Hydration Analysis of Antiviral Agent AZT by Means of DFT and MP2 Calculations

Abstract

A theoretical analysis of the effect of hydration on the molecular structure and energetics of the most stable conformers of the nucleoside analogue AZT (3'-azido-3'-deoxythymidine) was carried out. To simulate the first hydration shell, two models were considered, namely, the polarized continuum model (PCM) and the discrete model, including a variable number (from 1 to 13) of explicit water molecules surrounding the nucleoside. More than 200 cluster structures with water were analyzed by B3LYP and MP2 quantum chemical methods. In the isolated state, conformer I is the most stable by the B3LYP method, but by the MP2 method, conformer II is most stable. With nine water molecules, conformer II changes to conformer I, and this conformer I is the most stable with the further addition of water molecules. The CP-corrected formation and interaction energies for AZT and water molecules were determined. The effects of hydration on the total atomic charges and intermolecular distances were also investigated. Several general conclusions on hydrogen-bond network and involved energies are emphasized. The computed values were in good agreement with previous results for other nucleosides.