Discrimination between enantiomers of structurally related molecules: Separation of benzodiazepines by molecularly imprinted polymers

Molecular imprinting has been used to create synthetic receptor sites for a series of chiral benzodiazepines. A detailed HPLC analysis of binding prop erties using molecularly imprinted polymers (MIPs) as the stationary phase showed that binding, as measured by chromatographic retention, shows signif icant dependence on the chiral match or mismatch. In addition, the shape an d spatial orientation of functionality of the imprinted binding site is als o critical for recognition. Imprinted polymers, therefore, are not only abl e to discriminate between enantiomers of the imprinted molecule, they also demonstrate an ability to discriminate between a wide range of enantiomers of structurally related molecules that have not been imprinted. The ability of MIPs to discriminate between enantiomers of molecules in favor of the i mprinted absolute configuration, even as the structural homology between th e enantiomers and the original template decreases, indicates that the synth etic benzodiazepine receptors may serve as crude mimics of the natural rece ptor.