The low water solubility of benzodiazepines seriously affects their bioavailability and, in consequence, their biological activity. Since co-crystallization has been found to be a promising way to modify undesirable properties in active pharmaceutical ingredients, the objective of this study was to prepare co-crystals of two benzodiazepines, chlordiazepoxide and lorazepam. Using different co-crystallization procedures, slurry evaporation and liquid-assisted grinding, co-crystals of chlordiazepoxide with p-aminobenzoic acid and lorazepam with nicotinamide were prepared for the first time. Confirmation that co-crystals were obtained was achieved through a comparison of the data acquired for both co-crystals using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared (FTIR) and Raman spectroscopy, with comparisons acquired for the physical mixtures of both benzodiazepines and coformers. The compatibility of PXRD patterns of both benzodiazepines co-crystals with those contained in the base Powder Diffraction File (PDF-4+) suggests that new crystal structures were indeed created under the co-crystallization procedure. Single-crystal X-ray diffraction revealed that a chlordiazepoxide co-crystal with p-aminobenzoic acid and a lorazepam co-crystal with nicotinamide crystallized in the monoclinic P2₁/n and P2₁/c space group, respectively, with one molecule of benzodiazepine and one of coformer in the asymmetric unit. FTIR and Raman spectroscopy corroborated that benzodiazepine and coformer are linked by a hydrogen bond without proton exchange. Furthermore, a DSC study revealed that single endothermic DSC peaks assigned to the melting of co-crystals differ slightly depending on the co-crystallization procedures and solvent used, as well as differing from those of starting components.

In order to determine the influence of the ortho- and meta- halogen substituents in the phenyl ring of benzoic acid on the formation of C–H⋯X hydrogen bonds and X⋯O halogen bonds in crystal packing where the halogen (X) is a fluorine, chlorine, bromine or iodine atom, we synthesized and structurally characterized a series of nine co-crystals formed from acridine and benzoic acids: acridine·benzoic acid (1), acridine·2-fluorobenzoic acid (2), acridine·2-chlorobenzoic acid (3), acridine·2-bromobenzoic acid (4), acridine·2-iodobenzoic acid (5), acridine·3-fluorobenzoic acid (6), acridine·3-chlorobenzoic acid (7), acridine·3-bromobenzoic acid (8) and acridine·3-iodobenzoic acid (9). The number, type and strength of the hydrogen and halogen bonds, and the melting points of co-crystals 1–9 were compared. Systematic analysis of the intermolecular interactions taking place in the co-crystals of the title compounds indicates that competition between halogen and hydrogen bonding depends on the position and type of halo-substituent.

Oxidative stress plays an important role in the pathogenesis of many serious diseases, including cancer, atherosclerosis, coronary artery disease, Parkinson’s disease, Alzheimer’s disease, stroke and myocardial infarction. In the body’s natural biochemical processes, harmful free radicals are formed, which can be removed with the help of appropriate enzymes, a balanced diet or the supply of synthetic antioxidant substances such as flavonoids, vitamins or anthocyanins to the body. Due to the growing demand for antioxidant substances, new complex compounds of transition metal ions with potential antioxidant activity are constantly being sought. In this study, four oxovanadium(IV) and dioxovanadium(V) dipicolinate (dipic) complexes with 1,10-phenanthroline (phen), 2,2′-bipyridyl (bipy) and the protonated form of 2-phenylpyridine (2-phephyH): (1) [VO(dipic)(H₂O)₂]·2 H₂O, (2) [VO(dipic)(phen)]·3 H₂O, (3) [VO(dipic)(bipy)]·H₂O and (4) [VOO(dipic)](2-phepyH)·H₂O were synthesized including one new complex, so far unknown and not described in the literature, i.e., [VOO(dipic)](2-phepyH)·H₂O. The oxovanadium(IV) dipicolinate complexes with 1,10-phenanthroline and 2,2′-bipyridyl have been characterized by several physicochemical methods: NMR, MALDI-TOF-MS, IR, but new complex [VOO(dipic)](2-phepyH)·H₂O has been examined by XRD to confirm its structure. The antioxidant activities of four complexes have been examined by the nitrotetrazolium blue (NBT) method towards superoxide anion. All complexes exhibit high reactivity with superoxide anion and [VOO(dipic)](2-phepyH)·H₂O has higher antioxidant activity than L-ascorbic acid. Our studies confirmed that high basicity of the auxiliary ligand increases the reactivity of the complex with the superoxide radical.

