title: A structure-activity relationship study on the mechanisms of methacrylate-induced toxicity using NMR chemical shift of beta-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 [-(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.
authors.affiliation: Division of Basic Chemistry, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan. mariko@dent.meikai.ac.jp
authors.forename: Mariko
authors.initials: M
authors.lastname: Ishihara
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Fujisawa
mesh_terms: D000179:Acrylates / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D017438:Bisphenol A-Glycidyl Methacrylate / Q000737:chemistry / Q000633:toxicity; D002244:Carbon; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003764:Dental Materials / Q000737:chemistry* / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008689:Methacrylates / Q000737:chemistry* / Q000633:toxicity; D020366:Methylmethacrylate / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D008956:Models, Chemical; D008958:Models, Molecular; D011092:Polyethylene Glycols / Q000737:chemistry / Q000633:toxicity; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000633:toxicity; D012031:Refractometry; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
chemical_list: D000179:Acrylates; D003764:Dental Materials; D008689:Methacrylates; D011109:Polymethacrylic Acids; C020946:triethylene glycol dimethacrylate; D020366:Methylmethacrylate; D011092:Polyethylene Glycols; D017438:Bisphenol A-Glycidyl Methacrylate; D002244:Carbon; C016284:butyl methacrylate