Structure-activity relationships in the hydrolysis of acrylate and methacrylate esters by carboxylesterase in vitro

Acrylate esters are important chemicals in the plastics industry, whose toxicity is theorized to involve alkylation of critical cellular nucleophiles via the Michael addition. Carboxylesterase-mediated hydrolysis of acrylates may be a detoxification mechanism as the unsaturated acid produced is not electrophilic under physiological conditions. Using purified porcine liver carboxylesterase, the enzymatic hydrolysis of several acrylate esters was characterized to determine K-m and V-max values for each ester. The K-m (mu M) and V-max (nmol/min) values observed for ethyl acrylate were 134 +/- 16 (S.D.) and 8.9 +/- 2.0, respectively. While the K-m for ethyl methacrylate was not significantly different, the V-max, 5.5 +/- 2.5 was significantly lower compared with the corresponding value for ethyl acrylate. The K-m and V-max for butylacrylate were 33.3 +/- 8.5 mu M and 1.49 +/- 0.83 nmol/min, respectively, and the corresponding values for its alpha-methyl analog were not significantly different, The K-m and V-max for tetraethyleneglycol dimethacrylate were 39 +/- 15 mu M and 2.9 +/- 1.0 nmol/min, respectively. The V-max for ethyleneglycol dimethacrylate, 6.9 +/- 2.4 nmol/min, was significantly higher than that of the larger bifunctional ester tetraethyleneglycol dimethacrylate, but the K-m was not significantly different. These results indicate that alpha-methyl substitution appears to have a minor effect in the enzymatic hydrolysis of acrylates, and suggest that the relative toxicity of acrylates is not due to differences in carboxylesterase-mediated hydrolysis. Copyright (C) 1997 Elsevier Science Ireland Ltd.