Tire additives: Evaluation of joint toxicity, design of new derivatives and mechanism analysis of free radical oxidation

Abstract

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is one of the most widely used antioxidant agents in tire additives. Its ozonation by-product 6PPD-quinone has recently been recognized as inducing acute mortality in aquatic organisms such as coho salmon. In this study, we aimed to develop an in-silico method to design environmentally friendly 6PPD derivatives and evaluate the joint toxicity of 6PPD with other commonly used tire additives on coho salmon through full factorial design-molecular docking and molecular dynamic simulation. The toxicity mentioned in this study is represented by the binding energy of chemical(s) binding to the coho salmon growth hormone. The recommended formula for tire additives with relatively low toxicity was then proposed. To further reduce the toxicity of 6PPD, 129 6PPD derivatives were designed based on the N-H bond dissociation reaction, and three of these derivatives showed improved antioxidant activity and 6PPD-106 was finally screened as the optimum alternative with lower toxicity to coho salmon. Besides, the mechanism of free radical oxidation (i.e., antioxidation and ozonation metabolic pathway) for 6PPD-106 was also analyzed and found that after ozonation, the toxicity of 6PPD-106's by-products is much lower than that of 6PPD's by-products. This study provided a molecular modelling-based examination of 6PPD, which comprehensively advanced the understanding of 6PPD's environmental behaviors and provided more environmentally friendly 6PPD alternatives with desired functional property and lower ecological risks.