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 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.