NMR studies of hydrogen bonding interactions with secondary amide and urea groups

The cis/trans ratios for six model secondary amides were determined by H-1 NMR in a range of solvent systems. The trans to cis equilibrium in chloroform is only slightly affected by addition of the hydrogen bond donor, trifluorethanol, but the cis rotamer is stabilized by an average of 0.7 kcal mol(-1) when acetic acid is used as an intermolecular donor-acceptor template. Conversely, amide interaction with anionic hydrogen bond accepters decreases the percentage of cis rotamer. N-15 NMR spectroscopy was used to determine the effect of hydrogen bonding on the trans amide structure. The direction and the magnitude of N-15 complex-induced-shifts indicate that both hydrogen bond donors and accepters raise the secondary amide rotational barrier by increasing the C-N bond order. The relationship of these results to protein structure is discussed. Copyright (C) 2001 John Wiley & Sons, Ltd.