Theoretical Modeling of Compression Effects in Enzymic Methyl Transfer

The energetics of catalysis of methyl transfer in a degenerate displacement of methylammonium ion by ammonia via a symmetric S_N2 transition structure have been investigated by ab initio calculations at the 4-31G level of SCF-MO theory for catalyzed and uncatalyzed processes. The model catalyst comprises (a) a pair of helium atoms located a fixed distance apart on the N⋯C⋯N axis so as to compress the reacting system by repulsive (destabilizing) interactions and (b) a cage of point charges serving to stabilize both the reactant ion-molecule complex and the transition structure by attractive interactions. Schowen's hypothesis concerning the possible role of compression in enzymic catalysis of methyl transfer is examined. It is shown that the model with compression permits catalysis by preferential transition-state binding of the substrate to the catalyst, but in the absence of compression there is anti-catalysis. Kinetic isotope effects calculated for catalyzed and uncatalyzed model reactions are in accord with trends in experimental isotope effects for enzymic and non-enzymic methyl transfers.