Quantifying Weak Hydrogen Bonding in Uracil and 4-Cyano-4‘-ethynylbiphenyl: A Combined Computational and Experimental Investigation of NMR Chemical Shifts in the Solid State

Weak hydrogen bonding in uracil and 4-cyano-4‘-ethynylbiphenyl, for which single-crystal
diffraction structures reveal close CH···OC and C⋮CH···N⋮C distances, is investigated in a study that
combines the experimental determination of 1H, 13C, and 15N chemical shifts by magic-angle spinning (MAS)
solid-state NMR with first-principles calculations using plane-wave basis sets. An optimized synthetic route,
including the isolation and characterization of intermediates, to 4-cyano-4‘-ethynylbiphenyl at natural
abundance and with 13C⋮13CH and 15N⋮C labeling is described. The difference in chemical shifts calculated,
on the one hand, for the full crystal structure and, on the other hand, for an isolated molecule depends on
both intermolecular hydrogen bonding interactions and aromatic ring current effects. In this study, the two
effects are separated computationally by, first, determining the difference in chemical shift between that
calculated for a plane (uracil) or an isolated chain (4-cyano-4‘-ethynylbiphenyl) and that calculated for an
isolated molecule and by, second, calculating intraplane or intrachain nucleus-independent chemical shifts
that quantify the ring current effects caused by neighboring molecules. For uracil, isolated molecule to
plane changes in the 1H chemical shift of 2.0 and 2.2 ppm are determined for the CH protons involved in
CH···O weak hydrogen bonding; this compares to changes of 5.1 and 5.4 ppm for the NH protons involved
in conventional NH···O hydrogen bonding. A comparison of CH bond lengths for geometrically relaxed
uracil molecules in the crystal structure and for geometrically relaxed isolated molecules reveals differences
of no more than 0.002 Å, which corresponds to changes in the calculated 1H chemical shifts of at most 0.1
ppm. For the C⋮CH···N⋮C weak hydrogen bonds in 4-cyano-4‘-ethynylbiphenyl, the calculated molecule
to chain changes are of similar magnitude but opposite sign for the donor 13C and acceptor 15N nuclei. In
uracil and 4-cyano-4‘-ethynylbiphenyl, the CH hydrogen-bonding donors are sp2 and sp hybridized,
respectively; a comparison of the calculated changes in 1H chemical shift with those for the sp3 hybridized
CH donors in maltose (Yates et al. J. Am. Chem. Soc. 2005, 127, 10216) reveals no marked dependence
on hybridization for weak hydrogen-bonding strength.