Combining heteronuclear correlation NMR with spin-diffusion to detect relayed Cl-H-H and N-H-H proximities in molecular solids

Analysis of short-to-intermediate range intermolecular interactions offers a great way of characterizing the solidstate organization of small molecules and materials. This can be achieved by two-dimensional (2D) homo- and heteronuclear correlation NMR spectroscopy, for example, by carrying out experiments at high magnetic fields in conjunction with fast magic-angle spinning (MAS) techniques. But, detecting 2D peaks for heteronuclear dipolar coupled spin pairs separated by greater than 3 ?, is not always straightforward, particularly when low-gamma quadrupolar nuclei are involved. Here, we present a 2D correlation NMR experiment that combines the advantages of heteronuclear-multiple quantum coherence (HMQC) and proton-based spin-diffusion (SD) pulse sequences using radio-frequency-driven-recouping (RFDR) to probe inter and intramolecular 1H-X (X = 14N, 35Cl) interactions. This experiment can be used to acquire 2D 1H{X}-HMQC filtered 1H-1H correlation as well as 2D 1H-X HMQC spectra. Powder forms of dopamine center dot HCl and L-histidine center dot HCl center dot H2O are characterized at high fields (21.1 T and 18.8 T) with fast MAS (60 kHz) using the 2D HMQC-SD-RFDR approach. Solid-state NMR results are complemented with NMR crystallography analyses using the gauge-including projector augmented wave (GIPAW) approach. For histidine center dot HCl center dot H2O, 2D peaks associated with 14N-1H-1H and 35Cl-1H-1H distances of up to 4.4 and 3.9 ?, have been detected. This is further corroborated by the observation of 2D peaks corresponding to 14N-1H-1H and 35Cl-1H-1H distances of up to 4.2 and 3.7 ?, in dopamine center dot HCl, indicating the suitability of the HMQC-SD-RFDR experiments for detecting medium-range proximities in molecular solids.

Automated summary

Analysis of short-to-intermediate range intermolecular interactions provides a valuable approach to understanding the solid-state organization of small molecules and materials. A combination of 2D NMR spectroscopy techniques allows for the detection of intermolecular distances, particularly when low-gamma quadrupolar nuclei are involved. The presented experiment demonstrates the applicability of the HMQC-SD-RFDR approach in detecting medium-range proximities in molecular solids.