A Copolymerized Dodecacarborane Anion as Covalently Attached Cation Exchanger in Ion-Selective Sensors

Article abstract of DOI:10.1021/ac034447c

The traditional cation exchangers used in ion-selective electrodes and optodes are tetraphenylborate derivatives, which are generally adequate for most analytical applications but may in some cases suffer from decomposition by acid hydrolysis, oxidants, and light. Recently, halogenated dodecacarboranes were found to be improved cation exchangers in terms of lipophilicity and chemical stability. This forms the basis for the convenient covalent attachment of the cation exchanger to the polymeric backbone of the sensing material. This is a challenge that has not satisfactorily been solved and which is especially important in view of developing ultraminiaturized sensing arrays. Here, a C-derivative of the closo-dodecacarborane anion (CB₁₁H ₁₂^-) with a polymerizable group was synthesized as a chemically stable cation exchanger. This new derivative was copolymerized with methyl methacrylate and decyl methacrylate (MMA-DMA) to fabricate a plasticizer-free polymer with cation-exchange properties. This polymer could be conveniently blended with traditional plasticized poly(vinyl chloride) or with noncrosslinked methacrylic polymers to give solvent cast films that appear to be clear and homogeneous and that could be doped with ionophores. Optode leaching experiments supported the covalent grafting of the carborane anions. Ion-selective membranes and optode thin films were evaluated in terms of response function, response time, and selectivity. In all cases, the new material exhibited behavior similar to free tetraphenylborate derivative-based membranes. As a result of these studies, an all-polymeric plasticizer-free calcium-selective membrane was fabricated on the basis of the covalently attached carborane, a recently introduced grafted calcium ionophore, and an MMA-DMA polymer matrix. The resulting ion-selective electrodes showed Nernstian response slopes and rapid response times, demonstrating that covalent grafting of all sensing components is a feasible approach to the development of ion sensors.

Full text of DOI:10.1021/ac034447c

Anal. Chem. 2003, 75, 6002-6010
A Co p o lym e rize d Do d e c a c a rb o ra n e An io n a s
Co va le n t ly At t a c h e d Ca t io n Ex c h a n g e r in
Io n -S e le c t ive S e n s o rs
Yu Qin a nd Eric Ba kke r*
Department of Chemistry, Auburn University, Auburn, Alabama 36849
in particular, have found widespread use in clinical laboratories3
The traditional cation exchangers used in ion-selective
electrodes and optodes are tetraphenylborate derivatives,
which are generally adequate for most analytical applica-
tions but may in some cases suffer from decomposition
by acid hydrolysis, oxidants, and light. Recently, haloge-
nated dodecacarboranes were found to be improved
cation exchangers in terms of lipophilicity and chemical
stability. This forms the basis for the convenient covalent
attachment of the cation exchanger to the polymeric
backbone of the sensing material. This is a challenge that
has not satisfactorily been solved and which is especially
important in view of developing ultraminiaturized sensing
and are being explored for numerous other applications. Tradi-
tionally, these sensors are based on hydrophobic plasticized
polymeric membranes or films that are doped with one or more
ionophores in addition to a lipophilic ion exchanger. Each of these
components plays an important role in the sensor response.2,4 The
hydrophobicity of the polymer ensures that spontaneous, non-
specific electrolyte extraction from the sample is suppressed. At
the same time, the membrane matrix must act as a solvent of low
viscosity for all active sensing components in the film. Each
ionophore acts as a lipophilic complexing agent, and the ion
exchanger is responsible for extracting the analyte ions from the
sample to the membrane to satisfy electroneutrality. In many ways,
the basic composition and function of these ISEs still mimics that
of early liquid membrane electrodes, in which all components were
simply dissolved in an organic solvent. However, modern ion
sensors are moving toward drastic miniaturization, and these
sensors are often in contact with relatively lipophilic sample
environments, such as undiluted whole blood. Microelectrodes
have been used for a long time to probe intracellular ion
compositions and are also used for chemical profiling and chemical
arrays. Here, a C-derivative of the closo-dodecacarborane
-
anion (CB1 1
H
1 2 ) with a polymerizable group was syn-
thesized as a chemically stable cation exchanger. This new
derivative was copolymerized with methyl methacrylate
and decyl methacrylate (MMA-DMA) to fabricate a plas-
ticizer-free polymer with cation-exchange properties. This
polymer could be conveniently blended with traditional
plasticized poly(vinyl chloride) or with noncrosslinked
methacrylic polymers to give solvent cast films that appear
to be clear and homogeneous and that could be doped
with ionophores. Optode leaching experiments supported
the covalent grafting of the carborane anions. Ion-selective
membranes and optode thin films were evaluated in terms
of response function, response time, and selectivity. In
all cases, the new material exhibited behavior similar to
free tetraphenylborate derivative-based membranes. As
a result of these studies, an all-polymeric plasticizer-free
calcium-selective membrane was fabricated on the basis
of the covalently attached carborane, a recently introduced
grafted calcium ionophore, and an MMA-DMA polymer
matrix. The resulting ion-selective electrodes showed
Nernstian response slopes and rapid response times,
demonstrating that covalent grafting of all sensing com-
ponents is a feasible approach to the development of ion
sensors.
5
microscopy. Microsphere optodes with varying compositions are
today developed in view of the measurement of biological and
6
clinical samples. Optical sensing spheres that are a few hundred
nanometers in diameter are currently explored for intracellular
ion measurements.7 These important applications expect that
cross-contamination of sensors and leaching of active components
from the sensor membrane are reduced or even eliminated.
Earlier work has focused on improving the lipophilicity of all
sensing components for an improved lifetime of these sensors.
There is likely a practical limit to synthesizing ionophores and
plasticizers with longer alkyl chains to make them more lipo-
philic,8 since they still must remain soluble in the polymeric
membrane phase. It appears that an attractive solution to the
problem of insufficient retention is the covalent attachment of all
active sensing components onto the polymeric backbone. Over
(
(
3) Collison, M. E.; Meyerhoff, M. E. Anal. Chem. 1 9 9 0 , 62, A425.
4) Morf, W. E. The Principles of Ion-Selective Electrodes and of Membrane
Transport; Elsevier: New York, 1981.
Highly selective chemical sensors based on molecular recogni-
tion and extraction principles are a very important, well-understood
class of sensors.1,2 Ion-selective electrodes (ISEs) and optodes,
(5) Horrocks, B. R.; Mirkin, M. V.; Pierce, D. T.; Bard, A. J.; Nagy, G.; Toth, K.
Anal. Chem. 1 9 9 3 , 65, 1213.
(
(
6) Tsagkatakis, I.; Peper, S.; Bakker, E. Anal. Chem. 2 0 0 1 , 73, 6083.
7) Brasuel, M.; Kopelman, R.; Miller, T. J.; Tjalkens, R.; Philbert, M. A. Anal.
Chem. 2 0 0 1 , 73, 2221.
(
(
1) B u¨ hlmann, P.; Pretsch, E.; Bakker, E. Chem. Rev. 1 9 9 8 , 98, 1593.
