Discrimination between Enantiomers of Structurally Related Molecules:  Separation of Benzodiazepines by Molecularly Imprinted Polymers

Abstract

Molecular imprinting has been used to create synthetic receptor sites for a series of chiral benzodiazepines. A detailed HPLC analysis of binding properties using molecularly imprinted polymers (MIPs) as the stationary phase showed that binding, as measured by chromatographic retention, shows significant dependence on the chiral match or mismatch. In addition, the shape and spatial orientation of functionality of the imprinted binding site is also critical for recognition. Imprinted polymers, therefore, are not only able 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 imprinted absolute configuration, even as the structural homology between the enantiomers and the original template decreases, indicates that the synthetic benzodiazepine receptors may serve as crude mimics of the natural receptor.

Chiral separation by chromatographic and electromigration techniques. A Review

“…Molecular imprinted polymers (MIPs) were developed among others for the chiral separation of amino acids [176], amino acid derivatives [175,177], peptides [178], carboxylic acids [177], b-blockers [179,180], cinchona alkaloids [181,182], NSAIDs [183,184] and benzodiazepines [185].…”

Preparation and evaluation of uniform-sized molecularly imprinted polymer beads used for the separation of sulfamethazine

“…Similar changes were observed for the retention for other sulfonamides, but the retention factors of other sulfonamides were much lower than that of SMZ. This behaviour is a general observation that has been attributed to the intermediate polarity of the stationary phase with respect to the solvents being used (Hart et al, 2000). Figure 4(A, B) shows the retention factors of sulfonamides on the non-imprinted and imprinted polymer columns and the imprinted factor.…”

Chiral separation of 1,1′‐bi‐2‐naphthol and its analogue on molecular imprinting monolithic columns by HPLC

“…The advantages of MIPs, in particular high selectivity and physiochemical stability, have propelled the development of MIPs as chromatographic stationary phases, particularly, in HPLC and CEC where they have been utilized mainly as chiral stationary phases (CSPs). There are a variety of chiral compounds separated with MIP stationary phases by HPLC and CEC including amino acid derivatives, b-blockers, peptides, and sugars [6][7][8][9][10].…”