwa, R.; Ya , M. S., Cip o loxacin: e iew on
de elopmen s in syn he ic, analy ical, and medicinal aspec s AU - Sha ma,
P abodh Chande . Jou nal o Enzyme Inhibi ion and Medicinal Chemis y
2010, 25, (4), 577-589.
26. Palacio, D. A.; Ri as, B. L.; U bano, B. F., Ul a il a ion memb anes wi h
h ee wa e -soluble polyelec oly e copolyme s o emo e cip o loxacin om
aqueous sys ems. Chemical Enginee ing Jou nal 2018, 351, 85-93.
27. Che ing on, C. A.; Hin on, M.; Mead, G. C.; Chop a, I., O ganic Acids:
Chemis y, An ibac e ial Ac i i y and P ac ical Applica ions. In Ad ances in
Mic obial Physiology, Rose, A. H.; Tempes , D. W., Eds. Academic P ess:
1991; Vol. 32, pp 87-108.
28. Die z, C. H.J.T., E e, A., K oon, M. C., Annaland, M. . S., Gallucci, F.,
Held, C., The modynamic p ope ies o hyd ophobic deep eu ec ic sol en s
and solubili y o wa e and HMF in hem: Measu emen s and PC-SAFT
modeling, Fluid Phase Equilib ia 2019, 489, 75-82.
Chap e 3.4
254
A
B
C
sophis ica ed ma e ials, luo ine-bea ing co alen o ganic amewo ks (COFs)
c ys alline po ous ma e ials17 ha e been de eloped o ob ain high e iciency
in he emo al o ibup o en om wa e . Ne e heless, he complex and
expensi e syn hesis o he COF and he use o o ganic sol en s in he
egene a ion s eps o he ma e ial a e s ill majo d awbacks. The e o e,
sus ainabili y and ci cula economy always need o be aken in o accoun
upon de elopmen o a p omising indus ial p ocess.
He ein, we epo he de elopmen o cos -e ec i e adso ben ma e ial o
emo al o diclo enac om aqueous en i onmen s. The adso ben ma e ial
was p epa ed h ough he imp egna ion a hyd ophobic DES in o an ine
po ous suppo and used in di ec con ac wi h he aqueous phase. Aiming a
ull sus ainabili y, a ci cula p ocess was also de eloped by e-using se e al
imes he suppo ed DES ma e ial.
A scheme desc ibing he p epa a ion o DES-based adso ben ma e ial is
p esen ed in Figu e 1. B ie ly, i consis s on he imp egna ion, unde acuum,
o a selec ed hyd ophobic DES in a po ous PVDF suppo ( o mo e de ails,
see he Expe imen al Sec ion in supplemen a y In o ma ion). This suppo
was uni o mly cu in small ci cles wi h a de ined size h ough he use o a
mould.
Figu e 1. Scheme o he p epa a ion o suppo ed DESs: A) imp egna ion o
DES in po es o PVDF suppo using a acuum chambe B) emo al o DES-
based adso ben ma e ial and cu in o well-de ined sizes and C) use o Des-

Hyd ophobic deep eu ec ic sol en s as adso ben ma e ials o emo al o
mic opollu an s om wa e sou ces
255
cc
Dodecanoic acid,
C12
Decanoic acid,
C10
Decanoic acid, C10
Te aoc ylammoniumb omide,
[N8888]B
HYDROPHOBIC DESs POLLUTANT
cc
based adso ben ma e ial in con ac wi h wa e con amina ed wi h he
mic opollu an .
A as a ay o hyd ophobic DESs and o he eu ec ic mix u es was i s es ed
in liquid-liquid ex ac ion and he ex ac ion pa ame e s op imized. All he
de ails conce ning he sc eening o DESs, liquid-liquid ex ac ions and
op imiza ion o pa ame e s can be ound in he Supplemen a y In o ma ion.
These DESs we e selec ed due o hei negligible solubili y in wa e , o a oid
con amina ion o he wa e phase. F om his ini ial sc eening, wo DESs we e
selec ed o de elop he adso p ion ma e ial: one con aining a sal , [N8888]B :
C10 (1:2), and he o he con aining wo a y acids, C12: C10 (1:2). These wo
eu ec ic mix u es we e chosen no only due o hei excellen pe o mance,
wi h ex ac ion e iciencies o e 85%, bu also hei as kine ics, whe e
equilib ium was achie ed 5 min a e con ac .
The chemical s uc u es and ac onyms o hese wo eu ec ic sol en s, as well
as diclo enac, a e depic ed in Figu e 2.
Figu e 2. Chemical s uc u es as well as abb e ia ions o he hyd ophobic
DESs and a ge mic opollu an mainly s udied in his wo k.
These hyd ophobic DESs we e imp egna ed in PVDF po ous il e s using
acuum and hei pe o mance as adso ben s o emo e diclo enac om
Chap e 3.4
256
con amina ed wa e was e alua ed. The e ec o se e al pa ame e s, namely
ex ac ion ime and mass o DES in he adso p ion ma e ial, in he ex ac ion
o diclo enac was assessed. The ex ac ion e iciencies (EE %) we e
calcula ed om he Diclo enac Sal (Dic) concen a ion in he wa e - ich
phase be o e, 𝐶𝐷𝐼𝐶,0
𝑎𝑞 , and a e he ex ac ion, 𝐶𝐷𝐼𝐶,1
𝑎𝑞 :
In o de o e alua e he e ec o he DES mass used in he ex ac ion, small
adso p ion ci cles o wo di e en sizes; 5 mm and 2 mm, co esponding o 1
mg and 0.1 mg o DES/ adso p ion pa icle, espec i ely, we e p epa ed and
used o ex ac diclo enac om wa e . The main esul s a e summa ized in
Figu e 3.
One o he p omising ad an ages o his no el adso p ion echnology
compa ed o he liquid-liquid ex ac ion is he quick and easy sepa a ion o
he DES-based adso ben pa icles om he aqueous phase by simple
il a ion, wi hou any ime-consuming sepa a ion. Howe e , he mos ele an
aspec is undoub edly he amoun o DESs used, which is signi ican ly
smalle in DES adso ben ma e ial han in liquid-liquid ex ac ion, o he
same ex ac ion e iciency.
𝐸𝐸 (%) =
C
DIC,0
aq
−C
DIC,1
aq
C
DIC,0
aq
x 100
(eq. 1)
Hyd ophobic deep eu ec ic sol en s as adso ben ma e ials o emo al o
mic opollu an s om wa e sou ces
257
Figu e 3. E ec o ex ac ion ime and he mass o suppo ed DES in he
ex ac ion sodium diclo enac om wa e using C12: C10 (1:2) (g een) and
[N8888]B : C10 (1:2) (blue). Pa ame e s: size o adso p ion ma e ial 2mm
(~0.1mg o DES) and 5 mm o diame e (~1 mg o DES) (ini ial concen a ion
= 0.03 g/L, s i ing speed = 300 pm, empe a u e = 25 ºC).
F om Figu e 3, i can be seen ha he maximum ex ac ion e iciencies
(a ound 85 and 98%, depending on he DES) we e ypically achie ed
be ween 5 and 10 minu es, o bo h masses o he wo es ed DES. Howe e ,
i should be men ioned ha he ex ac ion ime is di ec ly in luenced by he
mass o DES adso ben ma e ial used. In he case o C12: C10 (1:2), only 6.4
Chap e 3.4
258
mg o DES a e needed o achie e 85% o ex ac ion e iciency, which is a
ema kable esul . In he case o [N8888]B : C10 (1:2), he esul s a e e en less
dependen o he mass and ime o he DESs used: only 0.5 mg o DES and 5
min o ex ac ion a e equi ed o each a maximum ex ac ion e iciency o
95%. These esul s clea ly show ha i high ex ac ion kine ics can be
a ained, hese DES-based adso ben ma e ials can be e y p omising no
only om he poin o iew o hei e iciency bu also om he economical
poin o iew.
Ano he impo an poin when de eloping a sus ainable p ocess is he
eusabili y o adso ben ma e ial. Fo ha pu pose, se e al cycles o
ex ac ion we e pe o med, whe e esh wa e wi h he mic opollu an was pu
in con ac wi h he same DES adso ben ma e ial in each one o he e-use
cycles. In his way, he same mass o adso ben ma e ial (30mg) o bo h
amilies o DES, C12: C10 (1:2) and [N8888]B : C10 (1:2), we e used and we e
eused up o ou imes. F om Figu e 4, i can be seen ha he ex ac ion
capaci y o bo h DES adso ben ma e ials emains unchanged a e 4 euse
cycles.
Hyd ophobic deep eu ec ic sol en s as adso ben ma e ials o emo al o
mic opollu an s om wa e sou ces
259
cycle 1
cycle 2
cycle 3
cycle 4
EE %
0
20
40
60
80
100
C12: C10 (1:2)
[N8888]B : C10 (1:2)
cycle 1
cycle 2
cycle 3
cycle 4
EE %
0
20
40
60
80
100
C12: C10 (1:2)
[N8888]B : C10 (1:2)
cycle 1
cycle 2
cycle 3
cycle 4
EE %
0
20
40
60
80
100
C12: C10 (1:2)
[N8888]B : C10 (1:2)
Figu e 4. Ex ac ion E iciencies o he euse o C12: C10 (1:2) (g een) and
[N8888]B : C10 (1:2) (blue) DES based adso ben ma e ial o ex ac diclo enac
om wa e (mass o DES adso ben = 30 mg, ini ial concen a ion = 0.03 g/L,
con ac ime = 10min s i ing speed = 300 pm, empe a u e = 25 ºC).
In o de o es a b oade applicabili y o he DES adso ben ma e ial o
emo e o he mic opollu an s p esen in esh wa e s eams, cip o loxacin
and bisphenol-A we e also es ed. Diclo enac, cip o loxacin and bisphenol-A
ha e qui e di e en chemical s uc u es and hus physical chemical
p ope ies. Fo example, diclo enac, cip o loxacin and bisphenol-A ha e 21.4
g/L,19 0.14 g/L,20 and 0.38 g/L21 o wa e solubili y. In Figu e 5, a b ie
compa ison o he ex ac ion e iciencies o liquid-liquid ex ac ion and
adso p ion o hese 3 mic opollu an s is p esen ed.