2) Bakker, E.; B u¨ hlmann, P.; Pretsch, E. Chem. Rev. 1 9 9 7 , 97, 3083.
(8) Gehrig, P.; Rusterholz, B.; Simon, W. Anal. Chim. Acta 1 9 9 0 , 233, 295.
6002 Analytical Chemistry, Vol. 75, No. 21, November 1, 2003
10.1021/ac034447c CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/09/2003

the years, plasticizer-free ion-selective membranes based on
different materials have been evaluated. Suitable matrixes
include polyurethanes,9 polysiloxanes,10,11 silicone rubber,12,13
polythiophenes,14 polyacrylates,15 epoxyacrylates,16 sol-gels,17,18
1
9-22
methacrylic-acrylic copolymers,
mers.
and methacrylate copoly-
2
3,24
Among them, the methacrylic-acrylic copolymers and
methacrylate copolymers are synthesized via free radical-initiated
mechanisms, which are attractive because various monomer
combinations and the numerous polymerization methods are
available to create polymers with different physical and mechanical
properties. Of the plasticizer-free copolymers reported, a methyl
methacrylate and decyl methacrylate copolymer (MMA-DMA)
has been studied by our group as a promising matrix, with
functional ISEs23 and optodes25 reported for Li , Na , K , Ca2+,
+
+
+
and Mg2+.
Early work toward covalent attachment of ionophores made
use of functionalized poly(vinyl chloride),26,27 which could not be
used without plasticizer. In later work, Na -, K -, and Pb2+-selective
ionophores were covalently grafted to a polysiloxane matrix and
applied to the fabrication of CHEMFET sensors.10,28 Another
notable direction in ionophore grafting by the sol-gel technique
has been introduced by Kimura, with demonstrated applications
to serum measurements.17,18 Very recently, neutral ionophores
were covalently attached by Pretsch and co-workers to a poly-
urethane membrane matrix in view of reducing ion fluxes across
the membrane.29 In other recent reports, two hydrophilic crown
ether-type potassium-selective ionophores, 4′-acryloylamidobenzo-
+
+
1
(
5-crown-5 (AAB15C5) and 4′-acryloylamidobenzo-18-crown-6
AAB18C6),20 a sodium-selective ionophore, 4-tert-butylcalix[4]-
arene tetraacetic acid tetraethyl ester,21 as well as a new
calcium ionophore N,N-dicyclohexyl-N′-phenyl-N′-3-(2-propenoyl)-
oxyphenyl-3-oxapentanediamide (AU-1; see Figure 1)24 have been
copolymerized with other acrylate monomers by a simple one-
step solution polymerization method. The simplicity of this
Fig u re 1 . Structures of Na ionophore (X), chromoionophore ETH
294, calcium ionophore AU-1, nitrite ionophore (I), the tetraphenyl-
borate derivative NaTFPB, and the closo-dodecacarborane anion.
5
procedure constitutes an important advantage over most other
methods described above. These polymers containing grafted
ionophores showed comparable selectivity and improved lifetime
when compared to ISEs with free, unbound ionophore present.
Numerous promising approaches are therefore available to obtain
plasticizer-free polymers containing covalently attached iono-
phores.
Unlike the grafting of ionophores, the covalent attachment of
ion exchangers has been much less explored. Reinhoudt reported
on the covalent attachment of the tetraphenylborate anion,
TPB-,10,28 and Kimura also successfully attached a cation ex-
changer (TPB-)17 as well as an anion exchanger (tetradecyldi-
methyl(3-trimethoxysilylpropyl)ammonium chloride) into a sol-
gel matrix.18 Unfortunately, it is known that the unsubstituted
(
9) Yun, S. Y.; Hong, Y. K.; Oh, B. K.; Cha, G. S.; Nam, H.; Lee, S. B.; Jin, J.-I.
Anal. Chem. 1 9 9 7 , 69, 868.
(
10) Reinhoudt, D. N.; Engbersen, J. F. J.; Brzozka, Z. Anal. Chem. 1 9 9 4 , 66,
618.
3
(
(
11) Hogg, G.; Lutze, O.; Cammann, K. Anal. Chim. Acta 1 9 9 6 , 335, 103.
12) Poplawski, M. E.; Brown, R. B.; Rho, K. L.; Yun, S. Y.; Lee, H. J.; Cha, G. S.;
Paeng, K.-J. Anal. Chim. Acta 1 9 9 7 , 355, 249.
(
13) Yoon, I. J.; Lee, D. K.; Nam, H.; Cha, G. S.; Strong, T. D.; Brown, R. B. J.
Electroanal. Chem. 1 9 9 9 , 464, 135.
(
(
(
(
14) Bobacka, J.; Ivaska, A.; Lewenstam, A. Anal. Chim. Acta 1 9 9 9 , 385, 195.
15) Peper, S.; Tsagkatakis, I.; Bakker, E. Anal. Chim. Acta 2 0 0 1 , 442, 25.
16) Dimitrakopoulos, T.; Farrell, J. R.; Iles, P. J. Electroanalysis 1 9 9 6 , 8, 391.
17) Kimura, K.; Sunagawa, T.; Yajima, S.; Miyake, S.; Yokoyama, M. Anal. Chem.
1
9 9 8 , 70, 4309.
18) Kimura, K.; Yajima, S.; Takase, H.; Yokoyama, M.; Sakurai, Y. Anal. Chem.
0 0 1 , 73, 1605.
(
2
(
(
(
19) Heng, L. Y.; Hall, E. A. H. Anal. Chem. 2 0 0 0 , 72, 42.
20) Heng, L. Y.; Hall, E. A. H. Electroanalysis 2 0 0 0 , 12, 178.
21) Malinowska, E.; Gawart, L.; Parzuchowski, P.; Rokicki, G.; Brzozka, Z. Anal.
Chim. Acta 2 0 0 0 , 421, 93.
tetraphenylborate is highly susceptible to decomposition by acid
hydrolysis, oxidants, and light.3
0-32
It was also reported that parts-
(
(
(
(
22) Mohr, G. J.; Tirelli, N.; Spichiger-Keller, U. E. Anal. Chem. 1 9 9 9 , 71, 1534.
23) Qin, Y.; Peper, S.; Bakker, E. Electroanalysis 2 0 0 2 , 13, 1375.
24) Qin, Y.; Peper, S.; Radu, A.; Bakker, E. Anal. Chem. 2 0 0 3 , 75, 3038.
25) Peper, S.; Ceresa, A.; Qin, Y.; Bakker, E. Anal. Chim. Acta 2 0 0 3 , 500, in
press.
per-billion levels of mercury ions in aqueous solution can cause
rapid decomposition of sodium tetraphenylborate and potassium
tetrakis(4-chlorophenyl) borate in plasticized PVC membranes.33
(
(
26) Daunert, S.; Bachas, L. G. Anal. Chem. 1 9 9 0 , 62, 1428.
27) Rosatzin, T.; Holy, P.; Seiler, K.; Rusterholz, B.; Simon, W. Anal. Chem.
(30) Meisters, M.; Vandeberg, J. T.; Cassaretto, F. P.; Posvic, H.; Moore, C. E.
