Ci a ion: E emenko, Y.; Mi sky, V.M.
3-Thienylbo onic Acid as a Recep o
o Diol-Con aining Compounds: A
S udy by Iso he mal Ti a ion
Calo ime y. Chemosenso s 2022,10,
251. h ps://doi.o g/10.3390/
chemosenso s10070251
Academic Edi o s: Xudong Wang
and Hongshang Peng
Recei ed: 6 June 2022
Accep ed: 27 June 2022
Published: 29 June 2022
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chemosenso s
Communica ion
3-Thienylbo onic Acid as a Recep o o Diol-Con aining
Compounds: A S udy by Iso he mal Ti a ion Calo ime y
Yulia E emenko and Vladimi M. Mi sky *
Nanobio echnology Depa men , Ins i u e o Bio echnology, B andenbu g Uni e si y o Technology
Co bus–Sen enbe g, 01968 Sen enbe g, Ge many; [email p o ec ed]
*Co espondence: [email p o ec ed]
Abs ac :
The elec ochemical ac i i y o 3- hienylbo onic acid and i s ea u e o o m polyme ilms
makes i a pe spec i e ecep o ma e ial o senso applica ions. The a ini y p ope ies o his
compound we e s udied he e by iso he mal i a ion calo ime y. A numbe o di e en analy es
we e es ed, and he highes binding en halpy was obse ed o so bi ol and uc ose. An inc ease o
pH in he ange o 5.5–10.6 esul s in he ise o he binding en halpy wi h an inc ease o he binding
cons an o ~8400 L/mol o so bi ol o ~3400 L/mol o uc ose. The dependence o he binding
cons an on pH has an in lec ion poin a pH 7.6 wi h a slope ha is a en- old binding cons an pe
one pH uni . The binding p ope ies o 3- hienylbo onic acid we e e alua ed o be e y close o ha o
he phenylbo onic acid, bu he elec ochemical ac i i y o 3- hienylbo onic acid p o ides a possibili y
o ex e nal elec ical con ol: dependence o he a ini y o 3- hienylbo onic acid on i s edox s a e
de ined by he p esence o e o/ e icyanide in di e en a ios was demons a ed. The esul s
show ha 3- hienylbo onic acid can be applied in sma chemical senso s wi h elec ochemically
con ollable ecep o a ini y.
Keywo ds:
chemical senso s; a ini y; iso he mal i a ion calo ime y; 3- hienylbo onic acid;
diol-con aining compounds
1. In oduc ion
Ligand- ecep o in e ac ions play a key ole in many biological p ocesses [
1
]. This
p inciple was ans e ed om na u al o a i icial sys ems and led o he de elopmen
o a ini y senso s [
2
] which possess a selec i e ecep o p o iding binding o speci ic
molecules and a ansduce epo ing he amoun o he bound analy e. The ecep o can be
o na u al o igin, like an ibodies, de ined sequences o nucleic acids o o he biomolecules.
Bu al eady a he beginning o es ablishing senso science, he exploi a ion o a i icial
ecep o s o chemical senso s was also in oduced. Du ing he las ew decades, o ganic
chemis s ha e syn hesized a la ge numbe o a ious a i icial ecep o s o chemical
senso s possessing di e en a ini y p ope ies. In compa ison wi h biomolecules, a i icial
ecep o s ha e such bene i s as high chemical s abili y, high shel -li e, and low cos s. Thei
p oduc ion can be scaled up easily. The de elopmen o a i icial ecep o s does no
include immuniza ion o animals; he e o e, hey can be p incipally de eloped o na u al
me aboli es o highly oxic compounds.
The complex o ma ion due o analy e binding o ecep o molecules can be cha ac e -
ized quan i a i ely by a se o kine ic and he modynamic pa ame e s [
3
]. The quan i a i e
da a [
4
] allow one o selec a i icial ecep o s wi h p edic able selec i i y [
5
] and de ec ion
limi o a pa icula applica ion. The de elopmen o new a i icial ecep o s wi h high
selec i i y and equi ed a ini y is he op-p io i y objec i e in senso science. Cu en ly, i
is pe o med also by combina o ial app oaches [
6
] using quan i a i e a ini y da a as de-
sc ip o s. A la ge numbe o a i icial ecep o s sugges ed o a ious compounds include
be a-cyclodex ins [
7
], c own e he s [
8
], calixa enes [
9
], sp eade -ba s abilized monomolec-
ula laye s [
10
], molecula ly imp in ed polyme s [
11
], and also bo onic acids [
12
]. The
Chemosenso s 2022,10, 251. h ps://doi.o g/10.3390/chemosenso s10070251 h ps://www.mdpi.com/jou nal/chemosenso s
Chemosenso s 2022,10, 251 2 o 10
bo onic acid unc ional g oup is one o he widely used a i icial ecep o s o he analy es
possessing 1,2 o 1,3-diol g oups ha a e Lewis base-con aining dono s [
13
]. Bo onic acid
o ms e e sible co alen complexes wi h hese moie ies in aqueous sys ems hus lead-
ing o he in e con e sion o bo onic acid in o co esponding diol-bo ona e complexes.
The in e change be ween bo onic acid and diol moie ies depends on he pH o he aque-
ous en i onmen , pK
a
alues o bo onic acid and analy e, and p obably on o he ac o s
oo [14–16].
The s ong bu e e sible co alen in e ac ions be ween bo onic acid and nucleophile
diol moie y make his unc ional g oup a well sui able o he de elopmen o a i icial
ecep o s o chemical sensing [
17
,
18
] o saccha ides and o he p ac ically impo an
molecules con aining diols. Such senso s can be based on di e en ansduce s, o example:
colo ime ic [
19
], luo escen [
20
], ampe ome ic [
21
], po en iome ic [
22
], impedime ic [
23
],
and su ace plasmon esonance [
24
]. The i s luo escen senso o saccha ides ecogni ion
by he di ec linking binding si e o bo onic acid wi h an h acene as a luo escen uni
was epo ed in he wo k [
25
]. The binding wi h D- uc ose a pH 7.4 led o a dec ease in
luo escence in ensi y. La e he design pa ame e s o luo escen senso s we e ex ended
using dibo onic acid ecep o s [26–28].
In mos cases immobiliza ion o ecep o s on a su ace o hei embedding in o polyme
backbones equi es. This led o he high a en ion o polyme izable monome s possessing
bo onic acid moie y [
29
–
31
]. As epo ed in [
32
] co-polyme ized wi h
3-aminophenylbo onic
acid polyaniline wi h nea -in a ed op ical esponse can be used o he de ec ion o di -
e en saccha ides. The shi in adso p ion spec a upon a binding was dependen on
saccha ide concen a ion. Senso s wi h po en iome ic signal- ansducing we e p oposed
as an al e na i e o elec ochemical senso s based on enzymes and he ca aly ic abil-
i y o he elec ode su ace [
33
] due o hei echnological impe ec ion. Po en iome ic
senso s also can be de eloped by including a bo onic acid moie y in o he polyme back-
bone [
22
,
34
,
35
]. La e his app oach was upg aded using modi ied gold nanopa icles in o
a polyme basis as ecep o uni s ansducing a po en iome ic signal [36].
