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Crystal engineering of multi-component molecular crystals, cocrystals, is a subject of growing interest, thanks in part to the potential utility of pharmaceutical cocrystals as drug substances with improved properties. Whereas molecular cocrystals (MCCs) are quite well studied from a design perspective, ionic cocrystals (ICCs) remain relatively underexplored despite there being several recently FDA-approved drug products based upon ICCs. Successful cocrystal design strategies typically depend on strong and directional noncovalent interactions between coformers, as exemplified by hydrogen bonds. Understanding of the hierarchy of such interactions is key to successful outcomes in cocrystal design. We herein address the crystal engineering of ICCs comprising azole functional groups, particularly imidazoles and triazoles, which are commonly encountered in biologically active molecules. Specifically, azoles were studied for their propensity to serve as coformers with strong organic (trifluoroacetic acid and p-toluenesulfonic acid) and inorganic (hydrochloric acid, hydrobromic acid and nitric acid) acids to gain insight into the hierarchy of NH+···N (azolium-azole) supramolecular heterosynthons. Accordingly, we combined data mining of the Cambridge Structural Database (CSD) with the structural characterization of 16 new ICCs (11 imidazoles, 4 triazoles, one imidazole-triazole). Analysis of the new ICCs and 66 relevant hits archived in the CSD revealed that supramolecular synthons between identical azole rings (A+B−A) are much more commonly encountered, 71, than supramolecular synthons between different azole rings (A+B−C), 11. The average NH+···N distance found in the new ICCs reported herein is 2.697(3) Å and binding energy calculations suggested that hydrogen bond strengths range from 31–46 kJ mol−1. The azolium-triazole ICC (A+B−C) was obtained via mechanochemistry and differed from the other ICCs studied as there was no NH+···N hydrogen bonding. That the CNC angles in imidazoles and 1,2,4-triazoles are sensitive to protonation, the cationic forms having larger (approximately 4.4 degrees) values than comparable neutral rings, was used as a parameter to distinguish between protonated and neutral azole rings. Our results indicate that ICCs based upon azolium-azole supramolecular heterosynthons are viable targets, which has implications for the development of new azole drug substances with improved properties.

Exploiting the kinetic domain provided by hydrothermal conditions, it was possible to isolate three transient metastable crystal structures, each bearing concomitant pairs of octamolybdate isomers, namely, α–β, γ–β or βcs–βgp stabilized by distinctive homoleptic [Co(bpy)3] n+ (bpy = 2,2′-bipyridine; n = 2 or 3) cations generated in situ: [Co(bpy)3]4[(α-Mo8O26)(β-Mo8O26)]·5H2O (1), [NH4][Co(bpy)3][(γ-Mo8O26)0.5(β-Mo8O26)0.5]·4H2O (2) and [Co(bpy)3]2[(βcs-Mo8O26)0.5(βgp-Mo8O26)]·12H2O (3). Solid 1 with the space group P21/n and unit-cell parameters a = 22.160 (6), b = 14.209 (3), c = 24.641 (4) Å, β = 99.10 (2)° and V = 7661 (3) Å3 resulted in the same crystal structure as that synthesized previously under different conditions by Sun et al. [J. Mol. Struct. (2005), 741, 149–153]. Factors directing the reaction, such as product composition and phase stability, were monitored by analysis of the PXRD patterns of the bulk solids obtained under different experimental conditions. The relative proportions of the mixed phases 1–3 or their stabilization are highly dependent on the initial Co:Mo molar ratio and the reaction temperature. In particular, an increase in temperature induces the transformation of 1–3 into more thermodynamically stable phases formed by one-dimensional coordination polymers [Co(bpy)2(β-Mo8O26)0.5] n (4) and [(MoO3)(bpy)] n (5). The crystal structures of 1–3 correspond to molecular salts self-assembled by C—H...O—Mo, C...H and H...H intermolecular contacts. A Hirshfeld surface analysis for 1 showed that the C...H and H...H interactions represent an average of 51.8% of the total cation–cation intermolecular contacts. In contrast, these interactions are vastly reduced in 2 (23.0%) and 3 (average 28.5% for both isomers). EPR experiments indicated that the crystal structures of 1 and 3 are paramagnetic, and that for 2 is diamagnetic. The paramagnetism of 3 stems from the in situ formation of [Co(bpy)3]3+ in a high-spin configuration. The structure-directing properties of the [Co(bpy)3] n+ cations in the isolation and self-assembly of concomitant octamolybdate isomers are also described from the viewpoint of crystal engineering.

