Ishihara Mariko, Fujisawa Seiichiro
Division of Basic Chemistry, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan.
Dent Mater J. 2009 Jan;28(1):113-20. doi: 10.4012/dmj.28.113.
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 [-(E(HOMO)+E(LUMO))/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 [E(HOMO) and/or log P]. Results showed that the 13C NMR chemical shift of beta-carbon for methacrylates was correlated with their E(HOMO). Findings of this study thus suggested that it might be possible to predict methacrylate-induced toxicity using physicochemical properties.
为阐明甲基丙烯酸酯诱导毒性的机制，共选择了24种丙烯酸酯、甲基丙烯酸酯和二甲基丙烯酸酯，从核磁共振化学位移、半经验分子描述符和反相（RP）-HPLC log P方面进行构效关系（SAR）研究。使用PM3/CONFLEX方法计算分子描述符以及体积、电子和能量描述符。甲基丙烯酸酯在小鼠中的显著多元线性回归方程表示为log 1/LD50（它是函数[-(E(HOMO)+E(LUMO))/2, log P]）。此外，甲基丙烯酸酯在HeLa S3细胞和HGF细胞中的显著线性回归方程表示为log 1/ED50，是函数[E(HOMO)和/或log P]。结果表明，甲基丙烯酸酯β-碳的13C核磁共振化学位移与其E(HOMO)相关。因此，本研究结果表明，利用物理化学性质预测甲基丙烯酸酯诱导的毒性可能是可行的。