Anal. Chim. Acta 1 9 7 0 , 49, 481.
1
9 9 2 , 64, 2029.
(31) Nishida, H.; Takada, N.; Yoshimura, M. Bull. Chem. Soc. Jpn. 1 9 8 4 , 57,
2600.
(32) Rosatzin, T.; Bakker, E.; Suzuki, K.; Simon, W. Anal. Chim. Acta 1 9 9 3 ,
280, 197.
(
(
28) Lugtenberg, R. J. W.; Egberink, R. J. M.; Berg, A. v. d.; Engbersen, J. F. J.;
Reinhoudt, D. N. J. Electroanal. Chem. 1 9 9 8 , 452, 69.
29) P u¨ ntener, M.; Fibbioli, M.; Bakker, E.; Pretsch, E. Electroanalysis 2 0 0 2 ,
1
4, 1329.
(33) Murkovic, I.; Wolfbeis, O. S. Sens. Actuators, B 1 9 9 7 , 38-39, 246.
Analytical Chemistry, Vol. 75, No. 21, November 1, 2003 6003

Therefore, the reported covalent attachments of a simple tetra-
phenylborate may likely not solve these inherent problems.
Although the highly substituted derivatives, such as sodium
tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB) have a
much improved stability, the borates can still be protonated under
acidic conditions and subsequently hydrolyze.32 A decrease in
selectivity and response slopes of ion-selective membranes after
prolonged exposure to a continuous water flow was observed,
which was explained on the basis of the change of ionophore and
ion exchanger (NaTFPB) ratio caused by slow degradation of the
borate anions.10 In addition, the preparation of highly substituted
borate anions, especially asymmetric analogues, is quite difficult
and synthetically complex.34,35 A further modification of these
compounds, such as the preparation of polymerizable derivatives,
has never been reported. It was recently shown that carboranes
obtained from Fisher Scientific (Pittsburgh, PA) and dried before
using.
The monomers methyl methacrylate, 99.5% and n-decyl meth-
acrylate, 99% were obtained from Polysciences, Inc. (Warrington,
PA). The polymerization initiator 2,2′-azobisisobutyronitrile, 98%,
(AIBN) was obtained from Aldrich. Benzene, dichloromethane,
and 1,4-dioxane were reagent grade and obtained from Fisher.
Benzene and dichloromethane were purified by fractional distil-
lation after refluxing with calcium hydride for 4 h. Inhibitors were
removed from the monomers by washing with a caustic solution
containing 5% (w/ v) NaOH and 20% NaCl in a 1:5 ratio (monomer/
caustic solution) and water. The organic phase was separated and
dried with anhydrous Na SO . This purification process has
2
4
previously been reported.23 AIBN was recrystallized from warm
methanol prior to use. 4-tert-Butylcalix[4]arene tetraacetic acid
tetraethyl ester (Na ionophore X), 9-(diethylamino)-5-octadecan-
oylimino-5H-benzo[a]phenoxazine (chromoionophore I, ETH 5294),
sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB),
cyanoaqua-cobyrinic acid heptakis(2-phenylethyl ester) (nitrite
ionophore I), o-nitrophenyloctyl ether (NPOE), bis(2-ethylhexyl)-
sebacate (DOS), high molecular weight poly(vinyl chloride),
tetrahydrofuran (THF), and all salts were purchased in Selecto-
phore or puriss quality from Fluka (Milwaukee, WI). Tris-
can be used as alternative cation exchangers in ion-selective
sensors.3
6-38
Carboranes are a relatively new class of weakly
coordinating anions based on an extremely stable boron cluster
framework (CB11
12-), as shown in Figure 1. Such carborane
H
anions are quite inert chemically and electrochemically and exhibit
no absorbance in the UV-vis range. These compounds have weak
coordination and ion-pair formation properties, which are attractive
for ion-sensing applications. Furthermore, both the boron vertexes
and carbon vertex can be quite easily modified chemically.39,40
Unfortunately, the commercially available cesium carborane
(
hydroxymethyl)aminomethane (TRIS) was of ACS grade from
Aldrich. Chloride salts of sodium, potassium, calcium, and
magnesium were of puriss quality from Fluka. Aqueous solutions
were prepared by dissolving the appropriate salts in Nanopure
purified water (18 MΩ cm).
(
CsCB11H12) is water-soluble, and its poor lipophilicity limits its
application as ion exchanger. In our laboratory, therefore, a
number of more lipophilic B-halogenated carborane anions were
recently synthesized, and many showed nearly identical ion-
exchange and improved retention properties when compared to
the best tetraphenylborate available, tetrakis[3,5-(trifluoromethyl)]-
phenyl borate (TFPB ).36,37 In this paper, we report on a new
polymerizable carborane derivative that is covalently attached onto
a hydrophobic polymer matrix for use in ion-selective electrodes
and optodes. This work also reports on the first plasticizer-free
ion-selective membrane selective for divalent ions with both
ionophore and ion exchanger covalently attached to the polymer,
thereby forming an all-polymeric sensing matrix with no leachable
components.
Syntheses: Trimethylammonium 2-Carborane Ethyl Acryl-
ate (TMCA). Step One: I(CH
2
)
2
OTBS (1). To a solution of
2
2
1
-iodoethanol (3 g, 17 mmol) and imidazole (1.74 g, 25 mmol) in
-
0 mL of anhydrous dichloromethane was added TBSCl (2.82 g,
8.7 mmol). The mixture was stirred at room temperature (r.t.)
overnight (12 h). The reaction mixture was washed with water (2
10 mL) and brine (10 mL) and dried over Na SO . Removal of
OTBS (1 ) (5.6 g, 98%
×
2
4
the solvent afforded pure product I(CH
yield, MW: 286.02).
2 2
)
Step Two: [Me
lithium (5.5 mmol) was added to a solution of [Me
12] (0.2 g, 1 mmol) in 15 mL of anhydrous THF at 0 °C
3
NH][TBSO(CH
2
)
2
-CB11
H
11
]
(2). n-Butyl-
3
NH][closo-
CB11
H
EXPERIMENTAL SECTION
under N . The mixture was brought to r.t. and stirred for 1 h.
2
Reagents. Trimethylammonium chloride, butyllithium, 2-iodo-
ethanol, butyldimethylsilyl chloride (TBSCl), imidazole, acryloyl
chloride, and triethylamine were of the highest grade from Aldrich
Compound 1 (0.372 g, 1.3 mmol) in 3 mL of THF was added
dropwise in a period of 5 min. After the reaction was stirred at
r.t. for 15 h, the solvent was removed. Me NHCl (6 mmol) in 10
3
(
Milwaukee, WI). Cesium carborane was purchased from Strem
Chemicals (Newburyport, MA). N,N-Dicyclohexyl-N′-phenyl-N′-
-(2-propenoyl)oxyphenyl-3-oxapentanediamide (AU-1) was syn-
thesized as reported.24 All solvents used for syntheses were
mL of water was added to the residue. A pale yellow solid was
formed. Filtration gave mainly the desired product. Further
purification was done by column chromatography (CH Cl / CH -
3
2
2
3
CN ) 4:1) and afforded the white solid [Me NH][TBSO(CH ) -
3
2
2
13
CB11
H
11] (2 ) (0.25 g, 50% yield, MW: 361.26). 1H NMR,
C
(
(
34) Bahr, S. R.; Boudjouk, P. J. Org. Chem. 1 9 9 2 , 57, 5545.