The mos common and well-s udied monome wi h in eg a ed bo onic acid moi-
e y is phenylbo onic acid (PBA). A unc ionalized de i a i e o phenylbo onic acid is
3-aminophenylbo onic acid. I can be conside ed as subs i u ed aniline–one o he mos
signi ican monome s gi ing conduc ing polyme s a e polyme iza ion. Namely, his
monome was used as he i s one o he syn hesis o polyme s wi h a bo onic acid moie y
which was applied in pho ome ic sensing o saccha ides [
32
] and la e o po en iome ic
sensing [
22
]. The common p oblem o his polyme is he pH sensi i i y o i s backbone [
37
];
in he case o analy ical applica ions, i leads o pH in e e ence and equi es using o s ong
bu e s. In [
38
] we ha e men ioned an unsuccess ul a emp o de elop a conduc ome ic
senso based on such polyme s: he pH in e e ence was so high ha i was impossible o
ge a eliable esponse o he saccha ides.
Along wi h subs i u ed aniline and some o he bo onic acid monome s, hiophene
unc ionalized by he bo onic acid g oup has ecen ly a ac ed a en ion as a pe spec i e
syn he ic ecep o [
23
]. In con as o aniline wi h in eg a ed bo onic acid moie y, a poly-
me iza ion o hiophene molecules con aining a bo onic acid side g oup leads o a polyme
ha has no basic si es in i s backbone. The e o e, one canno expec any pH in luence on
i s p ope ies due o changes in he backbone p o ona ion, e.g., he senso s based on such
ma e ial a e expec ed o ha e a much lowe in e e ence wi h pH changes in compa ison
wi h polyaniline backbone. This ad an age makes hiophene wi h bo onic acid moie ies a
p omising chemosensi i e ma e ial o ecognizing diol-con aining compounds. Recen ly,
we ha e al eady epo ed he p epa a ion o poly-3- hienylbo onic acid by elec ochemical
polyme iza ion o 3- hienylbo onic acid (TBA) and discussed he op ical, elec och omic,
and chemosensi i e p ope ies o his new ma e ial [38].
In his wo k, we de e mine he binding p ope ies o TBA. I has been done using
iso he mal i a ion calo ime y (ITC). ITC is a powe ul echnique allowing one o pe o m
a comp ehensi e he modynamic cha ac e iza ion o a ini y p ope ies [
39
,
40
]. He e we
Chemosenso s 2022,10, 251 3 o 10
used his app oach o cha ac e ize he a ini y o TBA owa d diol-con aining compounds
and compa ed he ob ained a ini y alues wi h PBA. Addi ionally, we ha e demons a ed
a possibili y o elec ochemical con ol o TBA a ini y.
2. Ma e ials and Me hods
ITC expe imen s we e pe o med using an iso he mal i a ion calo ime e Mic o Cal
PEAQ-ITC om Mal e n Ins umen s. The sys em has he sample and e e ence cells
made om Has elloy
™
alloy. All expe imen s we e pe o med a 25
◦
C. Each expe imen
in ol ed a se ies o 18 injec ions o 2
µ
L each a e he i s injec ion o 0.4
µ
L. The hea o a
ligand dilu ion was measu ed in he absence o ecep o molecules in sepa a e expe imen s
and sub ac ed. The esul ing i a ion iso he m was i ed wi h analysis so wa e o Mic o
Cal PEAQ-ITC sys em using he i ing model “One se o si es”. Redox po en ials we e
measu ed using Palm Sens Em S a
3
po en ios a wi h he gold elec ode as a wo king
elec ode and sil e /sil e chlo ide e e ence elec ode wi h double sal b idges (Me ohm)
illed wi h sa u a ed po assium chlo ide.
D-(
−
) uc ose was pu chased om Me ck o he saccha ides (D-(+) glucose, D-(+)
galac ose, D-so bi ol) as well as lac ic acid, R-2-hyd oxybu y ic acid, polye hylene glycol
wi h mola weigh 1500 g/mol, PBA, TBA, po assium e icyanide and po assium e o-
cyanide we e om Sigma-Ald ich. Fo bu e solu ions we e used po assium hyd ogen
phospha e, po assium dihyd ogen phospha e om Chem Solu e (Th. Geye ), sodium
ca bona e, sodium bica bona e om Ro h, and ace ic acid om Sigma-Ald ich. The pH
alues o bu e solu ions we e adjus ed using 1 M solu ions o NaOH o HCl om Ro h.
Deionized wa e addi ionally pu i ied by he sys em EGLA-classic was applied.
3. Resul s and Discussion
In analogy wi h he gene ally-accep ed scheme o PBA [
41
], we can sugges simila
eac ion pa hways o TBA (Figu e 1). In an aqueous en i onmen , bo onic acid is hy-
d olyzed wi h he o ma ion o anionic e ahed al bo ona e (2) and eleases a hyd ogen
ion. In he p esence o diols, he bo ona e anion (2) is ans o med in o i s co esponding
cyclic bo ona e es e (3). A di ec o ma ion o he igonal bo onic es e (4) om neu al
bo onic acid (1) is also possible, bu his eac ion is h ee- ou o de s o magni ude slowe
han he way h ough anionic e ahed al bo ona e (2) [12].
The a io be ween he igonal bo onic acid (1) and e ahed al bo ona e (2) a a speci ic
pH is de ined by he pK
a
alue o a bo onic acid de i a i e and cha ac e izes i s Lewis
acidi y. The ac ha mainly he e ahed al bo ona e (2) eac s wi h diols poin s o pH
in luence on he a ini y o bo onic acid.
All in es iga ed sys ems possessed a ela i ely low a ini y (Ka
<
10
4
L/mol). In
con as o he high a ini y sys ems, which gene a e binding iso he ms o sigmoidal shape,
binding iso he ms a low-a ini y o m la i a ion cu es, which lead o high unce ain ies
in he measu emen s o binding cons an s by using s anda d ITC analysis p ocedu es.
Acco ding o he analysis p esen ed in [
42
], he concen a ions o ligands du ing i a ion
we e inc eased, and he binding s oichiome y was pos ula ed o be equal o 1.0 [
43
]. The
excess o he i an allowed us o achie e essen ial ecep o sa u a ion by he end o
i a ions and o ex ac he alues o binding en halpy and binding cons an s mo e exac .
