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Time-averaged conformations of (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane hydrochloride (MDMA, "ecstasy") in D(2)O, and of its free base and trifluoroacetate in CDCl(3), were deduced from their (1)H NMR spectra and used to calculate their conformer distribution. Their rotational potential energy surface (PES) was calculated at the RHF/6-31G(d,p), B3LYP/6-31G(d,p), B3LYP/cc-pVDZ and AM1 levels. Solvent effects were evaluated using the polarizable continuum model. The NMR and theoretical studies showed that, in the free base, the N-methyl group and the ring are preferentially trans. This preference is stronger in the salts and corresponds to the X-ray structure of the hydrochloride. However, the energy barriers separating these forms are very low. The X-ray diffraction crystal structures of the anhydrous salt and its monohydrate differed mainly in the trans or cis relationship of the N-methyl group to the alpha-methyl, although these two forms interconvert freely in solution.

The ruthenium(II) compounds cis-[Ru(bpy)2(4-bzpy)(CO)](PF6)2 (I) and cis-[Ru(bpy)2(4-bzpy)(Cl)](PF6) (II) (4-bzpy=4-benzoylpyridine, bpy=2,2'-bipyridine) were synthesized and characterized by spectroscopic and electrochemical techniques. The crystal structure of II was determined by X-ray diffraction. The photochemical behavior of I in aqueous solution shows that irradiation with ultraviolet light (365nm) releases both CO and 4-bzpy leading to the formation of the cis-[Ru(bpy)2(H2O)2]2+ ion as identified by NMR and electronic spectroscopy. Carbon monoxide release was confirmed with the myoglobin method and by gas chromatographic analysis of the headspace. CO release was not observed when aqueous I was irradiated with blue light (453nm). Changes in the electronic and 1H NMR spectra indicate that I undergoes photoaquation of 4-bzpy to form cis-[Ru(bpy)2(CO)(H2O)]2+. Blue light irradiation of aqueous II released the coordinated 4-bzpy to give the cis-[Ru(bpy)2(H2O)(Cl)]2+ ion. When the latter reaction was carried out in the presence of the nucleobase guanine, Ru-guanine adducts were formed, indicating that the metal containing photoproduct may also participate in biologically relevant reactions. The photochemical behavior of I indicates that it can release either CO or 4-bzpy depending on the wavelength chosen, a feature that may have therapeutic application.

Lapachol (lap) is widely studied due to its biological application, as well as its importance in the coordination chemistry field. The structure of cis and trans isomers of new ruthenium(III) complex [RuCl2(PPh3)2(lap)] is reported here. The complexes present one molecule of the natural product lapachol, coordinated as bidentate by oxygen atoms, two monodentate triphenylphosphines and two chlorido ligands in a cis or trans configurations. All neutral complexes were characterized by single-crystal X-ray diffraction and these data were compared with Density Functional Theory (DFT) data results. This study highlights the stereochemistry and structural versatility of metal complexes containing lapachol as ligand. [ABSTRACT FROM AUTHOR]

This study reports the synthesis, structural characterization and cytotoxic activity of four new palladium/pyridylporphyrin complexes, with the general formula {TPyP[PdCl(P–P)]4}(PF6)4, where P–P is 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1,2-bis(diphenylphosphino)butane (dppb) or 1,1′-bis(diphenylphosphino)ferrocene (dppf). The complexes were characterized by elemental analysis, and by FT-IR, UV/Vis, 1H and 31P{1H} NMR (1D/2D) spectroscopy. The slow evaporation of a methanolic solution of {TPyP[PdCl(dppb)]4}(PF6)4 (in an excess of NaBF4 salt) resulted in single crystals suitable for X ray diffraction, allowing the determination of the tridimensional structure of this complex, which crystallized in the P21/a space group. The cytotoxicity of the complexes against MDA-MB-231 (breast cancer cells) and MCF-10A (non-tumor breast cancer cells), was determined by the colorimetric MTT method, which revealed that all four complexes show selective indexes close to 1.2, lower than that of cisplatin for the same cells (12.12). The interaction of the complexes with CT-DNA was evaluated by UV-visible and viscosity measurements and it was determined that the complexes interact moderately with CT-DNA, probably by H-bonding/π–π stacking and electrostatic interactions. [ABSTRACT FROM AUTHOR]

