3D-QSAR Model of Polybrominated Biphenyls Tri-effect Modified by Standard Deviation Standardization Method and Its Application in Environmental Friendly Molecular Modification †

doi:10.7503/cjcu20190402

Abstract

Abstract:

A CoMFA model of tri-effect comprehensive values of infrared vibration intensity, bioconcentration and toxicity of PBBs via standard deviation method was constructed. The influence of PBBs’ molecular force fields on comprehensive values were analyzed to determine substitution sites. And the modification for PBB-153 with easy infrared detection, low bioconcentration and toxicity was accomplished. The CoMFA model had a good fitting and predicting ability on PBBs comprehensive values of infrared vibration intensity, bioconcentration and toxicity and had a good stability, the influencing force fields were electrostatic fields(E, 59.9%) and steric fields(S, 40.1%), respectively. Five substituents with higher electropositivity than Br were selected for single and double substitution of the target molecule PBB-153 according to the contour maps of CoMFA model, and six PBB-153 derivatives with increased tri-effect comprehensive values were screened. Predicting or calculating results of single effect of PBB derivatives indicated that the constructed CoMFA model can be applied to the modification of PBBs molecules. In addition, the flame retardancy and environmental friendliness of designed derivatives was comparable to the target molecule and the stability of derivatives was well. The results of 2D-QSAR model showed that the influence trends of dipole moment, maximum negative charge and the number of ortho Br atomic on the three single effects and comprehensive values were consistent.

Key words: Bioconcentration, Infrared spectrum, Toxicity, Polybrominated biphenyl, Molecular modification

CLC Number:

TrendMD:

Luze YANG,Miao LIU. 3D-QSAR Model of Polybrominated Biphenyls Tri-effect Modified by Standard Deviation Standardization Method and Its Application in Environmental Friendly Molecular Modification ^†[J]. Chem. J. Chinese Universities, 2019, 40(12): 2471.

Figures/Tables 9

Fig.1 Molecular structure of PBBs(R1, R1': C; R2—R6: H, Br; R2'—R6' : H, Br)

Model	q²	n	SEE	R²	F	$r pred 2$	SEP	Q²	cSDEP	dq²/dr²yy
CoMFA	0.51	8	0.18	0.94	28.38	0.63	0.35	0.18	0.64	1.19

Model	q²	n	SEE	R²	F	$r pred 2$	SEP	Q²	cSDEP	dq²/dr²yy
CoMFA	0.51	8	0.18	0.94	28.38	0.63	0.35	0.18	0.64	1.19

Fig.2 Contour maps of CoMFA model of steric(A) and electrostatic fields(B)

No.	Compound	Comprehensive value of three properties	Change rate(%)
0	PBB-153	1.15	—
1	R₂-(CH₂)₃NO₂-PBB-153	1.38	20.71
2	R₂-C₂H₅-R₄-CH₂NO₂-PBB-153	1.26	9.63
3	R₂-C₂H₅-R₄-(CH₂)₂NO₂-PBB-153	1.95	69.81
4	R₂-(CH₂)₂NO₂-R₄-C₂H₅-PBB-153	1.52	32.3
5	R₂-(CH₂)₂NO₂-R₄-(CH₂)₃NO₂-PBB-153	1.38	20.18
6	R₂-(CH₂)₂NO₂-R₄-(CH₂)₄NO₂-PBB-153	1.84	60.65

Compound	Highest infrared vibration intensity	Change rate(%)	BCF	Change rate(%)	lgLC₅₀	Change rate(%)
PBB-153	688.69	—	4814	—	-3.66	—
R₂-(CH₂)₃NO₂-PBB-153	777.68	12.92	1619	66.37	-3.45	5.78
R₂-C₂H₅-R₄-CH₂NO₂-PBB-153	983.34	42.78	4147	13.86	-2.76	24.70
R₂-C₂H₅-R₄-(CH₂)₂NO₂-PBB-153	855.31	24.19	2383	50.50	-3.19	12.92
R₂-(CH₂)₂NO₂-R₄-C₂H₅-PBB-153	794.56	15.37	2383	50.50	-3.19	12.92
R₂-(CH₂)₂NO₂-R₄-(CH₂)₃NO₂-PBB-153	1523.49	121.22	3651	24.16	-2.81	23.34
R₂-(CH₂)₂NO₂-R₄-(CH₂)₄NO₂-PBB-153	1581.47	129.63	2098	56.42	-3.24	11.59

Fig.3 Infrared vibration intensity of PBB-153 and PBB-153 derivatives

Compound	lgt_1/2(air)	Change rate(%)	lgt_1/2(river)	Change rate(%)
PBB-153	1.92	—	2.82	—
R₂-(CH₂)₃NO₂-PBB-153	1.64	14.64	2.38	15.71
R₂-C₂H₅-R₄-CH₂NO₂-PBB-153	1.35	29.64	2.14	23.97
R₂-C₂H₅-R₄-(CH₂)₂NO₂-PBB-153	1.12	41.93	1.80	36.28
R₂-(CH₂)₂NO₂-R₄-C₂H₅-PBB-153	1.33	30.57	1.93	31.60
R₂-(CH₂)₂NO₂-R₄-(CH₂)₃NO₂-PBB-153	1.26	34.32	1.86	34.11
R₂-(CH₂)₂NO₂-R₄-(CH₂)₄NO₂-PBB-153	1.31	31.56	1.91	32.27

Compound	Frequency/cm^-1	Energy gap/a.u.	Change rate (%)	Dissociation enthalpy/ (kJ·mol^-1)	Change rate(%)
PBB-153	20.27	0.192	—	348.49	—
R₂-(CH₂)₃NO₂-PBB-153	12.72	0.186	-3.33	358.02	2.73
R₂-C₂H₅-R₄-CH₂NO₂-PBB-153	18.60	0.188	-1.98	357.68	2.64
R₂-C₂H₅-R₄-(CH₂)₂NO₂-PBB-153	17.91	0.185	-3.77	351.96	0.99
R₂-(CH₂)₂NO₂-R₄-C₂H₅-PBB-153	14.34	0.186	-3.23	359.31	3.10
R₂-(CH₂)₂NO₂-R₄-(CH₂)₃NO₂-PBB-153	12.96	0.189	-1.89	359.31	3.11
R₂-(CH₂)₂NO₂-R₄-(CH₂)₄NO₂-PBB-153	12.78	0.189	-1.87	359.15	3.06

Eq.	SC_i	Freq.	a	μ	q⁺	q^-	qH⁺	E_HOMO	E_LUMO	lgP	V	N₂
(3)	y	-50.94	319.73	-130.4	-13.91	-45.23	23.28	-2686.7	82.77	-79.15	429.63	-31.34
(4)	lgIR	0.02	0	-0.05	-0.01	-0.03	-0.04	-0.97	0.05	-0.05	0.31	-0.003
(5)	-lgBCF	-0.14	0	-0.03	0.04	-0.01	0.2	0.07	-0.02	0.04	0	-0.05
(6)	lgLC50	-0.02	0	-0.02	-0.02	-0.004	-0.11	-0.38	0.18	0.02	-0.88	-0.01

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