An absence o li e a u e da a on he binding o TBA wi h diols and o he po en ial
ligands was he eason o es a numbe o a ious compounds: galac ose, uc ose, so bi ol,
polye hylene glycol (PEG), 2-hyd oxybu y ic acid (HBA), and lac ic acid. The in eg a ed
i a ion cu es measu ed a neu al pH a e shown in Figu e 2. The highes alues o
he binding en halpy we e obse ed o so bi ol and uc ose. Fo galac ose, lac ic acid,
HBA, and PEG hese alues a e e y low. Fo he i s h ee compounds also he “slope”
o hese cu es is e y low (Figu e 2) hus indica ing he low-a ini y alues o TBA o
hese compounds. A eliable ITC in es iga ion o hese in e ac ions is ha dly possible. A
li le mo e op imis ic is he i a ion cu e o polye hylene glycol: he obse ed sa u a ion
wi hin he s udied concen a ion ange indica es he alue o he binding cons an which
Chemosenso s 2022,10, 251 4 o 10
may be compa able o ha o so bi ol and uc ose. Howe e , because o he low alue
o he binding en halpy, i was di icul o ge c edible quan i a i e alues. The eason o
so low binding en halpy o PEG can be a complex beha io o en opy o his polyme
du ing he binding p ocess, such e ec s we e discussed in ensi ely in li e a u e [
44
]. The
binding p ocess is go e ned by changes in Gibbs ene gy (
∆
G) and en opy (
∆
S), bu he
measu emen alue is binding en halpy (
∆
H), he e o e ITC is no sui able o p ocesses
wi h low en halpy. One can expec ha he PEG–TBA in e ac ion can be cha ac e ized
quan i a i ely using o he analy ical echniques, bu in he cu en wo k, we had o exclude
his impo an and in e es ing analy e om a mo e de ailed cha ac e iza ion.
Chemosenso s 2022, 10, x FOR PEER REVIEW 4 o 10
Figu e 1. Equilib ium be ween 3- hienylbo onic acid and i s es e upon in e ac ion wi h 1,2- o 1,3-
diols in an aqueous solu ion. The scheme is based on he ea ly sugges ed scheme o PBA [41].
All in es iga ed sys ems possessed a ela i ely low a ini y (Ka ˂ 104 L/mol). In con-
as o he high a ini y sys ems, which gene a e binding iso he ms o sigmoidal shape,
binding iso he ms a low-a ini y o m la i a ion cu es, which lead o high unce ain-
ies in he measu emen s o binding cons an s by using s anda d ITC analysis p ocedu es.
Acco ding o he analysis p esen ed in [42], he concen a ions o ligands du ing i a ion
we e inc eased, and he binding s oichiome y was pos ula ed o be equal o 1.0 [43]. The
excess o he i an allowed us o achie e essen ial ecep o sa u a ion by he end o i a-
ions and o ex ac he alues o binding en halpy and binding cons an s mo e exac .
An absence o li e a u e da a on he binding o TBA wi h diols and o he po en ial
ligands was he eason o es a numbe o a ious compounds: galac ose, uc ose, so bi-
ol, polye hylene glycol (PEG), 2-hyd oxybu y ic acid (HBA), and lac ic acid. The in e-
g a ed i a ion cu es measu ed a neu al pH a e shown in Figu e 2. The highes alues
o he binding en halpy we e obse ed o so bi ol and uc ose. Fo galac ose, lac ic acid,
HBA, and PEG hese alues a e e y low. Fo he i s h ee compounds also he “slope”
o hese cu es is e y low (Figu e 2) hus indica ing he low-a ini y alues o TBA o
hese compounds. A eliable ITC in es iga ion o hese in e ac ions is ha dly possible. A
li le mo e op imis ic is he i a ion cu e o polye hylene glycol: he obse ed sa u a ion
wi hin he s udied concen a ion ange indica es he alue o he binding cons an which
may be compa able o ha o so bi ol and uc ose. Howe e , because o he low alue o
he binding en halpy, i was di icul o ge c edible quan i a i e alues. The eason o so
low binding en halpy o PEG can be a complex beha io o en opy o his polyme du ing
he binding p ocess, such e ec s we e discussed in ensi ely in li e a u e [44]. The binding
p ocess is go e ned by changes in Gibbs ene gy (ΔG) and en opy (ΔS), bu he measu e-
men alue is binding en halpy (ΔH), he e o e ITC is no sui able o p ocesses wi h low
en halpy. One can expec ha he PEG–TBA in e ac ion can be cha ac e ized quan i a-
i ely using o he analy ical echniques, bu in he cu en wo k, we had o exclude his
impo an and in e es ing analy e om a mo e de ailed cha ac e iza ion.
Figu e 1.
Equilib ium be ween 3- hienylbo onic acid and i s es e upon in e ac ion wi h 1,2- o
1,3-diols in an aqueous solu ion. The scheme is based on he ea ly sugges ed scheme o PBA [41].
Chemosenso s 2022, 10, x FOR PEER REVIEW 5 o 10
Figu e 2. No malized hea plo measu ed o binding o di e en compounds o TBA. Ti a ion con-
di ions: 300 μL o 0.5 mM TBA in he cell and 25 mM o he co esponding compound in he i a ion
sy inge, pH 7.4.
A de ailed binding analysis was pe o med o so bi ol and uc ose displaying he
highes en halpy e ec s. The main ac o in luencing he binding o analy es o bo onic
acid is pH, he e o e he measu emen s we e pe o med a pH alues om 6.0 o 10.6. pH
inc ease leads o he essen ial inc ease o he binding en halpy (Figu e 3). This e ec be-
comes especially p onounced in he pH ange 7.4–9.2 while a u he pH inc ease has al-
mos no in luence.
Figu e 3. No malized hea plo s o so bi ol binding o TBA a di e en pH. Ti a ion condi ions:
300 μL o 0.5 mM TBA in he cell and 25 mM o so bi ol in he i a ion sy inge.
The high alues o binding en halpy obse ed o so bi ol and uc ose allowed us o
pe o m a quan i a i e analysis o he a ini y o TBA o hese compounds. The esul s a e
p esen ed in Figu e 4 and Table 1. pH inc ease om 5.5 o 10.6 leads o an inc ease o he
binding cons an om ~15 L/mol o ~ 8400 L/mol o om ~50 L/mol o ~3400 L/mol o
so bi ol and uc ose espec i ely (Figu e 4, Table 1). I co esponds o an inc ease in he
absolu e alue o binding ene gy −ΔG om 3.73 kJ/mol o 21.29 kJ/mol o so bi ol o om
4.24 kJ/mol o 18.9 kJ/mol o uc ose. The dependence o he binding cons an on pH
looks like a classical sigmoid i a ion cu e (Figu e 4). In he symme y poin a pH = 7.6,
he slope o his cu e is exac ly 10 imes he change in he binding cons an pe one pH
Figu e 2.
