Computational Insights on Solvation and Hydrogen Bonding Studies of Indomethacin

Abstract

Over a long time, non-steroidal anti-inflammatory drugs (NSAIDs) play a vital role in medical field. Indomethacin is a NSAID mainly used against inflammation and pain. But the poor solubility of indomethacin limits its therapeutic usage. Hydrotropy is a solubilization technique used to enhance the drug solubilization. Microscopic solvent effect is considered to be a part of hydrotropy in which hydrogen bond (H-bond) networks are formed with an isolated molecule with solvent molecules such as water. A comprehensive theoretical investigation was performed under density functional theory (DFT) to explore the isolated and monohydrated indomethacin complexes. The geometries were optimized on B3LYP method with 6-311G (2d,2p) basis set. The interaction energies of hydrated indomethacin complexes were computed by correcting the basis set superposition error. Natural bond orbital (NBO) study was performed in order to deepen the knowledge on O-H···O and C-H···O type H-bonds. A linear relationship between H-bond length and the stabilization energy (E(2))was observed in the solvated indomethacin complexes with a correlation coefficient of 0.8346. It identifies maximum E(2) (95.33 Kcal/mol) in INDO-12 complex. The molecular electrostatic potential mapping (MESP) for the optimized structures was also analyzed.