ENANTIOMERIC RESOLUTION ON MOLECULARLY IMPRINTED POLYMERS PREPARED WITH ONLY NONCOVALENT AND NONIONIC INTERACTIONS

Molecular imprints were prepared utilizing only weak bonds between the print molecule and functional monomers; the bonding forces used in the imprinting process were only those weaker than covalent and ionic bonds. Methacrylate-based molecular imprints were prepared using a number of chiral compounds, including N-protected amino acid derivatives, as print molecules. Methacrylic acid was used as the functional monomer because the acid function of the monomer forms hydrogen bonds with a variety of polar functionalities, such as carboxylic acids, carbamates, heteroatoms and carboxylic esters, of the print molecule. Bulk polymers were prepared, ground and sieved to particles of size <25 μm, packed into high-performance liquid chromatographic (HPLC) columns and used for enantiomeric separations in the HPLC mode. The polymers were shown to effect efficient enantiomeric resolution of a racemate of the print molecule in addition to substrate selectivity for the print molecule in a mixture of substrates with very similar structures. For example, the enantiomers of Cbz-aspartic acid and Cbz-glutamic acid (Cbz = carbobenzoxy) were resolved with separation factors of 1.9 and 2.5, respectively, on polymers with molecular imprints of the l-form of the respective compounds. In addition, these polymers, prepared against Cbz-l-aspartic acid and Cbz-l-glutamic acid, respectively, had the ability to bind selectively the print molecule from a mixture of both racemates, although the two compounds differ only by one methylene group. The results presented represent a substantial widening of the scope of molecular imprinting in that it may now be possible to prepare molecular imprints against a very large number of compounds. © 1990.