Chap e 3.4
260
Figu e 5. B ie compa ison o ex ac ion e iciencies ob ained o LLE and
adso p ion bo h using DES o 3 di e en mic opollu an s om wa e :
cip o loxacin 0.001 g/L o cip o loxacin, 0.03 g/L o diclo enac, and 0.1 g/L o
Bisphenol-A (con ac ime = 10 min, s i ing speed = 300 pm, empe a u e =
25 ºC, DES/wa e a io o LLE = 1/1 and DES/wa e a io o adso p ion = 15
mg/g o wa e ).
I can be obse ed ha bo h DES sol en s and DES adso ben s yielded
simila excellen %EE o di e en mic opollu an s unde s udy.
Fu he mo e, o comple ely e alua e he p oposed adso ben echnology
using suppo ed hyd ophobic DESs aking a s ep o wa d o indus ial
applica ion, some ele an pa ame e s such as lowe concen a ions, mix u e
o mic opollu an s and he e ec o eal wa e samples we e e alua ed in he
op imized condi ions. The main esul s a e summa ized in Figu e 6 and o he
esul s a e p esen ed in Supplemen a y In o ma ion. Un o una ely, wi h he
adop ed me hod in HPLC-UV, i was no possible o quan i y cip o loxacin
because i elu es in he dead olume. Howe e , om he p elimina y and
Hyd ophobic deep eu ec ic sol en s as adso ben ma e ials o emo al o
mic opollu an s om wa e sou ces
261
EE %
0
20
40
60
80
100
Milli-Q wa e
Tagus Ri e sample
C12: C10 [N8888]B : C10
BPA
DIC
Mix u e BPA
Mix u e DIC
BPA
DIC
Mix u e BPA
Mix u e DIC
quali a i e esul s, cip o loxacin p esen ed good esul s o ex ac ion, being
he p oposed adso p ion me hod also sui able o his mic opollu an .
Mo eo e , i should be no ed ha e en hough a quan i ica ion was no
possible, he mix u e samples p esen all mic opollu an s p e iously s udied,
cip o loxacin, bisphenol-A (BPA) and diclo enac (DIC).
F om Figu e 6, i can be seen he pe o mance o wo di e en suppo ed
hyd ophobic DES wi h eal and simula ed wa e samples.
Figu e 6. Compa ison o ex ac ion e iciencies ob ained o adso p ion
me hod, de ec ed by HPLC-UV, using wo di e en DES o di e en
mic opollu an s in Milli-Q wa e and Tagus i e samples wi h 0.002 g/L o
diclo enac, and 0.002 g/L o Bisphenol-A (con ac ime = 10 min, s i ing
speed = 300 pm, empe a u e = 25 ºC, suppo ed DES/wa e a io o
adso p ion = 15 mg/2g o wa e ).
Chap e 3.4
262
F om he esul s, i can be concluded ha he no el echnology p oposed
he e wo ks e y well a lowe concen a ions (< 2ppm) as well as being able
o ex ac om a complex mix u e and also om eal wa e samples wi h
complex ma ices. Mo eo e , i was once again con i med ha he s uc u e o
he DES and he mic opollu an in luence he pe o mance o he adso p ion
echnology used. I was no ed ha bo h hyd ophobic DES ha e e y good
pe o mances, howe e he bes sys em o ex ac all mic opollu an s and wi h
g ea ex ac ion e iciencies (> 95%) was [N8888]B : C10.
Compa ing he ex ac ion o he indi idual compounds and using mix u es o
a ious mic opollu an s, hese can be emo ed wi h he same success
wi hou any in e e ence. Di ec ly compa ing he ex ac ion o mic opollu an s
in simula ed wa e and aking a s ep o wa d o a eal applica ion using eal
wa e samples, he ex ac ion e iciency emains appealing, p esen ing he
same ema kable esul s.
Adso p ion is an ad an ageous al e na i e app oach o adi ional
echnologies since i is simple, as , low-cos and e ec i e. As a as
ele ance o an implemen a ion o a p ocess ollowing he es ed condi ions,
i was highligh ed ha LLE expe imen s equi ed he use o 100g o DES,
whe eas 250mg o suppo ed DES adso ben pe li e o wa e su iced o
achie e he highes ex ac ion e iciencies, o he same expe imen al
condi ions.
2. Conclusions
In conclusion, he de elopmen o adso ben ma e ials based on hyd ophobic
DES is a p omising app oach o wa e cleaning echnologies. The p oposed
adso p ion p ocess o e s se e al ad an ages compa ed o he liquid-liquid
adi ional p ocess such as he as and easy sepa a ion, he eusabili y
wi hou comp omising capaci y and he small amoun o DES needed, which
Hyd ophobic deep eu ec ic sol en s as adso ben ma e ials o emo al o
mic opollu an s om wa e sou ces
263
can be e y impo an in he case o DESs composed o expensi e
compounds.
3. Acknowledgemen s
Ca a ina Flo indo and Luis C. B anco g a e ully acknowledge he inancial
suppo o FCT/MCTES (Po ugal) o he PhD ellowship
SFRH/BD/102313/2014 and o he con ac unde P og ama In es igado
2013 (IF/0041/2013), espec i ely. This wo k was inanced by he CQE
p ojec (UID/QUI/00100/2013) and he Resea ch Uni GREEN-i
‘‘Bio esou ces o Sus ainabili y’’ (UID/Mul i/04551/2013).
4. Supplemen a y In o ma ion
4.1. Expe imen al de ails
Ma e ials. DL-Men hol (pu i y ≥ 95%), e ahep ylammonium b omide
([N7777]B ) (pu i y ≥ 99%), e aoc ylammonium b omide ([N8888]B ) (pu i y ≥
98%), me hyl ioc ylammonium b omide ([N8881]B ) (pu i y ≥ 97%), oc anoic
acid (C8) (pu i y ≥ 98%) and decanoic acid (C10) (pu i y ≥ 98%) we e
pu chased om Sigma-Ald ich and used as ecei ed. Du apo e po ous
hyd ophobic poly( inylidene luo ide) (PVDF) il e p o ided by Millipo e
Co po a ion (USA) wi h a po e size o 0.22 μm and an a e age hickness o
125 μm, we e used as he suppo o main ain he DES as a ca ie in he
po ous il e . Diclo enac sodium mic opollu an (mass ac ion pu i y ≥ 99 %)
was pu chased om Sigma Ald ich and used wi h no u he pu i ica ion. All
aqueous solu ions we e p epa ed using high pu i y wa e (Milli-Q wa e ) wi h
a speci ic conduc ance <0.1 mS/cm.
Chap e 3.4
270
These esul s show ha when he hyd ophobici y o he DES inc eases, i s
ex ac ion e iciency also inc eases. This could be seen in he men hol’s and
a y acids amilies, whe e he inc easing o he alkyl chain p o ides a isible
op imiza ion on he ex ac ion o mic opollu an . The same can be also
obse ed in he qua e na y ammonium sal s amily.
All he amilies o hyd ophobic DESs p esen ed a high ex ac ion e iciency
esul , which means ha all s udied DESs ha e po en ial o ex ac diclo enac
sodium om wa e en i onmen s. These esul s can be explained ei he by a
high solubili y o diclo enac sodium in he hyd ophobic DESs o by he
possible a ini y be ween he DES and he mic opollu an due o hei
s uc u al simila i ies.
4.3.2. E alua ion o Di e en Pa ame e s in he Ex ac ion o Diclo enac
Sodium
E ec o ime on ex ac ion. Di e en con ac imes we e employed in he
ex ac ion p ocess in o de o e i y i he sys em had al eady eached he
equilib ium. The esul s ob ained wi h he di e en con ac imes a e
p esen ed in Figu e S4.

Hyd ophobic deep eu ec ic sol en s as adso ben ma e ials o emo al o
mic opollu an s om wa e sou ces
271
Figu e S4. E ec o he con ac ime in he ex ac ion e iciencies (EE %) o
diclo enac sodium sal using he hyd ophobic DESs C12: C10 (1:2) ([C0]Dic =
0.03 g/L, s i ing speed = 300 pm, DES/wa e a io = 1/1, empe a u e = 25
ºC).
F om Figu e S4, i is possible o pe cei e ha he con ac ime does no a ec
he ex ac ion e iciency o he diclo enac sodium, since he sys em had
al eady eached he equilib ium a e 1 minu e. Fu he mo e, i is possible o
conclude ha he de elopmen o he ex ac ion p esen s a maximum alue,
and i is no always possible ex ac he o ali y o he pollu ing agen o
ce ain expe imen al condi ions.
E ec o s i ing speed. Di e en s i ing speeds we e also es ed in o de o
e alua e i s onge agi a ions would p o ide be e con ac be ween he DES
and he aqueous phases, wi hou b eaking he DES hyd ogen bonds. The
s i ing speeds we e es ed in a ange om 100 o 700 pm and ob ained
esul s a e p esen ed in Figu e S5.
1 min
5 min
10 min
20 min
EE %
0
20
40
60
80
100
Chap e 3.4
272
Figu e S5. E ec o he s i ing speed in he ex ac ion e iciencies (EE %) o
diclo enac sodium sal using he hyd ophobic DESs C12: C10 (1:2) ([C0]Dic =
0.03 g/L, con ac ime = 10 min, DES/wa e a io = 1/1, empe a u e = 25 ºC).
These esul s show ha he s i ing speed does no ha e a conside able
in luence on ex ac ion e iciency, since a low s i ing speed o 100 pm is
enough o ex ac mo e han 85% o he mic opollu an . Ne e heless, i was
obse ed ha o highe speeds, as 500 and 700 pm, he ex ac ion
e iciency may e en sligh ly dec ease, because he con ac be ween he wo
phases becomes oo as . Al hough, i is impo an o obse e ha e en i he
s i ing speed does no ha e a huge impac on he ex ac ion e iciency, he
quali y o he s i ing speed does ha e a isible impac on ex ac ions. I is
impo an o main ain always he same expe imen al condi ions.
E ec o he ini ial concen a ion o he mic opollu an . O he e y
impo an ac o o conside in an ex ac ion p ocess is he ini ial
concen a ion o mic opollu an , in his case, diclo enac sodium, in aqueous
en i onmen s since he ex ac ion p ocess should be applicable o any
pollu ed wa e sample. Fo his pu pose, h ee di e en aqueous solu ions o
100 pm
200 pm
300 pm
500 pm
700 pm
EE %
0
20
40
60
80
100
Hyd ophobic deep eu ec ic sol en s as adso ben ma e ials o emo al o
mic opollu an s om wa e sou ces
273
diclo enac sodium ( anging om 0.01 o 0.03 g/L) we e es ed o one
hyd ophobic DES o each amily, namely C12: C10 (1:2), DL-Men hol: C10 (1:1)
and [N8888]B : C10 (1:2). The ob ained esul s a e p esen ed in Figu e S6.
Figu e S6. E ec o he ini ial concen a ion o diclo enac sodium sal in he
ex ac ion e iciencies (EE %) using di e en hyd ophobic DESs (con ac ime
= 10 min, DES/wa e a io = 1/1, s i ing speed = 300 pm, empe a u e = 25
ºC).
I can be obse ed ha he ex ac ion e iciency dec eases o lowe
concen a ions o diclo enac sodium, which means ha his pollu an is mo e
di icul o emo e a lowe concen a ions in wa e . Howe e , i essen ially
depends on he amily o HBA o he hyd ophobic DESs and can be anked
as ollows: a y acids amily > men hol amily > qua e na y ammonium sal
amily, whe e he la e is he less p onounced. The qua e na y ammonium
sal amily shows be e and cons an ex ac ion e iciencies o lowe
concen a ions han he o he amilies. This can be explained by he chemical
s uc u al simila i y be ween diclo enac sodium and [N8888]B : C10 (1:2), whe e
C12: C10 (1:2)
Men hol: C10 (1:1)
[N8888B ]: C10 (1:2)
EE %
0
20
40
60
80
100
120 0.03 g/L
0.02 g/L
0.01 g/L
Chap e 3.4
274
bo h p esen ionic species. The e o e, i can be concluded ha he
hyd ophobici y and he pola i y o he hyd ophobic DESs a e c ucial ac o s o
he e iciency o he ex ac ion p ocess.
E ec o he a io be ween DES and wa e phases. The a io be ween he
pollu ed wa e and he DES phase is also a key ac o o be conside ed, since
i will de e mine i he ex ac ion p ocess is easible o no . Thus, di e en
concen a ions o aqueous solu ions o diclo enac sodium (C = 0.03 g/L and C
= 0.01 g/L) and wo hyd ophobic DESs ((C12: C10 (1:2) and DL-Men hol: C10
(1:1)) we e es ed o using di e en DES/wa e a ios a ied om 3/1 o
1/100. The ob ained esul s a e shown in Figu es S7 and S8.
Figu e S7. E ec o he DES/wa e a io in he ex ac ion e iciencies (EE %)
using wo hyd ophobic DESs a a high concen a ion o mic opollu an ([C0]Dic
= 0.03 g/L, con ac ime = 10 min, s i ing speed = 300 pm, empe a u e = 25
ºC).
DES 3/1 2/1 1/1 1/2 1/3 1/4 1/51/10
1/100H2O
EE %
0
20
40
60
80
100
C12: C10 (1:2)
Men hol: C10 (1:1)
3:1 2:1 1:1 1:2 1:3 1:4 1:5 1:10 1:100
EE %
0
20
40
60
80
100
C12: C10 (1:2)
Men hol: C10 (1:1)
3:1 2:1 1:1 1:2 1:3 1:4 1:5 1:10 1:100
EE %
0
20
40
60
80
100
C12: C10 (1:2)
Men hol: C10 (1:1)
Hyd ophobic deep eu ec ic sol en s as adso ben ma e ials o emo al o
mic opollu an s om wa e sou ces
275
Rega ding he esul s p esen ed in Figu e S7, i can be concluded ha
ex ac ion e iciency inc eases o lowe quan i ies o hyd ophobic DES
ela i e o he wa e phase. This can p obably be explained by he high
hyd ophobici y o hese sol en s as well as he high solubili y o
mic opollu an in DES. I DES is oo abundan in he sys em, an op imized
mass ans e can be challenging wi h he aqueous phase and he ex ac ion
can ac ually dec ease, due o an unp omising mass o olume a io. A small
amoun o DES in oduced in he sys em ends up playing a ele an ole
ega ding an appealing mass ans e as he DES can easily sp ead in o he
aqueous phase in he o m o small d ople s and he ex ac ion can be
imp o ed.
Mo eo e , he e ec o DES/wa e a io can be exploi ed in o de o
compensa e o he impo an pa ame e s, such as he imp o emen o he
ex ac ion in he less concen a ed pollu ed wa e samples. Thus, a u he
s udy was conduc ed ega ding he e ec o he DES/wa e a io o a
diclo enac sodium aqueous solu ion wi h a lowe concen a ion o 0.01 g/L,
which had p e iously shown lowe ex ac ions e iciencies. The esul s a e
shown in Figu e S8.

