Metal-1,10-Phenanthroline-Linked Dihydronicotinamides as Models for the NADH-Alcohol Dehydrogenase Coenzyme-Enzyme Couple

Article abstract of DOI:10.1021/jo00298a049

Two phenanthroline-linked dihydronicotinamides, 1,4-dihydro-1-(1,10-phenanthrolin-2-ylmethyl)-3-pyridinecarboxamide (3) and 1,4-dihydro-N-(1,10-phenanthrolin-2-ylmethyl)-1-(phenylmethyl)-3-pyridinecarboxamide (6), were synthesized.The phenanthroline moiety in these compounds is able to chelate metal ions into fixed positions toward the dihydronicotinamide group providing models for the NADH-alcohol dehydrogenase complex.The reactivity of 3-M(2+) and 6-M(2+) is investigated toward 2,4,6-trinitrobenzene sulfonate and methylene blue (M(2+) = Zn(2+)) and toward the metallophilic substrate 2-pyridinecarboxaldehyde (PyCHO) for which a detailed kinetic analysis is given.For reaction of 3-M(2+)and PyCHO the efficiency of metal ion activation is of the order Zn(2+) much greater than Mg(2+), Ni(2+) greater than Co(2+) greater than Cd(2+).It is concluded that hydride transfer proceeds in a ternary 3-M(2+)-PyCHO complex in an orientation in which carbonyl group and dihydropyridine are in a coplanar position with the carbonyl oxygen pointing to the ring nitrogen.