No malized hea plo measu ed o binding o di e en compounds o TBA. Ti a ion
condi ions: 300
µ
L o 0.5 mM TBA in he cell and 25 mM o he co esponding compound in he
i a ion sy inge, pH 7.4.
Chemosenso s 2022,10, 251 5 o 10
A de ailed binding analysis was pe o med o so bi ol and uc ose displaying he
highes en halpy e ec s. The main ac o in luencing he binding o analy es o bo onic
acid is pH, he e o e he measu emen s we e pe o med a pH alues om 6.0 o 10.6.
pH inc ease leads o he essen ial inc ease o he binding en halpy (Figu e 3). This e ec
becomes especially p onounced in he pH ange 7.4–9.2 while a u he pH inc ease has
almos no in luence.
Chemosenso s 2022, 10, x FOR PEER REVIEW 5 o 10
Figu e 2. No malized hea plo measu ed o binding o di e en compounds o TBA. Ti a ion con-
di ions: 300 μL o 0.5 mM TBA in he cell and 25 mM o he co esponding compound in he i a ion
sy inge, pH 7.4.
A de ailed binding analysis was pe o med o so bi ol and uc ose displaying he
highes en halpy e ec s. The main ac o in luencing he binding o analy es o bo onic
acid is pH, he e o e he measu emen s we e pe o med a pH alues om 6.0 o 10.6. pH
inc ease leads o he essen ial inc ease o he binding en halpy (Figu e 3). This e ec be-
comes especially p onounced in he pH ange 7.4–9.2 while a u he pH inc ease has al-
mos no in luence.
Figu e 3. No malized hea plo s o so bi ol binding o TBA a di e en pH. Ti a ion condi ions:
300 μL o 0.5 mM TBA in he cell and 25 mM o so bi ol in he i a ion sy inge.
The high alues o binding en halpy obse ed o so bi ol and uc ose allowed us o
pe o m a quan i a i e analysis o he a ini y o TBA o hese compounds. The esul s a e
p esen ed in Figu e 4 and Table 1. pH inc ease om 5.5 o 10.6 leads o an inc ease o he
binding cons an om ~15 L/mol o ~ 8400 L/mol o om ~50 L/mol o ~3400 L/mol o
so bi ol and uc ose espec i ely (Figu e 4, Table 1). I co esponds o an inc ease in he
absolu e alue o binding ene gy −ΔG om 3.73 kJ/mol o 21.29 kJ/mol o so bi ol o om
4.24 kJ/mol o 18.9 kJ/mol o uc ose. The dependence o he binding cons an on pH
looks like a classical sigmoid i a ion cu e (Figu e 4). In he symme y poin a pH = 7.6,
he slope o his cu e is exac ly 10 imes he change in he binding cons an pe one pH
Figu e 3.
No malized hea plo s o so bi ol binding o TBA a di e en pH. Ti a ion condi ions:
300 µL o 0.5 mM TBA in he cell and 25 mM o so bi ol in he i a ion sy inge.
The high alues o binding en halpy obse ed o so bi ol and uc ose allowed us
o pe o m a quan i a i e analysis o he a ini y o TBA o hese compounds. The esul s
a e p esen ed in Figu e 4and Table 1. pH inc ease om 5.5 o 10.6 leads o an inc ease o
he binding cons an om ~15 L/mol o ~ 8400 L/mol o om ~50 L/mol o ~3400 L/mol
o so bi ol and uc ose espec i ely (Figu e 4, Table 1). I co esponds o an inc ease in
he absolu e alue o binding ene gy
−∆
G om 3.73 kJ/mol o 21.29 kJ/mol o so bi ol
o om 4.24 kJ/mol o 18.9 kJ/mol o uc ose. The dependence o he binding cons an
on pH looks like a classical sigmoid i a ion cu e (Figu e 4). In he symme y poin a
pH = 7.6, he slope o his cu e is exac ly 10 imes he change in he binding cons an pe
one pH uni . One can sugges ha his poin co esponds o he pK
a
alue o any eac ion
pa icipan . To es , i his pH in luence can be explained by he equilib ium be ween he
o ms (1) and (2), a pH i a ion o TBA wi h NaOH was pe o med. This has gi en he
pK
a
poin o TBA~8.1. I is mo e alkalic alue han ha o he “appea ed pK
a
” ob ained
om he pH dependence o he binding cons an (Figu e 4). I may indica e an in luence
on he equilib ium be ween he o ms (3) and (4). Such equilib ia we e discussed in de ail
in [
45
,
46
]. The ac ha bo onic acid es e s a e mo e acidic han bo onic acid explains he
obse ed disc epancy be ween he pKao TBA and pH dependence in Figu e 4.
A de ailed analysis o pH in luence on he complexa ion o bo onic acid wi h diols
was pe o med in [
47
]. The au ho s sugges ed ha he op imal pH o such in e ac ion
is in he middle be ween he pKa alues o bo onic acid and he co esponding analy e.
The pKa alues o so bi ol and uc ose a e 13.6 and 12.06 espec i ely [
45
,
48
]. This gi es
he op imal pH o so bi ol binding 10.9, and o uc ose 10.1. This co esponds o ou
da a (Figu e 4) whe e a pe manen inc ease o he so bi ol binding was obse ed ill he
highes measu ed pH alue o 10.6 while he da a o uc ose demons a e a sa u a ion a
his poin .
The binding p ope ies o TBA we e compa ed wi h PBA which is he mos in es i-
ga ed compound wi h bo onic acid moie y (Table 1). The esul s demons a e e y close
alues o binding cons an s. The ob ained alues o binding cons an s we e alida ed by
“ e e sible i a ion” when TBA was in he i a ion sy inge and uc ose in he cell. A pH
Chemosenso s 2022,10, 251 6 o 10
8.0 he alues o binding cons an s 818
±
89 L/mol and 513
±
5 L/mol o PBA and TBA
co espondingly we e ob ained.
Chemosenso s 2022, 10, x FOR PEER REVIEW 6 o 10
uni . One can sugges ha his poin co esponds o he pKa alue o any eac ion pa ici-
pan . To es , i his pH in luence can be explained by he equilib ium be ween he o ms
(1) and (2), a pH i a ion o TBA wi h NaOH was pe o med. This has gi en he pKa poin
o TBA~8.1. I is mo e alkalic alue han ha o he “appea ed pKa” ob ained om he pH
dependence o he binding cons an (Figu e 4). I may indica e an in luence on he equi-
lib ium be ween he o ms (3) and (4). Such equilib ia we e discussed in de ail in [45,46].
