Hybrid organometallic/enzymic catalyst systems: regeneration of NADH using dihydrogen

Abstract

A mixture of a water-soluble bis(phosphine)rhodium complex and o- and l-lactate dehydrogenase catalyzes the reduction of nicotinamide adenine nucleotide (NAD+) to NADH by Hz in an aqueous solution containing pyruvate (Scheme I). Coupling of this system to the asymmetric reduction of 2-norbornanone using horse liver alcohol dehydrogenase is demonstrated. Organometallic and enzymatic catalysts generally exhibit their most characteristic activities on different classes of reactants: organometallic catalysts are especially effective with nonpolar substances (e.g., Hz, CO, and olefins), while enzymatic catalysts are most effective with polar, polyfunctional materials (e.g., carbohydrates, derivatives of acids, and biopolymers). Combi- nations of organometallic and enzymatic components which in- tegrate these two types of substrate selectivities may have un- common and useful catalytic activities. Here we demonstrate the operation of a hybrid system involving the combination of a water-soluble bis(phosphine)rhodium complex with two enzymes, whose overall action is to catalyze the reduction of NAD+ to NADH by Hr.t The operation of this system and illustrations of its application to enzyme-catalyzed reduction reactions requiring NADH regeneration are summarized in Scheme L The regen- eration of the nicotinamide cofactors (NAD(P)-NAD(P)H) has been the subject of previous research in our laboratories. Several procedures are presently available;ts8 the evaluation of their relative merits has not been completed. Results