THE CHANGE IN HYDROGEN-BOND STRENGTH ACCOMPANYING CHARGE REARRANGEMENT - IMPLICATIONS FOR ENZYMATIC CATALYSIS

The equilibrium for formation of the intramolecular hydrogen bond (K-H B) in a series of substituted salicylate monoanions was investigated a s a function of Delta pK(a), the difference between the pK(a) values o f the hydrogen bond donor and acceptor, in both water and dimethyl sul foxide. The dependence of log K-HB upon Delta pK(a) is linear in both solvents, but is steeper in dimethyl sulfoxide (slope = 0.73) than in water (slope = 0.05). Thus, hydrogen bond strength can undergo substan tially larger increases in nonaqueous media than aqueous solutions as the charge density on the donor or acceptor atom increases. These resu lts support a general mechanism for enzymatic catalysis, in which hydr ogen bonding to a substrate is strengthened as charge rearranges in go ing from the ground state to the transition state; the strengthening o f the hydrogen bond would be greater in a nonaqueous enzymatic active site than in water, thus providing a rate enhancement for an enzymatic reaction relative to the solution reaction. We suggest that binding e nergy of an enzyme is used to fix the substrate in the low-dielectric active site, where the strengthening of the hydrogen bond in the cours e of a reaction is increased.