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

Abstract

Weak hydrogen bonding in uracil and 4-cyano-4'-ethynylbiphenyl, for which single-crystal diffraction structures reveal close CH...O=C and C[triple bond]CH...N[triple bond]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[triple bond]13CH and 15N[triple bond]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 A, which corresponds to changes in the calculated 1H chemical shifts of at most 0.1 ppm. For the C[triple bond]CH...N[triple bond]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.

Magnetic resonance tensors in Uracil: Calculation of 13C, 15N, 17O NMR chemical shifts, 17O and 14N electric field gradients and measurement of 13C and 15N chemical shifts

“…1). We used just an isolated plane instead of a threedimensional periodic crystal in our calculations because it has been reported that there are only small differences in calculated data between isolated planes vs. the full structure for GIPAW periodic boundary conditions calculations [56]. Since it has been well-known that X-ray crystallography does not yield reliable positions for the hydrogen atoms, this cluster has been partially optimized at hydrogen positions using the B3LYP/6-311 + G** level of theory.…”

“…Beside the hydrogen bonding and geometry effects, another important factor affecting both the experimental and calculated data is aromatic ring current effects of the neighboring molecules [67]. Uldry et al [56] tried to separate hydrogen bonding and aromatic ring current effects on the calculated chemical shift values by nucleus-independent chemical shift (NICS) calculations. They found that not only the rings in the other crystal planes and those far from the molecule in question, but also the nearest neighbor rings do not contribute significantly in the calculated chemical shift values [56].…”

“…Uldry et al [56] tried to separate hydrogen bonding and aromatic ring current effects on the calculated chemical shift values by nucleus-independent chemical shift (NICS) calculations. They found that not only the rings in the other crystal planes and those far from the molecule in question, but also the nearest neighbor rings do not contribute significantly in the calculated chemical shift values [56]. So it will be omitted from our calculations and discussion and we will focus on the hydrogen bonding, geometry optimization, functional and basis set effects, which are the main ones on the calculated chemical shielding and EFG tensors of this molecule.…”

“…The only recent experimental 13 C chemical shift information for solid state uracil in the literature seems to be some solid state isotropic chemical shift values [56]. This encouraged us to measure the 13 C and 15 N chemical shift tensors of uracil in the solid state and survey the changes induced by the observed hydrogen bonds in its crystalline state [30-32, 47,57-60].…”

“…As the strong hydrogen bonds play crucial roles in the functional performance of the nucleic acid bases, the weak hydrogen bonds affect their structure and performance as well [61]. The existence of these weak contacts has been reported mainly by high resolution X-ray and neutron diffraction studies [62] and their presence in crystalline uracil has been studied previously [47,56].…”