In this work, the 2D Eu(III) coordination polymer {[Eu(HPDC)(PDC)]}n (PDC = 2,6-pyridinedicarboxylate) (1) was prepared in a fast manner via microwave-assisted hydrothermal synthesis. The same compound was obtained by a conventional hydrothermal route and had its structure determined through single crystal X-ray diffraction. In 1, the HPDC and PDC ligands exhibit terminal and chelating bridging modes, respectively, forming a coordination polymer through interconnected europium–carboxylate chains, leading to a highly ordered two-dimensional layer. The nanosheets in 1 self-organize in the solid-state by intermolecular interactions, producing a 3D supramolecular network. Solid-state photoluminescence studies have shown that the antenna effect is responsible for the red emission of the compound under ultraviolet excitation. In alcoholic solutions, it was possible to exfoliate the material by ultrasonication in a top-down approach, leading to single nanosheets of 1. In the chemical stability studies, there was observed a water-induced transformation of 1, leading to the compound {[Eu(PDC)(HPDC)(H2O)2]·4H2O}n (2). The aqueous suspension of this material shows strong red luminescence with the naked-eye. 2 demonstrates reversible behavior induced by heating under reduced pressure. Our work highlights the properties related to solvent-induced exfoliation and water-induced transformation. [ABSTRACT FROM AUTHOR]

Fluconazole (FLZ) is one of the most used antifungal drugs worldwide and has been the focus of various investigations with the aim of enhancing its biomedical application. Most of the new solid forms achieved for this drug were determined by powder X-ray diffraction, and a few reports on polymorphs, solvates, cocrystals, and one salt–cocrystal by single-crystal X-ray diffraction (SCXRD) are available. By considering that FLZ is a very weak base (pKa = 1.76, when protonated), salt formation with this drug is expected with the use of very strong organic acids, in order to dislocate the proton from the acid to the FLZ. To the best of our knowledge, only one organic salt of FLZ with picric acid (pKa = 0.38) and one salt–cocrystal (maleate–maleic, pKa1 = 1.92) were reported by SCXRD until now. Having in mind all the advantages that pharmaceutical salts have in drug delivery, in this work we depict the methodology and techniques employed to synthesize a new salt of FLZ using oxalic acid (pKa1 = 1.23). The screening process was initially monitored using Raman spectroscopy, while further characterization by X-ray diffraction (powder and single crystal) and thermal analysis (DSC and TG) was performed to confirm the new salt fluconazolium oxalate (1 : 1). Finally, salt equilibrium solubility studies confirmed an improvement, about 7-fold, when compared to the commercialized active pharmaceutical ingredient (polymorph II). In addition, this is the first reported GRAS (generally regarded as safe) salt of the antifungal drug fluconazole. [ABSTRACT FROM AUTHOR]

