Solution and Solid-State Models of Peptide CH···O Hydrogen Bonds

Fumaramide derivatives were analyzed in solution by 1H NMR spectroscopy and in the solid
state by X-ray crystallography in order to characterize the formation of CH···O interactions under each
condition and to thereby serve as models for these interactions in peptide and protein structure. Solutions
of fumaramides at 10 mM in CDCl3 were titrated with DMSO-d6, resulting in chemical shifts that moved
downfield for the CH groups thought to participate in CH···OS(CD3)2 hydrogen bonds concurrent with
NH···OS(CD3)2 hydrogen bonding. In this model, nonparticipating CH groups under the same conditions
showed no significant change in chemical shifts between 0.0 and 1.0 M DMSO-d6 and then moved upfield
at higher DMSO-d6 concentrations. At concentrations above 1.0 M DMSO-d6, the directed CH···OS(CD3)2
hydrogen bonds provide protection from random DMSO-d6 contact and prevent the chemical shifts for
participating CH groups from moving upfield beyond the original value observed in CDCl3. X-ray crystal
structures identified CH···OC hydrogen bonds alongside intermolecular NH···OC hydrogen bonding, a
result that supports the solution 1H NMR spectroscopy results. The solution and solid-state data therefore
both provide evidence for the presence of CH···O hydrogen bonds formed concurrent with NH···O hydrogen
bonding in these structures. The CH···OC hydrogen bonds in the X-ray crystal structures are similar to
those described for antiparallel β-sheet structure observed in protein X-ray crystal structures.