Theoretical study on the hydrolysis mechanism of N,N-dimethyl-N'-(2',3'-dideoxy-3'-thiacytidine)-formamidine

• 来源期刊: 中国科学B辑（英文版）
• 年，卷（期）: 2008,（10）
• 页码范围: 911-917
• 页数: 7页
• 语种: 英文
• DOI: 10.1007/s11426-008-0047-y

摘要

The hydrolysis mechanisms of N,N-dimethyl-N'-(2',3'-dideoxy-3'-thiacytidine)formamidine (FA-3TC) in the gas phase and in aqueous solution were studied by use of the density functional theory B3LYP/6-31+G(d, p) method. Two possible reaction pathways in the title reaction were considered. In one pathway water attacks the C=N double bond first (path A) while in the other water attacks the C-N single bond first (path B). The calculated results indicate that the first step in both pathways is the rate-limiting process and path A is more favorable than path B in the gas phase. The effect of solvent water on the title reaction was assessed at the B3LYP/6-31+G(d, p) level of theory based on the polarizable continuum model (CPCM). In water the first mechanism (path A) is also favored.