定量构效关系模型分析氯代烯烃中氯原子对其分子描述符的影响

Quantitative structure activity relationship( QSAR) of chlorine effect on molecular descriptors of chlorinated alkenes

定量构效关系(QSAR)模型在研究饮用水消毒副产物(DBPs)中氯原子数量与毒性的关系方面有一定进展,然而,能够反映DBPs毒理性的分子描述符和氯原子数量之间的相关性却从未被系统地和定量的研究。分子描述符的计算是QSAR研究的基础,其中分子轨道能,如最低空轨道能量(ELUMO)是应用最广的量化参数之一。基于QSAR方法建模筛选氯代烯烃同系物的相关量子化学参数,检验最高占据轨道能级(EHOMO)、碳原子数(NC)、氯原子数(NCl)对ELUMO的贡献作用。并通过统计学方法进行模型开发和内外交叉法验证发现,NCl和NC是预测氯代烯烃分子特性较重要的两个化学参数,即较稳健的模型为ELUMO=-0.0205NCl+0.0059NC+0.1641(n=11,R2=0.9956,F=102.8569,RMSE=0.0019)。此外,为了提高模型的准确性,使用蒙特卡罗法对模型进行不确定性分析,来进一步评估这些参数的误差源传输到ELUMO计算时,对ELUMO的影响。

Quantitative structure-activity relationship( QSAR) has been applied extensively in predicting the relationship between the chlorine and the toxicity of disinfection by-products( DBPs) in drinking water.However,the correlation between the chlorine and the molecular descriptors has never been studied systematically and quantitatively. Calculation of molecular descriptors are the basis of QSAR study,the molecular orbital energy,such as the lowest unoccupied molecular orbital energy( ELUMO) is one of the most widely used parameters.QSAR method was used to select the quantum chemical parameters of chlorinated alkenes,and to validate the contribution of the highest occupied orbital( EHOMO),the number of carbon atoms( NC),chlorine atoms( NCl)to the ELUMO. According to the statistical methods and cross validation results,NCland NCare more sensitively to estimate the ELUMOfor chlorinated alkenes,the most robust model is ELUMO=- 0. 0205NCl+ 0. 0059NC+ 0. 1641( n = 11,R2= 0. 9956,F = 102. 8569,RMSE = 0. 0019). The model uncertainties are also quantified through Monte Carlo Simulation to evaluate the propagation of the uncertainties of the elemental error sources into the ELUMO.