Chap e 3.4
276
Figu e S8. E ec o he DES/wa e a io in he ex ac ion e iciencies (EE %)
using wo hyd ophobic DESs using a di e en ini ial concen a ion o
mic opollu an a low concen a ion o mic opollu an ([C0]Dic = 0.01 g/L,
con ac ime = 10 min, s i ing speed = 300 pm, empe a u e = 25 ºC).
In gene al, i can be obse ed ha he ex ac ion e iciency was signi ican ly
enhanced o all he s udied hyd ophobic DESs. Once again, he e a e
di e ences in he ex ac ion e iciencies be ween he a ious amilies o
hyd ophobic DESs. I was ound ha o low concen a ions, hose ha ha e
he g ea es e ec on he a io a e men hol. I was e i ied ha o low
concen a ions o diclo enac sodium, hose ha a e mo e suscep ible o be
a ec ed by DES/wa e a io a e om he a y acid and men hol amilies.
This would be e y in e es ing o a la ge-scale applica ion, since i would
p o ide high ex ac ion e iciencies o mic opollu an using lowe quan i ies o
DESs. I also p o es ha he liquid-liquid ex ac ion will no be limi ed by he
ini ial concen a ion o he mic opollu an in wa e , since he e ec o he a io
will be able o compensa e he e ec o he concen a ion.
DES
3/1
2/1
1/1
1/2
1/3
H2O
EE %
0
20
40
60
80
100
C12: C10 (1:2)
Men hol: C10 (1:1)
[N8888]B : C10 (1:2)
DES
3/1
2/1
1/1
1/2
1/3
H2O
EE %
0
20
40
60
80
100
C12: C10 (1:2)
Men hol: C10 (1:1)
[N8888]B : C10 (1:2)
DES
3/1
2/1
1/1
1/2
1/3
H2O
EE %
0
20
40
60
80
100
C12: C10 (1:2)
Men hol: C10 (1:1)
[N8888]B : C10 (1:2)
DES
3/1
2/1
1/1
1/2
1/3
H2O
EE %
0
20
40
60
80
100
C12: C10 (1:2)
Men hol: C10 (1:1)
[N8888]B : C10 (1:2)
Hyd ophobic deep eu ec ic sol en s as adso ben ma e ials o emo al o
mic opollu an s om wa e sou ces
277
E ec o he HBA: HBD a io o DES. Ano he aspec o be explo ed in his
ield is he phase diag ams o hyd ophobic DESs as well as he se e al liquid
phase a ios a wo king condi ions a ailable in diag ams. The s udied DES
may also be ound in he liquid o m o di e en a ios HBA: HBD om hose
used p e iously and also di e en om he eu ec ic poin . In his sec ion, he
e ec o o he composi ions o C12: C10 (1:2) and DL-Men hol: C10 (1:1) will be
checked. The phase diag ams o he s udied hyd ophobic DESs a e
ep esen ed in Figu e S9 and he ob ained esul s a e shown in Figu e S10.
Figu e S9. Phase diag ams o C12: C10 (a) and DL-Men hol: C10 (b),
espec i ely. The blue poin s ep esen he es ed composi ions o he DES o
pe o m ex ac ions.
2D G aph 1
mola a io
0.0 0.2 0.4 0.6 0.8 1.0
Tempe a u e (ºC)
15
20
25
30
35
40
45
Col 4 s Col 2
Col 4 s Col 2
2D G aph 1
mola a io
0.0 0.2 0.4 0.6 0.8 1.0
Tempe a u e (ºC)
5
10
15
20
25
30
35
40
45
Col 8 s Col 6
Col 8 s Col 6
a)
b)
Chap e 3.4
278
Figu e S10. Liquid-liquid ex ac ions o diclo enac sodium sal using C12: C10
(g een) and DL-Men hol: C10 (blue) in di e en a ios HBA: HBD as
ep esen ed in he phase diag am abo e ([C0]Dic = 0.03 g/L, con ac ime = 10
min, s i ing speed = 300 pm, empe a u e = 25 ºC).
F om he esul s, i can be concluded ha he bes esul s o ex ac ion
e iciencies ob ained we e ound o C12: C10 (1:2) and DL-Men hol: C10 (1:1)
sys ems in he a io which we e used in he p e ious s udies, as well as
co esponding o he eu ec ic poin indica ed in he phase diag am.
Howe e , some e ec o HBA: HBD a io is mo e isible o he case o DL-
Men hol: C10, which seems o be ela ed o he amily o DES used. As i can
be seen, he HBA:HBD a io had almos no e ec on he ex ac ion
e iciencies, which means ha o he composi ions om he phase diag am as
well as di e en om eu ec ic poin can be used, p o ided ha DES emains
liquid and s able a wo king condi ions.
Reuse o he DES. F om an economical poin o iew, i is i al o a no el
sol en ha i can be eused mul iple imes be o e losing i s ex ac ion
2D G aph 1
3:1 2:1 1:1 1:2 1:3 1:4
EE %
0
20
40
60
80
100
Col 8 s Col 6
Col 3
Col 5
Hyd ophobic deep eu ec ic sol en s as adso ben ma e ials o emo al o
mic opollu an s om wa e sou ces
279
capabili y. In his s udy, C12: C10 (1:2) and [N8888]B : C10 (1:2) we e selec ed o
be eused in consecu i e liquid-liquid ex ac ions o di e en samples o a
sodium diclo enac solu ion wi h a concen a ion o 0.03 g/L. A e each
ex ac ion he DES phase was ea ed wi h “ esh” wa e in o de o e i y i i
was possible o imp o e o main ain he ex ac ion e iciency. The ob ained
esul s a e summa ized in Figu e S11.
Figu e S11. Se e al cycles o ex ac ion o diclo enac sodium sal using C12:
C10 (g een) and [N8888]B : C10 (o ange) ([C0]Dic = 0.03 g/L, con ac ime = 10
min, s i ing speed = 300 pm, empe a u e = 25 ºC).
F om he esul s, i can be concluded ha in bo h DESs, C12: C10 (1:2) and
[N8888]B : C10 (1:2), a e i e cycles o i s eu iliza ion, i keeps i s ex ac ion
capaci y and i is e en possible o obse e ha in some cases, he ex ac ion
e iciency can sligh ly inc ease in each cycle. This p obably happens because
he p esence o he mic opollu an in he used DESs, inc eases he a ini y
be ween he DES phase and he sodium diclo enac molecules o be ex ac ed
in he aqueous phase. Also, i is possible o see ha he a ia ions in he
2D G aph 1
Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5
EE %
0
20
40
60
80
100
C12: C10 (1:2)
[N8888]B : C10 (1:2)
DES
3/1
2/1
1/1
1/2
1/3
H2O
EE %
0
20
40
60
80
100
C12: C10 (1:2)
Men hol: C10 (1:1)
[N8888]B : C10 (1:2)
DES
3/1
2/1
1/1
1/2
1/3
H2O
EE %
0
20
40
60
80
100
C12: C10 (1:2)
Men hol: C10 (1:1)
[N8888]B : C10 (1:2)
Chap e 3.4
286

CHAPTER 4
Hyd ophilic
s.
Hyd ophobic
Deep Eu ec ic Sol en s
Miscible
Immiscible
F om miscible o immiscible
CHAPTER 4.1
A close look in o Deep Eu ec ic
Sol en s: explo ing in e molecula
in e ac ions using sol a och omic
p obes
A close look in o Deep Eu ec ic Sol en s: explo ing in e molecula in e ac ions
using sol a och omic p obes
3
Adap ed om: C. Flo indo, A. J. S. McIn osh, T. Wel on, L. C.
B anco, I. M. Ma ucho, A close look in o Deep Eu ec ic Sol en s:
explo ing in e molecula in e ac ions using sol a och omic p obes,
Phys. Chem. Chem. Phys. (2018), 20, 206-213.
The au ho con ibu ed o he execu ion o all cha ac e iza ion and
p ope ies expe imen s desc ibed in his chap e , as well as
in ol ed in he discussion and in e p e a ion o esul s and he
p epa a ion o he manusc ip .

Chap e 4.1
CONTENT
ABSTRACT ...................................................................................................... 294
1. INTRODUCTION ............................................................................ 294
2. EXPERIMENTAL SECTION .......................................................... 298
2.1. MATERIALS…………………………………………………… 298
2.2. METHODS…………………………………………………….. 299
2.2.1. Syn hesis o ILs ......................................................................... 299
2.2.2. P epa a ion o DESs .................................................................. 300
2.2.3. Sol a och omic P obes ............................................................. 300
3. RESULTS AND DISCUSSION ...................................................... 300
3.1. BETAINE DYE SCALE…………………………………………. 300
3.2. KAMLET-TAFT SCALE………………………………………… 306
3.2.1. Hyd ogen Bonding Accep o Abili y: β Pa ame e ..................... 306
3.2.2. Hyd ogen Bonding Dono Abili y: α Pa ame e ......................... 312
3.2.3. Pola isablili y/Dipola i y π* Pa ame e ....................................... 314
4. CONCLUSIONS ............................................................................. 317
5. ACKNOWLEDGEMENTS .............................................................. 318
6. REFERENCES ............................................................................... 318
A close look in o Deep Eu ec ic Sol en s: explo ing in e molecula in e ac ions using
sol a och omic p obes
293
Chap e 4.1
294
Abs ac
Deep eu ec ic sol en s (DESs) cons i u e a new class o ionic sol en s ha
has been de eloping a a as pace in ecen yea s. Since hese sol en s a e
commonly sugges ed as g een al e na i es o o ganic sol en s, i is impo an
o unde s and hei physical p ope ies. In pa icula , pola i y plays an
impo an ole in sol a ion phenomena. In his wo k, he pola i y o di e en
amilies o DESs was s udied h ough sol a och omic esponses o UV- is
abso p ion p obes. Kamle -Ta α, β, π* and ETN pa ame e s we e e alua ed
using di e en sol a och omic p obes, as 2,6-Dichlo o-4-(2,4,6- iphenyl-N-
py idino)-phenola e (Reicha d ’s be aine dye 33), 4-ni oaniline, and N,N-
die hyl-4-ni oaniline o se e al amilies o DESs based on cholinium
chlo ide, DL-Men hol and a qua e na y ammonium sal ([N4444]Cl). In addi ion,
a s udy o unde s and he di e ence in pola i y p ope ies be ween DESs and
he co esponding ILs, namely ILs based on cholinium ca ion and ca boxylic
acids as anions ([Ch][Le ], [Ch][Gly] and [Ch][Mal]), was ca ied ou . The
chemical s uc u e o he hyd ogen bond accep o (HBA) in a DES clea ly
con ols he dipola i y/pola izabili y a o ded by he DES. Mo eo e , Kamle -
Ta pa ame e s do no a y much wi hin he amily, bu hey di e among
amilies based on di e en HBA, ei he o DESs con aining sal s ([Ch]Cl o
[N4444]Cl) o neu al compounds (DL-Men hol). A subs i u ion o he HBD was
also ound o play an impo an ole in sol a och omic p obe beha iou o all
he s udied sys ems.
1. In oduc ion
Deep Eu ec ic Sol en s (DESs) ha e been eme ging since 2004 as a new
gene a ion o sol en s wi h a g ea po en ial o a a ie y o applica ions.1
DESs can be ega ded as a new class o ionic sol en s, ypically composed
o an o ganic sal and a leas one hyd ogen bond dono , which p esen s a
lowe mel ing poin han any o i s indi idual componen s.2 The o ma ion o a
A close look in o Deep Eu ec ic Sol en s: explo ing in e molecula in e ac ions using
sol a och omic p obes
295
liquid compound a oom empe a u e is due o he o ma ion o hyd ogen
bonds be ween a hyd ogen bond dono (HBD), and a hyd ogen bond
accep o (HBA).3 Bea ing in mind ha in a sal , he ca ion gene ally ac s as
an HBD and he anion as HBA, he DES o ma ion is due o he addi ion o an
ex a HBD. DESs a e cu en ly a ac ing widesp ead scien ific and
echnological in e es as al e na i es o ionic liquids (ILs).4-5
Al hough hese sol en s a e gene ally compa ed o ILs, mainly due o hei
equi alen ly negligible apou p essu es a oom empe a u e, hey ha e
impo an ad an ages such as hei s aigh o wa d and g een syn hesis, ha
does no need any sol en and pu i ica ion s eps and hei low oxici y and
cos , since he compounds used a e usually non- oxic, abundan and om
enewable esou ces.6-7 Jus like ILs, one o he mos a ac i e aspec s o
hese al e na i e sol en s is he abili y o ine- une hei physical-chemical
p ope ies, including hyd ogen bond dona ing/accep ing abili y and
pola izabili y, h ough he easy manipula ion o he chemical s uc u es o he
s a ing compounds. Howe e , he e is s ill a lack in he knowledge o some
impo an sol en p ope ies, such as pola i y.
The exac meaning o “pola i y” ( he sum o all possible in e ac ions be ween
a sol en and any po en ial solu e8) is complex as many di e en in a and
in e agg ega e/ion pai in e ac ions, such as hyd ogen bonding, π-
in e ac ions o an de Waals o ces, a e in ol ed. The molecula dynamics o
DESs sys ems ha e been ecen ly a e s udied using 1H pulsed ield g adien
NMR sel -diffusion coe icien s. This me hod is e y use ul o de ail and
unde s and he in e ac ions be ween ions, hos /gues molecules and
complexes o ma ion.9-11 On he o he hand, sol a och omic p obes ha e also
been used o in es iga e ILs and DES pola i y. In pa icula , Kamle –Ta
pa ame e s ha e been used o quan i y he hyd ogen-bond dona ing abili y
(α, acidi y), he hyd ogen bond accep ing abili y (β, basici y) and
pola i y/pola izabili y (π*) o ILs and DESs.5, 12-14 I should be ema ked ha
pola i y is no an absolu e p ope y o he pu e liquid15-16 and hence, he e is
Chap e 4.1
302
be ween 0 o TMS (ex emely non-pola ) and 1 o wa e (ex emely pola ).
Thus, i s use is ecommended ins ead o ET(30).
Abso bance spec a o Reicha d ’s 33 we e collec ed in se e al sol en s
(DESs and ILs) a oom empe a u e, and he co esponding alues o ET(33)
con e ed in o ET(30) alues, h ough a linea eg ession analysis using he
ollowing equa ion (2)14, 28:
ET(30)= 0.9953(±0.0287)× ET(33)− 8.1132(±1.6546) (eq. 2)
I Reicha d ’s dye is being used, he ETN pola i y pa ame e is easily ob ained
by measu ing he wa eleng h co esponding o he maximum o abso p ion o
he dye in he sol en unde s udy, acco ding o he ollowing equa ions:
ETN=[ET(30)sol en −ET(30)TMS]
[ET(30)wa e −ET(30)TMS] = ET(30)− 30.7
32.4 (eq. 3)
whe e ET(30) is gi en by equa ion (1).
In Figu e 4, he abso bance spec a o Reicha d ’s 33 dissol ed in se e al ILs
and DESs a e p esen ed.

