molecules
A icle
F om Oligo(Phenylenee hynylene) Monome s o
Sup amolecula Helices: The Role o In e molecula
In e ac ions in Agg ega ion
Be a Fe nández 1,* , Zulema Fe nández 2, Emilio Quiñoá2and Félix F ei e 2,*
Ci a ion: Fe nández, B.;
Fe nández, Z.; Quiñoá, E.; F ei e, F.
F om Oligo(Phenylenee hynylene)
Monome s o Sup amolecula
Helices: The Role o In e molecula
In e ac ions in Agg ega ion. Molecules
2021,26, 3530. h ps://doi.o g/
10.3390/molecules26123530
Academic Edi o s: Jo ge M.
C. Ma ques, F ede ico
Vasconcellos P uden e and
Fe nando Pi ani
Recei ed: 8 May 2021
Accep ed: 5 June 2021
Published: 9 June 2021
Publishe ’s No e: MDPI s ays neu al
wi h ega d o ju isdic ional claims in
published maps and ins i u ional a il-
ia ions.
Copy igh : © 2021 by he au ho s.
Licensee MDPI, Basel, Swi ze land.
This a icle is an open access a icle
dis ibu ed unde he e ms and
condi ions o he C ea i e Commons
A ibu ion (CC BY) license (h ps://
c ea i ecommons.o g/licenses/by/
4.0/).
1Depa amen o de Química Física, Uni e sidade de San iago de Compos ela,
15782 San iago de Compos ela, Spain
2Cen o Singula de In es igación en Química Biolóxica e Ma e iais Molecula es (CiQUS), Depa amen o de
Química O gánica, Uni e sidade de San iago de Compos ela, 15782 San iago de Compos ela, Spain;
[email p o ec ed] (Z.F.); [email p o ec ed] (E.Q.)
*Co espondence: [email p o ec ed] (B.F.); elix. ei [email p o ec ed] (F.F.)
Abs ac :
Sup amolecula helices ha a ise om he sel -assembly o small o ganic molecules ia
non-co alen in e ac ions play an impo an ole in he s uc u e and p ope ies o he co esponding
ma e ials. He e we s udy he sup amolecula helical agg ega ion o oligo(phenylenee hynylene)
monome s om a heo e ical poin o iew, always guiding he s udies wi h expe imen ally a ailable
da a. In his way, by sys ema ically inc easing he numbe o monome uni s, op imized n-me
geome ies a e ob ained along wi h he co esponding abso p ion and ci cula dich oism spec a. Fo
he geome y op imiza ions we use densi y unc ional heo y oge he wi h he B3LYP-D3 unc ional
and he 6–31G** basis se . Fo ob aining he spec a we eso o ime-dependen densi y unc ional
heo y using he CAM-B3LYP unc ional and he 3–21G basis se . These combina ions o densi y
unc ional and basis se we e selec ed a e sys ema ic con e gence s udies. The heo e ical esul s
a e analyzed and compa ed o he expe imen ally a ailable spec a, obse ing a good ag eemen .
Keywo ds:
oligo(phenylenee hynylene); monome agg ega ion; sup amolecula helices; densi y unc-
ional heo y and ime-dependen densi y unc ional heo y calcula ions; geome y op imiza ions;
abso p ion spec a; elec on ci cula dich oism spec a
1. In oduc ion
Sup amolecula helices a e ob ained h ough sel -assembly o small o ganic molecules
ia non-co alen in e ac ions, which will be esponsible o hei dynamic and e e sible
cha ac e . These in e ac ions de e mine he agg ega e g ow h mechanism and une he
sup amolecula s uc u e. The e o e, aking in o accoun he s uc u e/ unc ion ela-
ionship, he co esponding ma e ials will ha e in e es ing applica ions in ields such as:
ca alysis [
1
–
5
], nanoelec onics [
6
–
11
], o pha maceu ics [
12
–
15
], among o he s. Due o hei
high in e es , a conside able numbe o expe imen al s udies on sup amolecula agg ega es
ha e been epo ed in he li e a u e. I is wo h men ioning he wo k by
Meije e al. [16,17]
whe e he o ma ion mechanisms o se e al agg ega es ha e been s udied in de ail and he
key ole played by non-co alen o ces was poin ed ou .
The s uc u al de e mina ion a molecula and in e molecula le els is c ucial o unde -
s and he p ope ies o he agg ega es and is challenging om bo h he expe imen al and
he compu a ional poin o iew. Expe imen al me hods like elec on ci cula dich oism
(ECD), X- ay di ac ion, a omic o ce mic oscopy (AFM), in a ed (IR) spec oscopy o
Raman spec oscopy p o ide aluable in o ma ion o s udy he agg ega es, bu mos ly he
in o ma ion ob ained is no enough o no clea enough o sol e he idimensional s uc-
u e o he agg ega e [
18
–
20
]. Some imes, e en in he op imal expe imen al condi ions and
h ough he combina ion o se e al expe imen al echniques, i is no possible o pu all he
Molecules 2021,26, 3530. h ps://doi.o g/10.3390/molecules26123530 h ps://www.mdpi.com/jou nal/molecules
Molecules 2021,26, 3530 2 o 14
in o ma ion oge he and de e mine he agg ega e mo phology. The e o e, compu a ional
s udies could play a key ole in he s uc u al analysis o he sup amolecula agg ega es,
al hough he la ge size o he sys ems unde in es iga ion makes he s uc u al and spec-
oscopic compu a ions challenging. To su pass his limi a ion, and aking in o accoun he
possible lack o accu acy o he di e en heo e ical me hods, i is necessa y o combine
expe imen al and heo e ical app oaches. Following his line, Díaz-Cab e a e al. [
21
]
s udied he sel -assembly o achi al and chi al 1,3,5- iphenylbenzene ica boxamides. In
a simila way, G eciano e al. [
22
] analyzed he sel -assembly o N-annula ed pe ylene
bisimides [PBIs], showing he impo an ole o long- ange an de Waals and dipole-
dipole elec os a ic in e ac ions in he agg ega ion mechanism o compounds ha lack
H-bonding g oups.
