Combined QSAR/QSPR, Molecular Docking, and Molecular Dynamics Study of Environmentally Friendly PBDEs with Improved Insulating Properties

doi:10.1007/s40242-019-8353-9

摘要/Abstract

摘要： To improve the insulating properties of polybrominated diphenyl ethers(PBDEs), we studied the molecular structures and energy gap(E_g) values of 209 PBDEs using a three-dimensional quantitative structure-activity relationship(3D-QSAR) model, molecular docking, and molecular dynamics. We also analyzed the interaction mechanisms of PBDEs using a 2D-QSAR model, molecular substitution characteristics, and molecular docking. The 3D-QSAR model showed that the 2-, 4-, 5-, and 6-positions significantly influenced the PBDE insulating properties. Using BDE-34 as a template molecule, we designed six derivatives with 0.47%-28.44% higher insulation than BDE-34. Compared with BDE-34, the stability and flame retardancy of the above six derivatives were not adversely affected. These derivatives, except for 2,6-cyanomethyl-BDE, 2-cyanomethyl-BDE, and 2-aminomethyl-BDE, were more toxic and biodegradable than BDE-34, but showed weaker bioaccumulation and migration abilities than BDE-34. Mechanism analysis showed that the highest occupied orbital energy, the most negative charge, and the dipole moment were the main quantitative parameters that affected the PBDE insulating properties. PBDE insulation gradually decreased as the number of Br atoms increased. The level of similarity between the substitution patterns on the two benzene rings was significantly correlated with PBDE insulation, with hydrophobic groups having a more significant effect on PBDE insulation.

关键词: Polybrominated diphenyl ether, High insulation, Three-dimensional quantitative structure-activity relationship, Molecular docking, Molecular dynamics, Molecular modification

Abstract: To improve the insulating properties of polybrominated diphenyl ethers(PBDEs), we studied the molecular structures and energy gap(E_g) values of 209 PBDEs using a three-dimensional quantitative structure-activity relationship(3D-QSAR) model, molecular docking, and molecular dynamics. We also analyzed the interaction mechanisms of PBDEs using a 2D-QSAR model, molecular substitution characteristics, and molecular docking. The 3D-QSAR model showed that the 2-, 4-, 5-, and 6-positions significantly influenced the PBDE insulating properties. Using BDE-34 as a template molecule, we designed six derivatives with 0.47%-28.44% higher insulation than BDE-34. Compared with BDE-34, the stability and flame retardancy of the above six derivatives were not adversely affected. These derivatives, except for 2,6-cyanomethyl-BDE, 2-cyanomethyl-BDE, and 2-aminomethyl-BDE, were more toxic and biodegradable than BDE-34, but showed weaker bioaccumulation and migration abilities than BDE-34. Mechanism analysis showed that the highest occupied orbital energy, the most negative charge, and the dipole moment were the main quantitative parameters that affected the PBDE insulating properties. PBDE insulation gradually decreased as the number of Br atoms increased. The level of similarity between the substitution patterns on the two benzene rings was significantly correlated with PBDE insulation, with hydrophobic groups having a more significant effect on PBDE insulation.

Key words: Polybrominated diphenyl ether, High insulation, Three-dimensional quantitative structure-activity relationship, Molecular docking, Molecular dynamics, Molecular modification

LIU Sicheng, SUN Shijun. Combined QSAR/QSPR, Molecular Docking, and Molecular Dynamics Study of Environmentally Friendly PBDEs with Improved Insulating Properties[J]. 高等学校化学研究, 2019, 35(3): 478-484.

LIU Sicheng, SUN Shijun. Combined QSAR/QSPR, Molecular Docking, and Molecular Dynamics Study of Environmentally Friendly PBDEs with Improved Insulating Properties[J]. Chemical Research in Chinese Universities, 2019, 35(3): 478-484.