The ac ha bo onic acid es e s a e mo e acidic han bo onic acid explains he obse ed
disc epancy be ween he pKa o TBA and pH dependence in Figu e 4.
Figu e 4. pH dependence o he binding cons an o TBA o so bi ol and uc ose. Ti a ion condi-
ions: 300 μL o 0.5 mM TBA in he cell and 25 mM o so bi ol in he i a ion sy inge.
A de ailed analysis o pH in luence on he complexa ion o bo onic acid wi h diols
was pe o med in [47]. The au ho s sugges ed ha he op imal pH o such in e ac ion is
in he middle be ween he pKa alues o bo onic acid and he co esponding analy e. The
pKa alues o so bi ol and uc ose a e 13.6 and 12.06 espec i ely [45,48]. This gi es he
op imal pH o so bi ol binding 10.9, and o uc ose 10.1. This co esponds o ou da a
(Figu e 4) whe e a pe manen inc ease o he so bi ol binding was obse ed ill he highes
measu ed pH alue o 10.6 while he da a o uc ose demons a e a sa u a ion a his
poin .
The binding p ope ies o TBA we e compa ed wi h PBA which is he mos in es i-
ga ed compound wi h bo onic acid moie y (Table 1). The esul s demons a e e y close
alues o binding cons an s. The ob ained alues o binding cons an s we e alida ed by
“ e e sible i a ion” when TBA was in he i a ion sy inge and uc ose in he cell. A pH
8.0 he alues o binding cons an s 818 ± 89 L/mol and 513 ± 5 L/mol o PBA and TBA
co espondingly we e ob ained.
The ob ained alues o he binding cons an o PBA o uc ose a e e y close o ha
epo ed in [47] by compe i i e luo escence measu emen s using Aliza in Red S: 210
L/mol a pH 7.5 o 560 L/mol a pH 8.5. ITC measu emen s o 3-aminophenylbo onic acid
[37] gi e he alues which a e no d ama ically di e en om ha : 137 L/mol a pH 8.0
and 1330 L/mol a pH 9.0.
Ve y close alues o binding cons an s o TBA and PBA (Table 1) demons a e ha
subs i u ion o he phenyl ing by he hiophene one does no in luence he absolu e alue
o he a ini y o his ecep o : he alue o he a io o binding cons an s o uc ose o
hese compounds a pH 8.0 is 0.98 ± 0.04.
Figu e 4.
pH dependence o he binding cons an o TBA o so bi ol and uc ose. Ti a ion condi ions:
300 µL o 0.5 mM TBA in he cell and 25 mM o so bi ol in he i a ion sy inge.
Table 1.
Binding cons an s and binding ene gies o he in e ac ion o uc ose wi h TBA and
PBA. Measu emen condi ions: 300
µ
L o 1 mM TBA o PBA in he cell, 30 mM o uc ose in he
i a ion sy inge.
pH PBA TBA
Ka (L/mol) −∆G (kJ/mol) Ka (L/mol) −∆G (kJ/mol)
7.4 209 ±4 13.3 ±0.42 212 ±10 13.4 ±0.13
8.0 522 ±17 15.6 ±0.08 533 ±15 15.7 ±0.08
9.2 3090 ±222 20.0 ±0.17 2700 ±400 19.1 ±0.84
The ob ained alues o he binding cons an o PBA o uc ose a e e y close o ha
epo ed in [
47
] by compe i i e luo escence measu emen s using Aliza in Red S: 210 L/mol
a pH 7.5 o 560 L/mol a pH 8.5. ITC measu emen s o 3-aminophenylbo onic acid [
37
]
gi e he alues which a e no d ama ically di e en om ha : 137 L/mol a pH 8.0 and
1330 L/mol a pH 9.0.
Ve y close alues o binding cons an s o TBA and PBA (Table 1) demons a e ha
subs i u ion o he phenyl ing by he hiophene one does no in luence he absolu e alue
o he a ini y o his ecep o : he alue o he a io o binding cons an s o uc ose o hese
compounds a pH 8.0 is 0.98 ±0.04.
The main ea u e o TBA in compa ison wi h o he simila compounds is i s elec o-
chemical ac i i y. Due o his ac i i y, TBA can be elec ochemically polyme ized o ming
highly conduc ing polyme ilms [
38
]. I allows us o conside TBA as a p omising ma e ial
o applica ions in chemical senso s wi h elec ically con olled a ini y o in i ual senso
a ays wi h elec ochemical swi ching o chemosensi i e p ope ies [
49
]. This analy i-
cal p inciple was ealized ea lie in elec ochemical ansis o s based on poly hiophene,
polypy ole, and polyaniline [
49
–
52
]. Howe e , in ha wo k, only an in insic chemosensi-
i e ac i i y o conduc ing polyme s was exploi ed. The use o polyme ized TBA o his
pu pose is he way o make such a no el analy ical de ice based on conduc ing polyme
possessing inco po a ed ecep o g oups. I was he eason o s udy he e ec o he edox
s a e on he a ini y p ope ies. The measu emen s we e pe o med by ITC in he p esence
o K
4
Fe(CN)
6
/K
3
Fe(CN)
6
a di e en concen a ions and concen a ion a ios be ween
0.3 mM and 300 mM. The alue o he edox po en ial o he media was measu ed in
sepa a e expe imen s wi h a gold elec ode ela i e o Ag/AgCl elec ode wi h a sal b idge.
The esul s a e shown in Figu e 5. One can obse e an inc ease in he absolu e alue o
Chemosenso s 2022,10, 251 7 o 10
he binding ene gy o po en ial change be ween 0.13 V and 0.23 V and a dec ease o his
alue o u he po en ial inc ease ill ~0.4 V. The po en ial alue 0.23 V co esponds o he
maximal alue o he binding cons an . Un o una ely, he used me hod o po en ial a ia-
ion did no allow us o s udy highe po en ial alues a which he main elec ochemical
ac i i y o his compound is obse ed [
38
]. The maximal change in he binding cons an
be ween TBA and so bi ol in he s udied po en ial ange was 2.75; o he ea lie s udied
elec ochemical ansis o based on polyaniline and i s in e ac ion wi h ime hylamine his
alue was 2.47 a he much wide po en ial ange [52].
Chemosenso s 2022, 10, x FOR PEER REVIEW 7 o 10
Table 1. Binding cons an s and binding ene gies o he in e ac ion o uc ose wi h TBA and PBA.
