Study For Activity Analysis Of The Environmental Behaviors Of Fluoroquinolones Based On Computational Chemistry

Fluoroquinolones(FQs)are the most representative homologue of pharmaceuticals and personal care products(PPCPs).FQs not only showed effective medicinal properties of wide bactericidal spectrum,small side effect,and moderate price effectively,but also has brought direct and potential hazards on environmental microorganisms,animals and plants and human health as a kind of "new pollutants",and showed persistent organic pollutants(POPs)characteristics.Because there were many kinds of FQs,and new drugs are still synthesized and developed constantly,the exprimental values of the physicochemical properties of FQs,especially in terms of the environmental hazards is lack,which is inconvenience to summary,analysis and evaluation the law of environmental behavior for FQs systematically.In this study,fluoroquinolones were taken as target pollutants,existing data in literature review,the simulated data and the predicted data from established models were integrated.Based on the complement of basic data,the ground state reaction activities,genotoxicity,photodegradability and spectrum characteristics of FQs were analyzed,and the regulation of FQs'environmental behaviours were put forwarded from views of molecular modification,the enhancing effect of solvents on the photodegradation of FQs,and comprehensive evaluation of FQs' environmental behaviours.Firstly,the ground state reaction activities of FQs were compared;then,the genotoxicity mechanism of FQs was analyzed and the modification scheme for weakening the genotoxicity mechanism of FQs was proposed;the comprehensive evaluation index of the environmental hazard of FQs was established via the combination of genotoxicity and ground state reaction activities;the photodegradation mechanism of FQs under light irradation was explored,and the enhancing effect and mechanism of different solvents on the photodegradation of FQs were evaluated and analyzed;the vibration modes of FQs' IR spectra were assigned,and the correlation between FQs'comprehensive evaluation index of environmental hazard and the informations of FQs' IR spectra.The ground state activities of fluoroquinolones were analyzed from views of ground state reaction activity,binding capacity with water molecules,bioconcentration and environmental persistence.The results show that:the distribution of charge density of HOMO and LUMO regulates the ground state reaction activity of FQs significantly;014 can form hydrogen bonds with water molecules easily,and the charge of 014 was negative correlative with the solubility of FQs in water;the residence time in methanol was taken as the evaluation index of bioconcentration in this paper,and the charge of 014 associated with C7 regulate the retention time effectively;fluoroquinolones in the wavelength of the first excited state is significantly negatively related to the half-life of FQs under the light irradation.Through the establishment of QSAR model,3D pharmacophore model and factorial experimental design for the genotoxicity of FQs,the subsituent positions of R1,R5,R7 and R8 can regulate genotoxicity of FQs significantly(the decisive effects of R5 and R7 were main effects,and the he decisive effects of R1 and R8 were second-order interactional effects).The genotoxicity of modified homologues was reduced by 10.1%,and the values of three evaluation indexes of modified homologues were 2.63,1.14 and 1.80 times of those of the original FQs,respectively.Intermolecular forces,especially strong intermolecular forces of hydrogen bonding,electrostatic and polarity were main forces between FQs and DNA-gyrase A.The weaker intermolecular force betweem modified congener and DNA-gyrase A decrease the genotoxicity of modified congener.There are two electron transitions of fluoroquinolones in the UV spectrum,which are distributed in the ranges of 300?380 nm and 240?300 nm,respectively,belonging to n??*and ???*electron transitions.The transition of n??*is more sensitive to solvent than the transition of ???*,but solvant effect on the transition of ???*is stronger than the transition of n??*,and the strength of solvant effect is positive correlated with the dielectric constant of solvent.From the view of photo-induced reactions,the reaction between FQs*Ti and Solvent*TI has the decisive regulatory effect on the n??*transition of FQs in solvent,and the reaction between FQsS0 and Solvent*TI has an enhancing effect on the n??*transition.The similarity of IR spectra among 21 kinds of FQs is small;with the average value of correlation coefficient and the cosine angle are 0.694 and 0.712 respectively.21 kinds of FQs can be divided into 4 catogories via clustering analysis based on the vibration informations of IR spectra,then,the vibration assignment was implemented.The vibration mode of benzene ring stretching vibration,C12=O13 stretching vibration,C4=O11 stretching vibration and O14-H15 stretching vibration were selected as characteristic vibrations,and the key substitution positions for different vibration modes are different.The established QSAR model based on the spectral information of vibration assignment meet all requirements.The environmental hazardness of FQs was mainly controlled by 9 IR spectral regions based on principal component analysis.