Structure and conformational analysis of the anti-HIV AZT 5′-aminocarbonylphosphonate prodrug using DFT methods

Abstract: A comprehensive theoretical conformational analysis of the anti-HIV AZT 5′-aminocarbonylphosphonate prodrug was carried out, due to this prodrug has noticeable advantage over approved drugs AZT and Nikavir. The whole conformational parameters (χ, γ, β, α, δ, ε, τ, P, ν max) were analysed as well as the NBO Natural atomic charges. The calculations were carried out by means of B3LYP/6-31G∗∗ and B3LYP/6-311++G(3df,pd) DFT levels of theory with full relaxation of all geometrical parameters. The search located at least 86 stable structures, 6 of which are within a 1kcal/mol electronic energy range of the global minimum and 11 conformers are within a 1kcal/mol Gibbs energy range. The global minimum with the 6-311++G(3df,pd) basis set corresponds to the calculated values of the exocyclic torsional angles χ =−121.6°, β =153.0°, γ =−152.0° and α =−74.1°. The results obtained are in accordance to those found in related anti-HIV nucleoside Analogs. Comparisons of the conformers with those determined in the common anti-HIV drug AZT were carried out. Several correlations and general conclusions were emphasized. [Copyright &y& Elsevier]