Among all sup amolecula helices, hose o med by building blocks con aining
π
-conjuga ed co es—pe ylenebisimides [PBIs] [
23
–
25
], benzene-1,3,5- ica boxiamides
[BTAs] [
26
–
28
], oligo(phenylenee hynylene)s [OPEs] [
29
–
35
], pe i-hexabenzeneco onenes
[HBCs] [
36
–
38
] and o he s [
39
]—a ac wide in e es due o hei po en ial op ical and
elec onic p ope ies. In hese molecules he sel -assembly is led by
π
-
π
in e ac ions in ad-
di ion o o he non-co alen o ces. Mo eo e , he in oduc ion o long alkyl chains ensu es
good solubili y o he building blocks in non-pola sol en s and igge s he o ma ion o
sup amolecula helical agg ega es. Rega ding his, linea OPEs ha e d awn much a en ion
no only o hei in insic sup amolecula p ope ies, bu also o he possibili y o being
used in molecula elec onic de ices [
40
,
41
]. Al hough se e al s udies in he li e a u e use
linea achi al OPEs as building blocks o gene a ing sup amolecula sca olds ( he mos
ep esen a i e ones bea ing long alkyl chains on bo h edges o he OPE building blocks,
o e en on all he a oma ic ings [
42
–
45
]), ew chi al examples a e ound [
29
,
46
]. Recen ly,
we ha e epo ed a combined expe imen al- heo e ical s udy on he de e mina ion o he
agg ega ion mechanism in a sho , chi al and igid OPE [(S)-
1
] [
47
]. We concluded ha
he polyme iza ion p ocess o he monome led o a ema kable agg ega ion mechanism,
whe e ei he a he modynamic agg ega e o a kine ically apped one—bo h showing
opposi e sup amolecula chi ali ies—could selec i ely be ob ained jus by modi ying he
agg ega ion condi ions. In his way, while he o ma ion o sho P- wis ed oligome s
p oduced in-plane agg ega ion o gene a e b ick-like nanos uc u es, he o ma ion o la ge
helical sup amolecula polyme s yielded single-chain M- ype columna helical agg ega es.
He ein, we will analyze in de ail he agg ega ion p ocess o (S)-
1
(Figu e 1a) ha esul s
in he o ma ion o shee -like nanos uc u es (Figu e 1b,c). To pe o m his in es iga ion
he compu a ional s udies will be guided wi h ou expe imen ally a ailable da a. Fi s ,
di e en mo phologies o he agg ega e will be gene a ed by s acking he monome s in
di e en o ien a ions and, a e de e mining he op imal one, he numbe o monome
uni s in he agg ega e will be sys ema ically inc eased. Compu a ional s udies on hese
sys ems will allow us o analyze he s abili y o hese agg ega es and he in e molecula
o ces in ol ed in he sup amolecula assembly—mainly H-bonding and
π
-
π
in e ac ions.
Addi ionally, om he ob ained geome ies i will be possible o calcula e he abso p ion
and ci cula dich oism spec a. A compa ison o hese da a o he expe imen ally ob ained
will be pe o med looking o he bes i o p opose a 3D-model o he agg ega e.
The manusc ip is o ganized as ollows: in Sec ion 2we gi e he compu a ional de ails,
in Sec ion 3 he esul s a e p esen ed and discussed, and in he las Sec ion we summa ize
and conclude.
Molecules 2021,26, 3530 3 o 14
Molecules 2021, 26, x 3 o 14
Figu e 1. (a) Oligo(phenylenee hynylene) (OPE) [(S)-1] chemical s uc u e, dipole momen and elec-
os a ic po en ial on he 0.001 au isodensi y su ace ( dW su ace). (b) Sup amolecula agg ega e
o (S)-1 desc ibing a P- wis ed oligome helix. (c) AFM image o he ob ained shee -like nanos uc-
u es and inse o he b ick-like nanos uc u es gene a ed by he agg ega ion o se e al P- wis ed
oligome helices.
2. Compu a ional De ails
To s udy he ole o in e molecula o ces in agg ega ion, we i s analyzed he con-
o ma ional composi ion o monome (S)-1 (n = 1). Once he geome ies o he ele an
con o me s a e op imized, we s udied a dime o he op imized monome (n = 2), which
could be buil up ei he wi h he chi al moie ies s acked one on op o he o he (head- o-
head, hh-geome y) o in an al e na e ashion (head- o- ail, h -geome y). Nex , by linking
wo dime geome ies we c ea ed he 4-me s (n = 4) and inally, om he 4-me s, we con-
s uc ed he 8-me s (n = 8). These sequen ial addi ions allowed us o model a helix and
s udy he e olu ion o i s ECD spec um when he leng h o he helix is inc eased. In a
p e ious wo k, we analysed he ECD spec a o poly(phenylace hylene) (PPA) oligome s
[48] by inc easing he numbe o monome uni s (n) in he oligome . F om hese s udies i
was concluded ha 8–10 monome s we e enough o desc ibe he helix gene a ed by he
polyme s unde in es iga ion.
As a i s s ep in he geome y sea ch, o n = 1–4 we ca ied ou molecula dynamics
(MD) calcula ions using he Con o me Ro ame Ensemble Sampling Tool (CREST) p o-
g am [49] o ob ain he mos s able and con enien con o me s in e ms o s acking. The
de ails o he MD simula ions a e p o ided in he Supplemen a y Ma e ials. A e selec -
ing he con o me s, we u he op imized hei geome ies using Densi y Func ional The-
o y (DFT) [50,51], oge he wi h he B3LYP unc ional [52,53] wi h he D3 co ec ion o
dispe sion [54], and he 6-31G** basis se [55]. We selec ed his me hodology bea ing in
mind ha he main objec i e o his wo k is he s udy o agg ega es o monome s whe e
dispe sion plays an impo an ole.