A close look in o Deep Eu ec ic Sol en s: explo ing in e molecula in e ac ions using
sol a och omic p obes
303
Figu e 4. Example o he lowes ene gy in amolecula cha ge- ans e
abso p ion band o Reicha d ’s be aine dye 33 o some ILs and DESs
s udied in his wo k.
I can be obse ed ha he peaks o DL-Men hol: AceA and [N4444]Cl: Oc A in
he egion be ween 400 nm and 600 nm a e di icul o de ec . To o e come
his issue, i s de i a i es o he spec a we e used o de e mine he λmax. The
λmax alue, as well as ET(33) and ETN calcula ed using equa ions (1) and (3),
a e lis ed in Table 1 o all he ILs and DESs s udied in his wo k.
 (nm)
350 400 450 500 550 600 650
Abs
0.0
0.2
0.4
0.6
0.8
1.0
1.2
[Ch]Cl:E hy
Men hol:AceA
[N4444]Cl:Oc A
IL [Ch][Gly]
IL [Ch][Le ]
Chap e 4.1
304
Table 1. UV-Vis abso bance maxima (λmax) o Reicha d ’s 33, ET(33) and ETN
o all DESs and co esponding ILs.
λmax o
Reicha d ’s
33 (nm)
ET(33)
(Kcal.mol-1)
ETN
Ionic
Liquids
[Ch][Le ]
485.07
58.94
0.61
[Ch][Mal]
428.73
66.69
0.85
[Ch][Gly]
453.17
63.09
0.74
[Ch]Cl: Le A
568.89
50.26
0.35
Deep
Eu ec ic
Sol en s
[Ch]Cl: MalA
442.53
64.61
0.79
[Ch]Cl: GlyA
562.44
50.83
0.36
[Ch]Cl: U ea
434.84
65.75
0.81
[Ch]Cl: E hy
433.82
65.91
0.83
[Ch]Cl: Gly
429.99
66.49
0.84
DL-Men hol: AceA
457.80
62.45
0.72
DL-Men hol: Le A
456.56
62.62
0.73
DL-Men hol: Oc A
453.12
63.10
0.74
DL-Men hol: DodA
454.52
62.90
0.73
[N4444]Cl: Oc A
464.71
61.52
0.69
[N4444]Cl: DecA
474.72
60.23
0.65
[N4444]Cl: DodA
464.36
61.57
0.69
In o de o alida e ou expe imen al me hod, he ET(33) alues o [Ch]Cl:
U ea, [Ch]Cl: E hy and [Ch]Cl: Gly we e also measu ed in his wo k and
compa ed wi h hose published in li e a u e 65.418, 65.718 and 66.420 Kcal mol-
1, espec i ely. The e is a good ag eemen be ween ou esul s lis ed in Table
1 and hose epo ed in li e a u e, hus alida ing he me hodology he e used.
High ETN alues we e ob ained o he wo amilies o hyd ophobic DESs
s udied in his wo k, DL-Men hol-based and [N4444]Cl-based, lis ed in Table 1,
demons a ing ha hese sol en s a e hyd ophobic and pola . Fo example, i
one compa es he alues o DL-Men hol: Oc A (0.74) o DL-Men hol: DodA
(0.73) wi h hose o he co esponding qua e na y ammonium based DESs,
[N4444]Cl: Oc A (0.69) and [N4444]Cl: DodA (0.69), only small di e ences can
A close look in o Deep Eu ec ic Sol en s: explo ing in e molecula in e ac ions using
sol a och omic p obes
305
be obse ed. Ne e heless, he ETN alues ob ained o he DL-Men hol-
based DESs a e sligh ly highe han hose ob ained o [N4444]Cl-based DESs,
indica ing he impo an ole o HBA in de ining he pola i y o hyd ophobic
DESs. Ano he obse a ion is ha ETN alues a e almos cons an wi hin he
same HBA amily. Fo example, he same ETN alue (0.73) was ob ained o
DL-Men hol: Le A and DL-Men hol: DodA, despi e he ob ious chemical
di e ences be ween he HBD o he wo DESs. In he same way, simila ETN
alues we e ob ained o [N4444]Cl-based DESs, despi e he di e ences in he
chain leng h o he HBDs used. These obse a ions co obo a e he
conclusion ha he HBA plays a mo e impo an ole in o e all pola i y han
he HBD in hyd ophobic DESs.
Focusing now on he hyd ophilic [Ch]Cl-based DESs, a wide ange o ETN
can be obse ed: [Ch]Cl: MalA (0.79) has he highes ETN alue, while e y
simila alues we e ob ained o he o he wo DESs, [Ch]Cl: Le A (0.35) and
[Ch]Cl: GlyA (0.36). This means ha he DES wi h HBD based on he diacid
(MalA) as HBD is mo e pola han hose based on monoacids wi h di e en
chemical g oups, such as a ke one (in Le A) o an alcohol g oup (in Gly). In
o he wo ds, he in e ac ions be ween he p obe and he e e ed DESs
dec ease as he g oups change om acid o alcohol o ke one, as expec ed.
Compa ing he ETN alues ob ained o hyd ophilic and hyd ophobic DESs o
he same HBD, [Ch]Cl: Le A (0.35) and o DL-Men hol: Le A (0.73), i can
be concluded ha he la e is much mo e pola han he o me . This is
somehow su p ising since [Ch]Cl: Le A con ains an IL as HBA, while DL-
Men hol: Le A con ains a neu al molecule. Again, and as i was men ioned
be o e when wo hyd ophobic DESs wi h he same HBD we e compa ed, his
can be a ibu ed o he di e ences in he HBA: he chlo ide anion es ablishes
a mo e s able hyd ogen bond wi h he Le A han ha be ween DL-Men hol
and Le A, dec easing he HBD abili y o he o me and hus i s in e ac ion
wi h he p obe.
Chap e 4.1
306
The alues he e ob ained o he h ee s udied ILs a e e y simila o hose
ound in li e a u e o o he common and well-s udied ILs. In gene al, he ETN
alues o ILs a y signi ican ly depending upon he na u e o ca ion and
anion, anging om 0.5 o 0.7,29 in ag eemen wi h he esul s he e ob ained:
[Ch][Le ] (0.61), [Ch][Gly] (0.74), [Ch][Mal] (0.85). The explana ion o his
a ia ion is essen ially ela ed o he leng h and he hyd oxyl g oup
unc ionali ies o he alkyl chains o he anions and hei abili y o pa icipa e in
hyd ogen-bonding ne wo ks. Gene ally, o he same ca ion, he ETN alues
o ILs dec ease in he ollowing o de o anions: [HCO2]- > [NO3]- > [BF4]- >
[NT 2]- > [PF6]-, which is he o de o dec easing basici y o he anions.30
Finally, compa ing among he di e en ILs s udied, whe e he anion is
changed and he ca ion is kep cons an , i can be obse ed ha he ETN
scale is pa icula ly sensi i e o he HBD abili y o he anion.
Compa ing he DESs based on [Ch]Cl and acids wi h he co esponding ILs,
ILs a e gene ally much mo e pola han he co esponding DESs, since he
ETN o he ILs a e gene ally highe han hose o he co esponding DESs.
This is in ag eemen wi h Pandey’s obse a ions, who s udied DESs o med
om choline chlo ide combined wi h 1,2-e hanediol, glyce ol, and u ea, in 1:2
mola a ios.14, 18 Ano he impo an obse a ion is ha he pola i y o de
obse ed in he DESs and ILs is main ained, ha is, om he mos pola o
he less pola he ollowing o de is a ained: MalA > GlyA > Le A.
3.2. Kamle -Ta Scale
3.2.1. Hyd ogen Bonding Accep o Abili y: β Pa ame e
The Kamle -Ta HBA abili y (β) is ob ained by a sol a och omic compa ison
me hod, which compa es sol en -induced shi s o he abso p ion bands o
wo p obes. These p obes a e selec ed o be s uc u ally e y simila (i.e.
homomo phic) excep o hei capaci y as HBD, since one can ac as HBD
and he o he canno . Ano he cha ac e is ic o hese p obes is ha hey ha e
A close look in o Deep Eu ec ic Sol en s: explo ing in e molecula in e ac ions using
sol a och omic p obes
307
a good co ela ion o bo h hei spec a in non-HBA sol en s, bu wi h
signi ican de ia ions in hei spec a in hyd ogen bond accep ing sol en s, so
ha he cons uc ion o a scale based upon hese diffe ences is possible.16
Kamle and Ta 31 p oposed wo pai s o p obes, 4-ni oaniline/N,N-die hyl-4-
ni oaniline o 4-ni ophenol/ 4-ni oanisole, o cons uc he β scale. In his
wo k, he 4-ni oaniline/N,N-die hyl-4-ni oaniline p obe se was used, since
hey a e he mos commonly used pai o ionic liquids.32 The β alues o he
ILs and DESs unde s udy a e lis ed in Table 2 and we e calcula ed using he
ollowing equa ions:
𝛽 = 0.76 (∆ῡsol en −∆ῡcycloexane)
∆ῡDMSO−∆ῡcyclohexane ↔ (eq. 4)
𝛽 = 1.035 ῡN,N−die hyl−4−ni oaniline+2.64−ῡ4−ni oaniline
2.80 (eq. 5)
whe e ∆ῡ = ῡN,N−die hyl−4−ni oaniline − ῡ4−ni oaniline

Chap e 4.1
308
Table 2. Kamle –Ta pa ame e s, using he dye se : Reicha d ’s 33, N,N-
die hyl-4-ni oaniline and 4-ni oaniline.
α
β
π*
Ionic
Liquidsa
[Ch][Le ]
1.07
1.03
1.00
[Ch][Mal]
1.55
0.62
1.04
[Ch][Gly]
1.29
0.79
1.08
[Ch]Cl: AceA
b
0.53
1.10
Deep
Eu ec ic
Sol en s
[Ch]Cl: Le A
0.51
0.57
1.00
[Ch]Cl: MalA
1.39
0.42
1.08
[Ch]Cl: GlyA
0.49
0.50
1.08
[Ch]Cl: U ea
1.42
0.50
1.14
[Ch]Cl: E hy
1.47
0.57
1.07
[Ch]Cl: Gly
1.49
0.52
1.11
DL-Men hol: AceA
1.64
0.60
0.53
DL-Men hol: Le A
1.56
0.58
0.66
DL-Men hol: Oc A
1.77
0.50
0.41
DL-Men hol: DodA
1.79
0.57
0.37
[N4444]Cl: Le A
b
0.82
1.06
[N4444]Cl: Oc A
1.41
0.99
0.76
[N4444]Cl: DecA
1.36
0.97
0.73
[N4444]Cl: DodA
1.45
1.04
0.71
aO he ILs we e syn hesized in o de o p o ide di ec compa ison be ween ILs and
DESs, bu sol a och omic p obes measu emen s we e no possible due hei solid
physical s a e. bNo peak could be de ec ed using he same p obe o di ec
compa ison.
In Figu e 5, he ob ained Kamle -Ta β pa ame e o he s udied DESs,
o ganized by amilies o hyd ogen bond accep o s, [Ch]Cl, [N4444]Cl and DL-
Men hol-based DESs, a e p esen ed.
A close look in o Deep Eu ec ic Sol en s: explo ing in e molecula in e ac ions using
sol a och omic p obes
309
Figu e 5. Kamle -Ta β pa ame e ob ained o all DESs s udied in his wo k.
The β alues ob ained o [Ch]Cl: U ea, [Ch]Cl: E hy and [Ch]Cl: Gly a e in
ag eemen wi h hose epo ed in he li e a u e by Pandey e al.,18 whe e
[Ch]Cl: U ea has he lowes β alue, ollowed by [Ch]Cl: Gly and [Ch]Cl: E hy.
This can be a ibu ed o he basici y o he HBD, since u ea is by a he mos
basic compound, ollowed by glyce ol and e hylene glycol, wi h pKa alues o
0.10, 14.15 and 14.22, espec i ely. Rega ding he β alues ob ained o
[Ch]Cl: U ea, i is in e es ing o obse e ha he p esence o he C=O g oup
in u ea does no inc ease he β alue. In he case o [Ch]Cl: Le A, he e ec
o he C=O g oup in le ulinic acid is s ill he e, bu he e ec is smalle han
o he IL analogue. Ne e heless, no e ha le ulinic acid does ha e a
ca bonyl g oup which can ac as a HBA.
I can be seen ha he alues o he [Ch]Cl-based and he DL-Men hol-
based DESs a e mode a e and simila o each o he , while hose o [N4444]Cl-

