Internuclear distance measurements between 1H and 14N in multi-component rigid solids at fast MAS

Yutaro Ogaeri; Naoto Suzuki; Toshiro Fukami; Yusuke Nishiyama

doi:10.1016/j.jmr.2023.107378

Internuclear distance measurements between ¹H and ¹⁴N in multi-component rigid solids at fast MAS

J Magn Reson. 2023 Mar:348:107378. doi: 10.1016/j.jmr.2023.107378. Epub 2023 Jan 18.

Authors

Yutaro Ogaeri¹, Naoto Suzuki², Toshiro Fukami³, Yusuke Nishiyama⁴

Affiliations

¹ JEOL Ltd., Akishima, Tokyo 196-8558, Japan; RIKEN-JEOL Collaboration Center, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
² Laboratory of Pharmaceutics, School of Pharmacy, Nihon University, Chiba, Japan.
³ Department of Molecular Pharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan.
⁴ JEOL Ltd., Akishima, Tokyo 196-8558, Japan; RIKEN-JEOL Collaboration Center, RIKEN, Yokohama, Kanagawa 230-0045, Japan. Electronic address: yunishiy@jeol.co.jp.

PMID: 36702044
DOI: 10.1016/j.jmr.2023.107378

Abstract

¹H-¹⁴N internuclear distances are readily and accurately measured using the symmetry-based phase-modulated resonance-echo saturation-pulse double-resonance (PM-S-RESPDOR) method in rigid solids. The fraction curve, (S₀ - S')/S₀, is represented by a single variable of a ¹H-¹⁴N heteronuclear dipolar coupling, where S₀ and S' are the PM-S-RESPDOR signal intensity with and without ¹⁴N PM saturation pulse, respectively. Analytical equation of the fraction curve easily provides ¹H-¹⁴N couplings. This treatment is only applicable when NH proton resonance is well separated from the other proton peaks. With the limited ¹H resolution even at fast MAS > 60 kHz, unfortunately, this condition is not necessarily satisfied especially in multi-component systems which often appear in pharmaceutical applications. To overcome this problem, T-HMQC filtering is applied to suppress the ¹H signals other than NH proton prior to the PM-S-RESPDOR experiments. The method is well demonstrated on two components acetaminophen-oxalic acid (APAP-OXA) systems. Further analysis of orientation dependence of T-HMQC and PM-S-RESPDOR shows that the analytical equation can be safely applied in the analysis of T-HMQC filtered PM-S-RESPDOR experiments.

Keywords: Fast MAS; Heteronuclear distances; Nitrogen-14; RESPDOR; Solid-state NMR.