Stereoselective hydride uptake in model systems related to the redox-couple NAD+/NADH

The present work deals with the mechanistic investigations of the hydride transfer reactions concerning the redox couple NAD+/NADH. Based on the theoretical and experimental investigatins of NAD(H) model compounds as 3-carbamoyl pyridinium cations (3-carbamoyl-1,4-dihydropyridine) it was found that the out-of-plane rotation of the carbonyl function controls the stereo-and regiospecificity of the introduced hydride anion. It was found that the hydride anion transfered in the reaction, is always syn-positioned with respect to the carbonyl group. The unique stereoselectivity exhibits a strong coherence with the recent crystallographic 3D-data for the ternary complex of NAD bonded horse liver alcohol dehydrogenase. The results show that the amide group is 30° out of the plane with the carbonyl directed toward the A side. There are observations that the absolute configuration of the introduced chirality in the 3-carbamoyl pyridinium cations selects between the hydride uptake coresponding with the enzymatic A or B specificity