Schultz, T.W.; Yarbrough, J.W. Trends in structure-toxicity relationships for carbonyl-containing α,β-unsaturated compounds. SAR QSAR Environ. Res. 2004, 15, 2, 139–146.

Abstract

Using toxicity data for 30 aliphatic polarized alpha,beta-unsaturated derivatives of esters, aldehydes, and ketones, a series of six structure-toxicity relationships were evaluated. The structure feature of all assessed compounds, an acetylenic or olefinic moiety conjugated to a carbonyl group, is inherently electrophilic and conveys the capacity to exhibit enhanced toxicity. However, the toxic potency of alpha,beta-unsaturated carbonyl compounds is dependent on the specific molecular structure with several trends being observed. Specific observations include: (1) between homologues, the acetylenic-substituted derivative was more toxic than the corresponding olefinic-substituted one, respectively; (2) between olefinic-homologues, terminal vinyl-substituted derivative was more toxic than the internal vinylene-substituted one; (3) within alpha,beta-unsaturated ketones, methyl substitution on the vinyl carbon atoms reduces toxicity with methyl-substitution on the carbon atom farthest from the carbonyl group exhibiting the greater inhibition; (4) between alpha,beta-unsaturated carbonyl compounds with the carbon-carbon double bond on the end of the molecule (vinyl ketones) and those with carbon-oxygen double bonds on the end of the molecule (aldehydes), the ketones are more toxic than the aldehydes; (5) between homologues of alpha,beta-unsaturated esters, those with additional unsaturated moieties (allyl, propargyl, or vinyl groups) were more toxic than homologues having relevant unsaturated moieties (propyl or ethyl groups); (6) between alpha,beta-unsaturated carbonyl compounds with different shaped alkyl-groups (i.e. different degrees of branching), homologues with straight-chain hydrocarbon moieties were more toxic than those with branched groups.