0.0
0.2
0.4
0.6
0.8
1.0
1.2
[Ch]Cl: Gly (1:2)
DL-Men hol: DodA (2:1)
[N4444]Cl: Le A (1:2)
DL-Men hol: Oc A (1:1)
DL-Men hol: AceA (1:1)
[Ch]Cl: U ea (1:2)
[Ch]Cl: E hy (1:2)
[Ch]Cl: AceA (1:2)
DL-Men hol: Le A (1:1)
[Ch]Cl: Le A (1:2)
[Ch]Cl: MalA (1:2)
[Ch]Cl: GlyA (1:2)
[N4444]Cl: DodA (1:2)
[N4444]Cl: Oc A (1:2)
[N4444]Cl: DecA (1:2)
Chap e 4.1
310
based DESs a e much highe . Fo example, he β alue o [Ch]Cl: Le A
(0.58) is simila o ha o DL-Men hol: Le A (0.58) leading us o hink ha he
in luence o he HBA is negligible. Howe e , compa ing β alues ob ained o
DL-Men hol-based DESs wi h hose o [N4444]Cl-based DESs o he same
HBD, a la ge di e ence can be obse ed. Fo example, he β alue o DL-
Men hol: Oc A (0.50) is almos hal o ha o [N4444]Cl: Oc A (0.97). This ac
indica es ha he na u e o he HBA, o mo e p ecisely he in e ac ion
be ween he HBD and HBA which limi s hose wi h he p obe, is o c ucial
impo ance in modula ing he β esul s.
Rega ding only he hyd ophobic DESs s udied in his wo k, i can be
concluded ha al hough e y di e en alues we e ob ained o he wo
amilies, DL-Men hol- and [N4444]Cl-based DES, no la ge di e ences we e
ob ained among he membe s o he same amily, indica ing he small e ec
o he HBDs on he acidi y o he DESs. In pa icula , inc easing alkyl chain o
he HBD has e y li le e ec on his desc ip o in bo h amilies. Fu he mo e,
he ex a unabili y o DES pola i y by he easy in oduc ion o di e en
HBD/HBA a ios needs o be highligh ed. In Figu e 6, a compa ison o he
ob ained Kamle -Ta pa ame e o cholinium-based ILs and he
co esponding DESs is p esen ed.
A close look in o Deep Eu ec ic Sol en s: explo ing in e molecula in e ac ions using
sol a och omic p obes
311
Figu e 6. Compa ison o Kamle -Ta pa ame e s ob ained o cholinium-
based ILs and co esponding DESs.
The β alues o he s udied cholinium-based ILs a e consis en ly highe han
hose o he co esponding DESs. This is due o he ac ha he IL anion is
he dep o ona ed o m o he acid while he DES con ains he p o ona ed o m
acid, and hus he dep o ona ed o m should be less hyd ogen bonding
accep o han he p o ona ed o m. To be highligh ed he e y high alue o β
o [Ch][Le ], wi h a alue o 1.03, while he alue ound o [Ch]Cl: Le A is
0.58, simila o he o he cholinium-based DESs. Mo eo e , [Ch]Cl: Le A is
also composed o wo moles o le ulinic acid as opposed o he IL, whe e
only 1 mole is p esen . As men ioned be o e he la ge β o [Ch][Le ] can be
possibly explained due o he ac ha le ulinic acid anion can only ac as
HBA, while malonic and glycolic acid anions s ill ha e one acid g oup and
one alcohol g oup, espec i ely and hus a e able o ac as HBA and HBD.
[Ch]Cl:Le A (1:2)
[Ch][Le ]
1
[Ch]Cl:MalA (1:1)
[Ch][Mal]
2
[Ch]Cl:GlyA (1:1)
[Ch][Gly]
0.0
0.5
1.0
1.5
2.0



Chap e 4.1
318
DESs. In a DES he molecula s uc u e o he hyd ogen bond accep o
(HBA) clea ly con ols he dipola i y/pola izabili y a o ded by he DES.
Mo eo e , he Kamle -Ta and pola i y pa ame e s o se e al amilies o
DESs based on di e en accep o s, namely sal s (cholinium chlo ide and
[N4444]Cl) and a neu al compound (DL-Men hol) he e epo ed demons a e
ha DES displays a high capaci y o dona e and accep p o ons when
compa ed o common sol en s and also ILs. In summa y, DESs pola i y can
be easily designed by he con enien choice o hei componen s.
5. Acknowledgemen s
Ca a ina Flo indo is g a e ul o he g an om COST - EXIL wi h e e ence
COST Ac ion CM1206 and o he inancial suppo o FCT/MCTES o he
PhD g an SFRH/BD/102313/2014. Isabel M. Ma ucho and Luis C. B anco
g a e ully acknowledge o he con ac unde In es iga o FCT 2012
(IF/363/2012 and IF/0041/2013), espec i ely. This wo k was inanced by
CQE p ojec (UID/QUI/00100/2013) and Resea ch Uni s
UID/QUI/00100/2013 (CQE) and UID/Mul i/04551/2013 (GREEN-IT).
6. Re e ences
1. Abbo , A. P.; Cappe , G.; Da ies, D. L.; Rasheed, R. K.; Tamby ajah, V.,
No el sol en p ope ies o choline chlo ide/u ea mix u es. Chemical
Communica ions 2003, (1), 70-71.
2. Dai, Y.; an Sp onsen, J.; Wi kamp, G.-J.; Ve poo e, R.; Choi, Y. H.,
Na u al deep eu ec ic sol en s as new po en ial media o g een echnology.
Analy ica Chimica Ac a 2013, 766, 61-68.
3. Hou, Y.; Gu, Y.; Zhang, S.; Yang, F.; Ding, H.; Shan, Y., No el bina y
eu ec ic mix u es based on imidazole. Jou nal o Molecula Liquids 2008, 143
(2–3), 154-159.
4. Flo indo, C.; Oli ei a, F. S.; Rebelo, L. P. N.; Fe nandes, A. M.; Ma ucho,
I. M., Insigh s in o he Syn hesis and P ope ies o Deep Eu ec ic Sol en s

A close look in o Deep Eu ec ic Sol en s: explo ing in e molecula in e ac ions using
sol a och omic p obes
319
Based on Cholinium Chlo ide and Ca boxylic Acids. ACS Sus ainable
Chemis y & Enginee ing 2014, 2 (10), 2416-2425.
5. Abbo , A. P.; Boo hby, D.; Cappe , G.; Da ies, D. L.; Rasheed, R. K.,
Deep Eu ec ic Sol en s Fo med be ween Choline Chlo ide and Ca boxylic
Acids:  Ve sa ile Al e na i es o Ionic Liquids. Jou nal o he Ame ican
Chemical Socie y 2004, 126 (29), 9142-9147.
6. Pai a, A.; C a ei o, R.; A oso, I.; Ma ins, M.; Reis, R. L.; Dua e, A. R. C.,
Na u al Deep Eu ec ic Sol en s – Sol en s o he 21s Cen u y. ACS
Sus ainable Chemis y & Enginee ing 2014, 2 (5), 1063-1071.
7. F ancisco, M.; an den B uinho s , A.; K oon, M. C., Low-T ansi ion-
Tempe a u e Mix u es (LTTMs): A New Gene a ion o Designe Sol en s.
Angewand e Chemie In e na ional Edi ion 2013, 52 (11), 3074-3085.
8. Reicha d , C.; Wel on, T., Sol en s and sol en e ec s in o ganic
chemis y. John Wiley & Sons: 2011.
9. D'Agos ino, C.; Ha is, R. C.; Abbo , A. P.; Gladden, L. F.; Man le, M. D.,
Molecula mo ion and ion di usion in choline chlo ide based deep eu ec ic
sol en s s udied by 1H pulsed ield g adien NMR spec oscopy. Physical
Chemis y Chemical Physics 2011, 13 (48), 21383-21391.
10. Abbo , A. P.; D'Agos ino, C.; Da is, S. J.; Gladden, L. F.; Man le, M. D.,
Do g oup 1 me al sal s o m deep eu ec ic sol en s? Physical Chemis y
Chemical Physics 2016, 18 (36), 25528-25537.
11. D'Agos ino, C.; Gladden, L. F.; Man le, M. D.; Abbo , A. P.; Ahmed, E. I.;
Al-Mu shedi, A. Y. M.; Ha is, R. C., Molecula and ionic di usion in aqueous
- deep eu ec ic sol en mix u es: p obing in e -molecula in e ac ions using
PFG NMR. Physical Chemis y Chemical Physics 2015, 17 (23), 15297-
15304.
12. C owhu s , L.; Mawdsley, P. R.; Pe ez-A landis, J. M.; Sal e , P. A.;
Wel on, T., Sol en -solu e in e ac ions in ionic liquids. Physical Chemis y
Chemical Physics 2003, 5 (13), 2790-2794.
13. an Osch, D. J. G. P.; Kollau, L. J. B. M.; an den B uinho s , A.;
Asikainen, S.; Rocha, M. A. A.; K oon, M. C., Ionic liquids and deep eu ec ic
sol en s o lignocellulosic biomass ac iona ion. Physical Chemis y
Chemical Physics 2017, 19 (4), 2636-2665.
Chap e 4.1
320
14. Pandey, A.; Pandey, S., Sol a och omic P obe Beha io wi hin Choline
Chlo ide-Based Deep Eu ec ic Sol en s: E ec o Tempe a u e and Wa e .
The Jou nal o Physical Chemis y B 2014, 118 (50), 14652-14661.
15. Spange, S.; Lungwi z, R.; Schade, A., Co ela ion o molecula s uc u e
and pola i y o ionic liquids. Jou nal o Molecula Liquids 2014, 192, 137-143.
16. Ab Rani, M. A.; B an , A.; C owhu s , L.; Dolan, A.; Lui, M.; Hassan, N. H.;
Halle , J. P.; Hun , P. A.; Niede meye , H.; Pe ez-A landis, J. M.; Sch ems,
M.; Wel on, T.; Wilding, R., Unde s anding he pola i y o ionic liquids.
Physical Chemis y Chemical Physics 2011, 13 (37), 16831-16840.
17. Ka i zky, A. R.; Fa a, D. C.; Yang, H.; Tämm, K.; Tamm, T.; Ka elson, M.,
Quan i a i e Measu es o Sol en Pola i y. Chemical Re iews 2004, 104 (1),
175-198.
18. Pandey, A.; Rai, R.; Pal, M.; Pandey, S., How pola a e choline chlo ide-
based deep eu ec ic sol en s? Physical Chemis y Chemical Physics 2014,
16 (4), 1559-1568.
19. Ha i i-Mood, A. R.; Ghobadi, R.; Ma ić, S.; Mino a , B.; Řeha, D.,
Sol a ion analysis o some Sol a och omic p obes in bina y mix u es o
eline, e haline, and glyceline wi h DMSO. Jou nal o Molecula Liquids 2016,
222, 845-853.
20. Abbo , A. P.; Ha is, R. C.; Ryde , K. S.; D'Agos ino, C.; Gladden, L. F.;
Man le, M. D., Glyce ol eu ec ics as sus ainable sol en sys ems. G een
Chemis y 2011, 13 (1), 82-90.
21. Teles, A. R. R.; Capela, E. V.; Ca mo, R. S.; Cou inho, J. A. P.; Sil es e,
A. J. D.; F ei e, M. G., Sol a och omic pa ame e s o deep eu ec ic sol en s
o med by ammonium-based sal s and ca boxylic acids. Fluid Phase
Equilib ia 2017, 448, 15-21.
22. Ribei o, B. D.; Flo indo, C.; I , L. C.; Coelho, M. A. Z.; Ma ucho, I. M.,
Men hol-based Eu ec ic Mix u es: Hyd ophobic Low Viscosi y Sol en s. ACS
Sus ainable Chemis y & Enginee ing 2015, 3 (10), 2469-2477.
23. an Osch, D. J. G. P.; Zubei , L. F.; an den B uinho s , A.; Rocha, M. A.
A.; K oon, M. C., Hyd ophobic deep eu ec ic sol en s as wa e -immiscible
ex ac an s. G een Chemis y 2015, 17 (9), 4518-4521.
24. Mou ão, T.; Tomé, L. C.; Flo indo, C.; Rebelo, L. P. N.; Ma ucho, I. M.,
Unde s anding he Role o Cholinium Ca boxyla e Ionic Liquids in PEG-
A close look in o Deep Eu ec ic Sol en s: explo ing in e molecula in e ac ions using
sol a och omic p obes
321
Based Aqueous Biphasic Sys ems. ACS Sus ainable Chemis y &
Enginee ing 2014, 2 (10), 2426-2434.
25. Reicha d , C.; Wel on, T., Solu e-Sol en In e ac ions. In Sol en s and
Sol en E ec s in O ganic Chemis y, Wiley-VCH Ve lag GmbH & Co. KGaA:
2010; pp 7-64.
26. Reicha d , C., Pola i y o ionic liquids de e mined empi ically by means o
sol a och omic py idinium N-phenola e be aine dyes. G een Chemis y 2005,
7 (5), 339-351.
27. Reicha d , C.; Wel on, T., Empi ical Pa ame e s o Sol en Pola i y. In
Sol en s and Sol en E ec s in O ganic Chemis y, Wiley-VCH Ve lag GmbH
& Co. KGaA: 2010; pp 425-508.
28. Reicha d , C., Sol a och omic Dyes as Sol en Pola i y Indica o s.
Chemical Re iews 1994, 94 (8), 2319-2358.
29. Jessop, P. G.; Jessop, D. A.; Fu, D.; Phan, L., Sol a och omic
pa ame e s o sol en s o in e es in g een chemis y. G een Chemis y
2012, 14 (5), 1245-1259.
30. Reicha d , C.; Wel on, T., Sol en s and G een Chemis y. In Sol en s and
Sol en E ec s in O ganic Chemis y, Wiley-VCH Ve lag GmbH & Co. KGaA:
2010; pp 509-548.
31. Ta , R. W.; Kamle , M. J., The sol a och omic compa ison me hod. 2.
The .alpha.-scale o sol en hyd ogen-bond dono (HBD) acidi ies. Jou nal o
he Ame ican Chemical Socie y 1976, 98 (10), 2886-2894.
32. Fox, D., Mol en Sal s and Ionic Liquids 16. Elec ochemical Socie y: 2009.
33. Pi ula, S.; Mud ing, A.-V., Op ical basici y o ionic liquids. Physical
Chemis y Chemical Physics 2010, 12 (26), 7056-7063.
34. Ku nia, K. A.; Lima, F.; Cláudio, A. F. M.; Cou inho, J. A. P.; F ei e, M. G.,
Hyd ogen-bond acidi y o ionic liquids: an ex ended scale. Physical chemis y
chemical physics : PCCP 2015, 17 (29), 18980-18990.
35. Chiappe, C.; Pomelli, C. S.; Rajamani, S., In luence o S uc u al
Va ia ions in Ca ionic and Anionic Moie ies on he Pola i y o Ionic Liquids.
The Jou nal o Physical Chemis y B 2011, 115 (31), 9653-9661.
Chap e 4.2
CHAPTER 4.2
Sup amolecula Hyd ogel based on
Sodium Deep Eu ec ic Sol en
Sup amolecula Hyd ogel based on Sodium Deep Eu ec ic Sol en
323
Adap ed om: C. Flo indo, L. Celia-Sil a, L. F. G. Ma ins, L. C.
B anco and I. M. Ma ucho, Sup amolecula Hyd ogel based on
Sodium Deep Eu ec ic Sol en , Chem. Commun., 2018, 54, 7527-
7530.
The au ho con ibu ed o he execu ion o all cha ac e iza ion and
p ope ies expe imen s desc ibed in his chap e , as well as
in ol ed in he discussion and in e p e a ion o esul s and he
p epa a ion o he manusc ip .