To ge mo e insigh in o he na u e o he sup amolecula o ces, he in e ac ion en-
e gies, 𝐸𝐴−𝐵
{𝐴−𝐵} in Equa ion (1) we e e alua ed o he dime a he DFT(B3LYP-D3)/6–
31G** le el o heo y using he supe molecula app oach and he coun e poise me hod o
co ec o basis se supe posi ion e o [56];
∆𝐸𝐴−𝐵
{𝐴−𝐵} = 𝐸𝐴−𝐵
{𝐴−𝐵}−𝐸𝐵
{𝐴−𝐵}−𝐸𝐴
{𝐴−𝐵},
(1)
whe e 𝐸𝐵
{𝐴−𝐵} and 𝐸𝐴
{𝐴−𝐵} a e he ene gies o monome B and A, espec i ely, and supe -
sc ip {A − B} deno es ha he ene gies a e e alua ed in he dime basis se .
Addi ionally, o he mos s able con o me o he dime , in o de o elucida e he
di e en con ibu ions o he in e ac ion ene gy, a non-co alen in e ac ion (NCI) analysis
[57] was ca ied ou . The NCI index analysis is based on he densi y (ρ) and i s de i a i es.
The non-co alen in e ac ions can be iden i ied om he educed densi y g adien (s) and
Figu e 1.
(
a
) Oligo(phenylenee hynylene) (OPE) [(S)-
1
] chemical s uc u e, dipole momen and elec o-
s a ic po en ial on he 0.001 au isodensi y su ace ( dW su ace). (
b
) Sup amolecula agg ega e o (S)-
1
desc ibing a P- wis ed oligome helix. (
c
) AFM image o he ob ained shee -like nanos uc u es and
inse o he b ick-like nanos uc u es gene a ed by he agg ega ion o se e al P- wis ed oligome helices.
2. Compu a ional De ails
To s udy he ole o in e molecula o ces in agg ega ion, we i s analyzed he con-
o ma ional composi ion o monome (S)-
1
(n = 1). Once he geome ies o he ele an
con o me s a e op imized, we s udied a dime o he op imized monome (n = 2), which
could be buil up ei he wi h he chi al moie ies s acked one on op o he o he (head-
o-head, hh-geome y) o in an al e na e ashion (head- o- ail, h -geome y). Nex , by
linking wo dime geome ies we c ea ed he 4-me s (n = 4) and inally, om he 4-me s, we
cons uc ed he 8-me s (n = 8). These sequen ial addi ions allowed us o model a helix and
s udy he e olu ion o i s ECD spec um when he leng h o he helix is inc eased. In a p e-
ious wo k, we analysed he ECD spec a o poly(phenylace hylene) (PPA) oligome s [
48
]
by inc easing he numbe o monome uni s (n) in he oligome . F om hese s udies i
was concluded ha 8–10 monome s we e enough o desc ibe he helix gene a ed by he
polyme s unde in es iga ion.
As a i s s ep in he geome y sea ch, o n = 1–4 we ca ied ou molecula dynam-
ics (MD) calcula ions using he Con o me Ro ame Ensemble Sampling Tool (CREST)
p og am [
49
] o ob ain he mos s able and con enien con o me s in e ms o s acking.
The de ails o he MD simula ions a e p o ided in he Supplemen a y Ma e ials. A e
selec ing he con o me s, we u he op imized hei geome ies using Densi y Func ional
Theo y (DFT) [
50
,
51
], oge he wi h he B3LYP unc ional [
52
,
53
] wi h he D3 co ec ion o
dispe sion [
54
], and he 6-31G** basis se [
55
]. We selec ed his me hodology bea ing in
mind ha he main objec i e o his wo k is he s udy o agg ega es o monome s whe e
dispe sion plays an impo an ole.
To ge mo e insigh in o he na u e o he sup amolecula o ces, he in e ac ion
ene gies,
E{A−B}
A−B
in Equa ion (1) we e e alua ed o he dime a he DFT(B3LYP-D3)/6–
31G** le el o heo y using he supe molecula app oach and he coun e poise me hod o
co ec o basis se supe posi ion e o [56];
∆E{A−B}
A−B=E{A−B}
A−B−E{A−B}
B−E{A−B}
A, (1)
whe e
E{A−B}
B
and
E{A−B}
A
a e he ene gies o monome Band A, espec i ely, and supe -
sc ip {A−B} deno es ha he ene gies a e e alua ed in he dime basis se .
Addi ionally, o he mos s able con o me o he dime , in o de o elucida e he di -
e en con ibu ions o he in e ac ion ene gy, a non-co alen in e ac ion (NCI) analysis [
57
]
was ca ied ou . The NCI index analysis is based on he densi y (
ρ
) and i s de i a i es. The
non-co alen in e ac ions can be iden i ied om he educed densi y g adien (s) and he
sign o he second densi y Hessian eigen alue (
λ2
) is used o assign he di e en in e ac-
Molecules 2021,26, 3530 4 o 14
ions. In his way, plo s o he a ia ion o s e sus (
λ2
sign)
×ρ
show he na u e o he
in e ac ions, since his las e m can cha ac e ize he s eng h o he in e ac ion h ough
ρ
and i s na u e ia he λ2sign.
Fo he 4-me we ob ained he in e ac ion ene gy by gene alizing he exp ession in
Equa ion (1). Addi ionally, wo-body con ibu ions and coope a i e e ec s a e es ima ed,
using he me hodology desc ibed in e e ence [
58
]. In his way, he wo body con ibu ions,
∆E(2), a e gi en by
∆E(2)=
4
∑
i>j
∆Eij =
4
∑
i>j E{i−j}
ij −∑
k=i,j
E{i−j}
k!, (2)
whe e iand ja e indices ha go o e he 4 monome s in he 4-me , and supe sc ip
{I
−
j} deno es ha he dime basis se is used o he calcula ions. The o al many-body
con ibu ions a e gi en as he di e ence be ween he complex in e ac ion ene gy and
he wo- body con ibu ions in Equa ion (2). De e mining he size o hese con ibu ions
is impo an because, on he one hand, hey can cons i u e a conside able pa o he
in e ac ion ene gy, he e o e playing an impo an ole in he in e ac ion, and on he o he
hand, conside ing ha many in e ac ion po en ials o la ge molecules a e based only
on wo-body e ms, we can check how good a desc ip ion like his is in he case o he
p esen complexes.
