A model for phthalic acid esters’ biodegradability and biotoxicity multi-effect pharmacophore and its application in molecular modification

Abstract

The objective of this study was to investigate 13 phthalic acid esters (PAEs) with medium or long straight-alkyl-chain, branching or unsaturated side chains, because their structural characteristics make them difficult to biodegrade or highly toxic. A biodegradability and biotoxicity multi-effect pharmacophore model was built using comprehensive evaluation method. The results suggested that introducing hydrophobic groups to the side chains of the PAEs could improve the molecules’ biodegradability and biotoxicity effects simultaneously. Thus, 40 target PAE (HEHP, DNOP, DUP) derivatives were designed. Two environmentally friendly PAE derivatives (HEHP-Anthryl and HEHP-Naphthyl) were screened via the test of environmental friendliness and functionality. In addition, the biodegradation and biotoxicity of derivatives were found to have improved as a result of the change in van der Waals forces between molecules and their corresponding proteins. Moreover, the environmental safety of the screened PAE derivatives was confirmed by predicting the toxicity of their intermediates and calculating the energy barrier values for biodegradation and metabolic pathways. This study could provide theoretical guidance for the practical development of environmentally friendly plasticizer.