Measu emen condi ions: 300 μL o 1 mM TBA o PBA in he cell, 30 mM o uc ose in he i a ion
sy inge.
pH PBA TBA
Ka (L/mol) −ΔG (kJ/mol) Ka (L/mol) −ΔG (kJ/mol)
7.4 209 ± 4 13.3 ± 0.42 212 ± 10 13.4 ± 0.13
8.0 522 ± 17 15.6 ± 0.08 533 ± 15 15.7 ± 0.08
9.2 3090 ± 222 20.0 ± 0.17 2700 ± 400 19.1 ± 0.84
The main ea u e o TBA in compa ison wi h o he simila compounds is i s elec o-
chemical ac i i y. Due o his ac i i y, TBA can be elec ochemically polyme ized o ming
highly conduc ing polyme ilms [38]. I allows us o conside TBA as a p omising ma e ial
o applica ions in chemical senso s wi h elec ically con olled a ini y o in i ual senso
a ays wi h elec ochemical swi ching o chemosensi i e p ope ies [49]. This analy ical
p inciple was ealized ea lie in elec ochemical ansis o s based on poly hiophene,
polypy ole, and polyaniline [49–52]. Howe e , in ha wo k, only an in insic chemosen-
si i e ac i i y o conduc ing polyme s was exploi ed. The use o polyme ized TBA o his
pu pose is he way o make such a no el analy ical de ice based on conduc ing polyme
possessing inco po a ed ecep o g oups. I was he eason o s udy he e ec o he edox
s a e on he a ini y p ope ies. The measu emen s we e pe o med by ITC in he p esence
o K4Fe(CN)6/K3Fe(CN)6 a di e en concen a ions and concen a ion a ios be ween 0.3
mM and 300 mM. The alue o he edox po en ial o he media was measu ed in sepa a e
expe imen s wi h a gold elec ode ela i e o Ag/AgCl elec ode wi h a sal b idge. The
esul s a e shown in Figu e 5. One can obse e an inc ease in he absolu e alue o he
binding ene gy o po en ial change be ween 0.13 V and 0.23 V and a dec ease o his alue
o u he po en ial inc ease ill ~0.4 V. The po en ial alue 0.23 V co esponds o he
maximal alue o he binding cons an . Un o una ely, he used me hod o po en ial a -
ia ion did no allow us o s udy highe po en ial alues a which he main elec ochemical
ac i i y o his compound is obse ed [38]. The maximal change in he binding cons an
be ween TBA and so bi ol in he s udied po en ial ange was 2.75; o he ea lie s udied
elec ochemical ansis o based on polyaniline and i s in e ac ion wi h ime hylamine
his alue was 2.47 a he much wide po en ial ange [52].
Figu e 5. In luence o edox po en ial on he binding cons an o TBA o so bi ol a pH 8.0. Ti a ion
condi ions: 300 μL o 0.5 mM TBA and 0.3–300 mM o mix u es o K4[Fe(CN)6] and K3[Fe(CN)6] a
a ious a ios; 25 mM o so bi ol in he i a ion sy inge. The edox po en ial is indica ed s.
Ag/AgCl(sa ). The dash lines a e d awn o indica e he end o he da a dependence.
Figu e 5.
In luence o edox po en ial on he binding cons an o TBA o so bi ol a pH 8.0. Ti a ion
condi ions: 300
µ
L o 0.5 mM TBA and 0.3–300 mM o mix u es o K
4
[Fe(CN)
6
] and K
3
[Fe(CN)
6
]
a a ious a ios; 25 mM o so bi ol in he i a ion sy inge. The edox po en ial is indica ed s.
Ag/AgCl(sa ). The dash lines a e d awn o indica e he end o he da a dependence.
4. Conclusions
We ha e desc ibed a new a i icial ecep o based on hiophene wi h an inco po a ed
bo onic acid moie y ha p o ides i s chemical sensi i i y o diol-con aining compounds.
The ma e ial demons a es a p onounced a ini y owa d some saccha ides, o example,
so bi ol and uc ose. The maximal alue o he binding cons an is ~8000 M
−1
o so bi ol
a s ongly alkalic pH. In ela ion o applica ions in chemical senso s i means ha in
combina ion wi h a ansduce p o iding a signal/noise a io o ~1000, one can achie e he
limi o de ec ion o ~1
µ
M. To impo an ea u es o his ma e ial belong i s elec ochemical
ac i i y and he o ma ion o conduc ing polyme s. Analy ical p ope ies o chemical
senso s based on his ma e ial in he polyme ic o m will be p esen ed la e ( his wo k is
in p og ess) while in he cu en manusc ip we ha e pe o med an in es iga ion o he
a ini y o his ma e ial in i s monome ic o m–TBA.
We ha e demons a ed ha he a ini y can be elec ochemically con olled, he e o e
his ma e ial can be applied in chemical senso s wi h elec ically swi ched a ini y p o-
iles, like elec ochemical chemo ansis o s [
49
,
50
,
52
]. In his s udy, we modi ied edox
condi ions by in oducing edox-ac i e compounds. Acco ding o ou knowledge, i is
he i s applica ion o his app oach in ITC. Such a combina ion o ITC wi h he con ol
o elec ochemical condi ions o s udied compounds can be use ul in he in es iga ion o
each edox-ac i e analy e o ecep o molecules. In in eg a ed elec ochemical chemo an-
sis o s [
53
] he con ol o he edox s a e o chemosensi i e ma e ial is pe o med by he
applica ion o elec ical po en ial. To make ITC-measu emen s wi h elec ochemical con ol
mo e con enien and o p o ide a wide po en ial ange, a de elopmen o ITC ins u-
men s wi h in eg a ed edox- and e e ence elec odes is equi ed; in many expe imen s he
me allic cell wall o he de ice can ope a e as he edox elec ode.
Chemosenso s 2022,10, 251 8 o 10
The a ini y p ope ies o TBA a e e y simila o ha o o he known ma e ials which
do no allow applica ions in chemical senso s wi h con ollable a ini y ( o example, PBA),
he e o e e en wi hou using elec ochemical con ol he applica ion ange o TBA is no
smalle han ha o PBA. One can expec ha an exploi ing o ideas ha we e applied
success ully o o he compounds wi h bo onic acid moie ies o TBA imp o emen is
he way o u he inc ease i s binding cons an and selec i i y o desi ed analy es. Fo
example, one can make a design and chemical syn hesis o co esponding polyme izable
dime s wi h a equi ed posi ion o bo onic acids o e ec i e analy e binding [54].
Au ho Con ibu ions:
Concep ualiza ion, V.M.M.; expe imen al wo k, Y.E.; w i ing—o iginal d a
p epa a ion, Y.E.; w i ing— e iew and edi ing, V.M.M., Y.E.; isualiza ion, Y.E.; supe ision, V.M.M.
All au ho s ha e ead and ag eed o he published e sion o he manusc ip .
Funding:
We acknowledge he suppo by BMBF (p ojec Ag iNose wi hin WIR!-p og am) and
EU-G an 101060712 FishEUT us .
Ins i u ional Re iew Boa d S a emen : No applicable.