In addi ion, o he agg ega es unde in es iga ion i is known ha in e molecula
H-bonding plays a key ole in hei o ma ion and s abiliza ion. The s acking o molecules
h ough a hyd ogen-bond-ne wo k can cause a signi ican sho ening o he hyd ogen-bond
dono -accep o dis ance and an inc ease o he hyd ogen bond s eng h, whene e a new
molecule is inco po a ed o he sup amolecula agg ega e [
59
]. This phenomenon, known
as he coope a i e e ec , has been widely s udied in he con ex o in e ac ion ene gies,
equilib ium s uc u es and spec a [
58
]. Conside ing his, he e we ha e also es ima ed
he coope a i e e ec , de ining i wi h espec o he in e ac ion be ween monome A and
monome B in he ABCD 4-me agg ega e as:
∆Ecoop
ABCD =∆EA−BCD −∆EAB, (3)
being
∆EA−BCD =EABCD −EA−EBCD (4)
and co ec ing o basis se supe posi ion e o .
To e alua e he abso p ion and ECD spec a, we conside ed he size o he sup amolec-
ula helical s uc u es unde in es iga ion and he esul s o p e ious s udies on co alen ly
bonded polyme s [
60
] ha showed he e iciency o employing Time-Dependen DFT
(TD-DFT) [
61
] oge he wi h he CAM-B3LYP densi y unc ional [
62
] and he 3-21G basis
se [
63
]. Fo n = 1–4 we included 80 exci a ion ene gies in he calcula ions and 20 o he
8-me . To ge mo e insigh in o he main spec al bands, we e alua ed he elec on densi y
di e ences o he co esponding main ansi ions a he TD-DFT(CAM-B3LYP)/3-21G
le el o heo y. Fo he n = 1–4 DFT(B3LYP-D3)/6–31G** op imized s uc u es we also
e alua ed he a ia ion o he IR spec a a he same le el o heo y.
Due o he educed size o he monome , in his case we addi ionally pe o med
calcula ions o he UV and ECD spec a wi h he co ela ion consis en alence iple
ze a (cc-VTZ) basis se and a he expe imen al X- ay geome y in o de o check o
geome y and basis se con e gence in ou esul s. Also, o ge mo e insigh in o he lowes
ene gy abso p ion band o he UV spec um we e alua ed he co esponding ib onic
ansi ions using he CAM-B3LYP unc ional wi h he D3 dispe sion co ec ion and he
6–31G** basis se .
The op imized geome ies, IR and ib onic spec a we e ob ained wi h he Gaussian-
16 p og am [
64
]; all he UV-Vis and ECD spec a we e e alua ed wi h he ORCA p o-
g am [
65
]; he analysis o he nonco alen in e ac ions was ca ied ou wi h he NCIPLOT
Molecules 2021,26, 3530 5 o 14
p og am [
57
]. To plo he spec a, we used he GABEDIT p og am [
66
], and o he densi y
di e ences A ogad o [
67
]. Fo he UV-Vis and ECD spec a we selec ed a ull wid h a hal
heigh (FWHM) o 20.0 nm and employed gaussian cu es o he spec a and an iso alue
o 0.0002 in he densi y di e ences. De ails o he IR and ib onic spec a a e p o ided in
he Supplemen a y Ma e ials. No sol en e ec s we e included in he calcula ions.
3. Resul s and Discussion
The ob ained esul s a e summa ized in Table 1and Figu es 1–6. Those o he
Molecula Dynamics simula ions, he analysis o he nonco alen in e ac ions and he IR
and ib onic spec a a e p o ided in he Supplemen a y Ma e ials.
Table 1. DFT(B3LYP-D3)/6-31G** op imized con o me ene gies.
Ene gy (H)
monome Con o me 1 −1476.4953010
Con o me 2 −1476.4953009
dime hh −2953.0435193
h −2953.0400134
4-me hh −5906.1562241
Molecules 2021, 26, x 6 o 14
combined conside ing he con o me con ibu ions o ge he inal heo e ical ECD ace.
A compa ison be ween he ECD aces ob ained om he heo e ical and he expe imen al
s udies, in addi ion o he heo e ical spec um ob ained om he X- ay geome y, is
shown in Figu e 2d. I was ound ha bo h TD-DFT(CAM-B3LYP)/3–21G spec a— he
one ob ained om he con o ma ional s udies and he one ob ained om he X- ay geom-
e y—a e in ag eemen wi h he expe imen al one in he sign o he i s Co on e ec ,
be ween 300 and 320 nm. Also, he ECD aces ob ained om he heo e ical and he X-
ay geome ies show good ag eemen a ound 150 nm, while he in e media e egions o
he spec a a e conside ably di e en . F om he DFT(B3LYP)/6311++G(d,p) con o me ge-
ome ies we e alua ed he co esponding ECD spec um and epo he esul s in he Sup-
plemen a y Ma e ials, whe e i is compa ed o he 6–31G** one. When conside ing he
popula ions ob ained om he Gibbs ee ene gies, only small di e ences a e obse ed in
he spec al bands, ha a e mainly due o in ensi y changes in he high ene gy egions
(see Figu e S6 in he Supplemen a y Ma e ials).