Oral mucositis (OM) is a complex acute cytotoxicity of antineoplastic treatment that affects 40%-85% of patients undergoing hematopoietic stem-cell transplantation. OM is associated with prolonged hospitalization, increased extensive pharmacotherapy, need for parenteral nutrition, and elevated treatment costs. As OM onset relates with the mucosal microenvironment status, with a particular role for microbiota-driven inflammation, we aimed to investigate whether the oral mucosa microbiota was associated with the clinical course of OM in patients undergoing allogeneic hematopoietic stem-cell transplantation. We collected oral mucosa samples from 30 patients and analyzed the oral mucosa microbiota by 16S rRNA sequencing. A total of 13 patients (43%) developed ulcerative OM. We observed that specific taxa were associated with oral mucositis grade and time to oral mucositis healing. Porphyromonas relative abundance at preconditioning was positively correlated with ulcerative OM grade (Spearman ρ = 0.61, p = 0.028) and higher Lactobacillus relative abundance at ulcerative OM onset was associated with shortened ulcerative OM duration (p = 0.032). Additionally, we generated a machine-learning-based bacterial signature that uses pre-treatment microbial profiles to predict whether a patient will develop OM during treatment. Our findings suggest that further research should focus on host-microbiome interactions to better prevent and treat OM.

A series of related acetylacetonate–carbonyl–rhodium compounds substituted by functionalized phosphines has been prepared in good to excellent yields by the reaction of [Rh(acac)(CO)2] (acac is acetylacetonate) with the corresponding allyl-, cyanomethyl- or cyanoethyl-substituted phosphines. All compounds were fully characterized by 31P, 1H, 13C NMR and IR spectroscopy. The X-ray structures of (acetylacetonato-κ2 O,O′)(tert-butylphosphanedicarbonitrile-κP)carbonylrhodium(I), [Rh(C5H7O2)(CO)(C8H13N2)] or [Rh(acac)(CO)(tBuP(CH2CN)2}] (2b), (acetylacetonato-κ2 O,O′)carbonyl[3-(diphenylphosphanyl)propanenitrile-κP]rhodium(I), [Rh(C5H7O2)(C15H14N)(CO)] or [Rh(acac)(CO){Ph2P(CH2CH2CN)}] (2h), and (acetylacetonato-κ2 O,O′)carbonyl[3-(di-tert-butylphosphanyl)propanenitrile-κP]rhodium(I), [Rh(C5H7O2)(C11H22N)(CO)] or [Rh(acac)(CO){tBu2P(CH2CH2CN)}] (2i), showed a square-planar geometry around the Rh atom with a significant trans influence over the acetylacetonate moiety, evidenced by long Rh—O bond lengths as expected for poor π-acceptor phosphines. The Rh—P distances displayed an inverse linear dependence with the coupling constants J P-Rh and the IR ν(C[triple-bond]O) bands, which accounts for the Rh—P electronic bonding feature (poor π-acceptors) of these complexes. A combined study from density functional theory (DFT) calculations and an evaluation of the intramolecular H...Rh contacts from X-ray diffraction data allowed a comparison of the conformational preferences of these complexes in the solid state versus the isolated compounds in the gas phase. For 2b, 2h and 2i, an energy-framework study evidenced that the crystal structures are mainly governed by dispersive energy. In fact, strong pairwise molecular dispersive interactions are responsible for the columnar arrangement observed in these complexes. A Hirshfeld surface analysis employing three-dimensional molecular surface contours and two-dimensional fingerprint plots indicated that the structures are stabilized by H...H, C...H, H...O, H...N and H...Rh intermolecular interactions.

