A structure-activity relationship study on the mechanisms of methacrylate-induced toxicity using NMR chemical shift of β-carbon, RP-HPLC log P and semiempirical molecular descriptor

Abstract

To clarify the mechanism of methacrylate-induced toxicity, a total of 24 acrylates, methacrylates, and dimethacrylates were chosen for a structure-activity relationship (SAR) study in terms of NMR chemical shifts, semiempirical molecular descriptors, and reverse phase (RP)-HPLC log P. Molecular descriptors as well as bulk, electronic, and energy descriptors were calculated using the PM3/CONFLEX method. A significant multiple linear regression equation for methacrylates in mice was denoted as log 1/LD50 (which was function [-EHOMO+ELUMO)/2, log P]). Besides, significant linear regression equations for methacrylates were denoted as log 1/ED50 in HeLa S3 and in HGF cells as function [EHOMO and/or log P]. Results showed that the 13C NMR chemical shift of β-carbon for methacrylates was correlated with their EHOMO. Findings of this study thus suggested that it might be possible to predict methacrylate-induced toxicity using physicochemical properties.