35) Fujiki, K.; Kashiwagi, M.; Miyamoto, H.; Sonoda, A. J. Fluorine Chem. 1 9 9 2 ,
NMR: δ
H), 2.60-0.60 (m, 11H), 0.91 (s, 9H), 0.15 (s, 6H); δ
CDCl ) 68.8, 58.3, 54.8, 51.7, 26.3, 18.6, -5.5.
Step Three: [Me NH][HO(CH 11] (3). Compound 2
0.15 g, 0.40 mmol) was dissolved in 5 mL of THF, and 5 mL of
H
(250 MHz; CDCl
3
) 4.28 (m, 2 H), 3.77 (m, 2H), 3.44 (s,
9
C
(62.9 MHz;
5
7, 307.
(
(
(
36) Peper, S.; Qin, Y.; Almond, P.; McKee, M.; Telting-Diaz, M.; Albrecht-Schmitt,
T.; Bakker, E. Anal. Chem. 2 0 0 3 , 75, 2131.
37) Peper, S.; Telting-Diaz, M.; Almond, P.; Albrecht-Schmitt, T.; Bakker, E.
Anal. Chem. 2 0 0 2 , 74, 1327.
3
3
2 2
) -CB11H
(
38) Krondak, M.; Volf, R.; Kral, V. Collect. Czech. Chem. Commun. 2 0 0 1 , 66,
1 N HCl was added. The reaction solution was stirred at r.t. for 4
h. The solvent was removed and a white solid precipitated from
1
659.
(
(
39) Reed, C. Acc. Chem. Res. 1 9 9 8 , 31, 133.
40) Jelinek, T.; Baldwin, P.; Scheidt, W. R.; Reed, C. A. Inorg. Chem. 1 9 9 3 , 32,
the aqueous solution. Filtration gave pure product 3 (0.10 g, 90%
yield, MW: 194.33). H NMR, 13C NMR: δ
1
(250 MHz; CDCl
)
1
982.
H
3
6004 Analytical Chemistry, Vol. 75, No. 21, November 1, 2003

4
.22 (br, 1 H), 4.17 (m, 2H), 3.73 (m, 2H), 3.44 (s, 9H), 2.62-0.58
m, 11H); δ (62.9 MHz; CDCl ) 68.5, 56.5, 54.4, 51.2.
Step Four: [Me NH][CH CHCOO(CH 11] (TMCA)
4). The above solid was dissolved in 10 mL of THF at 0 °C. Et
0.66 mmol) was added. To this solution, acryloyl chloride (0.50
2
conditioned overnight in 0.01 M MgCl or 0.01 M NaCl solutions.
(
C
3
Disks 6 mm in diameter were cut from the parent membranes
and mounted into Philips electrode bodies (IS-561, Glasbl ¨a serei
3
2
2 2
) -CB11H
(
3
N
2
M o¨ ller, Zurich, Switzerland). MgCl (0.01 M) was used as the
inner filling solution for the unbiased selectivity measurements41
of ionophore-free membranes and plasticizer-free membranes with
grafted AU-1 and TMCA. NaCl (0.01 M) was used as the inner
(
mmol) in 2 mL of THF was added dropwise by a syringe. The
reaction was stirred at the same temperature for 0.5 h, after which
time it was warmed to r.t. in 1 h. The solvent was removed, and
filling solution for the measurements of NO
2
--I based membranes.
2
0 mL of EtOAc was added. The solution was washed with water
and brine and dried over Na SO . The solvent was removed and
the residue was purified by column chromatography (CH Cl
CH CN ) 3:1) to give the final product TMCA (4 ) as a white
solid (80 mg, 50% yield, MW: 301.25). H NMR: δ
CDCl ) 6.58 (dd, 1H), 6.27 (dd, 1H), 5.88 (dd, 1H), 4.02 (m, 2H),
.57 (m, 2H), 3.44 (s, 9H), 2.42-0.78 (m, 11H).
P olymer Synthesis. All polymers were synthesized via
The electrodes were measured in different sample solutions versus
a Ag/ AgCl reference electrode with a 1 M LiOAc bridge
electrolyte. All of the experimental results are the average of at
least three electrodes, with calculated standard deviations.
Optode Leaching Experiments. For optode thin films in
leaching experiments, a total of 300 mg of membrane components
containing 20 mmol/ kg Na ionophore (X), 10 mmol/ kg free
TMCA or 45 mg MMA-DMA-TMCA, 6 mmol/ kg ETH 5294,
and PVC and DOS (1:2) was dissolved in 1.75 mL of THF. A 200-
µL aliquot of the cocktail was transferred with a syringe onto a
quartz disk placed in a spin-coating device.42 For each cocktail,
two films of the same composition were cast. The films were
placed in a flow-through cell after drying in air for 1 h. The flow
cell was then mounted into a Hewlett-Packard 8452A diode array
UV-vis spectrophotometer. TRIS-HCl buffer (1 mM, pH 7.46)
was used to continuously flow through the cell at a rate of 1.2
mL/ min. Absorption spectra were recorded between 300 and 800
nm at 1-min intervals.
2
4
2
2
/
3
1
H
(250 MHz;
3
3
thermally initiated free radical solution polymerization. The
amount of methyl methacrylate and n-decyl methacrylate used
was the same as reported previously.23 For polymers containing
grafted Ca2+-selective ionophores, 5 wt % AU-1 was used. For
polymers containing grafted cation exchanger, 2 wt % TMCA (50
mg, 66 mmol/ kg) was used. Calculated amounts of MMA (0.48
g) and DMA (1.97 g)23 were added to 5 mL of dry benzene for
AU-1 or ethyl acetate for TMCA. The solution was purged with
2
N for 10 min before adding 5.1 mg of AIBN. The homogeneous
solution was continuously stirred, and the temperature was
ramped to 90 °C, which was maintained for 16 h. After the reaction
was complete, the solvent was evaporated, and the polymer was
redissolved in 10 mL of dioxane. Aliquots of polymer solution (2
mL) were added to 100 mL of distilled water under vigorous
stirring. The white precipitate was collected and dissolved in 25
mL of dichloromethane and washed with water. The organic phase
Response Time Experiments. The optode thin films (from
a total of 300 mg membrane components) were prepared by the
same spin-coating device as in the procedures described above.
Optode I contained 20 mmol/ kg Na ionophore (X), 10 mmol/ kg
NaTFPB, 5 mmol/ kg ETH 5294, 15 wt % blank MMA-DMA, and
8
5 wt % PVC and DOS (1:2). Optode II contained 20 mmol/ kg
Na ionophore (X), 15 wt % mg MMA-DMA-TMCA, 5 mmol/ kg
ETH 5294, and 85 wt % PVC and DOS (1:2). The films were placed
in a flow-through cell and measured by UV-vis. A flow rate of 5
mL/ min was used for rapid solution exchange. About 0.5 min was
needed to replace the solution in the flow-through cell.
