Study On The Spectral Enhancement Of Environmentally Friendly PAE Derivatives Through The Pharmacophore Model

Phthalate acid esters(PAEs)are one of the most widely used plasticizers and are widely used in the production of plastic products such as food packaging materials,toys,medical supplies and personal care products.When PAEs are combined with plastic molecules,they maintain relatively independent chemical properties.PAEs diffuse from plastics during use,and air,water,soil and food are contaminated.Therefore,the environmental effects of PAEs are gradually attracting social attention.PAEs are teratogenic,carcinogenic,and mutagenic to human health.Six of the PAEs are listed as priority pollutants by the US Environmental Protection Agency.PAEs are now known as "the second global PCB pollutant".However,most of the previous studies have been limited to photodegradation,biodegradation behavior,and processing technology research based on this,but lack of studies on the modification of molecular structure by using substituents.Therefore,this paper takes PAEs as the research object,and uses quantum chemical calculation and 3D QSAR pharmacophore model as the main research methods to carry out PAEs spectral identification and establish spectral enhancement detection technology of PAEs as the main research purpose,and provide a theoretical basis for guiding the design of environmentally friendly PAEs.Finally,the environmental behaviors of PAEs are controlled from spectral identification,spectral enhancement,and seeking alternatives to reduce their environmental hazards.Density functional theory was used to optimize the structure of various PAEs,and their Raman,infrared and ultraviolet spectra were calculated.The spectral information of PAEs was extracted,and the identification between PAEs was carried out.The enhancement of the PAEs spectra by the solvation effect were analyzed.The results show that the Raman characteristic spectra of 12 PAEs are identified according to the Raman vibration and wave number difference.The solvent(benzene)with significant solvation effect on PAEs characteristic Raman spectroscopy was screened.The difference in wavenumber between the largest Raman peaks is greater than the minimum detection limit of 0.2 cm-1 of the Raman spectrum.The theoretical identification of the vibrational spectra of 16 kinds of PAEs Raman characteristics is realized.The identification of a variety of PAEs can be achieved by relying on the ester-based vibration frequency of the infrared spectrum.The minimum wave number difference between the peaks of the UV absorption spectra of only 12 PAEs in the 16 PAEs is greater than the minimum resolution of 0.10 nm of the ultraviolet spectrum detector.The solvation effect makes the absorption peak distribution of the remaining four PAEs more dispersed and easy to distinguish.The 3D QSAR pharmacophore models of PAEs Raman,infrared and ultraviolet spectra was constructed by using Discovery Studio software.The spectral derivation enhancement of PAEs was studied based on the pharmacophore model,and the PAE derivatives were screened from the difficulty of derivatization.The results show that the the hydrophobic properties play the most important role in the established 3D QSAR pharmacophores corresponding to the three spectral properties of PAE,respectively.Three kinds of environmentally controlled PAEs(DMP,DBP,DNOP)were used as template molecules,a variety of PAE derivatives were designed for the template molecules.Among them,the maximum intensity enhancement degree of Raman characteristic vibration spectra are 6.25 times,2.05 times and 1.56 times.The maximum intensity enhancement degree of infrared characteristic vibrational spectra are 76.98%,26.49%and 16.42%,and the maximum enhancement degree of ultraviolet spectral intensity are 121.85%,105.20%and 191.11%,respectively,compared with the template molecules.In addition,the difficulty of the PAEs derivatization reaction was characterized,and the orders of difficulty in the substitution reaction between the substituent and the PAEs molecule were obtained.Fluorescence spectroscopy is one of the main detection methods for PAEs,and PAEs do not have fluorescent characteristics themselves.The construction of the fluorescence spectroscopy theoretical detection method based on single and double substitution modification of highly sensitive PAE derivatives shows that:compared to the fluorescence intensity of PAEs after binding to bovine serum(BSA)protein,the fluorescence intensity of PAEs mono-and di-substituted derivatives are significantly increased by 100%-1850%and 28.20-110.00 times,respectively,indicating high sensitivity.The PAE derivatives with fluorescence spectral properties have no effect on their functionality(stability,insulation),and their persistence,migration and toxicity are reduced to varying degrees,bioaccumulation has no obvious change,indicating environmentally friendly.In the same fluorescence spectral wavelength range(240-420 nm),there is no interference between PAE derivatives with fluorescence spectral characteristics and POPs(polycyclic aromatic hydrocarbons).The mechanism of fluorescence characteristics based on 2D QSAR shows that the occupied orbital energy value and the number of Mulliken charges are the main factors for the fluorescence spectral characteristics of PAE derivatives.The docking conformation of bovine serum(BSA)protein with target PAEs shows the key amino acid residues directly interacting with the target PAEs at the active site of BSA protein.A total of 8 amino acid sequence modification schemes of BSA protein were designed.The homology modeling method was used to obtain the structure of the novel BSA protein.The binding affinity of the novel BSA protein to the target PAEs was evaluated.The binding affinity of the novel BSA-3 protein was the most significant to the target DMP,DBP and DNOP,which was 3.37%,12.88%and 16.30%,respectively.At the same time,the fluorescence intensity of BSA protein binding to target PAEs before and after BSA protein modification was calculated by Gaussian09 software.It was found that the fluorescence intensity of the novel BSA-7 protein,the novel BSA-8 protein,and the novel BSA-4 protein combined with the target DMP,DBP and DNOP were enhanced by 1.80 times,103.50 times and 61.43 times,respectively,which could achieve rapid and efficient detection of target PAEs.In addition,a molecular design of PAEs with low estrogenic activity and fluorescent characteristics was also carried out.The 3D QSAR pharmacophore model of estrogen activity was constructed using the molecular structure and EC50 values of PAEs.The model has good predictive ability and stability,and carried out a molecular design with low estrogenic activity.Based on this,high fluorescence intensity was used as a screening method.The 12 kinds of PAE derivatives with low estrogen activity(down to 3 orders of magnitude)and high fluorescence intensity(significantly more than 20 times)were obtained and were environmentally friendly.The molecular docking technique was used to study the mechanism of the decrease in estrogen activity of PAE derivatives.It was found that the longer the bond length formed by the interaction,the lower the estrogenic activity when PAEs and their derivatives bind to estrogen receptors.