Mechanochemistry is considered an alternative attractive greener approach to prepare diverse molecular compounds and has become an important synthetic tool in different fields (e.g., physics, chemistry, and material science) since is considered an ecofriendly procedure that can be carried out under solvent free conditions or in the presence of minimal quantities of solvent (catalytic amounts). Being able to substitute, in many cases, classical solution reactions often requiring significant amounts of solvents. These sustainable methods have had an enormous impact on a great variety of chemistry fields, including catalysis, organic synthesis, metal complexes formation, preparation of multicomponent pharmaceutical solid forms, etc. In this sense, we are interested in highlighting the advantages of mechanochemical methods on the obtaining of pharmaceutical cocrystals. Hence, in this review, we describe and discuss the relevance of mechanochemical procedures in the formation of multicomponent solid forms focusing on pharmaceutical cocrystals. Additionally, at the end of this paper, we collect a chronological survey of the most representative scientific papers reporting the mechanochemical synthesis of cocrystals.

Sensitive and direct sensing of cyanide in buffered aqueous solutions at pH = 7.0 by three new blue photoluminescent zinc-1,4-cyclohexanedicarboxylato coordination polymers bearing di-alkyl-2,2′-bipyridines has been achieved. Specifically, a Zn-polymer with the general formula: {[Zn₂(H₂O)₂(e,a-cis-1,4-chdc)₂(4,4′-dtbb)₂]·7H₂O}_n, (1,4-chdc = 1,4-cyclohexanedicarboxylato and 4,4′-dtbb = 4,4′-ditert-butyl-2,2′-bipyridine) has been synthesized in high yield and studied as a luminescent chemosensor for halides, pseudohalides and a series of oxyanions in neutral water. CN⁻ ions can be quantitatively detected by this polymer based on complete quenching (λ_em = 434 nm) in the sub-micromolar concentration range with a pronounced selectivity over common anions such as acetate, bromide and iodide. The quenching response (K_SV = 9.7(±0.2) × 10⁴ M⁻¹) by the addition of CN⁻ was also observed in the presence of typical interfering anions with a very low detection limit of 0.9 μmol L⁻¹ in buffered water at pH = 7.0. On the basis of the crystal structure and solid state CPMAS ¹³C-NMR correlation and ¹H NMR, IR-ATR, MS-ESI(+) and SEM-EDS experiments, the optical change is attributed to the efficient release of its corresponding ditert-butyl-bipyridine, with the simultaneous formation of a zinc cyanide complex. The CPMAS ¹³C-NMR spectrum of the coordination polymer is consistent with the symmetry of the crystal structure. The use of flexible coordination polymers as fluorescent sensors for fast and selective detection of cyanide ions in pure aqueous solutions has been unexplored until now.

Fluorination of pharmaceutical agents has afforded crucial modifications to their pharmacological profiles, leading to important advances in medicinal chemistry. On the other hand, metallodrugs are considered to be valuable candidates in the treatment of several diseases, albeit with the caveat that they may exhibit pharmacological disadvantages, such as poor water solubility, low bioavailability and short circulating time. To surmount these limitations, two approaches have been developed: one based on the design of novel metallodrug-delivering carriers and the other based on optimizing the structure of the ligands bound to the metal center. In this context, fluorination of the ligands may bring beneficial changes (physicochemical and biological) that can help to elude the aforementioned drawbacks. Thus, in this review, we discuss the use of fluorinated ligands in the design of metallodrugs that may exhibit potential anticancer activity.

Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B inhibitors to date. Herein we describe the synthesis and evaluation of two series of indole- and N-phenylpyrazole-GA derivatives (4a–f and 5a–f). We measured their inhibitory activity and enzyme kinetics against PTP1B using p-nitrophenylphosphate (pNPP) assay. GA derivatives bearing substituted indoles or N-phenylpyrazoles fused to their A-ring showed a 50% inhibitory concentration for PTP1B in a range from 2.5 to 10.1 µM. The trifluoromethyl derivative of indole-GA (4f) exhibited non-competitive inhibition of PTP1B as well as higher potency (IC₅₀ = 2.5 µM) than that of positive controls ursolic acid (IC₅₀ = 5.6 µM), claramine (IC₅₀ = 13.7 µM) and suramin (IC₅₀ = 4.1 µM). Finally, docking and molecular dynamics simulations provided the theoretical basis for the favorable activity of the designed compounds.