Computational Approaches in the Design of Synthetic Receptors - Designing Receptors for the Next Generation of Biosensors - page 151

and Metformin [ 114 ]. Ideally, elaborate use of B3LYP/6-31+G//B3LYP/3-21G
level of theory for theophylline [ 67 ] has been shown to be more extensive as
a study, because of elaborate calculations that provide better representations of
binding between functional monomers and the template. Using PM3 calculations
and MP2/6-31G//HF/6-31G studies, the importance of the influence of binding
energies between template and functional monomers with relation to the resultant
capacity factor of the MIP was explained in a previous study [ 176 ]. QC approaches
can also compute binding energies for templates that differ from the target struc-
ture, as has been shown before [ 73 ]. Here the authors describe the design of a MIP
that mimicked cytochrome CYP2D6, the computations of which were based on
PM3, giving optimized template molecule geometries, which resulted in the forma-
tion of a MIP with good recognition properties (Table 1 ). An earlier example of the
calculation of binding energy [ 112 ], using an AM1 method for several complexes of
cocaine with MMA and 4VP leading to an optimized polymerization mixture,
proved to be a success, as further validation with NMR and rebinding studies
confirmed.
Chiral recognition was examined for a MIP synthesized for ( S )-nilvadipine using
MAA, TFMAA, 2-VP or 4-VP as a functional monomers and EGDMA as cross-
linker [ 111 ]. Molecular computations were done with CAChe MOPAC version 94
implemented in CAChe programs23. Molecular geometries of ( S )-nilvadipine and 4-
VP were optimized by the AM1 method. The simulation was performed on the
hydrogen-bonding complex model with the dihydropyridine and pyridine rings of
( S )-nilvadipine and 4-VP molecules, respectively. Molecular modeling revealed a
one-to-one hydrogen-bonding-based complex formation of ( S )-nilvadipine with 4-VP
in chloroform and that ( S )-nilvadipine imprinted EGDMA polymers should recognize
the template molecule by its molecular shape, and that hydrophobic and hydrogen-
bonding interactions seem to play important roles in the retention and chiral recogni-
tion of nilvadipine on the 4-VP- co -EGDMA polymers in hydro-organic mobile
phases. The ( S )-nilvadipine-imprinted 4-VPY- co -EGDMA polymers indeed gave
the highest resolution for nilvadipine among the MIPs prepared.
QC methods employing PM3 methods have also computed adsorption coefficients
of bile acids on a film of overoxidized polypyrrole imprinted with sodium
taurocholate [ 88 ]. PM3 methods are considered fairly simple and straightforward,
and their ability to compute adsorption coefficients successfully confirms the compu-
tational power of such methods. Further electronic structure computations for the
prediction of polymer properties were successfully demonstrated [ 176 ], where inter-
action energies were calculated for pre-polymerization complexes of nicotinamide or
iso -nicotinamide with methacrylic acid as functional monomer.
2.9 Rational Approaches to MIP Design Involving
Chemometrics and Neural Network Methods
Chemometrics uses mathematical and statistical methods to select the optimal
experimental procedures and for the extraction of data for the analysis [ 177 ].