The design of multicomponent crystals offers a means to modify the physicochemical properties of crystals without altering the chemical properties of a particular molecule. In this study, a multicomponent crystal, the salt of malonic acid with p-chloroaniline, was synthetized and structurally characterized. The title compound wasprepared by grinding in an agate mortar, and its structure was studied by powder and single-crystal X-ray diffraction. This compound crystallize in the monoclinic system with space group P21/c, Z = 4, and unit cell parameters a = 12.9776(7)Å, b = 9.2308(5)Å, c = 8.5170(5)Å, β = 93.474(3)°. The multicomponent compound, p-chloroanilinium semi-malonate, can be described as an ionic ensemble assisted by hydrogen bonds established between p-chloroanilinium cations and semi-malonate anions. The molecular structure and crystal packing are stabilized mainly by intermolecular O-H•••O and N-H•••O hydrogen bonds interactions. The molecules construct a supramolecular assembly with a two-dimensional hydrogen bonded network along the ca plane.

The 1:2 ratio salicylic acid/biimidazole co-crystal is studied in this work. I This compound was obtained from a flux with methanol followed by slow evaporation, rendering colorless plates, that crystallize in the monoclinic system, space group P21/n, with unit cell parameters a = 12.0969 (4) A, b = 5.0714 (1) A and c = 15.4825 (4) A, β = 99.007(2)o, and V = 938.11(4) A3. The experimental characterization is achieved through X-ray diffraction structure analyzes, infrared spectroscopy (FTIR) and thermal analysis (TGA/DSC). This characterization is complemented by theoretical calculations at the DFT/6–31++G(d,p) level, employing the HCTH407 functional. Geometrical optimizations are performed and a detailed Non-Covalent-Index analysis is carried out. It is found that the crystal structure is maintained by conventional and non-conventional hydrogen bonds, of the type N–H···O, O–H···N and C–H···O hydrogen bonds responsible for the formation of planar supramolecular units forming R2 2(9) rings and slip-stacked packing, which, through DFT/HCTH calculations, are shown to stabilize the structure. The synthesis and crystal structure of the title compound, C10H9N2O3, is reported. The bimidazole and salicylic acid form a co-crystal in a 1:2 ratio. Its crystal structure is maintained by conventional and non-conventional hydrogen bonds. Two conventional hydrogen bonds, of the type N–H···O and O–H···N, form planar supramolecular unit through R2 2(9) rings, the DFT/HCTH calculations shows us that the R2 2(9) rings formation stabilize the supramolecular structure.

The authors thank Fondo Nacional de Ciencia Tecnología e Innovación (FONACIT Proyecto de apoyo a Grupos No. G-2005000403). Proyecto 1063, Instituto Venezolano de Investigaciones Científicas (IVIC). A novel hydrazone, (E)-Ethyl-4-(2-(furan-2-ylmethylene)hydrazinyl)benzoate (EFHB), has been synthesized and characterized by FT-IR, NMR and Mass spectroscopy, and X-ray diffraction; compound crystallized as translucent light yellow thin plates. EFHB was studied for their binding to human serum albumin (HSA) using the fluorescence quench titration method. Molecular docking was also performed to get a more detailed insight into their interaction with HSA at the binding site. Addition of this hydrazone to HSA produced significant fluorescence quenching and splitting of emission spectra of HSA through static quenching mechanism with binding constants of about 104 M−1 at 292.15, 298.15, 304.15 and 310.15 K. According to the synchronous fluorescence, tryptophan and tyrosine residues of the protein are most perturbed by the binding process. Thermodynamic parameters ΔG, ΔH, and ΔS were got and the main sort of acting force between EFHB and HSA was studied. Results of molecular docking have shown that EFHB binds to subdomain IIA of HSA mainly by hydrophobic interaction, energy binding are in good agreement with those obtained by fluorescence study (ΔGthe = −7.32 ± 0.09 kcal mol−1 and ΔGexp = −6.76 ± 0.03 kcal mol−1). Postprint

The title compound has been synthesized by grinding in an agate mortar. Its structure was characterized by TGA-DSC studies, FT-IR, X-ray powder diffraction data, and single-crystal X-ray diffraction. This compound crystallize in the monoclinic system with space group P21/c, Z = 4, and unit cell parameters a = 6.9834(4) A, b = 9.8771(6) A, c = 13.6740(8) A, and β = 103.861(1)°. The salt, C6H7N2O+·C2H2NO3−, or NA+:OXAM−, is an ionic ensemble assisted by hydrogen bonds established between nicotinamidium cations and oxamate anions. The molecular structure and crystal packing are stabilized mainly by four intermolecular N–H···O hydrogen bonds, reinforced by two C–H···O hydrogen bonds and three intramolecular interactions. The two components thus construct a supramolecular assembly with a three-dimensional hydrogen bonded framework.

