Abstract
Heteronuclear multiple-quantum coherence (HMQC) pulse sequences for establishing heteronuclear correlation in solid-state nuclear magnetic resonance (NMR) between 35 Cl and 1 H nuclei in chloride salts under fast (60 kHz) magic-angle spinning (MAS) and at high magnetic field (a 1 H Larmor frequency of 850 MHz) are investigated. Specifically, recoupling of the 35 Cl-1 H dipolar interaction using rotary resonance recoupling with phase inversion every rotor period or the symmetry-based SR42 1 pulse sequences are compared. In our implementation of the population transfer (PT) dipolar (D) HMQC experiment, the satellite transitions of the 35 Cl nuclei are saturated with an off-resonance WURST sweep, at a low nutation frequency, over the second spinning sideband, whereby the WURST pulse must be of the same duration as the recoupling time. Numerical simulations of the 35 Cl-1 H MAS D-HMQC experiment performed separately for each crystallite orientation in a powder provide insight into the orientation dependence of changes in the second-order quadrupolar-broadened 35 Cl MAS NMR lineshape under the application of dipolar recoupling. Two-dimensional 35 Cl-1 H PT-D-HMQC MAS NMR spectra are presented for the amino acids glycine·HCl and l-tyrosine·HCl and the pharmaceuticals cimetidine·HCl, amitriptyline·HCl and lidocaine·HCl·H2 O. Experimentally observed 35 Cl lineshapes are compared with those simulated for 35 Cl chemical shift and quadrupolar parameters as calculated using the gauge-including projector-augmented wave (GIPAW) method: the calculated quadrupolar product (PQ ) values exceed those measured experimentally by a factor of between 1.3 and 1.9.
Highlights
Chloride salts have wide application in the isolation and purification of active pharmaceutical ingredients (APIs)
We explore the applicability of the 35Cl–1H population transfer (PT)-D-Heteronuclear multiple-quantum coherence (HMQC) experiment to probe proximities between hydrogen and chlorine atoms in the amino acids glycineÁHCl and L-tyrosineÁHCl and the pharmaceuticals cimetidineÁHCl, amitriptylineÁHCl and lidocaineÁHClÁH2O
On the 35Cl channel, a WURST saturation pulse[22,23,53,54] sweeping over the Venkatesh et al use a PT-dipolar HMQC (D-HMQC) pulse sequence similar to that shown in Figure 1b except that for saturation of the satellite transitions, they use rotor-assisted population transfer (RAPT),[19] whereas we found that at fast spinning frequency, a low-nutation frequency WURST shape pulse, sweeping a 40 kHz range over the second spinning side band, saturates the satellites transitions efficiently
Summary
Chloride salts have wide application in the isolation and purification of active pharmaceutical ingredients (APIs).
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