Chiral NADH Model Systems functionalized with Zn(II)-cyclen as Flavin Binding Site

Abstract

A series of chiral peptides has been prepared, bearing a 1,4-dihydronicotine amide and a zinc cyclen moiety. The metal complex reversibly binds flavins in aqueous solution, while the dihydronicotine amide serves as a NADH model transferring a hydride to the flavin within the assembly. The reaction rate of the redox reaction was monitored and determined by UV spectroscopy. The reaction rates of the substituted compounds were slower if compared to the non-substituted parent compound 1-H, but still show a 30–100 fold rate enhancement compared to the compound missing a flavin binding site. It was anticipated to probe the cryptic stereoselectivity of the hydride transfer from dihydropyridine to flavin. Spectroscopic data indicate that the introduction of deuterium labels upon reduction of the pyridinium salts to 1,4-dihydropyridine in D2O proceeds diastereoselectively, but identical isotope effects on the rate of flavin reduction as with a non-chiral NADH model revealed that the hydride transfer within the assembly proceeds not stereoselective. A more rigid chiral NADH model compound must be prepared to achieve this goal.

Zinc cyclen linked to 1,4-dihydronicotine amide by chiral peptides binds and reduces flavin in aqueous buffered solution, but not stereospecifically