Deuteron-proton isotope correlation spectroscopy at high magnetic fields

Abstract

A cross-polarization ²H–¹H isotope correlation spectroscopy (CP-iCOSY) approach is presented for characterizing a deuterated amino acid, pharmaceutical compound and a solid formulation. This can be achieved by isotopic enrichment in conjunction with high magnetic field (28.2 T) and fast magic-angle spinning (MAS), enabling the rapid detection of ²H NMR spectra in a few seconds to minutes. Specifically, two-dimensional (2D) ²H–¹H CP-iCOSY experiment allows the local structures and through-space interactions in a partially deuterated compounds to be elucidated. In doing so, we compare conventional spin-lock and rotor-echo-short-pulse-irradiation ^RESPIRATIONCP sequences for acquiring 2D ¹H–²H correlation spectra. The ^RESPIRATIONCP sequence allows the detection of 2D peaks at lower CP contact times (0.1–1 ms) than the conventional CP (0.2–4 ms) sequence. Analysis of partially deuterated L-histidine·HCl·H₂O and dopamine.HCl is presented, in which the detection of 2D peaks corresponding to ²H–¹H pairs separated by greater than 4 Å distance demonstrates the potential of the presented approach for the characterization of packing interactions. These results are corroborated by NMR crystallography analysis using the Gauge-Including Projector Augmented-Wave (GIPAW) approach.