In o med Consen S a emen : No applicable.
Da a A ailabili y S a emen : The da a a e a ailable om he au ho s by eques .
Acknowledgmen s:
The au ho s a e g a e ul o ou s uden s B. Sc. F. Togh aie, B. Pe kowski and
V. Sa a anakuma o pa icipa ing in he measu emen s o he in e ac ion o TBA and PBA wi h
di e en analy es and o he membe s o he Nanobio echnology Depa men o suppo and ui ul
discussions. Financial suppo o he BMBF p ojec Ag iNose wi hin WIR!-p og am and EU-G an
101060712 FishEUT us a e acknowledged. The wo k is de o ed o P o esso O o S. Wol beis. He has
done c ucial con ibu ions no only o he de elopmen o luo escen senso s bu is also he pionee
in applica ions o polyme izable de i a i es o phenylbo onic acid in chemical senso s [22].
Con lic s o In e es : The au ho s decla e no con lic o in e es .
Re e ences
1.
Gu yano , I.; Fio ucci, S.; Tenniko a, T. Recep o -ligand in e ac ions: Ad anced biomedical applica ions. Ma e . Sci. Eng. C
2016
,
68, 890–903. [C ossRe ] [PubMed]
2.
Gilson, M.K.; Gi en, J.A.; Head, M.S. A new class o models o compu ing ecep o -ligand binding a ini ies. Chem. Biol.
1997
,
4, 87–92. [C ossRe ]
3.
Mi sky, V.M. Quan i a i e cha ac e iza ion o a ini y p ope ies o immobilized ecep o s. In A i icial Recep o s o Chemical
Senso s; Mi sky, V.M., Ya smimi sky, K.A., Eds.; Wiley-VCH Ve lag GmbH & Co., KGaA: Weinheim, Ge many, 2011; pp. 1–15.
4.
Mi sky, V.M. Quan i a i e a ini y da a on selec ed a i icial ecep o s. In A i icial Recep o s o Chemical Senso s; Mi sky, V.M.,
Ya smimi sky, K.A., Eds.; Wiley-VCH Ve lag GmbH & Co., KGaA: Weinheim, Ge many, 2011; pp. 439–459.
5.
Schneide , H.; Ya smimi sky, K.A. Selec i i y o chemical ecep o s. In A i icial Recep o s o Chemical Senso s; Mi sky, V.M.,
Ya smimi sky, K.A., Eds.; Wiley-VCH Ve lag GmbH & Co., KGaA: Weinheim, Ge many, 2011; pp. 17–65.
6.
Mi sky, V.M. Combina o ial de elopmen o chemosensi i e conduc ing polyme s. In Combina o ial Me hods o Chemical and
Biological Senso s; Po y ailo, R.A., Mi sky, V.M., Eds.; Sp inge : Be lin/Heidelbe g, Ge many, 2009; pp. 315–330.
7.
Liu, L.; Guo, Q.X. The d i ing o ces in he inclusion complexa ion o cyclodex ins. J. Incl. Phenom. Mac ocycl. Chem.
2002
,
42, 1–14. [C ossRe ]
8.
Maje ski, K.M.; K agol, G. Design, syn hesis and ca ion-binding p ope ies o no el adaman ine and 2-oxaadaman ane-con aining
c own e he s. Te ahed on 2001,57, 449–457. [C ossRe ]
9.
Ko ochkina, M.; Fon anella, M.; Casna i, A.; A duini, A.; Sansone, F.; Unga o, R.; La ypo , S.; Ka ae , V.; Al onso , V. Syn hesis
and spec oscopic s udies o isos e iol calix[4]a ene and calix[6]a ene conjuga es. Te ahed on 2005,61, 5457–5463. [C ossRe ]
10.
Hi sch, T.; Ke enbe ge , H.; Wol beis, O.S.; Mi sky, V.M. A simple s a egy o p epa a ion o senso a ays: Nanos uc u ed
monolaye s as ecogni ion elemen s. Chem. Commun. 2003, 432–433. [C ossRe ]
11.
Bossi, A.; Bonini, F.; Tu ne , A.; Pile sky, S. Molecula ly imp in ed polyme s o he ecogni ion o p o eins he s a e o a . Biosens.
Bioelec on. 2007,22, 1131–1137. [C ossRe ]
12.
James, T.D. Bo onic acid-based ecep o s and senso s o saccha ides. In Bo onic Acids: P epa a ion and Applica ions in O ganic
Syn hesis and Medicine; Dennis, G.H., Ed.; Wiley-VCH Ve lag GmbH & Co., KGaA: Weinheim, Ge many, 2005; pp. 441–479.
13.
Hall, D.G. S uc u e, p ope ies, and p epa a ion o bo onic acids de i a i es. In Bo onic Acids: P epa a ion and Applica ions in
O ganic Syn hesis and Medicine; Dennis, G.H., Ed.; Wiley-VCH Ve lag GmbH & Co., KGaA: Weinheim, Ge many, 2005; pp. 1–99.
14.
Yang, X.; Cheng, Z.; Jin, S.; Wang, B. Bo onic acid-based ecep o s and chemosenso s. In A i icial Recep o s o Chemical Senso s;
Mi sky, V.M., Ya smimi sky, K.A., Eds.; Wiley-VCH Ve lag GmbH & Co., KGaA: Weinheim, Ge many, 2011; pp. 169–189.
Chemosenso s 2022,10, 251 9 o 10
15.
Sienkiewicz, P.A.; Robe s, D.C. pH dependence o bo onic acid-diol a ini y in aqueous solu ion. J. Ino g. Nucl. Chem.
1980
,
42, 1559–1575. [C ossRe ]
16.
Babcock, L.; Pize , R. Dynamics o bo on acid complexa ion eac ions. Fo ma ion o 1:1 bo on acid-ligand complexes. Ino g. Chem.
1980,19, 56–61. [C ossRe ]
17.
Made , H.S.; Wol beis, O.S. Bo onic acid based p obes o mic ode e nina ion o saccha ides and glycosyla ed biomolecules: A
e iew. Mic ochim. Ac a 2008,162, 1–34. [C ossRe ]
18.
Pappin, B.; Kie el, M.J.; Hous on, T.A. Bo on-Ca bohyd a e in e ac ions. In Ca bohyd a es—Comp ehensi e S udies on Glycobiology
and Glyco echnology; Chang, C.-F., Ed.; InTech: Tokyo, Japan, 2012; pp. 37–54.
19.
Nagasaki, T.; Shinmo i, H.; Shinkai, S. A emp s o change he colo o dye molecules by saccha ides. Te ahed on Le .
1994
,
35, 2201–2204. [C ossRe ]
20.
Fang, H.; Kau , G.; Wang, B. P og ess in bo onic acid-based luo escen glucose senso s. J. Fluo esc.
