NAD(P)+-NAD(P)H Models. 49. Proximity Effect of a Phenyl Group on the Electron Transfer Process

Abstract

Abstract 1-Propyl-1,4-dihydronicotinamide (PNAH), 1-(3-phenylpropyl)-1,4-dihydronicotinamide (1a), 1-(2-phenylthioethyl)-1,4-dihydronicotinamide (1b), and 1-(4-phenylthiobutyl)-1,4-dihydronicotinamide (1c) and their 4-deuterated analogs are synthesized as NAD(P)H-models and subjected to the reduction of m-nitro-α,α,α-trifluoroacetophenone in the presence or absence of magnesium ion in acetonitrile. Kinetics at 323 K have been studied. Kinetic isotope effect is small (2.33) only when 1a or 1b is employed for the reduction in the presence of magnesium ion, whereas it appears large (≈3.2) under other conditions. The result has been interpreted in terms of steric interference by a proximate phenyl group on the approach of the substrate to form a binary (in the absence of magnesium ion) or ternary (in the presence of magnesium ion) complexes. Thermodynamic parameters for the formation of complexes between the models and magnesium ion have been studied. It has been elucidated that enthalpy of complexation is small for 1a than others. However, the small enthalpy of complexation is compensated by small entropy of complexation affording almost constant free-energy of complexation throughout the models studied.