Chap e 4.2
324
CONTENT
ABSTRACT ...................................................................................................... 326
1. COMMUNICATION ........................................................................ 326
2. CONCLUSIONS ............................................................................. 336
3. ACKNOWLEDGEMENTS .............................................................. 336
4. SUPPLEMENTARY INFORMATION ............................................. 336
4.1. EXPERIMENTAL DETAILS……………………………………... 336
4.2. ANALYTICAL METHODOLOGIES………………………………. 339
4.3. FTIR ANALYSIS………………………………………………. 340
4.4. DSC ANALYSIS OF DES AND HYDROGEL……………………. 342
4.5. THERMOPHYSICAL PROPERTIES, DENSITIES AND
VISCOSITIES…………………………………………………………………… 345
4.6. RHEOLOGICAL PROPERTIES………………………………….. 347
5. REFERENCES ............................................................................... 351
Sup amolecula Hyd ogel based on Sodium Deep Eu ec ic Sol en
325
Chap e 4.2
326
Abs ac
Sup amolecula Hyd ogel based on a me al con aining Deep Eu ec ic Sol en
(DES) is he e p esen ed o he i s ime. Phase diag am o DES-based
hyd ogel was d awn and i s heological p ope ies de e mined.
1. Communica ion
Sup amolecula hyd ogels o low molecula -weigh gela o s (LMWG) a e
highly hyd a ed, po ous ma e ials, based on he o ma ion o a ib illa
ne wo k by he sel -assembly o molecula building blocks due o
complemen a y non-co alen in e ac ions, including hyd ogen bonding, π-π
in e ac ions, hyd ophobic in e ac ions and me al ligand in e ac ion.1-2 They
a e ypically o med h ough he use o ul asounds, hea ing o pH change,
which ea anges he agg ega ion o molecules by clea ing sel -locked
in amolecula hyd ogen bonds o π-s acking o o m c osslinked s uc u es
h ough in e molecula in e ac ions, usually in ol ing he pa icipa ion o wa e
molecules.3 Sup amolecula gels based on biocompa ible compounds, as
example u eas, amides, nucleobases, aminoacids, su ac an s, suga s, a y
acids, among o he s, ha e been deeply in es iga ed.1 Recen ly, gela ion
induced by me al ions gained huge in e es due o hei ascina ing p ope ies
and con ol o e sel -assembly by uning me al-ligand coo dina ion.
Mo eo e , he inco po a ion o di e en me al ions in hyd ogels allows a ine
con ol o he gel mechanical p ope ies, h ough he uning o me al-ligand
in e ac ion.4 Usually, sup amolecula gels a e composed by a long alipha ic
chain connec ed wi h a pola head and he endency o he head o in e ac in
a h ee dimensional ne wo k enhances he p obabili y o gel o ma ion. Deep
Eu ec ic Sol en s (DES) ha e been a ousing a lo o a en ion as new
sus ainable sol en s no only due o hei a ou able p ope ies such as easy
p epa a ion wi h no need o u he pu i ica ion, good biodeg adabili y, low
oxici y, low ola ili y and low p ices,5-6 bu also o hei applica ion in a wide
Sup amolecula Hyd ogel based on Sodium Deep Eu ec ic Sol en
327
ange o ields, such as ca alysis, o ganic syn hesis, elec ochemical de ices,
sola echnology, e c.7 DES ha e ound an unques ionable ole in ex ac ion
and sepa a ion p ocesses, o example in selec i e isola ion and eco e y o
me als,8 isola ion and eco e y o compounds om na u al p oduc s,9
desul u iza ion o uels,10 azeo ope b eaking,11 and wa e pu i ica ion.12-13
DESs ep esen a new gene a ion o uncon en ional sol en s which a e
ob ained jus by he mixing wo o mo e compounds, gene ally a sal and an
aminoacid,14 a ca bohyd a e,15 an alcohol,16 a ca boxylic acid17 e c, which ac
as hyd ogen bond accep o (HBA) and dono (HBD), espec i ely. This
combina ion o a HBA and a HBD leads o he o ma ion a inal liquid
compound, wi h a mel ing poin much lowe han hose o indi idual s a ing
componen s.18-19 The con ol o he DES p ope ies is essen ially made
h ough he chemis y o he chosen s a ing compounds, bu o he p ope ies
such as mola a io and wa e up ake, also ha e c ucial e ec .5 Fo example,
mos o he DESs epo ed a e e y hyd ophilic and hyg oscopic, due o he
hyd ophilic na u e and he apid es ablishmen o a hyd ogen bond ne wo k,
a ambien condi ions.20-21 La ely, he de elopmen o hyd ophobic DESs has
also been explo ed and hei s abili y when in con ac wi h wa e s udied.12, 22
Long chain ammonium and phosphonium sal s combined wi h hyd ophobic
acids and alcohols, o e en wo long chain a y acids, o na u al hyd ophobic
compounds combined wi h a y acids ha e been used o p epa e
hyd ophobic DES. In his wo k, we s ep o wa d and use a me al (sodium) sal
de i ed om a long chain a y acid (NaC12) and a long chain a y acid (C10),
as depic ed in Figu e 1, o p epa e a DES. The use o a sodium-based sal
wi h su ac an p ope ies should p o ide DES wi h di e en p ope ies om
hose based on ammonium and phosphonium sal s wi h long hyd oca bon
chains.
Chap e 4.2
334
0 2 4 6 8 10
G'', G' (Pa)
0
50
100
150
200
250
300

(º)
0
5
10
15
20
25
30
 (Hz)
Figu e 5. Oscilla ion expe imen s on equency sweep mode o gel mix u es
wi h angula speed (

) o composi ion A (), B (◼) and C (⚫) a 40 ºC (▬
s o age module (G’), ▬ loss module (G’’) and ▬ phase angle (

)).
A e he s eady s a e was a ained, emo ing he s ess allowed he gels o
sp ing back, wi h ul ima e ecoil alues o 0.0302 Pa-1 o a maximum c eep
compliance o 0.0595 Pa-1 [ (DES) o composi ion A] and 0.342 Pa-1 o a
maximum c eep compliance o 1.469 Pa-1 [ (DES) o composi ion C]. The
ac ha bo h alues o ul ima e ecoil a e non-ze o, ep esen ing a ac ion o
0.51 (A) and 0.23 (C) o he maximum compliance p o es he signi ican
sp ing back o he samples when s ess is emo ed due o hei elas ic
cha ac e ( ypical o gels).
The oscilla ion expe imen s in empe a u e sweep mode o ixed s ain and
oscilla ion equency, allowed us o de ec he low empe a u e limi o he gel
phase co esponding o he poin whe e a s eep inc ease in s o age module
occu s, as can be seen in Figu e 6 o mix u e wi h composi ion A o which
he phase ansi ion empe a u e was ound o be 16 ºC.

Sup amolecula Hyd ogel based on Sodium Deep Eu ec ic Sol en
335
T (ºC)
020 40 60 80
G' (Pa)
0
50
100
150
200
Figu e 6. Oscilla ion expe imen s on empe a u e sweep mode o gel mix u e
wi h angula speed (

) o DES mix u e wi h composi ion A o an oscilla ion
equency o 1 Hz and a s ain o 0.1%. S o age module as a unc ion o
empe a u e.
Finally, hese hyd ogels p o ed o be hixo opic as can be seen in he esul s
o c eep/ eco e y es s showed in Figu e S12 om Supplemen a y
In o ma ion. A cons an low shea a es, appa en iscosi y dec eases wi h
ime. Upon he applica ion o highe shea a es, he iscosi y deeply
dec eases (b eaking o he gel s uc u e). Howe e , once he high shea a e
is emo ed, hese gels p esen low ebuild imes, which is an indica ion o he
e e sibili y o he gel b eaking p ocess. Bo h he dec ease o iscosi y wi h
ime a cons an shea a e and he ebuild o o iginal s uc u e in a ini e ime
show he hixo opic na u e o hese gels.
Chap e 4.2
336
2. Conclusions
Fo he i s ime a new me al-based DES, combining dodecanoa e sodium
sal as HBA and a ca boxylic acid as HBD, ha can beha e as hyd ogel in a
p esence o wa e was epo ed. This new hyd ogel exhibi s a empe a u e
phase ansi ion, and also a he mo e e sible iscosi y depending essen ially
on he wa e con en .
3. Acknowledgemen s
The au ho s, C. Flo indo, I.M. Ma ucho and L.C. B anco, g a e ully
acknowledge he inancial suppo o FCT/MCTES (Po ugal) o he PhD
ellowship SFRH/BD/102313/2014 and o he con ac unde P og ama
In es igado FCT 2012 and 2013 (IF/363/2012 and IF/0041/2013),
espec i ely. This wo k was inanced by CQE p ojec (UID/QUI/00100/2013)
and Resea ch Uni GREEN-i "Bio esou ces o Sus ainabili y"
(UID/Mul i/04551/2013).
4. Supplemen a y In o ma ion
4.1. Expe imen al De ails
Ma e ials. Dodecanoa e sodium sal (NaC12) (pu i y 99-100%) and decanoic
acid (C10) (pu i y ≥ 98%) we e pu chased om Sigma-Ald ich. All ma e ials
we e used wi hou u he pu i ica ion. The wa e used was ul apu e; double
dis illed, passed h ough a e e se osmosis sys em and u he ea ed wi h
Milli-Q plus wa e pu i ica ion appa a us.
P epa a ion Me hodology o DES. Mix u es o sodium sal and ca boxylic
acid wi h long alkyl chain, in a p opo ion o 1 o 4 o mole a io, espec i ely,
we e p epa ed by adding he acid o he sodium sal in a sealed glass ial
Sup amolecula Hyd ogel based on Sodium Deep Eu ec ic Sol en
337
un il a homogeneous clea solu ion was o med. The wa e con en o DES
a e i s p epa a ion and a e d ying was ound o be abou 3000 ppm and
280 ppm, espec i ely. These esul s we e ob ained by Ka l Fische i a ion
(Me ohm 870 KF Ti ino Plus). The in luence o sodium ion on he DES
beha io owa ds wa e was no e iden du ing he syn hesis o DESs since
bo h d ied DES (NaC12: C10 and C12: C10) had app oxima ely he same
amoun o wa e (150 o 200ppm). Howe e , a clea di e ence can be
obse ed in he s udy o DES hyd ophobici y: one (C12: C10) ga e ise o a wo
phase sys em, displaying a e y hyd ophobic beha io wi h a maximum wa e
con en o 5000 ppm, while he o he (NaC12: C10) o med a mo e iscous
phase gi ing ise o he gel sys em.
P epa a ion o he Hyd ogel. A e he syn hesis o a mix u e composed o a
dodecanoa e sodium sal and decanoic acid (1:4 mole a io), he hyd ogel
was achie ed by homogeneously mixing di e en amoun s o DES and wa e ,
om 10 o 80 w %, a 25 °C.
Solid-liquid phase diag am de e mina ion. The phase diag am was
measu ed in a glass lask using he isual me hod a a mosphe ic p essu e,
unde cons an s i ing and a di e en empe a u es. B ie ly, o pe o m his
expe imen i was s a ed wi h pu e compounds HBA and HBD and hen
made mix u es in a ying mola p opo ions in o se e al glass lasks. Each
one o hese mix u es, plus he pu e HBA and pu e HBD ep esen di e en
composi ions, as can be seen in Figu e S1. In his case, we only e alua ed
he empe a u e a which he solid-liquid ansi ion occu s o di e en DES
composi ions, holding p essu e cons an a 1a m. The eu ec ic sys ems
composi ions we e de e mined by weigh quan i ica ion o all componen s
wi hin ± 10-4 g.
The eu ec ic composi ion was ob ained a only one empe a u e, he lowes
mel empe a u e when compa ed o he s a ing ma e ials. The abo e
Chap e 4.2
338
p ocedu e was epea ed o ob ain su icien da a o cons uc he phase
diag am o he s udied DES, shown in Figu e S1.
Figu e S1. Expe imen al (T,x) phase diag am ob ained o NaC12:C10 DES.
Sol-Gel phase diag am de e mina ion. The sol–gel phase ansi ion
empe a u e o he hyd ogel was de e mined using a ial con aining di e en
mass p opo ions o DES and wa e , as can be seen in Figu e 3, in an oil ba h
wi h cons an s i ing speed wi h a empe a u e inc emen o 5 °C. The
appea ance o he gel s a e was de e mined by isual obse a ion o he
change in he luidi y when empe a u e changes. The empe a u e was
measu ed wi h a p ecision o ± 1 °C.
x C10 acid
0.0 0.2 0.4 0.6 0.8 1.0
Mel ing Tempe a u e (ºC)
0
50
100
150
200
250
300
∆Tm≈70ºC
Sup amolecula Hyd ogel based on Sodium Deep Eu ec ic Sol en
339
4.2. Analy ical Me hodologies
Ka l-Fische measu emen s. In o de o measu e he quan i y o wa e o
DES a e he p epa a ion and d ying, a Ka l Fische i a ion analysis
(Me ohm 870 KF Ti ino Plus) was used.
The mophysical P ope ies. Measu emen s o iscosi y and densi y o he
DES we e ca ied ou in he empe a u e ange om 20 up o 80 ºC and a
a mosphe ic p essu e, using an An on Paa (model SVM 3000) au oma ed
o a ional S abinge iscome e -densime e . The empe a u e unce ain y is ±
0.01 ºC. The ela i e unce ain y o he dynamic iscosi y is ± 0.25 %, and he
absolu e unce ain y o he densi y is ± 0.0005 g·cm−3. A DSC (diffe en ial
scanning calo ime e TA Ins umen Model DSC Q200) was used o measu e
he he mal p ope ies o he p epa ed DES. In he DSC, he samples we e
con inuously pu ged wi h 50 mL min−1 o ni ogen. Abou 10 mg o he
compound was c imped in an aluminium s anda d sample pan and analyzed
unde a ni ogen a mosphe e by hea ing (10 K min−1) - cooling (5 K min−1)
cycles be ween 193.15 and 373.15 K.
FTIR analysis. FTIR measu emen s we e ca ied ou using a B üke IFS66/S
FTIR spec ome e (B üke Dal onics, MA, USA) wi h a single e lec ion ATR
cell (Du aDisk, equipped wi h a diamond c ys al). The da a ela i e o spec al
egion we e eco ded be ween 4000 cm-1 and 600 cm-1 a oom empe a u e.
Fo each sample, 290 scans we e eco ded a a spec al esolu ion o 4 cm-1
and i e eplica spec a we e collec ed in o de o e alua e ep oducibili y
(OPUS 5.0).
Rheological P ope ies. Rheological s udies comp ised iscome y
measu emen s in o a ional shea a e con olled mode (in gene al o shea
a es be ween 0.001 and 100 s-1), iscoelas ic es s in oscilla ion mode using
s ain ( o linea iscoelas ic egion – LVER), equency (in gene al, equency