Optode Na+ Response. For the Na ionophore (X)-based
optode, the spin-coated films were prepared with the same
procedure and composition as described above. The 2-3-µm-thick
spin-coated films were equilibrated in different sample solutions
containing chloride salts of sodium, potassium, magnesium, and
calcium with 1 mM TRIS buffer (pH 7.46) and characterized by
fluorescence spectroscopy as previously reported.6,43 All the data
points are the average of five measurements, with calculated
standard deviations.
was separated and followed by water removal with anhydrous Mg
2
-
SO and filtering. The solvent was evaporated, and the resultant
4
transparent polymer was dried under ambient laboratory condi-
tions. According to the reported method,19,24 here by analyzing
the peak intensities for the countercation of the carborane, the
concentration of the grafted TMCA in MMA-DMA polymer was
1
estimated from the H NMR spectrum as 40 mmol/ kg (61% yield).
ISE Membrane P reparation and P otentiometric Measure-
ments. Ionophore-free ISE membranes were prepared by dis-
solving 10 wt % MMA-DMA polymer with grafted TMCA, 90 wt
% PVC and plasticizer (DOS or NPOE) (1:2) to give a total cocktail
mass of 140 mg in 1.5 mL of THF. Nitrite-selective membranes
contained 10 mmol/ kg nitrite-ionophore I, 10 wt % MMA-DMA
polymer with grafted TMCA, 90 wt % PVC, and NPOE (1:2) to
give a total cocktail mass of 140 mg in 1.5 mL of THF. For the
plasticizer-free membrane with grafted calcium ionophore AU-1
and grafted ion exchanger TMCA, the cocktail contained 35 mg
of MMA-DMA-AU-1, 30 mg MMA-DMA-TMCA, and 75 mg
of blank MMA-DMA polymer in 1.5 mL of THF. Cocktails were
poured into glass rings (2.2-cm i.d.) affixed onto glass microscope
slides. The solvent was evaporated overnight to give a transparent
membrane. The plasticizer-free MMA-DMA membrane was
soaked in water for 1 h and carefully peeled from the glass slide
with a scalpel. The membranes containing TMCA were precon-
ditioned in 1 mM LiOH for 5 h in order to extract trimethylam-
monium into the aqueous solution. The membranes were then
RESULTS AND DISCUSSION
Carboranes are weakly coordinating anions that are based on
a relatively stable boron cluster framework. They also have
versatile functionalization chemistry, since both the boron vertexes
and carbon vertex can be chemically modified.39,40 The B-H bonds
-
of the parent closo-dodecacarborane (CB H ) are somewhat
11
12
hydridic and suitable for electrophilic substitution, such as
halogenation. Chlorinated, brominated, and iodinated carborane
anions at boron atoms have been prepared by solid-state synthe-
(
(
41) Bakker, E. Anal. Chem. 1 9 9 7 , 69, 1061.
42) Seiler, K.; Simon, W. Anal. Chim. Acta 1 9 9 2 , 266, 73.
(43) Tsagkatakis, I.; Peper, S.; Bakker, E. Anal. Chem. 2 0 0 1 , 73, 315.
Analytical Chemistry, Vol. 75, No. 21, November 1, 2003 6005

Fig u re 2 . Synthetic reactions for the preparation of the polymer-
izable carborane anion.
Fig u re 3 . Leaching of anionic sites in PVC-DOS (2:1) optode films
containing Na ionophore (X), ETH 5294 and free carborane anions
(curve B) or grafted carborane anions (curve A), monitored by the
change in absorbance of the protonated form at 650 nm.
sis.36,37 These boron derivatives have a much higher lipophilicity,
as compared to the water-soluble unsubstituted parent carborane
anion. They were demonstrated to be very promising alternatives
to the tetraphenylborates.36 In contrast, the C-H bond in the
+
without Na , the chromoionophore is protonated in the presence
-
of cation exchanger (R ). As the cation exchanger leaves the film
as a result of insufficient lipophilicity, a hydrogen ion must be
extracted from the chromoionophore to satisfy electroneutrality.
This slow deprotonation process can be conveniently followed by
UV-vis spectroscopy.32 For the films with unsubstituted carborane
CsCB H as cation exchanger, the chromoionophore could never
carborane anion is somewhat acidic. It was reported that C-
-
lithiation of CB11
H
12 followed by treatment with alkyl, silyl, or
phosphine halides leads to different carbon derivatives.40 In this
work, a polymerizable C-derivatized carborane anion (TMCA) was
synthesized with the procedure shown in Figure 2. Unlike the
synthesis of boron derivatives, the commercially available cesium
11
12
be protonated because of the high solubility of cesium carborane
in aqueous solution. Figure 3 shows the observed leaching
behavior, under continuous flowing conditions, of PVC-DOS films
containing either the free or the covalently attached carborane
anion derivative TMCA. Compared to the unsubstituted cesium
carborane, the polymerizable carborane anion (TMCA) has an
improved lipophilicity, since protonation of the chromoionophore
can be observed. Still, it eventually leached out of the film
quantitatively, as shown in Figure 3, trace B. To have a direct
comparison to the PVC-DOS films containing the free ion
exchanger, the optode films with grafted carborane anion were
prepared by doping 15 wt % MMA-DMA-TMCA into PVC-DOS.
The resulting films were transparent and homogeneous. The trace
of absorbance with time (A in Figure 3) shows that the absorbance
for ETH 5294 was stable for 16 h under the same conditions and
flow rate as for trace B. This strongly confirms that the ion
exchanger was indeed covalently attached to the polymer matrix
and that the resulting optode films show much improved lifetimes.
It is known that the linear MMA-DMA polymer has some
similarity to DOS plasticized membranes, such as an abundance
of ester groups and a comparable dielectric constant.23 The mixing
of some MMA-DMA polymer with excess PVC-DOS can
produce compatible and homogeneous membranes that do not
show significant changes in membrane and diffusion properties.23
A rapid leaching of free polymerizable carborane derivative
(TMCA) in PVC-DOS membrane containing 15 wt % blank
MMA-DMA was also observed and indicated that the free
carborane anion cannot be physically entrapped in such a matrix
(data not shown). Therefore, trace A in Figure 3 suggests that
the ion exchanger was indeed covalently attached to the polymer
matrix.
carborane (CsCB11
at the carbon atom because of the marked insolubility of Cs[1-
12] which inhibits the subsequent substitution chemistry.44
Therefore, it was important to first convert the parent CsCB11
H12) could not be used for the direct lithiation
LiCB11H
H
12
into a trimethylammonium salt, which was then reacted with
butyllithium to produce a soluble form of the C-litho derivative,
1
-LiCB11H
12-. The byproducts, butane and trimethylamine, could
be easily removed by evaporation. Treatment of this litho deriva-
tive in situ with TBSCl protected 2-iodoethanol led to the expected
C-alkyl derivative that could be precipitated by the addition of
trimethylammonium chloride. After removal of the protecting
group by acid hydrolysis, compound 3 was reacted with acryloyl
chloride to obtain the polymerizable carborane anion 4 (TMCA)
with trimethylammonium as countercation. This new derivative
had a good solubility in ethyl acetate and could be copolymerized
with methyl methacrylate and decyl methacrylate in ethyl acetate
by a one-step solution polymerization. The polymer with grafted
carborane anions was transparent and elastic, similar to unmodi-
fied MMA-DMA copolymer. On the other hand, it was softer
and stickier than blank MMA-DMA, with an increased tendency
to deform under mechanical or hydrodynamic pressure.
