Conformations and Rotational Barriers in NADH and NAD+ Analogues. A Dynamic NMR and Molecular Mechanics Investigation.

Abstract

The conformational preferences and rotational barriers about both the ring-amide bond and the C-N bond in NADH and NAD+ analogs have been investigated by dynamic NMR spectroscopy and mol. mechanics calcns. with the intention to clarify the stereodynamic situation in these types of cross-conjugated amide. The results can be summarized as follows. (I) The primary amides an thioamides are planar or nearly planar and possess ring-amide barriers (ΔG⧧ ≈ 4-7 kcal mol-1) over the 90° twisted state. (Ii) The cis conformation is strongly preferred for NADH analogs, but in an indole analog 6b the two conformations differ by only ca. 0.3 kcal mol-1. (Iii) The tertiary amides are twisted in the ground state and have steric barriers (ΔG⧧ = 6-10 kcal mol-1) over the planar state. (I.v.) The C-N barriers are considerably larger, (ΔG⧧ = 11-17 kcal mol-1 for amides, and 12-21 kcal mol-1 for thioamides). (V) The barrier heights are governed by the efficiency of the cross-conjugation in the ground and transition states, and by the steric interactions in the planar conformations. The exchange process obsd. in NMR for NADH by Redfield et al. is due to C-N rotation and not to amide group rotation. [on SciFinder(R)]