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Combining zinc nitrate with 3- and/or 4- aminocinnamic acid (3-ACA and 4-ACA, respectively) leads to the formation of the 0D complex [Zn(4-AC)2(H2O)2], the 1D coordination polymer [Zn(3-AC)(4-AC)], and the 2D and 3D MOFs [Zn(3-AC)2]∙2H2O and [Zn(4-AC)2]∙H2O, respectively. These compounds result from the deprotonation of the acid molecules, with the resulting 3- and 4-aminocinnamate anions serving as bidentate terminal or bridging ligands. All solids were fully characterized via single crystal and powder X-ray diffraction and thermal techniques. Given the mild antimicrobial properties of cinnamic acid derivatives and the antibacterial nature of the metal cation, these compounds were assessed and demonstrated very good planktonic cell killing as well as inhibition of biofilm growth against Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus.

In this paper, we address the problem of antimicrobial resistance in the case of Helicobacter pylori with a crystal engineering approach. Two antibiotics of the fluoroquinolone class, namely, levofloxacin (LEV) and ciprofloxacin (CIP), have been co-crystallized with the flavonoids quercetin (QUE), myricetin (MYR), and hesperetin (HES), resulting in the formation of four co-crystals, namely, LEV∙QUE, LEV∙MYR, LEV2∙HES, and CIP∙QUE. The co-crystals were obtained from solution, slurry, or mechanochemical mixing of the reactants. LEV∙QUE and LEV∙MYR were initially obtained as the ethanol solvates LEV∙QUE∙xEtOH and LEV∙MYR∙xEtOH, respectively, which upon thermal treatment yielded the unsolvated forms. All co-crystals were characterized by powder X-ray diffraction and thermal gravimetric analysis. The antibacterial performance of the four co-crystals LEV∙QUE, LEV∙MYR, LEV2∙HES, and CIP∙QUE in comparison with that of the physical mixtures of the separate components was tested via evaluation of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). The results obtained indicate that the association with the co-formers, whether co-crystallized or forming a physical mixture with the active pharmaceutical ingredients (API), enhances the antimicrobial activity of the fluoroquinolones, allowing them to significantly reduce the amount of API otherwise required to display the same activity against H. pylori.

Abstract The use of the gallium oxalate complex [Ga(ox)3]3− as a building block in the formation of a drug-drug salt with the antimicrobial agent proflavine (PF) as its proflavinium cation (HPF+), namely [HPF]3[Ga(ox)3]·4H2O, is reported together with the preparation of the potassium salt K3[Ga(ox)3] and the novel dimeric gallium(III) salt K4[Ga2(ox)4(μ-OH)2]·2H2O. All compounds have been characterized by solid state methods, and their performance as antimicrobial agents has been evaluated by disk diffusion assay against the bacteria strains Pseudomonas aeruginosa ATCC27853, Staphylococcus aureus ATCC25923, and Escherichia coli ATCC25922. While the [HPF]3[Ga(ox)3]·4H2O drug-drug salt is effective against all three strains, the gallium oxalate salt K3[Ga(ox)3] showed impressive selectivity towards P. aeruginosa, with little to no antimicrobial activity against the other two organisms. This work presents novel breakthroughs towards Ga based antimicrobial agents.

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 conceptual relationship between crystal reactivity, stability and metastability, solubility and morphology on the one hand and shape, charge distribution, chirality and distribution of functional groups over the molecular surfaces on the other hand is discussed, via a number of examples coming from three decades of research in the field of crystal engineering at the University of Bologna. The bottom-up preparation of mixed crystals, co-crystals and photoreactive materials starting from molecular building blocks across the borders of organic, organometallic and metalorganic chemistry is recounted.

Ionic co-crystals (ICCs) are constituted of inorganic salts and organic molecules. These crystals combine ionic interactions with classical supramolecular bonding such as hydrogen and dipole-bonding interactions. Such is the case of the hydrogen bonds between N–H and CO dipoles in primary and secondary amides when these cocrystallize with an ionic material such as CaCl2. Here, we report our results of the preparation and characterization of a series of ICCs in which the molecular component is an active pharmaceutical ingredient (API) or a precursor of APIs, namely, barbituric acid, diacetamide, malonamide, nicotinamide, and piracetam, while the inorganic salt coformer is CaCl2. CaCl2has been chosen, inter alia, for its nontoxicity and potential applications in the pharmaceutical field. Preparative methods include conventional crystallizations from solution, as well as slurry and solid state techniques (grinding and kneading). All crystal structures reported herein were determined either from single crystal diffraction data or from powder diffraction data, using simulated annealing procedures. Crystalline products were analyzed by differential scanning calorimetry, thermogravimetric analysis, and variable temperature X-ray powder diffraction. Intrinsic dissolution rate measurements were also performed on nicotinamide and piracetam ICCs. [ABSTRACT FROM AUTHOR]

