Quadrupolar NMR crystallography guided crystal structure prediction (QNMRX-CSP)

We describe a new quadrupolar NMR crystallography guided crystal structure prediction (QNMRX-CSP) protocol for the prediction and refinement of crystal structures, including its design, benchmarking, and application to seven organic HCl salts. Five HCl salts with a limited number of low-energy conformations were chosen as model systems for benchmarking: betaine HCl, glycine HCl, d -alanine HCl, guanidine HCl, and aminoguanidine HCl; two were chosen for blind tests: N , N ′-dimethylglycine HCl and metformin HCl. The QNMRX-CSP protocol uses experimental 35 Cl solid-state NMR (SSNMR) spectra and X-ray diffraction (XRD) data in tandem with Monte Carlo simulated annealing and dispersion-corrected plane-wave density functional theory (DFT-D2*) calculations. The protocol comprises three modules: (i) the assignment of motion groups, (ii) a Monte Carlo simulated annealing algorithm for generating tens of thousands of candidate structures, and (iii) DFT-D2* geometry optimizations of structural models and concomitant computation of 35 Cl EFG tensors. Key benchmarked metrics are used for retaining the best candidate structures, including unit cell parameters, static lattice energies, and EFG distances ( Γ EFG ). The protocol is shown to generate structural models that are excellent matches with experimental crystal structures that have been DFT-D2* geometry optimized, as validated by crystallographic R -factors ( R ) and root-mean squared distances (RMSDs) of atomic positions that are well below 10% and 0.2 Å, respectively. Finally, consideration is given to the use of the QNMRX-CSP protocol as a standalone technique or in concert with other NMRX methods and Rietveld refinements, and possible applications employing other quadrupolar nuclei ( i.e. , 14 N and 17 O). 35 Cl ( I = 3/2) solid-state NMR data is used in a nascent quadrupolar NMR crystallographic protocol, dubbed QNMRX-CSP, for the structural prediction, refinement, and validation of organic HCl salts.