NMR studies of hydrogen bonding interactions with secondary amide and ureagroups

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 chlorofo rm is only slightly affected by addition of the hydrogen bond donor, triflu orethanol, 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 decrease s the percentage of cis rotamer. N-15 NMR spectroscopy was used to determin e the effect of hydrogen bonding on the trans amide structure. The directio n and the magnitude of N-15 complex-induced-shifts indicate that both hydro gen bond donors and accepters raise the secondary amide rotational barrier by increasing the C-N bond order. The relationship of these results to prot ein structure is discussed. Copyright (C) 2001 John Wiley & Sons, Ltd.