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

Abstract

It has previously been shown that 14 N NMR spectra can be reliably obtained through indirect detection via HMQC experiments. This method exploits the transfer of coherence between single-(SQ) or double-quantum (DQ) 14 N coherences, and SQ coherences of a suitable spin-1/2 'spy' nucleus, e.g., 1 H. It must be noted that SQ-SQ methods require a carefully optimized setup to minimize the broadening related to the first-order quadrupole interaction (i.e., an extremely well-adjusted magic angle and a highly stable spinning speed), whereas DQ-SQ ones do not. In this work, the efficiencies of four 14 N excitation schemes (DANTE, XiX, Hard Pulse (HP), and Selective Long Pulse (SLP)) are compared using J-HMQC based numerical simulations and either SQ-SQ or DQ-SQ 1 H-{ 14 N} D-HMQC experiments on Lhistidine HCl and N-acetyl-L-valine at 18.8 T and 62.5 kHz MAS. The results demonstrate that both DANTE and SLP provide a more efficient 14 N excitation profile than XiX and HP. Furthermore, it is shown that the SLP scheme: (i) is efficient over a large range of quadrupole interaction, (ii) is highly robust to offset and rf-pulse length and amplitude, and (iii) is very simple to set up. These factors make SLP ideally suited to widespread, non-specialist use in solid-state NMR analyses of nitrogen-containing materials.

Advanced Solid-State NMR Analysis of Two Crystal Forms of Ranitidine Hydrochloride: Detection of ¹H–¹⁴N Intra-/Intermolecular Correlations

“…1 H-14 N dipolar-based heteronuclear multiple quantum coherence (D-HMQC) can be used to detect intermolecular interactions. 7,[15][16][17][18][19][20][21][22][23][24][25][26] However, there are few pharmaceutical applications for 1 H-14 N D-HMQC, although studies have reported 1 H-14 N D-HMQC measurements of biomolecules containing N atoms such as amino acids and nucleic acid derivatives. 7,26) Thus, we used 1 H-14 N D-HMQC to investigate the intermolecular correlation of ranitidine hydrochloride crystal polymorphs, Form 1 and 2, and compared the results with the structure reported using scXRD measurements.…”

Advances in the characterization of inorganic solids using NMR correlation experiments

“…The indirect detection of 14 N 1Q coherences requires an accurate adjustment of the magic angle with an accuracy better than ±0.002° and fluctuations of the MAS frequency smaller than a few hertz to refocus the first-order quadrupolar interaction. The indirect detection of 14 N 2Q coherences is less demanding in terms of accuracy and stability of the MAS but is often less efficient [263][264][265][266] . Coherence transfers have been mediated by first residual dipolar splitting 1,2,262 , which is the sum of the J-coupling and the second-order quadrupoledipole cross term.…”

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

“…Two independent groups had broken the barrier and paved a way to 14 N NMR using an ingenious idea of indirect detection via a handier spin-1/2, such as 13 C 3-5 or 1 H. [6][7][8][9][10] The most common method to observe the correlation between 1 H and 14 N is the two-dimensional 1 H/{ 14 N} dipolar-based heteronuclear multiple quantum coherence (2D D-HMQC) experiment under fast magic-angle spinning (MAS) conditions (n R Z 50 kHz, where n R represents the MAS frequency). 11 Several 14 N excitation/reconversion schemes [12][13][14][15][16][17][18] or de-/recoupling sequences [19][20][21][22] have been studied to improve the performance of D-HMQC. Other methods have also been developed, such as double crosspolarization (DCP) 23 and TRAPDOR-HMQC (or T-HMQC).…”