Rational manipulation of secondary bonding interactions is a crucial factor in the construction of new chalcogenadiazole-based materials. This article reports detailed experimental studies on phenanthro[9,10-c][1,2,5]chalcogenadiazolium and 2,1,3-benzochalcogenadiazolium salts and their precursors. The compounds were synthesized, characterized employing NMR and UV-Vis spectroscopy. TD-DFT calculations were also performed. The influence of the size of the aromatic system on the molecular motifs formed by the compounds in the solid state has been studied by means of single-crystal X-ray diffraction. In case of the salts, the nature of an anion was also taken into consideration. The results show that cyclic [E···N]₂ supramolecular synthon connects neighboring molecules of phenanthro[9,10-c][1,2,5]chalcogenadiazoles, with a relatively large aromatic system, in dimers regardless of the chalcogen atom in the molecule. Both N-methyl-2,1,3-benzothiadiazolium and N-methylphenanthro[9,10-c][1,2,5]chalcogenadiazolium cations have a strong affinity for triflate and iodide anions, therefore the formation of S···N or Se···N secondary bonding interactions is observed only in two out of the eight quaternary salts. Less coordinating anions must be used to enable the building blocks studied to form cyclic [E···N]₂ synthons. Moreover, for two of the triflate salts, which are isostructural, a new supramolecular motif has been observed.

The cocrystallization of active pharmaceutical ingredient naproxen with some acridines (acridine, 9-aminoacridine, 6,9-diamino-2-ethoxyacridine) has been explored and the conditions under which the crystallization can be carried out have been investigated. While the crystallization of acridine-based molecular crystals was widely studied under solution conditions, solvent-free and/or mechanochemical method potentialities are still unknown. To fill this gap, the cocrystallization of naproxen with the above-mentioned acridines was attempted using different approaches, e.g., by heat treatment of the dry mechanical mixture and by liquid-assisted grinding (LAG), as alternatives to the traditional precipitation by a proper solution. In the first case, the reaction is driven under dry conditions by the temperature and gave no results independently of the temperature used, below or above the melting point of the reactants. In the second case, the reaction is driven by the mechanical action of grinding assisted by a few drops of solvent to facilitate and improve the reaction. This screening allowed obtaining three new molecular crystals for naproxen coupled to acridine and a mono-aminoacridine and solved by single-crystal and powder X-ray diffraction (PXRD). Two host–guest structures were obtained by solution crystallization, while a layered structure was obtained under LAG conditions. Interconversion between molecular crystals formed by the same chemical species was hindered once a molecular crystal was obtained by a specific technique. Hirshfeld and energy framework calculations confirmed the remarkable structural differences between 1α and 1β packing and suggested that 1β is kinetically more stable. Variable-temperature PXRD, DSC and TGA were used to explore the stability of the compounds. 6,9-Diamino-2-ethoxyacridine proved to be too polar and/or too bulky to form crystals with naproxen regardless of the preparation method and the different stoichiometric ratios used. It is noteworthy that LAG allowed the preparation of the naproxen/acridine molecular crystal with a yield higher than 99% under almost solvent-free conditions. DSC indicated the formation of a eutectic between naproxen and acridine, with the possibility of recrystallizing the 1 : 1 complex also from the melt solution.

In order to determine the influence of halogen substituent on the self-assembly of the 6,9-diamino-2-ethoxyacridinium cations and 3-halobenzoate anions in the crystals formed from ethacridine and halobenzoic acids, the series of ethacridinium meta-halobenzoates dihydrates: ethacridinium 3-chlorobenzoate dihydrate (1), ethacridinium 3-bromobenzoate dihydrate (2), and ethacridinium 3-iodobenzoate dihydrate (3), were synthesized and structurally characterized. Single-crystal X-ray diffraction measurements showed that the title compounds crystallized in the monoclinic P2₁/c space group and are isostructural. In the crystals of title compounds, the ions and water molecules interact via N–H⋯O, O–H⋯O and C–H⋯O hydrogen bonds and π–π stacking interactions to produce blocks. The relationship between the distance X⋯O between the halogen atom (X=Cl, Br, I) of meta-halobenzoate anion and the O-atom from the ethoxy group of cation from neighbouring blocks and crystal packing is observed in the crystals of the title compounds.