The covalent attachment of the ion exchanger was confirmed
by performing leaching experiments from optode films. Thin
+
+
PVC-DOS films contained a Na ionophore, the H chromoiono-
phore ETH 5294, and either the covalently attached or the
dissolved carborane ion exchanger. The UV-vis spectrum of the
chromoionophore shows protonated and deprotonated absorption
maximums at 650 and 550 nm, respectively.45 In a pH 7.46 buffer
(
(
44) Knoth, W. H. Inorg. Chem. 1 9 7 1 , 10, 598.
45) Bakker, E.; Lerchi, M.; Rosatzin, T.; Rusterholz, B.; Simon, W. Anal. Chim.
Acta 1 9 9 3 , 278, 211.
To further study the basic ion-exchange properties of the
+
grafted carborane anion, the response of a Na -selective optode
6006 Analytical Chemistry, Vol. 75, No. 21, November 1, 2003

was measured. The PVC-DOS film contained again a sodium-
selective ionophore, ETH 5294, and MMA-DMA-TMCA as
active components. The MMA-DMA polymer with grafted car-
borane anions was quite soft, so it was necessary to blend it with
other polymer materials with improved physical and mechanic
properties, such as the MMA-DMA copolymer or plasticized
PVC. However, in most cases, completely plasticizer-free meth-
acrylate copolymer optode films showed slower diffusion behavior
and much longer response time than plasticized PVC films.25 It
was reported that relatively fast response times (<15 min) could
be obtained if 10 wt % MMA-DMA polymer with a covalently
attached calcium ionophore was blended with PVC and DOS.24
Therefore, PVC-DOS was used as an initial model polymer matrix
and plasticizer to evaluate the basic properties of the covalently
attached carborane anion. Here, 15 wt % MMA-DMA copolymer
with grafted TMCA was mixed with 85 wt % PVC and DOS. The
sensing principle for such an optode containing a neutral sodium
ionophore L forming a complex with stoichiometry n, a H+
Fig u re 4 . Normalized optode response curves and selectivity of
PVC-DOS film containing Na ionophore (X), MMA-DMA-TMCA,
and the chromoionophore ETH 5294 toward sodium (open circles),
magnesium, potassium, and calcium ions measured at pH 7.46 (n )
-
chromoionophore Ind, and a cation exchanger R , is based on an
ion-exchange mechanism between an analyte I+ and H .
+ 42
5
). The lines are theoretically predicted responses according to eq
+
+
+
+
-
2, with log Kexch ) -4.80 for Na (n ) 1), -7.85 for K (n ) 1), -17.50
IndH (org) + n L(org) + I (aq) + R (org) )
for Ca2 (n ) 1), and -17.55 for Mg (n ) 1).
+
2+
+
+
-
Ind(org) + n LI (org) + H (aq) + R (org) (1)
is the charge of the analyte (for sodium, z
ion-exchange constant (to describe eq 1).
I
) 1), and Kexch is the
The organic film phase and the aqueous phase are indicated
as (org) and (aq), respectively. Equilibrium 1 can only be observed
over the entire measuring range if all of the covalently attached
ion exchanger is chemically accessible. Successfully recording of
an optode response curve, therefore, should be evidence that
covalently attached ion exchangers are truly useful in ion sensor
applications. The sodium activity in a given sample was determined
by using the fluorescence emission of the neutral chromoiono-
phore ETH 5294. Peaks at 647 and 680 nm, corresponding to the
deprotonated and protonated forms of the chromoionophore,
respectively, were used to monitor ion exchange. As sodium ions
enter the film, hydrogen ions are exchanged out of the film, and
the chromoionophore is deprotonated to conserve electroneutral-
ity. Again, this leads to a measurable change in its fluorescence
properties. This corresponds to a decrease in fluorescence
intensity at 680 nm and, conversely, an increase in the deproto-
nated emission peaks at 647 nm. By taking the ratio of these two
emission peaks, a response curve may be generated. The use of
ratiometric fluorescence measurements to normalize response
curves in term of degree of protonation of the chromoionophore
has been reported.43,46 The response of the films based on the
ion-exchange equilibrium 1, given as a function of the experimen-
tally accessible mole fraction of unprotonated chromoionophore,
The observed response curve of the optode film toward Na+
and the observed selectivity to potential interferences (K+, Mg2+,
Ca2+) are shown in Figure 4. The data points correspond to mean
experimental values (n ) 5), with the error bars denoting standard
deviations (often smaller than plot symbols). The lines describe
the theoretical curves according to eq 2. The response curve
generated with Na ionophore (X), ETH 5294, and MMA-DMA-
TMCA corresponds very well to the theoretically predicted
response, which confirms that the cation exchanger remains fully
functional in a covalently bound state. The observed ion-exchange
constant was found to be log Kexch ) -4.8. The selectivity
coefficient of Na+ over K+, Mg2+, and Ca2+ was determined in 1
M solutions as log kOsel of -3.05, -4.84, -4.79 (at half protonation
of the chromoionophore).47 In contrast, PVC-DOS films contain-
ing the ionophore, the chromoionophore ETH 5294 and free
polymerizable carborane derivative (TMCA) as ion exchanger
could not give optimal sodium response. The films could initially
be protonated in pH 7.4 buffer without sodium ions, but gradually
became deprotonated in the same solution because the ion
exchangers leached out of the films as a result of the insufficient
lipophilicity of the compound. Similarly, PVC-DOS films with both
ionophores but without any added ion exchanger could not be
protonated at pH 7.4, as expected.
R, and ion activities of the two ions (a
I
and a
H
) is written as42,47
In Figure 5, the response times of the optode films containing
free and grafted ion exchangers are compared by using a flow-
through cell and UV-vis detection. Optode I (top) contained the
sodium ionophore and free ion exchanger NaTFPB in a matrix
consisting of 15 wt % blank MMA-DMA and 85 wt % PVC-DOS.
Optode II (bottom) contained the same ionophore in a matrix of
-
zI
Ra
R - (1 - R)C
)-1
H
T
T
a ) (z K
I
I
exch (1 - R) {
-
T
n
L - (R - (1 - R)C )(n/ z )}
T
T
I
(
2)
-
where L
T
, C
T
, and
R
are the total concentrations of ionophore,
chromoionophore, and lipophilic ion exchanger, respectively; z
T
1
5 wt % MMA-DMA with grafted ion exchanger TMCA and 85
I
wt % PVC-DOS. It was reported that the covalent attachment of
2
7
the chromoionophore in PVC slowed the response of the film.