Reaction in solution and in the solid state of 18-crown[6] with Cs2CO3and 5-substituted isophthalic acids yields the new organic–inorganic complexes 18-crown[6]·Cs[OH-isoH] (2), 18-crown[6]·Cs[CH3-isoH] (3), 18-crown[6]·Cs[Br-isoH] (4), 18-crown[6]·Cs[OCH3-isoH] (5), 18-crown[6]·Cs[NO2-isoH] (6) and 18-crown[6]·Cs[tert-Butyl-isoH] (8), which have all been characterized by X-ray diffraction. All compounds except the latter are isomorphous, in spite of the size, shape and chemical nature of the substituent and its ability to form hydrogen bonds. [ABSTRACT FROM AUTHOR]

Solid-state reactions of copper(i) iodide with 1,4-diazabicyclo[2.2.2]octane (DABCO) and piperazine in different conditions (kneading, vapour digestion, thermal treatment) resulted in the formation of four new luminescent systems, which have been characterized viaX-ray diffraction and photo-luminescence spectroscopy. At room temperature all compounds exhibit a bright emission in the solid state that markedly shifts bathochromically on cooling to 77 K. The luminescence of the almost isostructural 2D-coordination polymers [Cu2I2(L)2]∞(L = DABCO, piperazine) exhibits an unusually long lifetime (125 and 53 μs, respectively), which becomes even longer (609 and 420 μs, respectively) at 77 K. [ABSTRACT FROM AUTHOR]

Solid-state adducts (co-crystals and molecular salts) of 1,4-diazabicyclo-[2.2.2]-octane (DABCO) with aromatic polycarboxylic acids (isophthalic acid, isoH2, dinicotinic acid, dinH2and dipicolinic acid, dipH2) were prepared in the solid state by grinding and kneading techniques, and fully characterized viaX-ray diffraction. The polycarboxylic acids differ for the presence/absence and position of a nitrogen atom in the aromatic ring; the extent of proton transfer, from the carboxylic groups on the acids to the nitrogen atoms on DABCO, reflects the trend of solution acidity of the three polycarboxylic acids. [ABSTRACT FROM AUTHOR]

In this communication we describe the solid-state preparation and structural characterization of the coordination and hydrogen bonding networks formed by the antibiotic 4-aminosalicylic acid and the nootropic drug piracetam with silver and nickel cations, respectively; the silver complex formed viasolid-state reaction is anhydrous, while from solution its hydrated phase is obtained. [ABSTRACT FROM AUTHOR]

18-Crown[6] has been used to prepare new organic–inorganic complexes with Cs2CO3and aromatic mono-, di- and tricarboxylic acids (benzoic, isophthalic, terephthalic and trimesic acid). The complexes 18-crown[6]·Cs[trimH2] (1), 18-crown[6]·Cs[isoH] (2), 18-crown[6]·Cs2[isoH]2·2H2O (3), (18-crown[6])3·Cs3[trim]·9H2O (4), 18-crown[6]·Cs[ben]·H2O (5) and (18-crown[6])6·Cs4[tereH]2[tere]·5H2O (6) have been characterized by single-crystal X-ray diffraction. The thermal behaviour of 1, 2and 4has been investigated by a combination of solid-state techniques including differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and variable temperature X-ray powder diffraction (VT-XRPD); in the case of 2hot stage microscopy was used to clarify its thermal behaviour. [ABSTRACT FROM AUTHOR]