Figu e 2. Oligo(phenylenee hynylene) (OPE) [(S)-1] DFT(B3LYP-D3)/6–31G** op imized geome ies
o (a) he mos s able con o me and (b) he second mos s able con o me . TD-DFT (CAM-B3LYP)
ECD spec a: (c) 3–21G and cc-pVTZ (VTZ) basis se esul s o he X- ay (XR) geome ies; (d) 3–21G
basis se esul s ob ained o he X- ay (XR) and he DFT(B3LYP-D3)/6–31G** op imized geome ies
( he la e deno ed Calcula ed). The co esponding expe imen al spec a a e plo ed o compa ison.
No co ec ion ac o s a e included in he heo e ical wa eleng hs.
Simila s udies we e ca ied ou o a dime o (S)-1 made by he op imized con o m-
e s o he monome ic uni . The dime can be buil up in wo di e en ways, head- o-head
(hh) (Figu e 3a,b) o head- o- ail (h ) (Figu e 3c,d). The o me (hh) was ob ained as he
mos s able s uc u e, wi h an ene gy di e ence wi h espec o he la e (h ) o 2.2 kcal
mol−1 (see Table 1). This la ge ene gy gap implies a signi ican di e ence in popula ion o
he hh wi h espec o he h agg ega e a oom empe a u e, indica ing a negligible con-
ibu ion o he h -con o me o he ECD spec a. Addi ionally, using he coun e poise
co ec ion, we e alua ed he DFT(B3LYP-D3)/6–31G** in e ac ion ene gies o he hh and
h dime s, ob aining alues o −24.2 kcal mol−1 and −21.8 kcal mol−1, espec i ely. This co -
obo a es he la ge s abili y o he hh dime compa ed o he h one. To coun e poise
co ec he esul s is impo an , accoun ing he co ec ions o 12.5 kcal mol−1 and 10.1 kcal
mol−1 o he hh and h dime s, espec i ely. The esul s o he analysis o he non-co alen
100 200 300 400
-300
-200
-100
0
Wa eleng h [nm]
In ensi y
3-21G XR
VTZ XR
Expe imen al
a) b)
c) d)
100 200 300 400
-300
-200
-100
0
Wa eleng h [nm]
In ensi y
Calcula ed
XR
Expe imen al
–
–
–
–
–
–
Figu e 2.
Oligo(phenylenee hynylene) (OPE) [(S)-
1
] DFT(B3LYP-D3)/6–31G** op imized geome ies o (
a
) he mos s able
con o me and (
b
) he second mos s able con o me . TD-DFT (CAM-B3LYP) ECD spec a: (
c
) 3–21G and cc-pVTZ (VTZ)
basis se esul s o he X- ay (XR) geome ies; (
d
) 3–21G basis se esul s ob ained o he X- ay (XR) and he DFT(B3LYP-
D3)/6–31G** op imized geome ies ( he la e deno ed Calcula ed). The co esponding expe imen al spec a a e plo ed o
compa ison. No co ec ion ac o s a e included in he heo e ical wa eleng hs.
Molecules 2021,26, 3530 6 o 14
Molecules 2021, 26, x 7 o 14
in e ac ions in he hh-dime a e epo ed in he Supplemen a y Ma e ials (Figu e S4) and
show ha an de Waals o ces clea ly domina e he non-co alen in e ac ions. These e-
sul s a e in ag eemen wi h he an de Waals su ace shown in Figu e 1a, de ined as ha
wi h an elec on densi y equal o 0.001 au, and whe e he molecula elec os a ic po en ial
plo ed e lec s he elec os a ic con ibu ion o possible in e molecula in e ac ions [70].
Theo e ical ECD s udies—TD-DFT(CAM-B3LYP)/3–21G— o he wo o ien a ions o
he dime show ECD aces ha ag ee in he high wa eleng h egion; i s (335 nm, posi-
i e) and second co on bands (310–330 nm, nega i e) (Figu e 3e, ). In he low wa eleng h
egion (180 o 300 nm) bo h ECD aces a e qui e di e en ; hus, while he h dime dis-
plays many ansi ions wi h simila in ensi ies (Figu e 3 ), he hh dime shows jus a ew
ansi ions wi h signi ican in ensi y (Figu e 3e).
Figu e 3. Oligo(phenylenee hynylene) (OPE) (S)-1 dime DFT(B3LYP-D3)/6–31G** op imized geome ies: (a) hh pe pen-
dicula iew, (b) hh pa allel iew, (c) h pe pendicula iew and (d) h pa allel iew. TD-DFT (CAM-B3LYP)/3–21G ECD
spec a e alua ed a he DFT(B3LYP-D3)/6–31G** op imized geome ies: (e) hh dime and ( ) h dime . No co ec ion ac-
o s a e included in he heo e ical wa eleng hs.
Conside ing he highe s abili y o he hh dime , we con inued s udying he o -
ma ion o highe o de agg ega es using his geome y. In his way, 4-me s we e con-
s uc ed om he hh dime op imized geome y and submi ed o heo e ical s uc u al
s udies using he CREST p og am. The ob ained con o me s we e op imized a he
DFT(B3LYP-D3)/6–31G** le el, esul ing in a unique p e e ed con o me wi h signi ican
popula ion a oom empe a u e (Figu e 4a,b).
The coun e poise co ec ed in e ac ion ene gy was calcula ed a he DFT(B3LYP-
D3)/6–31G** le el o he 4-me as he di e ence be ween he complex ene gy and he
ene gies o he co esponding monome s. The alue ob ained (−91.9 kcal mol−1) is lowe
by 19.3 kcal mol−1 han h ee imes he dime in e ac ion ene gy, indica ing ha he o -
ma ion o he e ame is a o ed. Using he me hodology ou lined in e e ence [24], wo-
body con ibu ions and coope a i e e ec s we e es ima ed. The o me added up o −91.7
kcal/mol, being he e o e he many-body con ibu ions negligible and equal o −0.2
kcal/mol. These esul s clea ly show ha i can be a good app oxima ion o include only
wo-body e ms when conside ing he e alua ion o he in e ac ion ene gies in he agg e-
ga es, since hese con ibu ions amoun o he mos impo an pa o he in e ac ion en-
e gy in he 4-me . To ge insigh in o he coope a i e e ec s due o he p esence o ex a
monome molecules, we calcula ed hem using he same me hod and basis se and aking
a) b)
c) d)
150 200 250 300 350 400
-500
0
500
Wa eleng h [nm]
In ensi y
(S)-1 hh dime
150 200 250 300 350 400
-200
0
200
Wa eleng h [nm]
In ensi y
(S)-1 h dime
e) )
––
Figu e 3.
