Chem. J. Chinese Universities ›› 2018, Vol. 39 ›› Issue (12): 2707.doi: 10.7503/cjcu20180475

• Physical Chemistry • Previous Articles     Next Articles

Molecular Design of Lower Photodegradation Fluoroquinolone Antibiotics and Their Photolysis Paths Inference

ZHAO Xiaohui1,2, CHU Zhenhua1,2, LI Yu1,2,*()   

  1. 1. College of Environmental Science and Engineering, North China Electric Power University, Beijing 102206, China
    2. The Key Laboratory of Resources and Environmental Systems Optimization, Ministry of Education,North China Electric Power University, Beijing 102206, China
  • Received:2018-07-02 Online:2018-11-20 Published:2018-11-20
  • Contact: LI Yu E-mail:liyuxx@jlu.edu.cn

Abstract:

Dividing the obtained data of photodegradation half-life(t1/2) for 12 fluoroquinolones(FQs) into the training set and test set in a radio of 4:1(random combination), comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA) were used to establish 3D-QSAR models to predict the lgt1/2 values of the remaining 14 FQs, with the structural parameters as independent variables and the lgt1/2 values as the dependent variables through the Sybyl-x software. The results showed that the cross-validation correlation coefficients(q2) for CoMFA and CoMSIA models constructed by random combination were 0.564—0.655(>0.5) and the non-cross-validated correlation coefficients(r2) were 0.996—1.000(>0.9), indicating that the models were robust and predictive. The prediction of the photolysis t1/2 found that the fourth type of FQs generally had a higher t1/2 value than the third type of FQs. Taking ciprofloxacin(CIP) as the target molecule, introducing the smaller groups at the selected C13 position of CIP helped to design 9 modified CIP molecules with t1/2 values significantly decreased, and the t1/2 value of the modified molecule with the introduction of OH groups reduced most(27.2%). The photodegradation paths inference of CIP molecules and modified molecules indicated that the minimum energy barrier was required for the path of aromatic ring hydroxylation during CIP photodegradation, and the oxidative decarboxylation reaction had the largest energy barrier and the most paths of piperazine ring fracture. For the modified CIP molecules, the energy barriers of three reactions, aromatic ring hydroxylation, oxidative decarboxylation, and hydroxylation defluorination remained basically unchanged but the energy barrier required for the piperazine ring fracture significantly reduced. Evaluation of the biodegradability of modified CIP molecules and their photolysis products revealed that not only the photolytic activity of modified CIP molecules increased, but also the biodegradability increased by 0.26% to 59.71%, and the biodegradability of the photolysis products also increased significantly(12.03%—34.38%). It indicated that CIP and modified CIP molecules can eventually generate products with significantly improved biodegradability through photodegradation in favor to further control the environmental behaviors of FQs.

Key words: Fluoroquinolone, Half-life, Molecular modification, Photolysis path, Biodegradation

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