普通有机分子或药物热分解稳定性的理论预测  

Theoretic Prediction of Heat Decomposition Stability for General Organic Molecular or Drug

作　　者：丁晓琴[1] 丁俊杰[1] 李大禹[1] 孙杨[2] 陈冀胜[1] 

机构地区：[1]北京药物化学研究所,北京102205 [2]防化指挥工程学院,北京102205

出　　处：《高等学校化学学报》2012年第5期1063-1068,共6页Chemical Journal of Chinese Universities

摘　　要：采用密度泛函理论方法,在B3LYP/6-31+G(d,p)水平上,对任意选定的32个有机化合物或药物进行最低能量构象优化和结构参数理论计算.建立了四极矩参数Qii与半数摩尔热分解函数Yd(1/2)的相关方程,其定量构性关系(QSPR)方程为Yd(1/2)=-8.65747-3.8954Qii,相关系数为r2=-0.99297,交叉验证相关系数为XV-r2=0.99188,F检验结果为4237.343321.训练集化合物的半数分解温度Td(1/2)的平均绝对预测误差(AVEDEV)为14.70 K.进一步利用该方程对测试集中43个分子进行预测验证,Td(1/2)的预测值与实验值的相关系数为0.92304,Yd的预测值与实验值的相关系数为0.99345,证实了所建立方法的可靠性.结构差异性分析表明,训练集和测试集中的化合物均较均匀地分布在结构参数的3D空间中,化合物结构具有较好的多样性和差异性.Density functional theory（DFT） calculations at the B3LYP/6-31G＋（d,p） level were carried out for 32 random selected compounds in training set and 43 ones in testing set after determining the experimental half decomposition temperature T_d（1/2） or partial ones from literature.The calculated quantum chemical descriptors were used to construct quantitative structure-property relationship（QSPR） models of quadrupole moments（Q_ii） parameters with the molar thermal decomposition function Y_d（1/2）.The equation of QSPR is Y_d（1/2）=-8.65747-3.8954Q_ii for training set possessing a correlation coefficient of r2=-0.99297,cross validation XV-r2=0.99188 and F-test=4237.343321.Further,the proposed model is validated by examining 43 compounds in testing set with a correlation coefficient of 0.92304 between prediction and experiment T_d（1/2） values and a correlation coefficient of 0.99345 between prediction and experiment Y_d values.The selected compounds rank well with a certain space distribution of structure descriptors.The developed equation can be used to predict the heat decomposition stability for new designed or synthesized compounds or drugs in virtual screening.

关 键 词：有机分子或药物 半数分解温度 摩尔热分解函数 四极矩参数(Qii) 定量构性关系 

分 类 号：O641[理学—物理化学]