拉米夫定的热分解机理及其动力学

目的测定拉米夫定(lamivudine,LMVD)的热性质,研究LMVD的热分解机理、热分解动力学和LMVD的热稳定性。方法采用热重法(thermogravimetry,TG)和差示扫描量热法(differentialscanning calorimetry,DSC)测定LMVD在氮气氛和空气氛中的热分解过程,测定LMVD及其在热分解过程中不同阶段残留物的红外光谱,运用量子化学GAMESS软件计算LMVD分子的键级,根据不同升温速率下的热重曲线计算得到LMVD第一阶段热分解反应动力学参数,应用Dakin方程推算LMVD在不同使用温度下的预期寿命。结果 LMVD的热分解过程是一个二阶段过程,起始步骤是胞核嘧啶环中的C-N键断裂。在氮气氛中,表观活化能Ea=126.5 kJ.mol-1,指前因子A=2.88×1011min-1,在空气氛中,Ea=133.0 kJ.mol-1,A=1.15×1012min-1。结论 LMVD在常温下具有很好的热稳定性。

Mechanism and kinetics of thermal decomposition of lamivudine

Objective To probe into the thermal property，the mechanism of the thermal decomposition and the prospective lifetime of lamivudine (LMVD). Methods The thermal decomposition of LMVD was measured by thermogravimetry (TG) and differential scanning calorimetry（DSC），the IR spectra of LMVD and its remainders from thermal decomposition at various temperatures were determined, the molecular bond orders were calculated by GAMESS method of quantum chemistry, the kinetics parameters of thermal decomposition of STVD were obtained by thermogravimetry and the prospective lifetime of LMVD at different temperature was speculated by Dakin equation. Results The results indicated that the thermal decomposition of LMVD was a two-stage process. The initial step was the C-N bond in cytosine ring cleaved. The kinetic parameters, such as activation energy E_a = 126.5 kJ·mol^-1 , pre-exponential factor A =2.88×10¹¹ in N₂，and E_a =1 68.1 kJ·mol^-1 , A =2.188×10¹⁹ in air，were obtained. Conclusion The thermal property of LMVD is quite stable in the routine temperature.