Oligo(phenylenee hynylene) (OPE) (S)-
1
dime DFT(B3LYP-D3)/6–31G** op imized geome ies: (
a
) hh pe pen-
dicula iew, (
b
) hh pa allel iew, (
c
) h pe pendicula iew and (
d
) h pa allel iew. TD-DFT (CAM-B3LYP)/3–21G ECD
spec a e alua ed a he DFT(B3LYP-D3)/6–31G** op imized geome ies: (
e
) hh dime and (
) h dime . No co ec ion
ac o s a e included in he heo e ical wa eleng hs.
Molecules 2021, 26, x 8 o 14
as e e ence he wo i s monome s in he 4-me (Equa ion (3)). A alue o −13.5 kcal/mol
esul ed, showing ha hey a e impo an a leas o he small n-me s.
Subsequen ly, he ECD and abso p ion TD-DFT(CAM-B3LYP)/3–21G spec a we e
calcula ed and he esul s a e p esen ed in Figu e 4c,d, espec i ely. Thus, he UV-Vis
spec um shows one dominan ansi ion a 300 nm and wo seconda ies a 299 and 302
nm, esul ing in one band cen e ed a ca. 300 nm. On he o he hand, he heo e ical ECD
spec um shows wo in ense Co on bands ha go e n he spec um, a i s posi i e Co -
on e ec a 330 nm and a nega i e one a abou 300 nm. These wo bands a e conside ably
mo e in ense han he es o he spec um.
Figu e 4. Oligo(phenylenee hynylene) (OPE) (S)-1 hh 4-me DFT(B3LYP-D3)/6–31G** op imized
s uc u e: (a) pe pendicula iew and (b) pa allel iew. TD-DFT (CAM-B3LYP)/3–21G spec a e al-
ua ed a he DFT(B3LYP-D3)/6–31G** op imized geome y: (c) ECD and (d) UV-Vis. No co ec ion
ac o s a e included in he heo e ical wa eleng hs.
Finally, om he op imized 4-me s, 8-me oligome s we e cons uc ed. Due o he
la ge size o he 8-me s, we could no op imize he co esponding s uc u es. As in all
s eps o he geome y assembly p ocess isual inspec ion o he con o me s was manda-
o y, in o de o selec he uni s ha we e adequa e o an inc ease in clus e size; hence,
o en con o me s wi h lack o p ope o de o monome s loca ed a he edges o he ag-
g ega e needed o be dis ega ded. This esul ed in he 8-me geome y displayed in Figu e
5a,b. To ge u he insigh in o he coope a i e e ec s, we e alua ed o all he n-me s (n
= 1–8) o he 8-me s uc u e he in e ac ion ene gy pe monome uni and con e gence
was achie ed a a ound n = 5.
a) b)
c) d)
150 200 250 300 350 400
-1000
0
1000
Wa eleng h [nm]
In ensi y
(S)-
1
hh 4-me
200 250 300 350 400
0
5
10
Wa eleng h [nm]
In ensi y
–
Figu e 4.
Oligo(phenylenee hynylene) (OPE) (S)-
1
hh 4-me DFT(B3LYP-D3)/6–31G** op imized s uc u e: (
a
) pe pendicula
iew and (
b
) pa allel iew. TD-DFT (CAM-B3LYP)/3–21G spec a e alua ed a he DFT(B3LYP-D3)/6–31G** op imized
geome y: (c) ECD and (d) UV-Vis. No co ec ion ac o s a e included in he heo e ical wa eleng hs.
Molecules 2021,26, 3530 7 o 14
Molecules 2021, 26, x 9 o 14
Figu e 5. Oligo(phenylenee hynylene) (OPE) (S)-1 hh 8-me s uc u e: (a) pe pendicula iew and
(b) hh pa allel iew. TD-DFT (CAM-B3LYP)/3–21G spec a: (c) ECD and (d) UV-Vis. The co e-
sponding expe imen al spec a a e plo ed o compa ison. No co ec ion ac o s a e included in he
heo e ical wa eleng hs. Elec on densi y di e ences (pu ple colo nega i e and blue posi i e,
iso alue = 0.0002) o ansi ions: (e) S0 → S7 and ( ) S0→ S9.
250 300 350 400
-20000
0
20000
Wa eleng h [nm]
In ensi y
Calcula ed
Expe imen al
–
a) b)
c) d)
e) )
250 300 350 400
0
5
10
15
20
Wa eleng h [nm]
In ensi y
,
,
Figu e 5.
Oligo(phenylenee hynylene) (OPE) (S)-
1
hh 8-me s uc u e: (
a
) pe pendicula iew and (
b
) hh pa allel iew.
TD-DFT (CAM-B3LYP)/3–21G spec a: (
c
) ECD and (
d
) UV-Vis. The co esponding expe imen al spec a a e plo ed o
compa ison. No co ec ion ac o s a e included in he heo e ical wa eleng hs. Elec on densi y di e ences (pu ple colo
nega i e and blue posi i e, iso alue = 0.0002) o ansi ions: (e) S0→S7and ( ) S0→S9.
Molecules 2021,26, 3530 8 o 14
Molecules 2021, 26, x 11 o 14
Figu e 6. E ec o he agg ega ion on he TD-DFT (CAM-B3LYP)/3–21G (a) ECD and (b) UV-Vis spec a o oligo(phe-
nylenee hynylene) (OPE) (S)-1 hh n-me s, n = 2, 4, and 8. The co esponding expe imen al spec a a e included o com-
pa ison. No co ec ion ac o s a e conside ed in he heo e ical wa eleng hs. The 8-me in ensi ies we e no malized wi h
espec o he expe imen al ones and he 2,4-me in ensi ies scaled wi h he same ac o s.