A range of crystallisation experiments seeking to investigate the chloro/methyl structural similarity of o-toluic acid (o-methylbenzoic acid) and o-chlorobenzoic acid, including heterogeneous seeding experiments, has produced single crystals of both acids, and a 1 : 1 co-crystal (1) in which the chlorine atom and methyl group are disordered. All structures are characterized by the same hydrogen bonded ribbons, but they are not isostructural because of significant differences in the packing of the ribbons. Additional polymorphs of o-toluic acid were detected: microcrystalline form II, and form III with a large unit cell. The observed structures were compared with computationally generated isomorphs and ordered models, and alternative low energy structures generated in computational searches. These calculations show that the structures generated by interchanging the chloro and methyl groups are slightly less stable than the experimentally observed forms. The small energy differences associated with interchanging the two functional groups and between alternative packing arrangements of the hydrogen-bonded ribbons is consistent with the polymorphism of o-toluic acid and the observed disorder in the co-crystal. [ABSTRACT FROM AUTHOR]

The reactions of solid 1,3-dimethylbarbituric acid (DMBA) with vapours of NH3 and of the volatile amines NH2(CH3) and NH(CH3)2 have been investigated. The barbiturate salts (DMB) [NH4]DMB (1), [NH3(CH3)]DMB (2) and [NH2(CH3)2]DMB (3) have been characterized by X-ray powder diffraction, differential scanning calorimetry and thermogravimetric analysis. The solid–gas reactions were monitored by UV–Vis spectroscopy in the solid state. Single crystal X-ray diffraction was used to characterize compounds 1, obtained by recrystallization from methanol, and 3, obtained by direct reaction of DMBA with aqueous NH(CH3)2. In the case of 3, recrystallization from methanol yields the salt [NH2(CH3)2][DMB]·2[DMBA] (3a), while recrystallization of 2 yields both the dimerization product [NH3(CH3)][(C6O3N2H6)2-OH]·2H2O (2a) and the hydurilate salt [NH3(CH3)]2[(C6O3N2H6)2] (2b), i.e. the product 2 is only accessible via the solid–gas reaction. [ABSTRACT FROM AUTHOR]

Hydrogen bonding interactions are the strongest of the non-covalent interactions and are highly directional (hence transportable and reproducible). With respect to hydrogen bonds between neutral molecules the hydrogen bonding interactions between ions (inter-ionic hydrogen bonds) respond to additional energetic and topological constrains that depend on the convolution of the proton donor- proton acceptor interactions with the Coulombic field generated by the presence of ions. Directionality and strength are exploited in the design of molecular crystals, hence in molecular crystal engineering strategies. Molecular crystal engineering is the planning and utilisation of crystal-oriented syntheses for the bottom-up construction of functional molecular solids from molecules and ions. The success of crystal engineering strategies depends on the availability of robust and transferable interactions to glue together construction materials. This chapter is devoted to an important subset of non-covalent interactions, namely those involving hydrogen bonding and p-stacking interactions between ions. Some relevant analogies and differences between organic-type intermolecular interactions and those in which metal atoms are involved will be outlined. Selected examples of the utilization of inter-ionic hydrogen bonding interactions in crystal reactivity will also be described. [ABSTRACT FROM AUTHOR]

Co-crystals of dextro-(R,R), levo-(S,S), meso-(R,S) and racemic(R,R–S,S)-tartaric acid with pyrazine were obtained by manual kneading and slurry experiments; subsequent reactions in the solid state between these co-crystals and the various forms of tartaric acid in the solid state and viaslurry show that co-former exchange takes place according to the sequence of stability [(R,S)-ta]2·py > (S,S/R,R)-ta·py > (R,R)-ta·py or (S,S)-ta·py. [ABSTRACT FROM AUTHOR]

In this communication we describe the solid-state preparation and structural characterization of the first two coordination complexes of the neuroleptic drug gabapentin, obtained by grinding together solid gabapentin and the inorganic salts ZnCl2 and CuCl2·2H2O. [ABSTRACT FROM AUTHOR]

On heating the hydrated complexes 18-Crown[6]·M[H2PO4]·xH2O (x= 2 for M = K, Rb; x= 1.5 for M = Cs), quantitatively prepared by mechanical mixing of crystalline 18-Crown[6] and M[H2PO4], to ca. 60 °C, water loss takes place, accompanied by the extrusion of the crown ether from the crystalline complex and followed by reconstruction of the inorganic phase M[H2PO4](M = K, Rb, Cs); the resulting solid mixture reverts to 18-Crown[6]·M[H2PO4]·xH2O (x= 2 for M = K, Rb; x= 1.5 for M = Cs) upon grinding in air. [ABSTRACT FROM AUTHOR]