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N ‐Benzylnicotinamide and N ‐benzyl‐1,4‐dihydronicotinamide: useful models for NAD + and NADH
Author(s) -
Moore John M.,
Hall Jasmine M.,
Dilling Wendell L.,
Jensen Anton W.,
Squattrito Philip J.,
Giolando Patrick,
Kirschbaum Kristin
Publication year - 2017
Publication title -
acta crystallographica section c
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.304
H-Index - 17
ISSN - 2053-2296
DOI - 10.1107/s2053229617008877
Subject(s) - nad+ kinase , chemistry , benzyl alcohol , medicinal chemistry , stereochemistry , biochemistry , catalysis , enzyme
3‐Aminocarbonyl‐1‐benzylpyridinium bromide ( N ‐benzylnicotinamide, BNA), C 13 H 13 N 2 O + ·Br − , (I), and 1‐benzyl‐1,4‐dihydropyridine‐3‐carboxamide ( N ‐benzyl‐1,4‐dihydronicotinamide, rBNA), C 13 H 14 N 2 O, (II), are valuable model compounds used to study the enzymatic cofactors NAD(P) + and NAD(P)H. BNA was crystallized successfully and its structure determined for the first time, while a low‐temperature high‐resolution structure of rBNA was obtained. Together, these structures provide the most detailed view of the reactive portions of NAD(P) + and NAD(P)H. The amide group in BNA is rotated 8.4 (4)° out of the plane of the pyridine ring, while the two rings display a dihedral angle of 70.48 (17)°. In the rBNA structure, the dihydropyridine ring is essentially planar, indicating significant delocalization of the formal double bonds, and the amide group is coplanar with the ring [dihedral angle = 4.35 (9)°]. This rBNA conformation may lower the transition‐state energy of an ene reaction between a substrate double bond and the dihydropyridine ring. The transition state would involve one atom of the double bond binding to the carbon ortho to both the ring N atom and the amide substituent of the dihydropyridine ring, while the other end of the double bond accepts an H atom from the methylene group para to the N atom.