4. Summa y and Conclusions
Conside ing he wide in e es linea OPEs ha e a ac ed due o hei sup amolecula
p ope ies and hei possible applica ions o elec onic de ices, he e we ha e ca ied ou
a de ailed s uc u al in es iga ion on he agg ega ion p ocess o (S)-1, which yields wo
shee -like nanos uc u es. Th ough sys ema ically inc easing he numbe o monome
uni s, we ha e de e mined a possible s uc u e o he agg ega e and analyzed he in e -
molecula o ces in ol ed in he sup amolecula assembly. Fo he geome y op imiza-
ions we used densi y unc ional heo y oge he wi h he B3LYP-D3 unc ional and he
6–31G** basis se . Addi ionally, om he ob ained geome ies we calcula ed he TD-
DFT(CAM-B3LYP)/3–21G abso p ion and ci cula dich oism spec a, ha a e in ag ee-
men wi h he expe imen al esul s a ailable. The e o e, we can conclude ha he me h-
odology used can be expec ed o p o ide an e icien app oxima ion o he s uc u e and
spec a in ou ine s udies o simila agg ega es and polyme s.
Supplemen a y Ma e ials: The ollowing supplemen a y da a a e a ailable online. Molecula Dy-
namics s udy, Table S1: Molecula Dynamics main esul s, Table S2: Geome ies used in he e alu-
a ion o he spec a, Table S3: Monome ib onic spec um ansi ions, Figu e S1: MD con o me s
o he monome , Figu e S2: MD mos s able con o me s o he dime , Figu e S3: MD mos s able
con o me s o he 4-me , Figu e S4: Analysis o he dime in e molecula in e ac ions, Figu es S5
and S6: Addi ional ECD spec a o he monome , Figu e S7: Monome ib onic spec um, Figu e
S8: Monome and 4-me IR spec a.
Au ho Con ibu ions: B.F.: in es iga ion, w i ing- e iew & edi ing, Z.F.: in es iga ion, w i ing- e-
iew & edi ing, E.Q.: in es iga ion, w i ing- e iew & edi ing, F.F.: in es iga ion, w i ing- e iew &
edi ing. All au ho s ha e ead and ag eed o he published e sion o he manusc ip .
Funding: This esea ch was unded by Minis e io de Ciencia e Inno ación, g an numbe PID2019-
107307RB-100; Xun a de Galicia, g an s numbe and ED431C 2018/30, ED431C 2017/17 and ED431G
2019/03; and he Eu opean Regional De elopmen Fund (ERDF).
Acknowledgmen s: We hank Se icio de Nano ecnología y Análisis de Supe icies (CACTI,
UVIGO). Z. F. hanks Xun a de Galicia o he PhD ellowship and B. F. acknowledges CESGA o
compu a ional ime.
Figu e 6.
E ec o he agg ega ion on he TD-DFT (CAM-B3LYP)/3–21G (
a
) ECD and (
b
) UV-Vis spec a o
oligo(phenylenee hynylene) (OPE) (S)-
1
hh n-me s, n = 2, 4, and 8. The co esponding expe imen al spec a a e in-
cluded o compa ison. No co ec ion ac o s a e conside ed in he heo e ical wa eleng hs. The 8-me in ensi ies we e
no malized wi h espec o he expe imen al ones and he 2,4-me in ensi ies scaled wi h he same ac o s.
Fi s heo e ical s udies we e ca ied ou o monome (S)-
1
. The molecule was buil
up using he geome y de e mined om X- ay s udies [
68
] as a s a ing poin , and he
mos s able con o me s we e ob ained using he CREST p og am. This e ealed he
p esence o wo majo con o me s a oom empe a u e ha con ibu e signi ican ly o
he spec a. These con ibu ions a e o 70% (degene acy 58) o he mos s able con o me
(Con o me 1) and 30% (degene acy 52) o he second one (Con o me 2). Nex , u he
op imiza ion o hese wo s uc u es was ca ied ou a he DFT(B3LYP-D3)/6–31G**
le el, ob aining o Con o me 1 a (O = )C-C
α
-O-C(Me) dihed al angle equal o
−
162
◦
(
Figu e 2a
), while Con o me 2 has a (O = )C-C
α
-O-C(Me) dihed al angle equal o
−
78
◦
(Figu e 2b). The ene gies o hese wo con o me s a e shown in Table 1, co esponding o a
popula ion o 52.7% o Con o me 1 and o 47.3% o Con o me 2 a oom empe a u e.
We also e alua ed he popula ions using he di e ence in Gibbs ee ene gy, and he
co esponding esul s a e epo ed in he Supplemen a y Ma e ials (Sec ion 4). Due o he
nea degene acy o he wo con o me s, we addi ionally ca ied ou he abo e calcula ions
wi h he 6311++G(d,p) basis se . The esul s p o ided simila con o me s in e ms o
he dihed al angles—(O = )C-C
α
-O-C(Me) dihed al angle equal o
−
164
◦
and
−
78
◦
o
Con o me 1 and 2, espec i ely—and wi h an ene gy di e ence o 0.49 kcal mol
−1
. Fo
consis ency, we include he e he 6–31G** alues and epo he 6311++G(d,p) ones in
he Supplemen a y Ma e ials. Bo h molecula dynamics and DFT calcula ions p o ide
Con o me 1 as he mos s able.