Chap e 4.2
340
be ween 0.01 and 100 s-1) and empe a u e (single equency) sweep,
c eep/ eco e y and hixo opy es s. All he measu emen s we e made in a
Kinexus p o o a ional heome e om Mal e n wi h cone and pla e geome y
(cone wi h 40 mm o diame e , an angle o 4º and a gap o 0.15 mm).
Tempe a u e was con olled by a Pel ie elemen a he bo om o he ixed
pla e and measu ed wi h a p ecision o 0.01 ºC. The sys ems s udied we e
gels wi h 0.803, 0.650 and 0.502 weigh ac ions o wa e a 40 and 60 ºC.
4.3. FTIR Analysis
As al eady p o en, di e en in e molecula in e ac ions a e esponsible o
he o ma ion o a eu ec ic mix u e, depending on he compounds. In
con en ional DES based on a sal and a ca boxylic acid, which ac s as
hyd ogen bond accep o and dono , espec i ely, he es ablishmen o
hyd ogen bonds be ween he wo compounds is esponsible o he eu ec ic
sol en o ma ion. Thus, i is impo an o obse e how dodecanoa e sodium
sal in e ac s wi h decanoic acid, in he DES p epa ed in his wo k. Fo ha
pu pose, FTIR expe imen s we e pe o med o he pu e s a ing ma e ials,
dodecanoa e sodium sal and decanoic acid, and he DES. The FTIR spec a
ob ained a e p esen ed in Figu e S2.
Sup amolecula Hyd ogel based on Sodium Deep Eu ec ic Sol en
341
Figu e S2. FTIR spec a o he pu e dodecanoa e sodium sal (NaC12 sal ),
decanoic acid (C10 acid) and NaC12: C10 (1:4 mole a io) DES.
FTIR analysis is also used o con i m he o ma ion o he new compound,
h ough he es ablishmen o hyd ogen bonds, be ween he sal and he
hyd ogen bond dono . As can be seen om he Figu e S3, an in e molecula
hyd ogen-bond in e ac ion be ween he hyd ogen bond dono and he sal ,
mos ly in he ca boxyl g oup egion, is o med. I can be obse ed ha he
ca bonyl band om he HBD was o iginally loca ed a lowe wa enumbe
alues (~1700 cm-1) and i b oadens and shi s o highe alues (~1750 cm-
1) in he eu ec ic mix u e. This is a s ong indica ion o a new hyd ogen bond
o ma ion, hus p o ing ha a new compound was o med. This e idence can
be u he con i med h ough he physical s a e o he compounds: ini ially, he
physical s a e o bo h hese compounds was solid and a e DES o ma ion an
homogeneous liquid is ob ained a oom empe a u e.
C: Use s use Desk op FTIR NEW ITQB NaC6 sal _REPPP.0 NaC6 sal _REPPP SENSITIVITY TEST MIR, DTGS, Globa
2017/11/28
1000150020002500300035004000
Wa enumbe cm-1
-0.2 -0.0 0.2 0.4 0.6 0.8 1.0
ATR Uni s
Page 1/1
NaC12: C10 (1:4)
NaC12 sal
C10 acid
C: Use s use Desk op FTIR NEW ITQB decanoic acid.0 decanoic acid SENSITIVITY TEST MIR, DTGS, Globa
2017/07/25
1000150020002500300035004000
Wa enumbe cm-1
-0.2 -0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7
Abso bance Uni s
Page 1/1
C: Use s use Desk op FTIR NEW ITQB NaC12 sal _ ep.2 NaC12 sal _ ep SENSITIVITY TEST MIR, DTGS, Globa
2017/11/28
1000150020002500300035004000
Wa enumbe cm-1
-0.2 0.0 0.2 0.4 0.6 0.8 1.0 1.2
ATR Uni s
Page 1/1
C: Use s use Desk op FTIR ITQB 15.11 NaC12_C10.1 NaC12_C10 SENSITIVITY TEST MIR, DTGS, Globa
2017/11/15
1000150020002500300035004000
Wa enumbe cm-1
-0.2 -0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7
ATR Uni s
Page 1/1
Chap e 4.2
342
Figu e S3. Compa ison o FTIR spec a o he sodium sal -based DES
(NaC12 sal ) wi hou wa e and he co esponding hyd ogel (50 w % DES o
NaC12: C10 (1:4 mole a io) and 50 w % o wa e ).
4.4. DSC analysis o DES and Hyd ogel
The new NaC12:C10 DES and he co esponding hyd ogel (50% o DES and
50% o wa e ) we e also cha ac e ized using di e en ial scanning calo ime y
(DSC). In o de o p o e he eu ec ic beha iou o his new sys em, in Figu e
S4, a compa ison o DSC he mog ams be ween he pu e sodium sal -based
(NaC12:C10) and he pu e decanoic acid (C10 acid) s a ing ma e ial is
p esen ed.
C: Use s use Desk op FTIR NEW ITQB NaC6 sal _REPPP.0 NaC6 sal _REPPP SENSITIVITY TEST MIR, DTGS, Globa
2017/11/28
1000150020002500300035004000
Wa enumbe cm-1
-0.2 -0.0 0.2 0.4 0.6 0.8 1.0
ATR Uni s
Page 1/1
NaC12: C10 (1:4)
C: Use s use Desk op FTIR ITQB 15.11 NaC12_C10.1 NaC12_C10 SENSITIVITY TEST MIR, DTGS, Globa
2017/11/15
1000150020002500300035004000
Wa enumbe cm-1
-0.2 -0.1 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7
ATR Uni s
Page 1/1
C: Use s use D opbox Cenas IST sodium sal s DES pape FTIR ITQB 15.11 FTIR NEW ITQB NaC12_C10_sol4.0 NaC12_C10_sol4 SENSITIVITY TEST MIR, DTGS, Globa
2017/11/28
5001000150020002500300035004000
Wa enumbe cm-1
-0.5 0.0 0.5 1.0 1.5
ATR Uni s
Page 1/1
Hyd ogel
Sup amolecula Hyd ogel based on Sodium Deep Eu ec ic Sol en
343
Figu e S4. Compa ison o DSC he mog am be ween he pu e sodium sal -
based (NaC12:C10) and he pu e decanoic acid (C10 acid) s a ing ma e ial.
(No e: Due o he limi a ions o he equipmen , i was no possible o measu e
he mel ing poin o he ini ial ma e ial (dodecanoa e sodium sal ), al hough
his is well de ined in he li e a u e and in he sa e y da a shee , being a 245
ºC.)
As can be seen in Figu e S4, he e is a di e ence in mel ing empe a u es o
bo h pu e compounds and he DES: sodium dodecanoa e sal and decanoic
acid ha e a mel ing poin o 245 ºC and 36.7 ºC, espec i ely, and DES in a
mole a io o 1:4 p esen s a mel ing poin o 23.1 ºC. DES (NaC12:C10 (1:4))
also p esen s a cold c ys alliza ion a 2.59 ºC and a hea c ys alliza ion a
2.19 ºC, which does no occu o he s a ing ma e ial.
These esul s a e in ag eemen wi h hose ob ained by isual inspec ion o
he mel ing poin s and ha a e epo ed in he (T, x) phase diag am in Figu e
2D G aph 1
Tempe a u e (ºC)
-80 -60 -40 -20 0 20 40 60 80 100 120 140
DSC (mW/mg)
-5
-4
-3
-2
-1
0
1
2
3
4
5
C10 acid
NaC12: C10 DES (1:4)
Tm = 36.7 ºC
Tm = 23.1 ºC
↑ exo
Tc(cooling)= 2.59 ºC
Tc(hea ing)= 2.19 ºC
Chap e 4.2
350
Figu e S10. C eep/ eco e y es s. Shea compliance as a unc ion o ime o
gel mix u es wi h (DES) equal o 0.197 o composi ion A (g ey), and 0.498
C (black) a 40 ºC.
Figu e S11. Thixo opy es o gel mix u e wi h

(DES) o composi ion A a
40 ºC; Viscosi y as a unc ion o ime o shea a es equal o 0.01 s-1 (▬ and
▬) and 25 s-1 (▬). S uc u e ebuild: ▬.
(s)
02000 4000 6000 8000 10000
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
J( ) (Pa-1)
0.00
0.01
0.02
0.03
0.04
0.05
0.06
0.07
J( ) (Pa-1)
(s)
0500 1000 1500 2000 2500 3000
(Pa.s)
0
20
40
60
80
100
120
140
160