Derivatives hydrazone are attributed interesting pharmacological properties. The compound under study (E)-ethyl 4-(2-(thiofen-2-ylmethylene) hydrazinyl)benzoate (1), crystallized from ethanol as translucent light yellow thin plates. They are monoclinic, space group P21/c, with unit cell parameters a = 8.846(6), b = 20.734(14), c = 7.583(5) A, β = 95.743(13)°, V = 1383.8(16) A3. Three hydrogen bonds and two intermolecular π-interaction perpendiculars to the hydrogen bonds patterns are observed in the crystal structure. A detailed description of these interactions will be presented. Also, semiempirical calculations (PM6) show the formation in the gas phase of a supramolecular chain, emulating the C(8) graph set seen in the crystal structure of the compound. The synthesis and crystal structure of the title compound, C14H14N2O2S, is reported.

Clenbuterol hydrochloride is an active pharmaceutical ingredient usually prescribed for treatment of respiratory diseases due to its activity as a decongestant and bronchodilator. It has also been used as a performance-enhancing drug. In the PDF-4/Organics 2012 database there are six entries related to this compound: three for its hydrochloride phase calculated using single-crystal data, two for a MeOH and a DMSO solvate of two Cu-clenbuterol complexes, and one experimental unindexed pattern. In this contribution the powder diffraction pattern and the crystal structure, determined using single crystal X-ray diffraction techniques of clenbuterol hemihydrate, C12H18Cl2N2O·0.5H2O, an unreported phase, are presented.

Two compounds isolated from the aerial parts of Verbesina turbacensis H.B.K, are reported in this work. Both compounds crystallize in the orthorhombic system, space group P212121. Compound (1), 6β-[cinnamoyloxy]-3β,4α-dihydroxyeudesmane, formula C24H34O4, has unit cell parameters a = 9.6234(2), b = 12.3137(3) and c = 18.6277(5) A, V = 2207.38(9) A3, Z = 4. On the other hand, 6β-[cinnamoyloxy]-eudesman-15-oic acid (2), formula C24H32O4, has cell parameters a = 8.7035(3), b = 14.2020(4), c = 17.1590(5) A, V = 2120.97(11) A3, Z = 4. Extensive and interesting hydrogen bond patterns are present in the structure of two eudesmane derivatives from Verbesina Turbasencis H.B.K.

La hidantoina del ácido L-aspártico, C5H6N2O4, cristaliza en el sistema ortorrómbico con grupo espacial P212121 (Nº19), Z=4, y parámetros de celda unidad a= 7,597(1) Å, b= 8,591(1) Å, c= 9,447(1) Å, V= 616,6(2) Å3. En la estructura cristalina de este compuesto, las moléculas están unidas por enlaces de hidrógeno del tipo N---H···O y O---H···O, creando estructuras en cadenas y ciclos con grafos C(4), C(6), C(8), R33(15), R44(20) que forman una red tridimensional Hydantoin-L-aspartic acid, C5H6N2O4, crystallize in the orthorhombic system with space group P212121 (Nº19), Z=4, and unit cell parameters a= 7.597(1) Å, b= 8.591(1) Å, c= 9.447(1) Å, V= 616.6(2) Å3. In the crystal structure of the title compound the molecules are joined by N---H···O and O---H···O hydrogen bonds into chain and cyclic structures with graph-set C(4), C(6), C(8), R33(15), R44(20) forming a three-dimensional network. 59-64 gerzon@ula.ve Cuatrimestral

The structure of cubebin [systematic name: 3,4-bis­(1,3-benzodioxol-5-ylmeth­yl)tetra­hydro­furan-2-ol], C20H20O6, is stabilized by O—H⋯O and C—H⋯O hydrogen bonds.