The role of molecular interaction fields on enantioselective and nonselective separation of chiral sulfoxides

Abstract

The separation of a series of 23 asymmetric sulfoxides, including the three proton pump inhibitors (PPI) omeprazole, lansoprazole and pantoprazole was investigated by HPLC, under reversed-phase elution with amylose tris(3,5-dimethylphenylcarbamate), amylose tris[( S)-1-phenylethylcarbamate] and amylose tris(3,5-dimethoxyphenylcarbamate) chiral stationary phases, CSP1-3, respectively. The whole set of sulfoxides showed better enantioselectivity and enantioresolution on CSP1. However, the three PPI were enantioseparated only when using CSP1 and CSP3. It was observed an improved enantioselectivity and enantioresolution on CSP3. The mechanisms of retention were evaluated by molecular interaction fields (MIF) generated via GRID force field, which yielded the geometric reasons leading to the scenario outlined. The enantioselective and nonselective interactions are discussed in terms of the reported selectivity. The steric structural outline of the CSP nonselective interaction sites is of major importance to deliver the sulfoxides to the chiral selective sites where the enantioselective interactions take place.