Nex , he heo e ical UV-Vis and ECD spec a we e e alua ed. To pe o m hese
s udies he TD-DFT me hod, use o he CAM-B3LYP unc ional wi h ei he he 3-21G [
63
] o
he cc-pVTZ basis se [
69
], was employed. In a i s app oach, we e alua ed he heo e ical
ECD spec um o he geome y ob ained om he X- ay s udies. Compa ison be ween he
wo heo e ical ECD spec a, calcula ed using he 3–21G and he cc-pVTZ bases, and he
expe imen al spec um, is shown in Figu e 2c. A good ag eemen is obse ed o he i s
Co on band in he h ee ECD spec a. Mo eo e , in he case o he wo heo e ical ECD
aces, he gene al shape o he spec a p o ided by he wo bases is e y simila , wi h a
displacemen o a ound 30 nm o he igh in he case o he cc-pVTZ spec um.
Then, he ECD spec a o he DFT(B3LYP-D3)/6–31G** op imized geome ies o he
wo con o me s wi h signi ican popula ion a oom empe a u e we e calcula ed and
Molecules 2021,26, 3530 9 o 14
combined conside ing he con o me con ibu ions o ge he inal heo e ical ECD ace. A
compa ison be ween he ECD aces ob ained om he heo e ical and he expe imen al
s udies, in addi ion o he heo e ical spec um ob ained om he X- ay geome y, is shown
in Figu e 2d. I was ound ha bo h TD-DFT(CAM-B3LYP)/3–21G spec a— he one ob-
ained om he con o ma ional s udies and he one ob ained om he X- ay geome y—a e
in ag eemen wi h he expe imen al one in he sign o he i s Co on e ec , be ween
300 and 320 nm. Also, he ECD aces ob ained om he heo e ical and he X- ay geome-
ies show good ag eemen a ound 150 nm, while he in e media e egions o he spec a
a e conside ably di e en . F om he DFT(B3LYP)/6311++G(d,p) con o me geome ies we
e alua ed he co esponding ECD spec um and epo he esul s in he Supplemen a y
Ma e ials, whe e i is compa ed o he 6–31G** one. When conside ing he popula ions
ob ained om he Gibbs ee ene gies, only small di e ences a e obse ed in he spec al
bands, ha a e mainly due o in ensi y changes in he high ene gy egions (see Figu e S6 in
he Supplemen a y Ma e ials).
Simila s udies we e ca ied ou o a dime o (S)-
1
made by he op imized con o me s
o he monome ic uni . The dime can be buil up in wo di e en ways, head- o-head (hh)
(Figu e 3a,b) o head- o- ail (h ) (Figu e 3c,d). The o me (hh) was ob ained as he mos
s able s uc u e, wi h an ene gy di e ence wi h espec o he la e (h ) o
2.2 kcal mol−1
(see Table 1). This la ge ene gy gap implies a signi ican di e ence in popula ion o he hh
wi h espec o he h agg ega e a oom empe a u e, indica ing a negligible con ibu ion
o he h -con o me o he ECD spec a. Addi ionally, using he coun e poise co ec ion,
we e alua ed he DFT(B3LYP-D3)/6–31G** in e ac ion ene gies o he hh and h dime s,
ob aining alues o
−
24.2 kcal mol
−1
and
−
21.8 kcal mol
−1
, espec i ely. This co obo a es
he la ge s abili y o he hh dime compa ed o he h one. To coun e poise co ec he
esul s is impo an , accoun ing he co ec ions o
12.5 kcal mol−1
and 10.1 kcal mol
−1
o he hh and h dime s, espec i ely. The esul s o he analysis o he non-co alen
in e ac ions in he hh-dime a e epo ed in he Supplemen a y Ma e ials (Figu e S4) and
show ha an de Waals o ces clea ly domina e he non-co alen in e ac ions. These
esul s a e in ag eemen wi h he an de Waals su ace shown in Figu e 1a, de ined as ha
wi h an elec on densi y equal o 0.001 au, and whe e he molecula elec os a ic po en ial
plo ed e lec s he elec os a ic con ibu ion o possible in e molecula in e ac ions [70].
Theo e ical ECD s udies—TD-DFT(CAM-B3LYP)/3–21G— o he wo o ien a ions o
he dime show ECD aces ha ag ee in he high wa eleng h egion; i s (335 nm, posi i e)
and second co on bands (310–330 nm, nega i e) (Figu e 3e, ). In he low wa eleng h egion
(180 o 300 nm) bo h ECD aces a e qui e di e en ; hus, while he h dime displays many
ansi ions wi h simila in ensi ies (Figu e 3 ), he hh dime shows jus a ew ansi ions
wi h signi ican in ensi y (Figu e 3e).
Conside ing he highe s abili y o he hh dime , we con inued s udying he o ma ion
o highe o de agg ega es using his geome y. In his way, 4-me s we e cons uc ed om
he hh dime op imized geome y and submi ed o heo e ical s uc u al s udies using
he CREST p og am. The ob ained con o me s we e op imized a he DFT(B3LYP-D3)/6–
31G** le el, esul ing in a unique p e e ed con o me wi h signi ican popula ion a oom
empe a u e (Figu e 4a,b).
The coun e poise co ec ed in e ac ion ene gy was calcula ed a he DFT(B3LYP-
D3)/6–31G** le el o he 4-me as he di e ence be ween he complex ene gy and he
ene gies o he co esponding monome s. The alue ob ained (
−
91.9 kcal mol
−1
) is lowe
by 19.3 kcal mol
−1
han h ee imes he dime in e ac ion ene gy, indica ing ha he
o ma ion o he e ame is a o ed. Using he me hodology ou lined in e e ence [
24
],
wo-body con ibu ions and coope a i e e ec s we e es ima ed. The o me added up
o
−
91.7 kcal/mol, being he e o e he many-body con ibu ions negligible and equal o
−
0.2 kcal/mol. These esul s clea ly show ha i can be a good app oxima ion o include
only wo-body e ms when conside ing he e alua ion o he in e ac ion ene gies in he
agg ega es, since hese con ibu ions amoun o he mos impo an pa o he in e ac ion
ene gy in he 4-me . To ge insigh in o he coope a i e e ec s due o he p esence o ex a
