PBBs分子多光谱效应3D-QSAR模型构建及其在分子修饰中的应用

Construction of a 3D-QSAR Model With Dual Spectral Effects and Its Application in Molecular Modification of Environmentally Friendly PBBs

多溴联苯(PBBs)作为一种添加型阻燃剂,可从产品中缓慢释放出来,并在环境介质和生物体中富集并产生危害,红外和紫外光谱可以对PBBs进行检测,具有检测迅速、无二次污染、操作简单等优点。结合功效系数法综合PBBs红外振动和紫外吸收两种光谱效应,构建兼具双光谱效应的CoMFA模型,根据模型三维等势图设计红外、紫外光谱增强的衍生物,并对衍生物进行稳定性、功能性和环境友好性评价。研究结果表明,CoMFA模型主成分n为3,交叉验证系数q2为0.532(>0.5),表明所建模型具有好的预测能力;模型标准偏差SEE为0.013(<0.95),检验值F为38.281,非交叉验证系数R^2为0.935(>0.9),表明模型具有较好的拟合能力;加扰稳定性试验参数Q2为0.51,cSDEP为0.04,d q2/d r^2yy为0.95(<1.2),模型具有好的鲁棒性;通过测试集进行外部验证,标准误差SEP为0.03,r^2 pred为0.73(>0.6),表明模型具有好的外部预测能力,立体场和静电场贡献率分别为44.8%和55.2%。根据模型三维等势图信息引入正电性、体积大的取代基团对目标分子PBB-153进行取代修饰,共设计了7个PBB-153衍生物,双光谱效应综合值较目标分子增加10.15%~29.12%。高斯计算结果表明所设计的衍生物吉布斯自由能值小于0,正频值大于0,C-Br键解离焓与目标分子相比变化较小,衍生物具有较好的环境稳定性和功能性。此外,所设计的衍生物环境持久性、远距离传输性、毒性和生物富集性降低,具有环境友好性特征。模型验证发现衍生物红外、紫外单光谱效应均上升,衍生物(4-OCN-5-NO-PBB-153)两种光谱变化比率为0.79,接近模型所设置的权重比例1∶1,且双光谱效应模型三维等势图基本包含了单光谱效应模型三维等势图的信息,所构建的综合模型具有一定的准确性和可靠性。所建立的双光谱效应模型可以实现对两种单光谱效应的同步修饰和综合分析,为其他污染物光谱检测综合评价提供思路。

As a kind of additive flame retardant,polybrominated biphenyls(PBBs)will be released from the product slowly and enriched in environmental media and organisms to cause harm.Infrared and ultraviolet spectra can detect PBBs,which have the advantages of rapid detection,no secondary pollution and simple operation,etc.In this paper,the efficacy coefficient method was used to synthesize the two spectral effects of infrared vibration and ultraviolet absorption of PBBs and a CoMFA model with dual spectral effects was established.PBB-153 Derivatives with increased infrared and ultraviolet spectral intensity are designed according to the contour maps of the model.The stability,functionality and environmentally friendliness of derivatives were evaluated.The results showed that the main component n of the CoMFA model is 3,and the cross-validation coefficient q^2 was 0.532(>0.5),indicating that the model has a good prediction ability;SEE was 0.013(<0.95),F was 38.281,and non-cross-validation coefficient R^2 was 0.935(>0.9),which indicates that the model has the good fitting ability;the scrambling stability test parameters Q2,cSDEP and d q^2/d r 2yy were 0.51,0.04,and 0.95(<1.2),respectively,the model has good robustness.External verification was constructed through the test set,SEP was 0.03,r 2 pred was 0.73(>0.6),indicating that the model has a good external prediction ability,and the steric and electrostatic field’s contribution rates are 44.8%and 55.2%,respectively.According to the contour maps’information of the model,7 PBB-153 derivatives were designed,the change rates of comprehensive values of the dual spectral increased ranged 10.15%~29.12%.The Gaussian calculation results showed that the Gibbs free energy value of the derivative was less than 0 and the frequency was greater than 0.The C-Br bond dissociation enthalpy changeds lightly,indicating that the derivatives have good environmental stability and function.In addition,the environmental persistence,long-distance transmission,toxicity and bioenrichment of all derivatives were reduced,and the environmental friendliness was improved.Model validation results showed that the derivatives’single effects of infrared and ultraviolet were rising,and two spectral intensities changed the ratio of derivative No.4(4-OCN-5-NO-PBB-153)was 0.79,close to the set proportion of 1∶1,and the contour maps of dual effects basically contained the information of that of the single spectra effects model,indicating that the established CoMFA model has a certain accuracy and reliability.The established CoMFA model can accomplish the modification and comprehensive analysis of two single spectral effects simultaneously,providing the idea for the comprehensive evaluation of the spectral detection of other pollutants.