Computational Study of Electrochemical Properties Related to the Degradation of Endocrine Disruptors

Abstract

This project proposes the use of computational techniques to understand process of electrochemical degradation, generation of subproducts and prediction of reactivity sites of five molecules that act as endocrine disruptors (ibuprofen, estradiol, ciprofloxacin, malathion e acetochlor). In addition, a chemical-biological analysis of two hormone receptors (progesterone receptor and sex hormone-binding globulin) will be perform and the possible interactions that may exist with three molecules used in plastics, and we propose the change of DEHP (considered an endocrine disruptor) by two possible substitutes (DL9TH and ATEC). So, important methodologies will be used in the electronic study of molecular structures, such as (i) the choice of the basis set to be used in the calculations from the comparison of the theoretical values (obtained from TD-DFT, implemented in Gaussian09) and experimental values of absorption »max; (ii) geometric optimization of the five endocrine disruptors and calculation of the energy values of HOMO, LUMO, SOMO and the atomic charges, which will be related to electrochemical data; (iii) NBO analysis from the donor-acceptor point of view of electronic pair, allowing the description of possible electronic transfers; (iv) use of the QTAIM methodology in order to determine the types of bonds and the possible sites of reactivity. The second part of the project involves the study of the two hormone receptors and the molecules DEHP, DL9TH and ATEC, in which the following methods will be used: (v) molecular docking to simulate the three molecules in the active sites of the receptors and obtaining possible bioactive conformations; (vi) molecular dynamics simulations to evaluate the dynamic behavior of DEHP, DL9TH and ATEC at the biological receptors; (vii) calculations of binding free energy with the MM-GBSA and MM-PBSA methods to evaluate the stability of the three compounds interacting with the hormone receptors and (viii) use of a tool implemented in Amber 18 to calculate the redox potential of the three molecules interacting with the two selected receptors. In this way, the use of the computational methodologies cited above will be fundamental for the electronic and chemical-biological study of endocrine disruptors.