参考文献 34

[1]	Zhou J., Chen Q. S., Huang S. X., Wang Y., Zou P. Y., National Symposium on Insulation Materials and Insulation Technology, 2010
[2]	Liu X., Science and Technology Innovation, 2010, 27, 30
[3]	Stiborova H., Vrkoslavova J., Lovecka P., Pulkrabova J., Hradkova P., Hajslova J., Demnerova K., Chemosphere, 2015, 118, 315
[4]	Zhang X., Gao Y. J., Yan C. Z., Ecology and Environmental Sciences, 2009, 18, 761
[5]	Aznar-Alemany Ò., Aminot Y., Vilà-Cano J., Köck-Schulmeyer M., Readman W., Marques A., Godinho L., Botteon E., Ferrari F., Boti V., Albanis T., Eljarrat E., Barceló D., Science of the Total Environment, 2018, 612, 492
[6]	McDonald T. A., Chemosphere, 2002, 46, 745
[7]	Schecter A., Pavuk M., Päpke O., Ryan J., Birnbaum L., Rosen R., Environmental Health Perspectives, 2003, 111, 1723
[8]	Christensen H., Glasius M., Pécseli M., Platz J., Pritzl G., Chemosphere, 2002, 47, 631
[9]	Parolini M., Guazzoni N., Binelli A., Tremolada P., Archives of Environmental Contamination & Toxicology, 2012, 63, 29
[10]	Stoker T. E., Cooper R. L., Lambright C. S., Wilson V. S., Furr J., Gray L. E., Toxicology & Applied Pharmacology, 2005, 207, 78
[11]	Eriksson P., Fischer C., Fredriksson A., Toxicological Sciences, 2006, 94, 302
[12]	Wu W., Nie F. Q., Zhai J. H., Ecology and Environmental Sciences, 2009, 18, 408
[13]	Usenko C. Y., Robinson E. M., Usenko S., Brooks B. W., Bruce E. D., Environmental Toxicology & Chemistry, 2011, 30, 1865
[14]	Gu W. W., Chen Y., Li Y., Bulletin of Environmental Contamination & Toxicology, 2017, 99, 276
[16]	Shi J. Q., Qu R. J., Feng M. B., Wang X. H., Wang L. S., Yang S. G., Wang Z. Y., Environmental Science & Technology, 2015, 49, 4209
[17]	Wang X. L., Gu W. W., Guo E., Cai C., Li Y., Environmental Science & Pollution Research, 2017, 24, 14802
[18]	Jiang L., Li Y., Journal of Hazardous Materials, 2016, 307, 202
[19]	Qu R. J., Liu H. X., Feng M. B., Yang X., Wang Z. Y., Journal of Chemical and Engineering Data, 2012, 57, 2442
[20]	Li W. L., Si H. Z., Li Y., Ge C. Z., Song F. C., Ma X. T., Duan Y. B., Zhai H. L., Journal of Molecular Structure, 2016, 1117, 227
[21]	Holt P. A., Chaires J. B., Trent J. O., ChemInform, 2010, 39, 1602
[22]	Yang M., Zhou L., Zuo Z. L., Tang X. Y., Liu J., M X., Molecular Simulation, 2008, 34, 849
[23]	Li X., Fu J., Shi W., Luo Y., Zhang X., Zhu H., Yu H., Bull. Korean Chem. Soc., 2013, 34,2387
[24]	Zhang L. Z., Ren Z. J., Lu A., Zhao Z., Xu W., Bao Q. Q., Ding W. J., Yang C. L., Chem. Res. Chinese Universities, 2015, 31(2), 228
[25]	Yang G. F., Ding Y., Yang H. Z., Wu X. J., Chem. J. Chinese Universities, 2004, 25(1), 71
[26]	Brinkman W., Brinkman W., Briels J., Verweij H., Chemical Physics Letters, 2017, 247, 386
[27]	Chu Z. H., Li Y., Journal of Hazardous Materials, 2019, 364, 151
[28]	Zhang S. J., Qiu Y. L., Li Y., Current Analytical Chemistry, 2018, 14, 1
[29]	Robrock K. R., Mohn W. W., Eltis L. D., Alvarezcohen L., Biotechnology & Bioengineering, 2011, 108, 313
[30]	Li X. L., Ye L., Wang X. X., Wang X. Z., Liu H. L., Zhu Y. L., Yu H. X., Toxicology & Applied Pharmacology, 2012, 265, 300
[31]	Wang X. L., Chu Z. H., Yang J. W., Li Y., Environmental Science & Pollution Research, 2017, 24, 1
[32]	Meerts I. A., Letcher R. J., Hoving S., Marsh G., Bergman A., Lemmen J. G., Burg B., Brouwer A., Environmental Health Perspectives, 2001, 109, 399
[33]	Hamers T., Kamstra J. H., Sonneveld E., Murk A. J., Kester M. H., Andersson P. L., Legler J., Brouwer A., Toxicological Sciences, 2006, 92, 157
[34]	Minerva M. F., Bigsby R. M., Environmental Health Perspectives, 2008, 116, 1315

