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

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 cou-pling, 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 lim-ited 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.(c) 2023 Elsevier Inc. All rights reserved.

Automated summary

The symmetry-based phase-modulated resonance-echo saturation-pulse double-resonance (PM-S-RESPDOR) method can efficiently and accurately measure the 1H-14N internuclear distances in rigid solids. The fraction curve, represented by (S0 - S')/S0, is derived from the PM-S-RESPDOR signal intensity with and without 14N PM saturation pulse, providing analytical equations for 1H-14N couplings. However, in multi-component systems commonly found in pharmaceutical applications, the limited 1H resolution at fast MAS may lead to the NH proton resonance not being well separated from other proton peaks. To address this issue, T-HMQC filtering is applied to suppress other 1H signals before conducting PM-S-RESPDOR experiments. The method is successfully demonstrated using the acetaminophen-oxalic acid (APAP-OXA) system. The analysis shows that the analytical equation can be safely applied in the analysis of T-HMQC filtered PM-S-RESPDOR experiments.