ALPHA-DEUTERIUM AND C-13 ISOTOPE EFFECTS FOR METHYL TRANSFER CATALYZED BY CATECHOL O-METHYLTRANSFERASE - SN2-LIKE TRANSITION-STATE

The rate at near saturation of methylation of 3,4-dihydroxyacetophenone by S-adenosyl-L-methionine, catalyzed by rat-liver catechol O-methyltransferase at pH 7.58 and 37.00±0.05°C, is increased by deuteration of the methyl group (VCH3/VCD3= 0.83±0.05) and decreased by introduction ofl3C to the methyl group (V12/V13= 1.09±0.05). This shows the rate-determining step to be transfer of the methyl group, with an SN2-like transition state in which the methyl is located “symmetrically” and “tightly” between leaving group and nucleophile. © 1979, American Chemical Society. All rights reserved.