¹⁵N and ¹H Solid-State NMR Investigation of a Canonical Low-Barrier Hydrogen-Bond Compound: 1,8-Bis(dimethylamino)naphthalene

Abstract

Strong or low-barrier hydrogen bonds have often been proposed in proteins to explain enzyme catalysis and proton-transfer reactions. So far ¹H chemical shifts and scalar couplings have been used as the main NMR spectroscopic signatures for strong H-bonds. In this work, we report simultaneous measurements of ¹⁵N and ¹H chemical shifts and N–H bond lengths by solid-state NMR in ¹⁵N-labeled 1,8-bis(dimethylamino)naphthalene (DMAN), which contains a well-known strong NHN H-bond. We complexed DMAN with three different counteranions to examine the effects of the chemical environment on the H-bond lengths and chemical shifts. All three DMAN compounds exhibit significantly elongated N–H distances compared to the covalent bond length, and the ¹H[superscript N] chemical shifts are larger than ∼17 ppm, consistent with strong NHN H-bonds in the DMAN cation. However, the ¹⁵N and ¹H chemical shifts and the precise N–H distances differ among the three compounds, and the ¹⁵N chemical shifts show opposite dependences on the proton localization from the general trend in organic compounds, indicating the significant effects of the counteranions on the electronic structure of the H-bond. These data provide useful NMR benchmarks for strong H-bonds and caution against the sole reliance on chemical shifts for identifying strong H-bonds in proteins since neighboring side chains can exert influences on chemical shifts similar to those of the bulky organic anions in DMAN. Instead, N–H bond lengths should be measured, in conjunction with chemical shifts, as a more fundamental parameter of H-bond strength.