硝基芳烃化合物急性毒性预测的理论研究

摘要

硝基芳烃是重要的化工原料,但对生物具有一定的毒性.为建立硝基芳烃对梨形四膜虫(Tetrahymena pyriformis)急性毒性的定量结构-活性相关性(QSAR)模型,分析了45种硝基芳烃的分子结构与其对梨形四膜虫毒性之间的相关关系,计算了硝基芳烃的电性拓扑状态指数和电性距离矢量,并优化筛选了电性拓扑状态指数的E9和E28、电性距离矢量的m15、m26和m66等5种结构参数,将其与硝基芳烃对梨形四膜虫的毒性进行多元回归分析,得到多元回归方程的相关系数r为0.985.为提高预测精度,将这5种分子结构参数作为神经网络的输入层变量,急性毒性值作为输出层变量,采用5:4:1的网络结构,获得令人满意的QSAR神经网络预测模型,总相关系数rt为0.994,计算得到的急性毒性预测值与实验值非常吻合,平均误差仅为0.04.结果表明,该模型具有良好的预测硝基芳烃急性毒性的能力,神经网络法预测结果比多元线性回归法更为准确.该研究揭示了硝基等基团对生物急性毒性影响的变化规律,有利于对硝基芳烃化合物在环境中的危害性进行有效评价.%Nitroaromatic compounds are important chemical raw materials, but they have some toxicity to organism. In order to establish quantitative structure-activity relationship (QSAR) model of acute toxicity of nitroaromatic compounds to tetrahymena pyriformis, the relationship between molecular structure of 45 kinds of nitroaromatic compounds and the acute toxicity to tetrahymena pyriformis was analyzed. Moreover, the electro-topological state indices and electronegativity distance vectors of nitroaromatic compounds were calculated. The electro-topological state indices, E9 and E28, and electronegativity distance vectors, m15, m26 and m66, were selected. Then, multi-linear method was applied in analyzing the five indices and the acute toxicity to tetrahymena pyriformis. The correlation coefficient r was 0.985. In order to improve accuracy, the five indices were used as input layer variables of neural network and the acute toxicity was used as output layer variable, and the 5:4:1 network structure was adopted and neural network method was used to establish a satisfying QSAR model. The total correlation coefficient rt was 0.994. The predicted values and experimental values were very close, and the mean error was 0.04. The results showed that the model had good predictive ability of the acute toxicity of nitroaromatic compounds. It showed neural network method was more accurate than multi-linear method. The results of our research have revealed the effect of nitro groups on biological acute toxicity. Therefore, it will be helpful to assess the hazards of the nitroaromatic compounds to the environment.