Conformational Analysis of Topiramate and Related Anion in the Solution and Interaction Between the Most Stable Conformer of Topiramate with Active Center of Carbonic Anhydrase Enzyme

GRAPHICAL ABSTRACT

Abstract

Density functional theory using the B3LYP/6-311++G** method was employed to calculate the details of the electronic structure and electronic energy of the carbonic anhydrase enzyme active center (CA); topiramate, a sulfamate substituted monosaccharide; and the complex between topiramate and CA. The calculated results indicate that topiramate appears to adopt a twist-boat conformation in the solution. The conformational analysis around the S-N bond (H-N-S-O dihedral angle) in deprotonated topiramate shows that the conformers with a H-N-S-O torsion of 270, 0, and 180 degrees are the minimum, transition state, and maximum energy conformers, respectively. The deprotonated form of topiramate is coordinated to the Zn²⁺ ion.

Keywords:

• Carbonic anhydrase
• Topiramate
• Inhibitor
• Thermodynamic functions
• Conformational analysis

ACKNOWLEDGMENTS

The authors gratefully acknowledge the research council of Alzahra University. Also, the authors would like to thank Professor Claudiu T. Supuran and Dr. Hamdollah Saeidian for their advice on this work.