Abstract
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.
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Supported by the National Natural Science Foundation of China (Grant Nos. 20473055 and 20773089) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (Grant No. 20071108-18-15)
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Zhang, C., Xue, Y. Theoretical study on the hydrolysis mechanism of N,N-dimethyl-N′-(2′,3′-dideoxy-3′-thiacytidine)formamidine. Sci. China Ser. B-Chem. 51, 911–917 (2008). https://doi.org/10.1007/s11426-008-0047-y
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DOI: https://doi.org/10.1007/s11426-008-0047-y