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We present SpeedMixing, a rapid blending technology, as an approach for fast mechanosynthesis and discovery of model pharmaceutical cocrystals through rapid spinning in the absence of bulk solvents and milling/grinding media. Syntheses of pharmaceutical cocrystals based on the active pharmaceutical ingredients (APIs) carbamazepine, dihydrocarbamazepine, and nicotinamide demonstrate SpeedMixing as a method for rapid, scalable, as well as controllable and selective synthesis of cocrystals, cocrystal polymorphs and stoichiomorphs, including the discovery of an unexpected methanol solvate of the archetypal cocrystal of carbamazepine and saccharin, which has eluded extensive screens over 20 years.

Supercritical carbon dioxide (CO2) is an established medium for synthesizing molecular compounds and activation of microporous solids, but is much less explored for transformations of high-melting ionic reactants, such as metal oxides. We show that supercritical CO2 enables direct, clean, and rapid transformation of zinc oxide into zeolitic imidazolate frameworks (ZIFs), without requiring toxic or corrosive metal nitrate or chloride precursors, organic or aqueous solvents, additives, or auxiliaries. While recent syntheses of coordination polymers and metal–organic frameworks from supercritical CO2 highlighted the need for specialized metal reagents designed for solubility, we unexpectedly find that ZnO is quantitatively converted into grams of diverse ZIFs in minutes, with hundred grams of popular ZIF-8 accessible within an hour.

Mechanochemistry enables enzymatic cleavage of cellulose into glucose without bulk solvents, acids, other aggressive reagents, or substrate pre-treatment. This clean mechanoenzymatic process (coined RAging) is also directly applicable to biomass, avoids many limitations associated with the use of cellulases, and produces glucose concentrations greater than three times that obtained by conventional methods.