This Dalton Perspective deals with solvent-free reactions taking place within solids or between solids or involving a solid and a vapour. The focus is on reactions involving organometallic and coordination compounds and occurring via reassembling of non-covalent bonding, e.g. hydrogen bonds, and/or formation of ligand-metal coordination bonds. It is argued that reactions activated by mechanical mixing of solid reactants as well as those obtained by exposing a crystalline solid to a vapour can be exploited to "make crystals", which is the quintessence of crystal engineering. It is demonstrated through a number of examples that solvent-free methods, such as co-grinding, kneading, milling of molecular solids, or reactions of solid with vapours represent viable alternative, when not unique, routes for the preparation of novel molecular and supramolecular solids as well as for the preparation of polymorphic or solvate modifications of a same species. The structural characterization of the products requires the preparation of single crystals suitable for X-ray diffraction, a goal often achieved by seeding.

Kneading them in: A versatile porous material based on the 1D coordination network [CuCl2(dace)]∞ (dace=trans‐1,4‐diaminocyclohexane) can be inexpensively prepared by a mechanochemical reaction followed by mild thermal treatment. The system is able to reversibly absorb molecules from solution or by simple kneading, while guest desorption from the product invariably leads back to the unsolvated form.

This Article reports the solvent-free synthesis and characterization of a number of different crystal forms of niclosamide (HNic), which is an API belonging to the Salicilamide class. The synthesized compounds are four new salt cocrystals (KNic·HNic·H 2 O, KNic·HNic·3H 2 O, NaNic· HNic·3H 2 O, NaNic·HNic·2H 2 O), a classic cocrystal with imidazole (IM) (HNic·IM), and two sodium salts, (NaNic· DMSO·H 2 O and NaNic·DMSO·2H 2 O). The peculiarity of these salt cocrystals is the API's concomitant presence as both a neutral component and as a salt coformer and the fact that they interact via hydrogen bond formation. HNic's poor aqueous solubility makes the enhancement of its dissolution rate via the modulation of its physical properties extremely important. All samples have been investigated using a combination of solid-state experimental techniques which provide complementary information on powdered samples. These techniques are X-ray powder diffraction, solid-state NMR, IR, and Raman. Single crystals were only obtained for KNic·HNic·H 2 O and NaNic·DMSO·2H 2 O. The nature of the adducts (whether salt or cocrystal), their stoichiometry and the presence of independent molecules in the unit cell of the other samples were thus all determined by means of solid-state NMR and the comparative analysis of 13 C and 15 N CPMAS (Cross-Polarization Magic Angle Spinning) and 1 H MAS spectra. Furthermore, differential scanning calorimetry, thermogravimetric analysis and intrinsic dissolution rate measurements completed the characterization and enabled us to evaluate the effects of microscopic changes (molecular packing, weak interactions, conformations, etc.) on the macroscopic properties (thermal stability and bioavailability) of the multicomponent forms. The results obtained indicate that the formation of salt cocrystals provides a reliable method with which to improve the HNic intrinsic dissolution rate.

Solid-state co-grinding of silver acetate and solid trans-1,4-diaminocyclohexane, [H2NC6H10NH2] yields two isomeric coordination networks depending on the crystallization conditions; a third isomeric form is obtained when the same reaction is carried out in solution.

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