Sup amolecula Hyd ogel based on Sodium Deep Eu ec ic Sol en
351
5. Re e ences
1. S eed, J. W., Sup amolecula gel chemis y: de elopmen s o e he las
decade. Chemical Communica ions 2011, 47 (5), 1379-1383.
2. Bha acha jee, S.; Bha acha ya, S., Role o syne gis ic [small pi]-[small pi]
s acking and X-H[ h ee do s, cen e ed]Cl (X = C, N, O) H-bonding in e ac ions
in gela ion and gel phase c ys alliza ion. Chemical Communica ions 2015, 51
(32), 7019-7022.
3. Basak, S.; Nanda, J.; Bane jee, A., Mul i-s imuli esponsi e sel -healing
me allo-hyd ogels: uning o he gel eco e y p ope y. Chemical
Communica ions 2014, 50 (18), 2356-2359.
4. Basak, S.; Singh, I.; Bane jee, A.; K aa z, H.-B., Amino acid-based
amphiphilic hyd ogels: me al ion induced uning o mechanical and he mal
s abili y. RSC Ad ances 2017, 7 (24), 14461-14465.
5. Zhang, Q.; De Oli ei a Vigie , K.; Roye , S.; Je ome, F., Deep eu ec ic
sol en s: syn heses, p ope ies and applica ions. Chemical Socie y Re iews
2012, 41 (21), 7108-7146.
6. Dai, Y.; an Sp onsen, J.; Wi kamp, G.-J.; Ve poo e, R.; Choi, Y. H.,
Na u al deep eu ec ic sol en s as new po en ial media o g een echnology.
Analy ica Chimica Ac a 2013, 766, 61-68.
7. Smi h, E. L.; Abbo , A. P.; Ryde , K. S., Deep Eu ec ic Sol en s (DESs)
and Thei Applica ions. Chemical Re iews 2014, 114 (21), 11060-11082.
8. an Osch, D. J. G. P.; Pa men ie , D.; Die z, C. H. J. T.; an den
B uinho s , A.; Tuinie , R.; K oon, M. C., Remo al o alkali and ansi ion
me al ions om wa e wi h hyd ophobic deep eu ec ic sol en s. Chemical
Communica ions 2016, 52 (80), 11987-11990.
9. Nam, M. W.; Zhao, J.; Lee, M. S.; Jeong, J. H.; Lee, J., Enhanced
ex ac ion o bioac i e na u al p oduc s using ailo -made deep eu ec ic
sol en s: applica ion o la onoid ex ac ion om Flos sopho ae. G een
Chemis y 2015, 17 (3), 1718-1727.
10. Niawan i, H.; Zullaikah, S.; Rachimoellah, M., Pu i ica ion o biodiesel by
choline chlo ide based deep eu ec ic sol en . AIP Con e ence P oceedings
2017, 1840 (1), 050006.
11. Gou eia, A. S. L.; Oli ei a, F. S.; Ku nia, K. A.; Ma ucho, I. M., Deep
Eu ec ic Sol en s as Azeo ope B eake s: Liquid–Liquid Ex ac ion and
Chap e 4.2
352
COSMO-RS P edic ion. ACS Sus ainable Chemis y & Enginee ing 2016, 4
(10), 5640-5650.
12. Flo indo, C.; B anco, L. C.; Ma ucho, I. M., De elopmen o hyd ophobic
deep eu ec ic sol en s o ex ac ion o pes icides om aqueous
en i onmen s. Fluid Phase Equilib ia 2017, 448, 135-142.
13. Flo indo, C.; Rome o, L.; Rin oul, I.; B anco, L. C.; Ma ucho, I. M., F om
Phase Change Ma e ials o G een Sol en s: Hyd ophobic Low Viscous Fa y
Acid–Based Deep Eu ec ic Sol en s. ACS Sus ainable Chemis y &
Enginee ing 2018.
14. Mjalli, F. S.; Al-Haj i, R.; Al-Muh aseb, A. a.; Ahmed, O.; Naga aju, M.,
No el amino acid-based ionic liquid analogues: neu al hyd oxylic and sul u -
con aining amino acids. Asia-Paci ic Jou nal o Chemical Enginee ing 2016,
11 (5), 683-694.
15. Flo indo, C.; Oli ei a, M. M.; B anco, L. C.; Ma ucho, I. M.,
Ca bohyd a es-based deep eu ec ic sol en s: The mophysical p ope ies and
ice s aw dissolu ion. Jou nal o Molecula Liquids 2017, 247, 441-447.
16. K isan i, E.; Te ahadi, F.; Fauzia, F.; Pu i, S., Alcohol-based na u al deep
eu ec ic sol en s (NADES) as g een sol en s o ex ac ion o mangos ins
om Ga cinia mangos ana pe ica p. Plan a Med 2015, 81 (16), PW_163.
17. Flo indo, C.; Oli ei a, F. S.; Rebelo, L. P. N.; Fe nandes, A. M.; Ma ucho,
I. M., Insigh s in o he Syn hesis and P ope ies o Deep Eu ec ic Sol en s
Based on Cholinium Chlo ide and Ca boxylic Acids. ACS Sus ainable
Chemis y & Enginee ing 2014, 2 (10), 2416-2425.
18. F ancisco, M.; an den B uinho s , A.; K oon, M. C., Low-T ansi ion-
Tempe a u e Mix u es (LTTMs): A New Gene a ion o Designe Sol en s.
Angewand e Chemie In e na ional Edi ion 2013, 52 (11), 3074-3085.
19. Abbo , A. P.; Boo hby, D.; Cappe , G.; Da ies, D. L.; Rasheed, R. K.,
Deep Eu ec ic Sol en s Fo med be ween Choline Chlo ide and Ca boxylic
Acids:  Ve sa ile Al e na i es o Ionic Liquids. Jou nal o he Ame ican
Chemical Socie y 2004, 126 (29), 9142-9147.
20. Hammond, O. S.; Bow on, D. T.; Edle , K. J., The E ec o Wa e upon
Deep Eu ec ic Sol en Nanos uc u e: An Unusual T ansi ion om Ionic
Mix u e o Aqueous Solu ion. Angewand e Chemie (In e na ional Ed. in
English) 2017, 56 (33), 9782-9785.
Sup amolecula Hyd ogel based on Sodium Deep Eu ec ic Sol en
353
21. Shah, D.; Mjalli, F. S., E ec o wa e on he he mo-physical p ope ies o
Reline: An expe imen al and molecula simula ion based app oach. Physical
Chemis y Chemical Physics 2014, 16 (43), 23900-23907.
22. an Osch, D. J. G. P.; Zubei , L. F.; an den B uinho s , A.; Rocha, M. A.
A.; K oon, M. C., Hyd ophobic deep eu ec ic sol en s as wa e -immiscible
ex ac an s. G een Chemis y 2015, 17 (9), 4518-4521.
23. Abbo , A. P.; D'Agos ino, C.; Da is, S. J.; Gladden, L. F.; Man le, M. D.,
Do g oup 1 me al sal s o m deep eu ec ic sol en s? Physical Chemis y
Chemical Physics 2016, 18 (36), 25528-25537.
24. Ahmed, E. M., Hyd ogel: P epa a ion, cha ac e iza ion, and applica ions:
A e iew. Jou nal o Ad anced Resea ch 2015, 6 (2), 105-121.
25. Men, D.; Zhou, F.; Hang, L.; Li, X.; Duan, G.; Cai, W.; Li, Y., A unc ional
hyd ogel ilm a ached wi h a 2D Au nanosphe e a ay and i s ul ahigh op ical
di ac ion in ensi y as a isualized senso . Jou nal o Ma e ials Chemis y C
2016, 4 (11), 2117-2122.
26. Coukouma, A. E.; Ashe , S. A., Inc eased olume esponsi eness o
mac opo ous hyd ogels. Senso s and Ac ua o s B: Chemical 2018, 255,
2900-2903.
27. Sak hi el, M.; F anklin, D. S.; Guhana han, S., pH-sensi i e I aconic acid
based polyme ic hyd ogels o dye emo al applica ions. Eco oxicology and
En i onmen al Sa e y 2016, 134, 427-432.
Chap e 4.2
354
CHAPTER 5
FINAL REMARKS

Seeking new doo s and
oppo uni ies in he ield
CHAPTER 5.1
Concluding Rema ks and Ou look
Concluding Rema ks and Ou look
359
“You wo k is going o ill a la ge pa o you li e, and he only way o
be uly sa is ied is o do wha you belie e is g ea wo k. And he only
way o do g ea wo k is o lo e wha you do. I you ha en' ound i ye ,
keep looking. Don' se le. As wi h all ma e s o he hea , you'll know
when you ind i ."
S e e Jobs
Chap e 5.1
366
amily o mic opollu an o emo e om wa e (ex ac ion e iciencies up o 80%
o he ou s udied pes icides), whe eas BPA and diclo enac was e icien ly
ex ac ed wi h ex ac ion e iciencies eaching 100% o mos o he
hyd ophobic DES es ed. The mos cu ious esul ob ained using LLE app oach
was ha ega ding he emo al o cip o loxacin. Gene ally, li e a u e epo s
ha ionic hyd ophobic DES a e mo e e icien ex ac an s. In his wo k, i was
ound ha neu al hyd ophobic DES display much highe cip o loxacin
ex ac ion e iciencies ( om 40 o 90 %) han ionic DES based on ammonium
sal s ( om 0 - 20%, ypically a ound 0%), e en when cip o loxacin is in he
cha ged o m.
Mo eo e , he appealing eusabili y and ecyclabili y o he hyd ophobic DESs
used was also demons a ed, highligh ing hei possible ele an ole as
sus ainable sol en s in indus ial applica ions. I was ound ha hese
hyd ophobic DES had he abili y o be used o nume ous cycles o ex ac ion
wi hou losing he abili y o ex ac he mic opollu an s as well as being able o
be cleaned up and ecycled and each ex ac ion e iciencies up o almos 90%.
In wha conce ns he second app oach used in his hesis o pu i y wa e
samples, he suppo ed hyd ophobic DES, he adso ben ma e ial was
p epa ed h ough he imp egna ion o a hyd ophobic DES in o an ine po ous
suppo and used in di ec con ac wi h he aqueous phase in o de o emo e
he same mic opollu an s. I was ound ha i is possible o ob ain simila esul s
as hose obse ed in he LLE app oach. The maximum ex ac ion e iciencies
(a ound 85 and 98%, depending essen ially on he DES) we e ypically
achie ed be ween 5 and 10 minu es, wi h a much smalle mass han ha
equi ed by he LLE app oach. Howe e , i should be no ed ha in his
adso p ion app oach, he ex ac ion ime is di ec ly in luenced by he selec ed
DES adso ben ma e ial mass.
Finally, bo h sepa a ion echnologies explo ed in his hesis we e di ec ly
compa ed, and i was obse ed ha bo h DES sol en s and DES adso ben s
yielded simila appealing esul s o di e en mic opollu an s unde s udy.

Concluding Rema ks and Ou look
367
Howe e , adso p ion is an ad an ageous al e na i e app oach o adi ional
echnologies including LLE, since i is simple, as , cos -e ec i e and e icien .
As a as ele ance o an implemen a ion o a p ocess ollowing he es ed
condi ions, i was highligh ed ha LLE expe imen s equi ed he use o 100g o
DES pe li e o wa e , whe eas 250mg o suppo ed DES adso ben is enough
o achie e he highes ex ac ion e iciencies, o he same expe imen al
condi ions. I is possible o conclude ha he de elopmen o adso ben
ma e ials based on hyd ophobic DES is a p omising app oach o wa e
cleaning echnologies. The p oposed adso p ion p ocess o e s se e al
ad an ages compa ed o he liquid-liquid adi ional p ocess such as he as
and easy sepa a ion, he eusabili y wi hou comp omising capaci y and he
small amoun o DES needed, which can be e y impo an in he case o DESs
composed o expensi e compounds.
To sum up, low cos and highly e icien me hodologies, ei he based on liquid-
liquid ex ac ion o solid-liquid ex ac ion, we e de eloped using hyd ophobic
DES in his PhD hesis and i has been demons a ed ha hey can be
e icien ly in oduced in a inal s age o wa e pu i ica ion p ocess o he
comple e emo al o mic opollu an s.
3. Ou look
In his PhD hesis, p omising and inno a i e esul s o he de elopmen o
no el hyd ophobic DES and hei use as e icien ex ac an s in wa e
pu i ica ion echnologies we e achie ed. The design o hyd ophobic DESs
chemical s uc u es speci ically o he emo al o hyd ophobic pollu an s
signi ican ly imp o es he e iciency o sepa a ion p ocesses. Addi ionally, he
esul s p esen ed he ein a es he ema kable po en ial o DESs in gene al as
designe sol en s. As his wo k is only he ip o he icebe g in e ms o
applica ion o DES wi h di e en p ope ies, u he applica ions conce ning
hyd ophobic DESs should be explo ed. Fo example, ollowing up he esul s
he e p esen ed and aking ad an age o he d ama ic change in he mass o
Chap e 5.1
368
sol en om LLE o he adso p ion p ocess, while a aining he same
pe o mance, a low sys em should be implemen ed using a packed column o
hyd ophobic DES so ha a con inuous emo al p ocess could be designed.
Conside ing ha he goal o he wo k is he applica ion o hyd ophobic DES as
sui able ma e ials o no el sepa a ion echnologies o apply in a inal s age o
a wa e pu i ica ion p ocess, addi ional in es iga ion on he echnologies scale-
up also a e equi ed. Taking in o accoun he indus ial implemen a ion o he
p oposed me hodologies using no el sus ainable sol en s, an o e all
sus ainabili y s udy, in ol ing economic and en i onmen al pe spec i es,
should be pe o med in o de o mee he mos appealing solu ion.
The sepa a ion s a egies de eloped in his hesis can be e y use ul no only
in pu i ica ion o d inking wa e bu also in he e icien , easy and cheap eco e
and ecycle ac i e pha maceu ical ing edien s (APIs) p esen in was e s eams
o pha maceu ical indus y o be o e hei discha ge in o public wa e s. In he
same ein, hese sol en s can be o g ea alue in he pu i ica ion s eps o
APIs, since hey migh p o ide al e na i e solubili y solu ions and pola i y
anges o non- oxic ola ile o ganic sol en s.
Since he ield o DES is s ill in i s in ancy, he iden i ica ion o o he s a ing
compounds, especially na u e de i ed, non- oxic and biodeg adable
compounds, can be used o p epa e new eu ec ic mix u es, ei he deep o no
so deep, p o iding di e en p ope ies han hose cu en ly unde s udy, is
c ucial o he o eseen boom o hese sus ainable sol en s and hei
applica ions.
Concluding Rema ks and Ou look
369
“In e e y end he e is always a new beginning.”