Liquid reagents are not enough for liquid assisted grinding in the synthesis of [(AgBr)(n-pica)]n.

This study investigates the mechanochemical reactions between AgBr 3-picolylamine and 4-picolylamine. The use of different stoichiometry ratios of the reagents allows [(AgBr)(n-pica)]n and [(AgBr)2(n-pica)]n to be obtained, and we report the new structures of [(AgBr)2(3-pica)]n and [(AgBr)2(4-pica)]n which are characterized by the presence of the following: (a) infinite inorganic chains, (b) silver atom coordinated only by bromide atoms and (c) argentophilic interactions. Furthermore, we studied the interconversion of [(AgBr)(n-pica)]n/[(AgBr)2(n-pica)]n by mechanochemical and thermal properties. The in situ experiments suggest that [(AgBr)(3-pica)]n is kinetically favoured while [(AgBr)2(3-pica)]n is converted into [(AgBr)(3-pica)]n only with a high excess of the ligand. Finally, the liquid nature of the ligands is not sufficient to assist the grinding process, and the complete reaction is observed with the addition of a small quantity of acetonitrile.

Searching for Suitable Kojic Acid Coformers: From Cocrystals and Salt to Eutectics.

The possibility of obtaining cocrystals of kojic acid with organic coformers has been investigated by both computational and experimental approaches. Cocrystallization attempts have been carried out with about 50 coformers, in different stoichiometric ratios, by solution, slurry, and mechanochemical methods. Cocrystals were obtained with 3-hydroxybenzoic acid, imidazole, 4-pyridone, DABCO, and urotropine, while piperazine yielded a salt with the kojiate anion; cocrystallization with theophylline and 4-aminopyridine resulted in stoichiometric crystalline complexes that could not be described with certainty as cocrystals or salts. In the cases of panthenol, nicotinamide, urea, and salicylic acid the eutectic systems with kojic acid were investigated via differential scanning calorimetry. In all other preparations the resulting materials were constituted of a mixture of the reactants. All compounds were investigated by powder X-ray diffraction; the five cocrystals and the salt were fully characterized via single crystal X-ray diffraction. The stability of the cocrystals and the intermolecular interactions in all characterized compounds have been investigated by computational methods based on the electronic structure and pairwise energy calculations, respectively.

Exploring the Co-Crystallization of Kojic Acid with Silver(I), Copper(II), Zinc(II), and Gallium(III) for Potential Antibacterial Applications.

Co-crystallization of kojic acid (HKA) with silver(I), copper(II), zinc(II), or gallium(III) salts yielded three 1D coordination polymers and one 0D complex in which kojic acid was present as a neutral or anionic terminal or bridging ligand. All reactions were conducted mechanochemically via ball milling and manual grinding, or via slurry. All solids were fully characterized via single-crystal and/or powder X-ray diffraction. As kojic acid is a mild antimicrobial compound that is widely used in cosmetics, and the metal cations possess antibacterial properties, their combinations were tested for potential antibacterial applications. The minimal inhibition concentrations (MICs) and minimal biocidal concentrations (MBCs) for all compounds were measured against standard strains of the bacteria P. aeruginosa, S. aureus, and E. coli. All compounds exerted appreciable antimicrobial activity in the order of silver, zinc, copper, and gallium complexes.

The Relevance of Crystal Forms in the Pharmaceutical Field: Sword of Damocles or Innovation Tools?

This review is aimed to provide to an "educated but non-expert" readership and an overview of the scientific, commercial, and ethical importance of investigating the crystalline forms (polymorphs, hydrates, and co-crystals) of active pharmaceutical ingredients (API). The existence of multiple crystal forms of an API is relevant not only for the selection of the best solid material to carry through the various stages of drug development, including the choice of dosage and of excipients suitable for drug development and marketing, but also in terms of intellectual property protection and/or extension. This is because the physico-chemical properties, such as solubility, dissolution rate, thermal stability, processability, etc., of the solid API may depend, sometimes dramatically, on the crystal form, with important implications on the drug's ultimate efficacy. This review will recount how the scientific community and the pharmaceutical industry learned from the catastrophic consequences of the appearance of new, more stable, and unsuspected crystal forms. The relevant aspects of hydrates, the most common pharmaceutical solid solvates, and of co-crystals, the association of two or more solid components in the same crystalline materials, will also be discussed. Examples will be provided of how to tackle multiple crystal forms with screening protocols and theoretical approaches, and ultimately how to turn into discovery and innovation the purposed preparation of new crystalline forms of an API.

Steps towards a nature inspired inorganic crystal engineering.

This Perspective outlines the results obtained at the University of Bologna by applying crystal engineering strategies to develop nature inspired organic-inorganic materials to tackle challenges in the health and environment sectors. It is shown by means of a number of examples that co-crystallization of inorganic salts, such as alkali and transition metal halides, with organic compounds, such as amino acids, urea, thiourea and quaternary ammonium salts, can be successfully used for (i) chiral resolution and conglomerate formation from racemic compounds, (ii) inhibition of soil enzyme activity in order to reduce urea decomposition and environmental pollution, and (iii) preparation of novel agents to tackle antimicrobial resistance. All materials described in this Perspective have been obtained by mechanochemical solvent-free or slurry methods and characterized by solid state techniques. The fundamental idea is that a crystal engineering approach based on the choice of intermolecular interactions (coordination and hydrogen bonds) between organic and inorganic compounds allows obtaining materials with collective properties that are different, and often very much superior to those of the separate components. It is also demonstrated that the success of this strategy depends crucially on cross-disciplinary synergistic exchange with expert scientists in the areas of bioinorganics, microbiology, and chirality application-oriented developments of these novel materials.

Smart urea ionic co-crystals with enhanced urease inhibition activity for improved nitrogen cycle management.

A smart ionic co-crystal of urea with KCl and ZnCl2 has been obtained in two polymorphic modifications via mechanochemical and solution methods and proven to be a very efficient urease inhibitor while, simultaneously, able to provide soil nutrients to complement N supply.