[1]	QIAN Shengjie, WANG Yanggang, LI Jun. Single Iron-dimer Catalysts on MoS₂ Nanosheet for Potential Nitrogen Activation[J]. 高等学校化学研究, 2022, 38(5): 1226-1231.
[2]	Ghadah F. ALJOHANI, Fatma A. A. EL-HAG, Mohamed S. BEKHEIT, Ewies F. EWIES, May A. EL-MANAWATY. An Efficient One-pot Synthesis of Certain Stereoselective Spiro[pyrazole-4,5'-isoxazoline]-5-one Derivatives: In vitro Evaluation of Antitumor Activities,Molecular Docking and In silico ADME Predictions[J]. 高等学校化学研究, 2022, 38(4): 1073-1082.
[3]	XIAO Jiapeng, ZHANG Wenhui, ZHANG Shujing, LI Yu. Molecular Modification of Benzophenone Derivatives for Lower Bioenrichment and Toxicity Through the Pharmacophore Model[J]. 高等学校化学研究, 2022, 38(2): 535-545.
[4]	QUAN Jishun, ZHANG Dongping, ZHANG Zhuo, WANG Jian, MA Chao, CHENG Maosheng. Design, Synthesis and Biological Evaluation of Pyrrolo[2,1-c] [1,4]benzodiazepine-3,11-dione Derivatives as Novel Neuroprotective Agents[J]. 高等学校化学研究, 2021, 37(3): 647-654.
[5]	LI Huangong, ZHAO Yangyang, SUN Pengwei, GAO Li, XIONG Lixia, YANG Na, ZHOU Sha, LI Yuxin, LI Zhengming. Targeted Synthesis of Anthranilic Diamides Insecticides Containing Trifluoroethoxyl Phenylpyrazole[J]. 高等学校化学研究, 2021, 37(3): 655-661.
[6]	ZHANG Shujing, XIAO Jiapeng, CHEN Xinyi, LI Yu. Insulation and Flame Retardancy Improvement of PBDEs Using 3D-QSAR Model Combined with a Fuzzy Membership Function Method[J]. 高等学校化学研究, 2021, 37(3): 729-738.
[7]	CHEN Aiyu, LIANG Yongdong, YE Jiao, HU Aixi, LIAN Wenwen, LIU Ailin, DU Guanhua. Synthesis of Chalcone Derivatives Containing Furan or/and Pyran Ring as Neuraminidase Inhibitors[J]. 高等学校化学研究, 2019, 35(3): 395-402.
[8]	MA Junjie, HUANG Kun, NI Xin, CHEN Roufen, XU Boxuan, WANG Cuifang. Design, Synthesis, Biological Activity and Molecular Docking Study of Coumarin Derivatives Bearing 2-Methyl b iphenyl Moiety[J]. 高等学校化学研究, 2019, 35(3): 410-417.
[9]	ZANG Dongyun, ZHAO Guanjia, LIU Xiaona, YIN Jianguo, MA Suxia. Experimental and Molecular Simulation of Volumetric Properties of Methyl Nonanoate, n-Dodecane, and Their Binary Mixtures[J]. 高等学校化学研究, 2019, 35(2): 299-303.
[10]	ZHAO Xiaohui, QIU Youli, JIANG Long, LI Yu. Analysis of Affinity Energy Between Biphenyl Dioxygenase and Polychlorinated Biphenyls Using Molecular Docking[J]. 高等学校化学研究, 2019, 35(2): 325-332.
[11]	JIN Bo, TAO Ye, YANG Hongliang. Synthesis, Biological Evaluation and Molecular Docking of Novel Phenylpyrimidine Derivatives as Potential Anticancer Agents[J]. 高等学校化学研究, 2018, 34(6): 912-917.
[12]	WU Leichao, HAN Yong, ZHANG Qianrui, ZHU Lin, ZHANG Chuanxin and ZHAO Ruikuan. Molecular Dynamics Simulation: Influence of External Electric Field on Bubble Interface in Air Flotation Process[J]. 高等学校化学研究, 2018, 34(6): 939-944.
[13]	HE Wei, ZHAO Anran, ZOU Jiajia, LUO Xuan, LIN Xiao, WANG Lisheng, LIN Cuiwu. Synthesis, In vitro Coagulation Activities and Molecular Docking Studies on Three L-Histidine Amide Derivatives[J]. 高等学校化学研究, 2018, 34(1): 90-94.
[14]	LIANG Guangping, CHUNG Tseyu, GUO Jinhua, ZHANG Rongrong, XÜ Wei, TZEN Jason T. C., JIANG Renwang. Novel Cinobufagin Oxime Ether Derivatives as Potential Na⁺/K⁺-ATPase Inhibitors: Synthesis, Biological Screening and Molecular Docking[J]. 高等学校化学研究, 2017, 33(3): 378-383.
[15]	LI Hui, ZOU Huiyuan, LIU Linlin, ZHAO Dongxia, YANG Zhongzhi. Studies on Hydrolysis Mechanism of Anticancer Ruthenium Drug ImH[trans-Ru(Im)₂Cl₄] via ABEEMσπ Polarizable Force Field Combined with QM and MD-FEP[J]. 高等学校化学研究, 2017, 33(2): 239-247.