Mechanochemistry salts

Lehmann drew attention to some features in solid-state reactions, including the curious observations described in 1834 by Faraday, which are now considered as pioneering experimental studies of the structural sensitivity of the dehydration rate of crystalline hydrates. Crystals of easily eroding sodium salts (carbonates, phosphates, and sulphates), stored by Faraday for a few years, did not exhibit any visible deterioration. A fresh scratch on the crystal surface (birth of mechanochemistry) initiated, however, the onset of intense dehydration with a gradual expansion of the erosion zone until it covered the crystal s entire surface. 

Hasa D, Perissutti B, Cepek C, Bhardway S, carlino E, Grassi M, et al. Drug salt formation via mechanochemistry The case study of Vincamine. Mol Pharm 2013 10 (l) 211-24. 

Application of Mechanochemistry in the Synthesis and Discovery of New Pharmaceutical Forms Co-crystals, Salts and Coordination Compounds... 

Coordination complexes with active pharmacological molecules, which comprise metallodrugs and metallopharmaceuticals, are a much less explored class of reactions. Metallodrugs, in which the metal ion is also the biologically active component, and metallopharmaceuticals, in which the metal ion plays the role of a carrier for the API molecule, similar to the counterion in a pharmaceutical salt or the coformer in a pharmaceutical cocrystal, have been successfully prepared by mechanochemistry [16]. 

Beltran published a review on mechanochemistry (at that time mechano-chemistry was synonym of grinding) that, although it does not report heterocycles it discusses the reaction of organic acids with amines in the solid state to form ammonimn salts (99PAC581), this process being relevant for aspects discussed in other parts of the present review. 

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