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 14 N (99.6% natural abundance) and the spin I = 1/2 15 N (0.4% natural abundance). The reduced natural abundance and smaller magnetogyric ratio as compared to 13 C explain the comparative scarcity of nitrogen-proton spectra for 15 N in the literature. While this article describes these few examples of 1 H-15 N and 15 N-1 H experiments, including the first applications of DNP to increase sensitivity, the focus is on 14 N-1 H heteronuclear multiple-quantum coherence (HMQC) MAS NMR spectroscopy using inverse (i.e., 1 H) detection. Specifically, HMQC can be created following free evolution under heteronuclear through-bond 14 N-1 H J-couplings as well as residual second-order quadrupolar-dipolar couplings that are not removed by MAS or by recoupling of 14 N-1 H dipolar couplings using n = 2 rotary resonance recoupling (R 3 ) or symmetry-based sequences. The quadrupolar interaction for 14 N causes anisotropic broadening and an isotropic second-order quadrupolar shift and affects the optimization of 14 N RF irradiation, for which high 14 N nutation frequencies are important. Fast MAS improves sensitivity by narrowing 1 H resonances and lengthening 1 H coherence lifetimes. The creation of double-quantum or overtone 14 N coherence has the advantage of insensitivity (compared to 14 N 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.

Evaluation of excitation schemes for indirect detection of 14N via solid-state HMQC NMR experiments

“…For protonated samples, the lack of resolution and sensitivity of direct 14 N detection can be partially overcome by the indirect detection of 14 N SQ or 14 N DQ transitions via protons, denoted 1 H-{ 14 N SQ } and 1 H-{ 14 N DQ } respectively [5,[25][26][27], using two-dimensional (2D) experiments at high MAS frequencies, such as HMQC (heteronuclear multiple-quantum correlation) [25,28], HSQC (heteronuclear single-quantum correlation) [29,30], double cross-polarization [31], or sequences using 14 N rf-irradiation lasting hundreds of microseconds to generate 1 H-14 N multiple-quantum coherences [32]. It has been shown that the HSQC sequence is less sensitive than the HMQC one [29,33].…”

Detection of remote proton–nitrogen correlations by 1H-detected 14N overtone solid-state NMR at fast MAS

“…[24][25][26] D-HMQC, DCP, and T-HMQC experiments have found applications on many biological, chemical, and pharmaceutical solids. [27][28][29][30][31][32][33][34][35][36] The detection of the one-bond 1 H- 14 N correlation by the three experiments above is simple and highly efficient. It typically takes only several minutes to hours.…”

“…24–26 D-HMQC, DCP, and T-HMQC experiments have found applications on many biological, chemical, and pharmaceutical solids. 27–36…”

Selective 1H-14N Distance Measurements by 14N Overtone Solid-State NMR Spectroscopy at Fast MAS

“…The development of fast magic-angle spinning (MAS, ] R ≥ 60 kHz) with proton detection has made 14 N NMR spectroscopy a routinely used method, overcoming the difficulty associated with quadrupolar interaction (Cavadini et al, 2006;Gan et al, 2007;Cavadini, 2010;Nishiyama et al, 2011;Brown, 2014;Pandey and Nishiyama, 2015;Shen et al, 2015;Pandey et al, 2016;Carnevale et al, 2017;Hung et al, 2019;Jarvis et al, 2019;Rankin et al, 2019;Wijesekara et al, 2020). Furthermore, under fast MAS conditions, the strong 1 H-1 H dipolar network is largely suppressed (Nishiyama, 2016).…”