Solid State Nuclear Magnet. Res. 65, 49–63 (2015)

DOI:10.1016/j.ssnmr.2014.12.005

Diazole-based powdered cocrystal featuring a helical hydrogen-bonded network: Structure determination from PXRD, solid-state NMR and computer modeling

We present the structure of a new equimolar 1:1 cocrystal formed by 3,5-dimethyl-1H-pyrazole (dmpz) and 4,5-dimethyl-1H-imidazole (dmim), determined by means of powder X-ray diffraction data combined with solid-state NMR that provided insight into topological details of hydrogen bonding connectivities and weak interactions such as Csingle bondH···π contacts. The use of various 1D/2D 13C, 15N and 1H high-resolution solid-state NMR techniques provided structural insight on local length scales revealing internuclear proximities and relative orientations between the dmim and dmpz molecular building blocks of the studied cocrystal. Molecular modeling and DFT calculations were also employed to generate meaningful structures. DFT refinement was able to decrease the figure of merit R(F2) from ~11% (PXRD only) to 5.4%. An attempt was made to rationalize the role of Nsingle bondH···N and Csingle bondH···π contacts in stabilizing the reported cocrystal. For this purpose four imidazole derivatives with distinct placement of methyl substituents were reacted withdmpz to understand the effect of methylation in blocking or enabling certain intermolecular contacts. Only one imidazole derivative (dmim) was able to incorporate into the dmpz trimeric motif thus resulting in a cocrystal, which contains both hydrophobic (methyl groups) and hydrophilic components that self-assemble to form an atypical 1D network of helicoidal hydrogen bonded pattern, featuring structural similarities with alpha-helix arrangements in proteins. The 1:1 dmpz···dmim compound I is the first example of a cocrystal formed by two different azoles.