ALPHA-DEUTERIUM ISOTOPE EFFECTS AND TRANSITION-STATE STRUCTURE IN AN INTRA-MOLECULAR MODEL SYSTEM FOR METHYL-TRANSFER ENZYMES

The α-deuterium isotope effects for the general base catalyzed ring-closure reaction of 2-(2-m-hydroxycyclopentyl) ethylmethyl-4-nitrophenylsulfonium tetrafluoroborate (1) are k2H/k2D= 1.17±0.02 (water catalysis), 1.104±0.014 (carbonate buffer catalysis), and 0.998±0.001 (hydroxide ion catalysis) in aqueous solution (μ = 1.0) at 40.00±0.05°C. These are all considerably more normal (i.e., larger in the direction kH> kD) than the effect for the catechol O-methyltransferase reaction (k3H/k3D= 0.83±0.05) for which the reactions of 1 are a model. This indicates the model-reaction transition states to be looser (i.e., to possess a longer oxygen-to-sulfur distance) than the enzymic transition state and suggests that the enzyme may achieve all or part of its catalysis of methyl transfer from processes that are associated with compression of the transition state. © 1979, American Chemical Society. All rights reserved.