De novo crystal structure determination of L-alaninamide HCl by quadrupolar NMR crystallography guided crystal structure prediction (QNMRX-CSP)

Abstract

Quadrupolar NMR crystallography guided crystal structure prediction (QNMRX-CSP) is a method for determining the crystal structures of organic solids. To date, our two previous QNMRX-CSP studies have relied upon on 35Cl solid-state NMR (SSNMR) spectroscopy, powder X-ray diffraction (PXRD), Monte-Carlo simulated annealing (MC-SA), and dispersion-corrected density functional theory (DFT-D2∗) calculations for the determination of crystal structures for organic HCl salts with known crystal structures, in order to benchmark the method and subject it to blind tests. Herein, we apply QNMRX-CSP for the de novo crystal structure determination of L-alaninamide HCl (L-Ala-NH2), for which no crystal structure has been reported, using 35Cl SSNMR and PXRD data for structural prediction and refinement, along with 13C and 14N SSNMR data for subsequent structural validation. To further validate our structural models, we determined the crystal structure of L-Ala-NH2 using single-crystal X-ray diffraction (SCXRD); however, this structure was not obtained until the completion of the QNMRX-CSP analysis and validation. This study highlights the current capabilities of QNMRX-CSP and underscores the benefits of incorporating multinuclear SSNMR data to enhance de novo crystal structure determination across a wide range of organic solids.