Nitrogen-Proton Correlation Experiments of Organic Solids at Natural Isotopic Abundance

Abstract

Solid-state NMR methods for recording two-dimensional nitrogen–proton correlation spectra at natural isotopic abundance are presented. There are two isotopes of nitrogen: the spin I = 1 14N (99.6% natural abundance) and the spin I = 1/2 15N (0.4% natural abundance). The reduced natural abundance and smaller magnetogyric ratio as compared to 13C explain the comparative scarcity of nitrogen–proton spectra for 15N in the literature. While this article describes these few examples of 1H–15N and 15N–1H experiments, including the first applications of DNP to increase sensitivity, the focus is on 14N–1H heteronuclear multiple-quantum coherence (HMQC) MAS NMR spectroscopy using inverse (i.e., 1H) detection. Specifically, HMQC can be created following free evolution under heteronuclear through-bond 14N–1H J-couplings as well as residual second-order quadrupolar–dipolar couplings that are not removed by MAS or by recoupling of 14N–1H dipolar couplings using n = 2 rotary resonance recoupling (R3) or symmetry-based sequences. The quadrupolar interaction for 14N causes anisotropic broadening and an isotropic second-order quadrupolar shift and affects the optimization of 14N RF irradiation, for which high 14N nutation frequencies are important. Fast MAS improves sensitivity by narrowing 1H resonances and lengthening 1H coherence lifetimes. The creation of double-quantum or overtone 14N coherence has the advantage of insensitivity (compared to 14N single-quantum coherence) to motion and small deviations away from the perfect setting of the magic angle. Applications to supramolecular chemistry and pharmaceuticals are presented; changing the recoupling duration allows longer range N⋯H proximities to be identified, thus identifying specific intermolecular hydrogen bonding arrangements. Keywords: solid-state NMR; MAS; 1H; 14N; 15N; dipolar couplings; hydrogen bonding