Starting from easily prepared (cyclobutylsulfonyl)benzene ( 1), a stereoselective synthesis of (±)-grandisol, accomplished in nine steps, with an overall yield of ca. 18 %, has been presented by Monteiro and Stefani (Eur J Org Chem 14:2659-2663, ). Most of the synthetic intermediates were secured in good to excellent yields as crystalline compounds requiring no or minimal purification, should being amenable to scale up. The structures and absolute stereochemistry of ( 2), ( 3), ( 4a), ( 5), ( 8) and ( 9) were established by IR and NMR (H, C) spectroscopies and confirmed by X-ray diffraction analysis. Compound ( 2) crystallizes in orthorhombic Pbca, a = 16.0565(5), b = 9.5144(6), c = 23.9728(7) Å, the ( 3) crystallizes in monoclinic P2/ c, a = 5.6390(5), b = 17.8630(16), c = 12.8678(12) Å and β = 111.928(7)°, the ( 4a) crystallizes in monoclinic P2/ c, a = 5.7002(9) Å, b = 17.2752(14) Å, c = 14.9168(9) Å and β = 109.464(8)°. The other three cyclobutylsulfonyl derivatives crystallize in the same monoclinic space group P2/ c with cell parameters ( 5) a = 8.072(4), b = 11.486(9), c = 14.565(8) Å and β = 101.373(4)°, ( 8) a = 11.3448(2), b = 7.9377(1), c = 18.5329(4) Å and β = 94.147(1)° and ( 9) a = 37.7571(9), b = 11.4434(3), c = 8.1824(2) Å and β = 90.748(1)°. Graphical Abstract: X-ray crystal structures of six synthetic intermediates prepared from the stereoselective synthesis of (±)-grandisol.[Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Oxygenated xanthones have been extensively investigated over the years, but there are few reports concerning their crystal structure. Our chemical investigations of Brazilian plants resulted in the isolation of four natural products named 1-hydroxyxanthone (I), 1-hydroxy-7-methoxyxanthone (II), 1,5-dihydroxy-3-methoxyxanthone (III), and 1,7-dihydroxy-3,8-dimethoxyxanthone (IV). The structures of these compounds were established on the basis of single crystal X-ray diffraction. The xanthone nucleus conformation is essentially planar with the substituents adopting the orientations less sterically hindered. In addition, classical intermolecular hydrogen bonds (O–H···O) present in III and IV give rise to infinite ribbons. However, the xanthone I does not present any intermolecular hydrogen bonds, meanwhile the xanthone II presents only a non-classical one (C–H···O). The crystal packing of all xanthone structures is also stabilized by π–π interactions. The fingerprint plots, derived from the Hirshfeld surfaces, exhibited significant features of each crystal structures. [ABSTRACT FROM AUTHOR]

In a search for new antitumoral agents, a series of homoleptic copper(II) complexes with amino acids and dipeptides, as well as heteroleptic complexes containing both dipeptides and 1,10-phenanthroline, were studied. Furthermore, a single-crystal structure containing alanyl-leucinato ([Cu3(AlaLeu)3(H2O)3(CO3)]·PF6·H2O), which is the first homotrinuclear carbonato-bridged copper(II) complex with a dipeptide moiety, is presented. To assess possible antitumor action mechanisms, we focused on the comparative analysis of pro- and antioxidant behaviors. Pro-oxidant activity, in which the reactive oxygen species (ROS) formed by the reaction of the complexes with H2O2 produce oxidative damage to 2-deoxy-d-ribose, was evaluated using the TBARS method. Additionally, the antioxidant action was quantified through the superoxide dismutase (SOD)-like activity, using a protocol based on the inhibitory effect of SOD on the reduction of nitrobluetetrazolium (NBT) by the superoxide anion generated by the xanthine/xanthine oxidase system. Our findings show that Cu–amino acid complexes are strong ROS producers and moderate SOD mimics. Conversely, Cu–dipeptide–phen complexes are good SOD mimics but poor ROS producers. The activity of Cu–dipeptide complexes was strongly dependent on the dipeptide. A DFT computational analysis revealed that complexes with high SOD-like activity tend to display a large dipole moment and condensed-to-copper charge, softness and LUMO contribution. Moreover, good ROS producers have higher global hardness and copper electrophilicity, lower copper softness and flexible and freely accessible coordination polyhedra. [ABSTRACT FROM AUTHOR]

Discusses the preparation and structures of caesium lithium sulfate and caesium lithium rubidium sulfate in the context of simple and double sulfate polymorphism. Crystal structure of compounds; Use of X-ray diffraction for the determination of crystal structure; Crystallization system of compounds.

