基于药效团模型设计的PAEs分子拉曼特征振动光谱衍生增强研究

对17个PAEs训练集分子、五个PAEs测试集分子，应用Discovery Studio软件构建PAEs分子拉曼特征振动光谱的3D QSAR 药效团模型，并对PAEs分子(以环境优先控制污染物DMP，DBP和DNOP为例)进行9种常见的疏水基团取代反应，同时利用密度泛函理论B3LYP/6-31G(d)计算气态环境中取代前后PAEs的拉曼特征振动光谱，筛选PAEs拉曼特征振动光谱显著增强的衍生物。研究结果表明：药效团模型(Hypo1)具有最大的相关系数(R2)0.83、最小的均方根值(RMS)0.182和总消耗值(total cost)71.865，且Configuration值为12.68(<17)，说明所构建模型具有显著性及较好的预测能力；获得基于Hypo 1药效团模型设计的PAEs分子衍生物23个：DMP(9), DBP(9)和DNOP(5)，上述衍生物分子正频计算值均大于0，说明所设计的PAEs分子衍生物结构稳定，其中DMP-CH₂CH₃，DBP-Cl，DNOP-C₆H₅的拉曼特征振动光谱峰强较DMP，DBP和DNOP分别增大了6.25倍、2.05倍、1.56倍，说明PAEs分子衍生化对其拉曼特征振动光谱峰强具有显著增强作用。此外，利用密度泛函理论在相同的基组水平下计算了PAEs分子衍生物的取代反应能垒(以DNOP为例)，取代反应的难易程度：-CH₂CH₂CH₃>-C₆H₅>-NO₂>-SH>-Cl，可作为筛选PAEs分子衍生化拉曼光谱增强反应的依据，并为建立增强PAEs分子拉曼光谱的检测技术提供理论支撑。

Derivatization Enhanced Raman Characteristic Vibration Spectrum of PAEs Based on Pharmacophore Model

In this paper, 3D QSAR pharmacophore models of PAEs Raman characteristic vibration spectrum were established by Discovery Studio software for 17 phthalic acid esters were used as training set and 5phthalic acid esters used as test set. The substitution reaction of PAEs (take environmental priority controlled pollutants DMP, DBP and DNOP for example) used the optimal pharmacophore model built by Hypo 1 and 9 kinds of common hydrophobic groups. At the same time, the Raman characteristic vibration spectrum of PAEs and derivatives in gaseous environment were calculated by using density functional theory at B3LYP/6-31g(d) level, which was to screen derivative reaction of PAEs Raman characteristic vibration spectrum enhanced significantly. The results showed that the pharmacophore model (Hypo 1) was significant and had good predictive abilities with the greatest correlation coefficient (R2) of 0.83, the smallest value of root mean square (RMS) of 0.182 and the total cost of 71.865, the configuration value of 12.68 (<17). There were 23PAEs derivatives based on Hypo 1, including 9 DMP derivatives, 9 DBP derivatives, 5 DNOP derivatives, and the positive frequencies of derivative molecules were greater than 0, which illustrate the structure of PAEs derivatives were stable. The Raman characteristic vibration spectrum intensity of DMP-CH₂CH₃, DBP-Cl, DNOP-C₆H₅ increased comparing with DMP, DBP, DNOP by 6.25 times, 2.05 times and 1.56 times respectively, which indicated that PAEs derivatization had significantly enhanced effect on Raman characteristic vibration spectrum intensity. In addition, the substitution reaction energy barriers of PAEs derivatives were calculated by using density functional theory at B3LYP/6-31g(d) level, (take DNOP for example), and the substitution reaction order of the substituent -C₆H₅, -CH₂CH₂CH₃, -SH, -Cl, -NO₂ and DNOP molecule was -CH₂CH₂CH₃>-C₆H₅>-NO₂>-SH>-Cl, which can be uesd as the basis of screening PAEs molecular derivatization enhanced Raman spectrum reaction and provide theoretical support for the enhanced Raman spectrum detection technology.