(
(
46) Shortreed, M.; Bakker, E.; Kopelman, R. Anal. Chem. 1 9 9 6 , 68, 2656.
47) Bakker, E.; Simon, W. Anal. Chem. 1 9 9 2 , 64, 1805.
As shown in Figure 5, upon a 10-fold increase or decrease of Na+
Analytical Chemistry, Vol. 75, No. 21, November 1, 2003 6007

Ta b le 1 . S lo p e s a n d S e le c t ivit y Co e ffic ie n t s o f Io n o p h o re -Fre e P VC-DOS Me m b ra n e s Co n t a in in g Diffe re n t Ca t io n
Ex c h a n g e rs
grafted TMCA
log K
TFPB-
37
UBC- 37
pot
Na,J
pot
Na,J
pot
ions
slope
slope
log K
slope
log K
Na,J
2
+
Mg
22.1 ( 1.5
28.5 ( 2.4
58.5 ( 0.1
59.8 ( 0.3
60.6 ( 0.1
-3.15 ( 0.05
-2.94 ( 0.01
-0.43 ( 0.01
0
24 ( 3
-2.37 ( 0.08
-2.0 ( 0.1
-0.27 ( 0.02
0
22.7 ( 0.7
29 ( 2
57.6 ( 0.2
56.5 ( 0.1
56.6 ( 0.1
-2.91 ( 0.03
-2.57 ( 0.04
-0.14 ( 0.01
0
2
+
Ca
28 ( 1
+
Li
58.4 ( 0.5
58.9 ( 0.7
59.1 ( 0.6
+
Na
+
K
0.26 ( 0.02
0.55 ( 0.02
0.45 ( 0.01
potentiometrically because ion pairing effects have their strongest
influence on membrane selectivity under such conditions.32 Three
-
different ion exchangers, grafted TMCA, free TFPB , and free
-
UBC , were compared. A PVC-DOS membrane with 10% MMA-
DMA-TMCA as ion exchanger again appeared to be clear and
homogeneous upon visual inspection. The membrane had re-
sponse times comparable to the plasticized PVC membranes with
free ion exchangers. Slopes and selectivity of the membranes were
determined by unbiased selectivity measurements (Table 1).48
PVC-DOS membranes with MMA-DMA-TMCA exhibited
Nernstian or near-Nernstian slopes to all the ions measured. The
selectivity pattern observed with the copolymer membrane was
the same as that demonstrated elsewhere for an all-MMA-DMA
matrix containing NaTFPB.23 In ionophore-free membranes, the
selectivity is dictated by the hydration enthalpies of the sample
2
ions. As shown in Table 1, the selectivity pattern indeed followed
the increase of the lipophilicity of the cations. This indicates that
the ion-exchange properties of covalently attached carborane
anions are similar to those found in established PVC-DOS
membranes containing NaTFPB.
The MMA-DMA polymer with grafted carborane anion was
also tested in charged carrier-based ion-selective membrane. It is
known that the electrically charged ionophore in principle does
not require an ion exchanger to maintain electroneutrality in the
membrane and to yield functional sensors.49 However, the use of
an ion exchanger with opposite charge to the ionophore may
induce the highest possible selectivity of the electrode by creating
a defined amount of uncomplexed ionophore.50 To further dem-
onstrate the function of the grafted ion exchanger, therefore, the
Fig u re 5 . Response time comparison of PVC-DOS optode thin
films containing Na ionophore (X), ETH 5294, and either NaTFPB in
addition to 15 wt % blank MMA-DMA (top) and TMCA covalently
grafted to MMA-DMA (bottom). The absorbance values were
-
4
recorded at 650 nm. Concentrations were changed between 10
M
-
3
+
and 10 M Na at a flow rate of 5 mL/min.
nitrite ionophore I was taken as a classical example for a positively
concentration, optode I (with free ion exchanger) showed re-
sponse times of <5 min. Under the same conditions, optode II
-
charged ionophore (see Figure 1). It was reported that NO
2
(I)-
based membranes with anion exchanger (TDMACl) result in the
loss of nitrite selectivity; instead, the membranes showed selectiv-
ity according to the Hofmeister series.50 On the contrary, the
addition of cation exchangers could improve the selectivity by
more than one logarithmic unit. The overall ratio of KTFPB was
found to be optimal between 10 and 60 mol %.50 Here, PVC-NPOE
membranes without any additives and with grafted carborane
anions were measured potentiometrically. Their selectivities are
(
with grafted ion exchanger) exhibited longer response times, with
a deprotonation time of ∼15 min. This is perhaps still reasonably
fast in view of further miniaturization and compares well to other
optodes with immobilized ionophore.27 The result indicates that
the different deprotonation rates are due not to the mixing of the
different polymer materials but instead to the covalent attachment
of active components in the polymer. In addition, the covalent
attachment of the ion exchanger does not appear to slow the
response time of the sensor dramatically if it is blended with
plasticized PVC. The optode experiments suggest that the meth-
acrylate polymer with grafted carborane anion appears to be a
suitable cation exchanger for ion-selective sensors.
-
compared to the literature values of TFPB based membranes in
-
Table 2. The selectivity of the membrane with only NO
2
(I) was
repeated here, with results that were close to the literature values.
By adding grafted TMCA as cation exchanger, the selectivity of
In addition to the optical experiments, the potentiometric
response and selectivity of membranes with grafted carborane
anion in ion-selective membranes were evaluated. First, ionophore-
free membranes containing only ion exchanger were measured
(48) Bakker, E.; Pretsch, E.; B u¨ hlmann, P. Anal. Chem. 2 0 0 0 , 72, 1127.
(
49) Schulthess, P.; Ammann, D.; Kr ¨a utler, B.; Caderas, C.; Step a´ nek, R.; Simon,
W. Anal. Chem. 1 9 8 5 , 57, 1397.
(
50) Schaller, U.; Bakker, E.; Spichiger, U. E.; Pretsch, E. Anal. Chem. 1 9 9 4 ,
66, 391.
