Molecular modeling of chiral‐modified zeolite HY employed in enantioselective separation

Abstract

Insight into enantioselective separation utilizing chiral-modified zeolite HY could be useful in designing a chiral stationary phase for resolving pharmaceutical compounds. A model was employed to better understand the enantioseparation of valinol in zeolite HY that contains (+)-(1R;2R)-hydrobenzoin as a chiral modifier. This model incorporates the zeolite support and accounts for the flexible change. Results from grand canonical Monte Carlo and molecular dynamics simulations indicate that the associated diastereomeric complex consists of a single (+)-(1R;2R)-hydrobenzoin and a single valinol molecules located in the zeolite HY supercage. Supercage-based docking simulation predicted an enantioselectivity of 2.6 compared with that of 1.4 measured experimentally. Also, the supercage-based docking simulation demonstrated a single binding motif in the S complex, and two binding motifs in the R complex. The multiple binding modes in the R complex resulted in its lower stability. This is hypothesized to be the origin of the weaker binding between (-)-(R)-valinol and the chiral modifier, and explains why (+)-(R)-valinol is retained more in the chiral-modified zeolite system studied.

Computational study of enantioseparation by amylose tris(3,5‐dimethylphenylcarbamate)‐based chiral stationary phase

“…Zhao and Cann defined the silica gel surface according to the surface coverage of functional groups estimated based on the experimental data 25, 26, 33. Jirapongphan et al also constructed the molecular model of CSP in the presence of zeolite HY as the support material, although the CSP they studied was not based on silica gel 34. However, there has not yet been any report on computational study of the polysaccharide derivative‐based CSP combined with silica gel surface in the molecular model.…”

Enantioseparation of phenylglycinol in chiral‐modified zeolite HY: A molecular simulation study

“…The binding motifs 1 and 2 in the phenylglycinol system (Table 2) are similar to those in the valinol system. 1 For both systems, the S enantiomer was predicted to be better retained in the chiral-modified zeolite. However, the role of the effective configuration that is responsible for the enantioselective discrimination in each system is different.…”

“…In 2004, nine of the top-ten selling drugs ($53.5 billion (US) in global sales) had chiral active ingredients. 1 Isolation of the desired enantiomer is needed to obtain the desired therapeutic effect in the chiral drugs. In a resolution of valinol enantiomers in a chiral-modified zeolite HY, the (+)-(S)-valinol was better retained inside the pores of the modified zeolite at experimental conditions (i.e., 294 K).…”

“…1). [1][2][3][4][5] The supercages are the repeating sphere-like cavities (*12.6 Å in diameter) connected to each other in three dimensions in the zeolite HY structure. A separation mechanism has been proposed for this (i.e., valinol) enantioseparation system based on low energy configurations that were obtained from supercagebased docking simulations.…”

“…A separation mechanism has been proposed for this (i.e., valinol) enantioseparation system based on low energy configurations that were obtained from supercagebased docking simulations. 1 To demonstrate the usefulness of the proposed mechanism, an enantioseparation of phenylglycinol molecules (i.e., (+)-(S)-phenylglycinol and (À)-(R)-phenylglycinol) in the chiral-modified zeolite HY was simulated in the present investigation. The enantiomeric pair of phenylglycinol molecules was selected for the new separation system because of: (1) a potential application of (À)-(R)-phenylglycinol in the synthesis of a key precursor of HIV-1 protease inhibitors, 6 and (2) the similarity between phenylglycinol and valinol molecules in terms of the presence of polar (i.e., amine and hydroxyl, Fig.…”