This study introduces a methodology that incorporates supplementary structural information about intermolecular distances obtained from solid-state NMR (ssNMR) measurements into direct-space approach for crystal structure determination from powder diffraction (PD) data [1]. In these methods, such intermolecular distances are applied as restraints within the global optimization process. Direct-space techniques are highly effective for solving structures from PD data, particularly when only a laboratory diffractometer is available. They employ global optimization algorithms which, iteratively test candidate structural models for agreement with experimental diffraction patterns.
For structurally simple, well-diffracting compounds, the probability of identifying the correct model is high. However, the success rate decreases rapidly with the number of degrees of freedom (DOF). A compound with six DOF can often be solved within seconds, whereas those with around 40 DOF are frequently unsolvable using PD data alone, except in rare cases [2]. The problem becomes even worst for poorly crystalline materials, where peak broadening reduces the resolution of diffraction data.
In this work, selected intermolecular distances determined from ssNMR experiments were used as additional restraints in the structure determination process. The FOX software [3] was modified to include a new term in the cost function that enforces agreement with experimentally derived interatomic distances between specific atoms of different molecules. These restraints, assigned tolerances based on NMR measurement precision, were tested on a series of relatively simple isothiouronium salts. To simulate challenging experimental conditions, diffraction peak profiles were artificially broadened. The results demonstrate that including ssNMR-based restraints significantly improves the likelihood of obtaining the correct structural solution, even from low-quality PD data.
[1] J. Rohlíček, V. Eigner, J. Czernek, J. Brus, J. Appl. Crystallogr. 58 (2025) 321–332.
[2] M. Husak, A. Jegorov, J. Czernek, J. Rohlicek, S. Zizkova, P. Vraspir, P. Kolesa, A. Fitch, J. Brus, Cryst. Growth Des. 19 (2019) 4625–4631.
[3] V. Favre-Nicolin, R. Černý, Z. Für Krist. - Cryst. Mater. 219 (2004) 847–856.
This work was supported by the Grant Agency of the Czech Republic, project no. 23-05293S.