New trends in ion-selective electrodes - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 97

4.4 NEW SENSOR MATERIALS

4.4.1 Membrane components
Solvent polymeric membranes conventionally consist of ionophore, ion exchanger,
plasticizer, and polymer. The majority of modern polymeric ISEs are based on neutral
carriers, making the ionophore the most important membrane component. Substantial
research efforts have focused on the development of highly selective ionophores for a
variety of analytes [3]. Some of the most successful ionophores relevant to biomedical
applications are depicted in Fig. 4.1.
During the early stages of polymeric membrane ISE research, the trail-and-error
method prevailed for the development of new ionophores. However, recent advances of
synthetic organic chemistry provided more sophisticated and powerful strategies, using
basically two principles, rational design and the biomimetic approach. In the former
the number of ionophore parameters is simultaneously taken into account in order to
optimize the molecular structure and to endow an ionophore with a strong binding abil-
ity with a target analyte. Computational chemistry methods are used to model binding
and stabilizing interactions, including Lewis acid/base chemistry, hydrogen bonding,
electrostatic and

-electron interactions. Modifi cation of the binding site setting with
various substituents, capable of withdrawing/donating electron density, increasing/
decreasing steric hindrance, etc., is also an instrument in the development of supe-
rior ionophores. Moreover, the binding sites are to be complemented with a molecular
periphery, which ensures suffi cient lipophilicity of the ionophore and its compatibil-
ity with the sensor membrane matrix. At last, the synthesis of the designed ionophore
must not be too complicated. The ionophore optimization is very similar to drug design
procedures. Unfortunately, the comprehensive modeling of analyte-ionophore interac-
tions in the membrane still has many shortcomings, mainly due to imperfections of the
available theories, which restricts the prediction power of such calculations. Further
development of computational chemistry will hopefully allow a better quantifi cation of
sensor properties a priori .
The biomimetic approach, on the other hand, may help one to avoid some of the
complexities of rational design, as it exploits natural binding sites and receptors, fi ne
tuned by millions of years of natural evolution. Valinomycin and nonactin, naturally
occurring antibiotics with high selectivity to potassium and ammonium, correspond-
ingly proposed in the mid-1960s, are good examples of such an approach and pro-
moted the development of ISEs for decades. More recent success has been achieved
with multiple anion ionophores inspired by nature, e.g. metalloporphyrins, guanidin-
ium salts, and functionalized ureas [11].
Cation-selective ionophores are the most successful in polymeric ISEs and selectivi-
ties exceeding ten orders of magnitude became quite common. The cation-ionophore
binding occurs dominantly due to Lewis interactions and could be understood in terms
of hard and soft acid and bases theory (HSAB). While hard base oxygen atoms origi-
nate from ester, ether or carbonyl functionalities, and interact with hard acid alkaline
cations, the softer sulfur or nitrogen atoms better bind with transition metal ions. Cation

π