Bioorganometallic chemistry:: biocatalytic oxidation reactions with biomimetic NAD+/NADH co-factors and [Cp*Rh(bpy)H]+ for selective organic synthesis

The biocatalytic, regioselective hydroxylation of 2-hydroxybiphenyl to the corresponding catechol was accomplished utilizing the monooxygenase 2-hydroxybiphenyl 3-monooxygenase (HbpA). The necessary natural 1,4-dihydronicotinamde adenine dinucleotide (NADH) co-factor for this biocatalytic process was replaced by a biornimetic co-factor, N-benzyl-1,4-dihydronicotinamide, 1b. The interaction between the flavin (FAD) containing HbpA enzyme and the corresponding biornimetic NADH compound, N-benzyl1,4-dihdronicotinamide, 1b, for hydride transfer, was shown to readily occur. The in situ recycling of the reduced NADH biomimic 1b from la was accomplished with [Cp*Rh(bpy)H](Cl); however, productive coupling of this regeneration reaction to the enzymatic hydroxylation reaction was not totally successful, due to a deactivation process concerning the HbpA enzyme peripheral groups; i.e., -SH or NH2 possibly reacting with the precatalyst, [Cp*Rh(bpy)(H2O)]Cl)(2), and thus inhibiting the co-factor regeneration process. The deactivation mechanism was studied, and a promising strategy of derivatizing these peripheral -SH or -NH2 groups with a polymer containing epoxide was successful in circumventing the undesired interaction between HbpA and the precatalyst. This latter strategy allowed tandem co-factor regeneration using la or 2a, [Cp*Rh(bpy)(H2O)]Cl)(2), and formate ion, in conjunction with the polymer bound, FAD containing HbpA enzyme to provide the catechol product. (C) 2004 Elsevier B.V. All rights reserved.