Experimental and theoretical investigation on mandelic acid (r, s) enantioselective separation using vancomycin chiral column in high performance liquid chromatography

Yahya Sefidbakht,1,* Mostafa shahnani,2 Hassan rezadoost,3 Alireza ghassempour,4

1. Protein Research Center, Shahid Beheshti University, G.C., Tehran, Iran
2. Medicinal Plants and Drug Research Institute, Shahid Beheshti University, G.C, Tehran, Iran
3. Medicinal Plants and Drug Research Institute, Shahid Beheshti University, G.C, Tehran, Iran
4. Medicinal Plants and Drug Research Institute, Shahid Beheshti University, G.C, Tehran, Iran

Abstract

Introduction

Nowadays, antibiotic chiral columns can be used in various chromatography separations. the high potential of these compounds in chromatographic separations is due to their structural characteristics. presence of aromatic rings, functional groups and a lots of chiral centers, causes many interactions such as π- π, dipole- dipole, van der waals interactions. also, the spatial arrangement of aromatic rings in the vancomycin structure has created three baskets in its structure which have certain roles in chiral separations. until now, there is no detailed view on the interactions between vancomycin and racemic compounds like mandelic acid.

Methods

The exact understanding of these interactions in antibiotic columns, creates an insight by which chromatographists can make predictions on the choice of hplc chirobiotic column and the candidate racemic compound for separation. therefore, simulation of mandelic acid enantiomers (r, s) and vancomycin interaction may reveal aspects of enantioselective separation on vancomycin chiral columns. the vancomycin structure was modeled based on 1aa5 crystal structure with 0.89 Å resolution. the avogadro program was used to add missed atoms and the structure was minimized. molecular dynamics of target receptor (vancomycin) was done which creates vancomycin in the lowest energy conformation. the receptor ligands interaction was then studied by autodock vina. the whole vancomycin molecule has been centered in the grid box so that the binding algorithm could scan all possible interactions.

Results

Results showed that two complex of r and s mandelic acid- receptor differs in relative binding energy. this difference in binding energy is around 0.1 kcal/mol. these difference was also observed in chromatographic enantioselectivity.

Conclusion

. therefore, the variation of possible interactions between vancomycin and different enantiomers have been showed to be useful in separation of r and s mandelic acid.

Keywords

Vancomycin , chiral column, mandelic acid , enantioselective