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

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• 作者：A.  ; Tamara Molina ; M.  ; Alcolea Palafox  ; ;   ; ^{alcolea@quim.ucm.es}
• 关键词：AZT 5&prime ; -aminocarbonylphosphonate ; Anti-HIV ; AIDS ; DFT ; Conformations ; Geometry optimization
• 刊名：Chemical Physics
• 出版年：2011
• 出版时间：25 August 2011
• 年：2011
• 卷：387
• 期：1-3
• 页码：11-24
• 全文大小：2115 K

文摘

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 (¦Ö, ¦Ã, ¦Â, ¦Á, ¦Ä, ¦Å, ¦Ó, P, ¦Í_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 1 kcal/mol electronic energy range of the global minimum and 11 conformers are within a 1 kcal/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 ¦Ö = ?21.6¡ã, ¦Â = 153.0¡ã, ¦Ã = ?52.0¡ã and ¦Á = ?4.1¡ã. 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.