GLUTATHIONE TRANSFERASE MIMICS - MICELLAR CATALYSIS OF AN ENZYMATIC-REACTION

Substances that mimic the enzyme action of glutathione transferases (w hich serve in detoxification) are described. These micellar catalysts enhance the reaction rate between thiols and activated halogenated nit roarenes as well as alpha,beta-unsaturated carbonyls. The nucleophilic aromatic substitution reaction is enhanced by the following surfactan ts in descending order: yldiallylammonium-co-dodecylmethyldiallylammon ium) bromide (86/14) much greater than cetyltrimethylammonium bromide > zwittergent 3-16 adecyl-N,N-dimethyl-3-ammonio-1-propanesulphonate) > zwittergent 3-14 adecyl-N,N-dimethyl-3-ammonio-1-propanesulphonate) approximate to N,N-dimethyl-lauryl-amine N-oxide > N,N-dimethyloctylam ine N-oxide. The most efficient catalyst studied is a polymeric materi al that incorporates surfactant properties (n-dodecylmethyldiallylammo nium bromide) and opens up possibilities for engineering sequences of reactions on a polymeric support. Michael addition to alpha,beta-unsat urated carbonyls is exemplified by a model substance, trans-4-phenylbu t-3-en-2-one, and a toxic compound that is formed during oxidative str ess, 4-hydroxy-2-undecenal. The latter compound is conjugated with the highest efficiency of those tested. Micellar catalysts can thus be vi ewed as simple models for the glutathione transferases highlighting th e influence of a positive electrostatic field and a non-specific hydro phobic binding site, pertaining to two catalytic aspects, namely thiol ate anion stabilization and solvent shielding.