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Crystal structures of two furazidin polymorphs revealed by a joint effort of crystal structure prediction and NMR crystallography

In this work we present crystal structure determination of two elusive polymorphs of furazidin, an antibacterial agent, employing a combination of crystal structure prediction (CSP) calculations and NMR crystallography approach. Two previously uncharacterized neat crystal forms, one of which has two symmetry independent molecules (form I), whereas the other one has only one molecule (form II), crystallize in P21/c and P-1 space groups, respectively, and are both built by different conformers, displaying different intermolecular interactions. We demonstrate that the usage of either crystal structure prediction or NMR crystallography alone is insufficient to successfully elucidate the mentioned crystal structures, especially in the case with two independent molecules in the polymorph structure. In addition, cases of serendipitous agreement in terms of 1H or 13C NMR data obtained for the crystal structure prediction generated crystal structures different from the ones observed in laboratory (false-positive matches) are analyzed and described. Although for majority of analyzed crystal structures the obtained agreement with the NMR experiment is indicative of some structural features in common with the experimental structure, the mentioned serendipity observed in exceptional cases points to the necessity of caution when using NMR crystallography approach in crystal structure determination.