2004
,14, 481–489. [C ossRe ]
[PubMed]
21.
¸Senel, M.; De ise ic, M.; Çe ik, E. A no el ampe ome ic glucose biosenso based on ecogni ion o glucose oxidase on
hiophene-3-bo onic acid polyme laye . Cu . Appl. Phys. 2013,13, 1199–1204. [C ossRe ]
22.
Shoji, E.; F eund, M.S. Po en iome ic saccha ide de ec ion based on he pKa changes o poly(aniline bo onic acid). J. Am. Chem.
Soc. 2002,124, 12486–12493. [C ossRe ]
23.
De ise ic, M.; Senel, M.; Ce ik, E. No el impedime ic dopamine biosenso based on bo onic acid unc ional poly hiophene
modi ied elec odes. Ma e . Sci. Eng. C 2017,72, 641–649. [C ossRe ] [PubMed]
24.
To un, Ö.; Dudak, F.C.; Bas, D. Tame , U.; Boyaci, I.H. The modynamic analysis o he in e ac ion be ween 3-aminophenylbo onic
acid and monosaccha ides o de elopmen o biosenso . Sens. Ac ua o s B Chem. 2009,140, 597–602. [C ossRe ]
25.
Yoon, J.; Cza nik, A.W. Fluo escen chemosenso s o ca bohyd a es. A means o chemically communica ing he binding o polyols
in wa e based on chela ion-enhanced quenching. J. Am. Chem. Soc. 1992,114, 5874–5875. [C ossRe ]
26.
Zang, W.; Fan, H.; Gao, X.; Ka na i, V.V.R.; Ni, W.; Hooks, W.B.; Ca son, J.; Wes on, B. Wang, B. The i s dibo onic acid senso
speci ic o hep acellula ca cinoma cells exp essing sialyl Lewis X. Chem. Biol. 2004,11, 439–448.
27.
James, T.D.; Sandanayake, K.R.A.S.; Iguchi, R.; Shinkai, S. No el saccha ide-pho oinduced elec on ans e senso s based on he
in e ac ion o bo onic acid and amine. J. Am. Chem. Soc. 1995,117, 8982–8987. [C ossRe ]
28.
Heo, Y.J.; Shiba a, H.; Oki su, T.; Kawanishi, T.; Takeuchi, S. Long- e m
in i o
glucose moni o ing using luo escen hyd ogel
ibe s. P oc. Na l. Acad. Sci. USA 2011,108, 13399–133403. [C ossRe ]
29.
Vancoillie, G.; Hoogenboom, R. Syn hesis and polyme iza ion o bo onic acid con aining monome s. Polym. Chem.
2016
,7, 5484–5495.
[C ossRe ]
30. Camb e, J.N.; Sume lin, B.S. Biomedical applica ions o bo onic acid polyme s. Polyme 2011,52, 4631–4643. [C ossRe ]
31.
B ooks, W.; Sume lin, B.S. Syn hesis and applica ions o bo onic acid-con aining polyme s: F om ma e ials o medicine. Chem.
Re . 2016,116, 1375–1397. [C ossRe ] [PubMed]
32.
P ingsheim, E.; Te pe sehnig, E.; Pile sky, S.A.; Wol beis, O.S. A polyaniline wi h nea -in a ed op ical esponse o saccha ides.
Ad . Ma e . 1999,11, 865–868. [C ossRe ]
33.
Wang, G.; He, X.; Wang, L.; Gu, A.; Huang, Z.; Fang, B.; Geng, B.; Zhang, X. Non-enyzma ic elec ochemical sensing o glucose.
Mic ochim. Ac a 2013,18, 161–186. [C ossRe ]
34.
Çi ci, H.; Tame , U.; Teke , M.¸S.; Pekmey, N.Ö. An enzyme ee po en iome ic de ec ion o glucose based on conduc ing polyme
poly (3-aminophenylbo onic acid-co-3-co yl hiophene). Elec . Ac a 2013,90, 358–365. [C ossRe ]
35.
Ay aç, S.; Ku alay, F.; Boyaci, H.; Unale oglu, C. A no el polypy ole-phenylbo onic acid based elec ochemical saccha ide senso .
Sens. Ac ua o s B Chem. 2011,160, 405–411. [C ossRe ]
36.
Shishkano a, T.; Fi l, R.; K al, V.; Ba ek, J. Nanopa icles unc ionalized wi h phenylbo onic acid o he po en iome ic de ec ion
o saccha ides. J. Elec oanal. Chem. 2013,761, 106–111. [C ossRe ]
37.
Deo e, B.A.; Hachey, S.; F eund, M.S. Elec oac i i y o elec ochemically syn hesized poly(aniline bo onic acid) as a unc ion o
pH: Role o sel -doping. Chem. Ma e . 2004,16, 1427–1432. [C ossRe ]
38.
E emenko, Y.; Mi sky, V.M. Poly-3- hienylbo onic acid: A chemosensi i e de i a i e o poly hiophene. J. Solid S a e Elec ochem.
2020,24, 3105–3111. [C ossRe ]
39.
Falcone , R.J.; Penko a, A.; Jelesa o , I.; Collins, B.M. Su ey o he yea 2008: Applica ions o iso he mal i a ion calo ime y.
J. Mo. Recogni . 2010,33, 395–413. [C ossRe ] [PubMed]
40.
F eye , M.W.; Lewis, E.A. Iso he mal i a ion calo ime y: Expe imen al design, da a analysis, and p obing mac omolecule/ligand
binding and kine ic in e ac ions. Me hods Cell Biol. 2008,84, 79–113.
41.
Ni, N.; Laughlin, S.; Wang, Z.; Yheng, Z.F.; Wang, B. P obing he gene al ime scale ques ion o bo onic acid binding wi h suga s
in aqueous solu ion a physiological pH. Bioo ganic Med. Chem. 2012,20, 2957–2961. [C ossRe ] [PubMed]
42. Tu nbull, W.B.; Da anas, A.H. On he alue o c: Can low a ini y sys ems be s udied by iso he mal i a ion calo ime y? J. Am.
Chem. Soc. 2003,125, 14859–14866. [C ossRe ] [PubMed]
43.
Kan onen, S.A.; Hen iksen, N.M.; Gilson, M.K. E alua ion and minimiza ion o unce ain y in ITC binding measu emen s: Hea
e o , concen a ion e o , sa u a ion, and s oichiome y. Biochim. Biophys. Ac a 2017,1861, 485–498. [C ossRe ] [PubMed]
44.
Lodge, T.P.; Mu hukuma , M. Physical chemis y o polyme s: En opy, in e ac ions, and dynamics. J. Phys. Chem.
1996
,
100, 13275–13292. [C ossRe ]
