1-取代-2-氨基苯并咪唑化合物毒性和热力学性质的密度泛函理论研究

Density Functional Theory Study on the Toxicity and Thermodynamic Property of 1-Replaced-2-Amino Benzimidazole Compounds

用密度泛函理论(DFT)B3LYP方法,在6-31G(d)基组水平上,对8个1-取代-2-氨基苯并咪唑化合物分子进行了全优化计算,得到其轨道能(ENHOMO、ENLUMO以及二者轨道能隙ΔE2)、原子电荷(Q)等量子化学参数,以及热能校正值Eth、恒容热容Cv、熵S等热力学性质,并计算了8种1-取代-2-氨基苯并咪唑化合物分子的电性拓扑状态指数Em。通过最佳变量子集回归建立这些化合物毒性的QSAR模型,以及热力学性质的QSPR模型。模型的相关系数R2和采用逐一剔除法得到的交叉验证相关系数R2cv均大于0.84和0.72,利用2个模型得到毒性的预测值与实验值的误差分别为0.11和0.20,3个热力学性质预测模型的误差分别为3.89%、4.03%和2.64%,吻合度较好,经检验证明所建模型具有良好的鲁棒性和预测能力。研究工作揭示了基团对毒性大小影响的变化规律、有利于对苯并咪唑类化合物在生态环境中的危害性进行评价,可为研发高效、低毒的苯并咪唑类新型药物提供理论依据。

Theory of density function （DFT） was used to calculate the quantum chemical parameters such as orbital energy （EN.oMo,EHOMO、ENLUMO）, energy gap of them（AE2）, atomic charge （Q）, and the thermodynamic parameters such as thermal correction value （Eth）, heat capacity at constant volume （C）, standard entropy （S） , and electrotopological state index （Era） of eight compounds based on 1-replaced-2-amino benzimidazole at B3LYP/ 6-31G（d） level. Two models of quantitative structure-activity relationships （QSAR） about toxicity of the com- pounds and three models of quantitative structure-property relationships （QSPR） about thermodynamic prop- erty of them were established by the leaps-and-bounds regression analysis respectively. Correlation coefficients R2 of the models and R2ov based on leave-one-out （LOO） cross validation were greater than 0.84 and 0.72respectively. Deviations between calculated values and predicted values ot lgLLD50 were 0.11 and 0.20 respec-tively, and relative mean error＇between calculated values and predicted values of Eth, Cv＋ and S＊were 3.89% , 4.03% and 2.64% respectively, which exhibited a good robustness and good prediction capability. The results of our research have revealed effect of groups on toxicity. Therefore, it would facilitate to assess hazard of thecompounds based on 1-replaced-2-amino benzimidazole in environment, and provide theoretical foundation for research and development of new drugs with high efficiency and low toxicity based on benzimidazole.