Activation of oxygen nucleophiles in enzyme catalysis

The application of tools developed by physical organic chemists to enzyme reactions to ascertain how the environment of the enzyme active site affects the reactivity of oxygen nucleophiles is reviewed. The three molecular mechanisms of generating enhanced electron density in the reactant state of the nucleophile by altering the coordination and/or bonding of the nucleophile are outlined as follows: desolvation, coordination of the alcohol proton and ionization. The nucleophilic activation of alcohols by enzymes and the spectroscopic characterization of nucleophiles at enzyme active sites are also illustrated.