6008 Analytical Chemistry, Vol. 75, No. 21, November 1, 2003

Ta b le 2 . S lo p e s a n d S e le c t ivit ie s o f Nit rit e Io n o p h o re I-Ba s e d P VC-NP OE Me m b ra n e s Co n t a in in g No Io n ic S it e s ,
Na TFP B, o r Gra ft e d TMCA
no sites 50
37 mol % TFPB- 50
no sites (this work)
with grafted TMCA
pot
NO2,J
pot
NO2,J
pot
NO2,J
pot
J
log K
log K
log K
slope
log K
NO2,J
SO42
-
-3.1
-3.0
-3.0
-2.7
-1.0
0.4
-4.1
-3.8
-3.7
-3.4
-1.8
0.3
-3.14 ( 0.05
-2.72 ( 0.08
-3.07 ( 0.08
-2.80 ( 0.04
-0.55 ( 0.02
0.42 ( 0.07
0
-4.14 ( 0.08
-3.71 ( 0.06
-3.67 ( 0.03
-3.52 ( 0.08
-1.68 ( 0.01
0.17 ( 0.09
0
-
OAc
-
Cl
32.3 ( 1.1
48.2 ( 2.3
53.3 ( 0.5
58.4 ( 0.3
56.8 ( 1.0
-
NO3
-
ClO4
-
SCN
NO2
-
0
0
Ta b le 3 . S lo p e s a n d S e le c t ivit ie s o f P la s t ic ize r-Fre e MMA-DMA Me m b ra n e s Co n t a in in g Eit h e r Fre e o r Gra ft e d
Ca lc iu m Io n o p h o re (AU-1 ) a n d Io n Ex c h a n g e rs
grafted AU-1 and TMCA
grafted AU-1 and free NaTFPB 24
free AU-1 and NaTFPB 24
pot
Ca,J
pot
Ca,J
pot
J
slope
log K
slope
log K
slope
log K
Ca,J
2
+
Mg
14.6 ( 2.0
30.2 ( 1.8
33.0 ( 2.1
29.5 ( 0.9
<-3.21 ( 0.05
<-3.34 ( 0.02
<-3.15 ( 0.03
0
20.3 ( 2.3
36.8 ( 2.5
38.5 ( 1.1
32.1 ( 1.0
<-4.6 ( 0.1
<-3.3 ( 0.2
<-4.3 ( 0.1
0
25.2 ( 2.2
45.3 ( 1.5
49.7 ( 1.4
31.6 ( 1.8
<-5.8 ( 0.2
<-3.5 ( 0.1
<-4.2 ( 0.2
0
+
Na
+
K
2
+
Ca
-
2-
-
-
-, and ClO
-
NO
2
over SO
4
, OAc , Cl , NO
3
4
improved by almost
1
order of magnitude. The selectivity values were also very close
to the one with an optimized amount of KTFPB. These results
again demonstrate the function and capability of MMA-DMA
polymers with covalently attached carboranes.
As explained at the beginning of this paper, plasticized PVC
membranes are not really desired in view of an application
in biological samples, especially when sensors are drastically
miniaturized. Therefore, the ultimate goal is the fabrication of
all-polymeric sensing membranes that contain no leachable
components. Some work in this direction has already been
reported. Polysiloxane-based CHEMFET10 and modified sol-gel17
sensors in which both ionophore and ion exchanger were
covalently immobilized have been described. Such membranes
+
exhibited Nernstian responses and good selectivities for Na and
+
K . However, such CHEMFETs based on polysiloxane with
grafted lead ionophore and cation exchanger had no linear
response to Pb2+, which at the time was explained by the
insufficient exchange of Pb2 with K (the counterions of borates),
because the divalent charge of Pb2 could presumably not be
efficiently compensated by the covalently attached ion exchanger.28
In previous work, we reported on the first calcium sensors based
on the plasticizer-free MMA-DMA with a covalently grafted ETH
+
+
+
2
4
1
29 derivative (AU-1, see Figure 1). In this work, we report on
Fig u re 6 . Calibration curve (top) and corresponding experimental
time traces (bottom) for the EMF measurements of an all-polymeric
plasticizer-free calcium-selective membrane with both ionophore (AU-
1) and ion exchanger (TMCA) covalently grafted to the MMA-DMA
polymer. The indicated calcium chloride concentrations in the sample
the first calcium-selective plasticizer-free ion-selective membrane
with covalently attached ionophore and ion exchanger by using a
blend of MMA-DMA-AU-1, MMA-DMA-TMCA, and blank
MMA-DMA polymer. The response slopes and selectivities
are shown in Table 3 and Figure 6 (top). The plasticizer-free
all-polymeric membrane, with all active components covalently
grafted, showed a Nernstian response slope to calcium ions but
sub-Nernstian responses to the interfering ions, which was also
observed for MMA-DMA-AU-1 membrane with free NaTFPB.
As a result, the selectivities of the membrane with both active
components grafted appear to be inferior to the membranes with
free components. As discussed elsewhere, sub-Nernstian response
-
5
range from 10 to 1 M.
slopes toward interfering ions yield only upper limits for selectivity
coefficients.48 Figure 6 (bottom) shows the potential-time traces
for the membrane upon changing calcium chloride concentrations
in the range of 10- to 1 M. The membrane shows a relatively
fast response time, which suggests that sufficient mobility of the
active components can be maintained in the membranes with
5
Analytical Chemistry, Vol. 75, No. 21, November 1, 2003 6009

covalently attached components. The required mobility for ion-
selective electrodes is clearly much smaller than that required
for optical sensors, because no appreciable membrane concen-
plications. Ion selectivities are most drastically influenced by ion
pairing processes in the absence of ionophore in the membrane.
The corresponding potentiometric experiments did not reveal any
unusual selectivity differences for the system studied here, as
compared to membranes containing tetraphenylborates. The new
carborane was also shown to be useful in improving the selectivity
of charged-carrier-based membranes, in analogy to tetraphenylbo-
rates. These results were sufficiently encouraging to demonstrate
the fabrication of an all-polymeric calcium-selective membrane,
with no plasticizer and no leachable components. The resulting
potentiometric responses were adequate and encourage further
development of this area. The finding of Nernstian response slopes
and rapid response times might at first be seen as a contradiction
to the traditional notion that immobilization of sensing components
is not permitted in potentiometry, because a small current must
be able to pass during measurement. However, the components
are likely not truly immobile, but rather part of a flexible,
noncrosslinked polymeric network with a low glass transition
temperature. A sufficiently high ion mobility is apparently pre-
served to ensure reliable potentiometric measurements.
2
tration changes occur in the Nernstian response range. The
ion mobility in the membrane is obviously kept reasonably high
by the low glass transition temperature of the polymer. Therefore,
such all-polymeric membranes likely do not contain truly im-
mobilized species, but rather, nonleachable components with a
limited mobility adequate for ion-selective electrode applications.
CONCLUSIONS
Covalent attachment of active sensing components into meth-
acrylic polymers forms a promising route to improve on limits of
ion sensors in view of miniaturization and their application in
biological samples. In this paper, a polymerizable carborane ion
exchanger was introduced and shown to possess characteristics
that makes it an attractive replacement for the traditional tet-
raphenylborate derivatives used today. Earlier routes to covalent
attachment of cation exchangers have utilized tetraphenylborates,
which are difficult to synthesize and likely still suffer from
chemical instability. To demonstrate the utility of the new
carborane, leaching experiments and optode response curves were
evaluated. The results support the notion that the carborane was
covalently attached, since only the freely dissolved derivative
leached out of the thin film optode in a matter of hours.
Ion-exchange optode response functions with films containing the
grafted carborane followed theoretical predictions perfectly and
exhibited response times that were comparably fast to established
systems. This demonstrated that the covalently attached carborane
behaved as theoretically expected and acted as a functional,
homogeneously dissolved ion exchanger with no apparent com-
ACKNOWLEDGMENT
The authors are grateful to the National Institutes of Health
(
GM59716 and DE14950) and Beckman-Coulter, Inc., for financial
support of this research.
Received for review April 29, 2003. Accepted August 8,
2003.
AC034447C
6010 Analytical Chemistry, Vol. 75, No. 21, November 1, 2003