Bioorganometallic Chemistry at the Interface with Biocatalysis: Chemoselective Reduction of Biomimetic NAD+ Cofactors with [Cp*Rh(bpy)H]+, Tandem Catalysis with 1,4-NADH-Dependent Enzymes, Chiral Synthesis, Organotin Metabolites, and DFT Mechanism Studies

This Review will focus on our studies of the utilization of the [Cp*Rh(bpy)H](+) complex as a biomimetic hydrogenase, regeneration reagent for chemoselective reduction of biomimetic NAD+ cofactors, N-benzylnicotinamide triflate, 1, beta-nicotinamide ribose-5 '-methyl phosphate, 2, and natural NAD(+), 3, in the conversion to their 1,4-NADH analogues, 1,4-dihydro-N-benzylnicotinamide, 4, and beta-1,4-dihydronicotinamide-5 '-ribose methyl phosphate, 5, and natural 1,4-NADH, 6, respectively. This regeneration reaction with 1,4-NADH biomimetics 4 and 5 was used in tandem with 1,4-NADH-dependent enzymes for organic synthesis. The enzyme examples will encompass horse liver alcohol dehydrogenase (HLADH) reductions of prochiral ketones to chiral S-alcohols; cytochrome P450 enzymes for selective C-H oxidation reactions of organic compounds, and organometallic substrates, tributyltin acetate and cyclohexyltriphenyltin, with 1,4-NAD(P)H; and the biomimetic 1,4-NADH cofactor, 4, with the 2-hydroxybiphenyl-3-monooxygenase enzyme, HbpA, a FAD-containing monooxygenase enzyme, for hydroxylation of ortho-substituted phenols to catechols. This Review also includes discussions on in-depth DFT mechanism studies, and other chemical mechanistic aspects, of all tandem catalytic reactions that demonstrate, utilizing a simplified model of the HLADH-Zn(II)-mediated enzyme, the unprecedented role of Zn(II) in the hydride transfer reaction. Moreover, sitedirected mutagenesis with 1,4-NAD(P)H-dependent cytochrome P450 BM-3 improved the molecular recognition process for biomimetic 1,4-NADH cofactors in organic compound C-H oxidation reactions. The 1,4-NADH-dependent cytochrome P450 CAM recognized the biomimetic 1,4-NADH cofactors; however, site-directed mutagenesis of the putidaredoxin reductase (PdR) component increased the kinetics for the C-H oxidation reaction of camphor. Cyclohexyltriphenyltin demonstrated the differences in hydroxylation regioselectivity, when comparing the cytochrome P450 enzyme with biomimetic P450 porphyrin Fe(III) and Mn(III) models. The biomimetic 1,4-NADH cofactor, 1,4-dihydro-N-benzylnicotinamide, 4, was also utilized as a reducing agent, providing the reduced, chemoselective coenzyme, the FADH(-) anion, that further reacts with O-2/H+ to provide the 4 alpha-hydroperoxide flavin, for the HbpA enzymatic oxidative conversion of ortho-substituted phenols to catechols.