This work focused on analyzing the properties of N‐(5‐nitrothiazol‐2‐yl)furan‐2‐carboxamide (C8H5N3O4S, NTFC) as a possible inhibitor of the rheumatoid arthritis process. The synthesis of NTFC was carried out and good‐quality crystals were obtained and studied by NMR (1H and 13C), DEPT 135, UV–Vis, IR, MS and single‐crystal X‐ray diffraction. The structure of NTFC consists of two rings, thiazole and furan, and a central C—N—C(=O)—C segment, which appears to be planar. This central amide segment forms angles of 2.61 (10) and 7.97 (11)° with the planes of the thiazole and furan rings, respectively. The crystal structure of NTFC exhibits N—H…N, N—H…O and C—H…O hydrogen bonds, and C—H…π and π–π interactions that facilitate self‐assembly and the formation of hydrogen‐bonded dimers, which implies the appearance of R22(8) graph‐set motifs in this interaction. The stability of the dimeric unit is complemented by the formation of strong intramolecular C—S…O interactions of chalcogen character, with an S…O distance of 2.6040 (18) Å. Hirshfeld surface (HS) analysis revealed that O…H/H…O interactions were dominant, accounting for 36.8% of the total HS, and that N—H…N interactions were fundamental to the formation of the dimeric structure. The molecular electrostatic potential (MEP) map showed a maximum energy of 46.73 kcal mol−1 and a minimum of −36.06 kcal mol−1. The interaction energies of molecular pairs around NTFC are highest for those interactions linked by N—H hydrogen bonds. The properties of the NTFC ligand as a potential inhibitor of the DHODH (dihydroorotate dehydrogenase) enzyme were evaluated by molecular docking, showing coupling energies very close to those obtained with the control drug for rheumatoid arthritis, i.e. leflunomide. [ABSTRACT FROM AUTHOR]

Famotidine ( FMT), a histamine H2-receptor antagonist, is a drug commonly used in treatments of gastroesophageal diseases that presents solid-state polymorphism ( A and B forms), the marketed form being the metastable polymorph B. A new stable salt was obtained by combination of FMT and maleic acid as coformer. FMT maleate ( FMT- MLT) was prepared either by solvent evaporation or comilling methods. Single-crystal X-ray diffraction reveals that ( FMT)+ in FMT- MLT adopts an extended conformation that is stabilized by classical and nonclassical H-bonds. The three-dimensional packing consists of tapes along the axis b that further develop a columnar array based on H-bonds involving ( FMT)+ side chain. Nonconventional π-stacking interactions between adjacent tapes were also identified. Fourier transform infrared, differential scanning calorimetry, thermogravimetric analysis, polarized light thermal microscopy, and scanning electron microscopy were employed to characterize the multicomponent complex. According to the solubility values in water and simulated gastric fluid, FMT- MLT exhibits such a performance that improves on the solubility of the commercially available polymorph. Finally, the higher stability of FMT- MLT regarding both FMT forms, as well as its easy preparation from either A or B forms or a mixture of them, also allows to consider this salt as a valuable alternative to avoid the polymorphism issue in marketed formulations containing FMT. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3754-3763, 2014 [ABSTRACT FROM AUTHOR]

• Polybromination by NBS and IR activation of potential antileishmanial guanidine. • Conformational study is performed by Nuclear Magnetic Resonance and SCXRD. • Hirshfeld surface and fingerprint plots of compounds showed a high Br—C contact. • XRPD and SCXRD X-ray patterns agree. • Conformational changes from Z to E promoted by polybromination. Leishmaniasis is a neglected disease that affects regions such as South Asia, South Africa, and Latin America, less developed regions. The research proposed the conformational study of brominated guanidine compounds with potential antileishmanial activity using Nuclear Magnetic Resonance (NMR) and X-ray diffraction (XRD) techniques. The present study involves the brominated molecules LQOF-G2, LQOF-G30, LQOF-G35 and LQOF-G35-Br. The latter was synthesized by the reaction of LQOF-G35 with NBS under IR irradiation at 120 Watts of potency and dichloromethane as solvent by 12 h of exposition. The obtained results demonstrated the efficiency of the bromination method, since two bromine atoms entered the molecule. Furthermore, NMR analysis showed a conformational change from Z to E when compound LQOF-G35 was brominated to LQOF-G35-Br. This behavior was confirmed by a comparative XRD study of the LQOF-G35 and LQOF-G35-Br compounds. The antileishmanial activity of LQOF-G2 e LQOF-G35 motivated the synthesis of new brominated compounds LQOF-G30 e LQOF-G35-Br. [Display omitted] [ABSTRACT FROM AUTHOR]

Mebendazole (MBZ) is a common benzimidazole anthelmintic that exists in three different polymorphic forms, A, B, and C. Polymorph C is the pharmaceutically preferred form due to its adequated aqueous solubility. No single crystal structure determinations depicting the nature of the crystal packing and molecular conformation and geometry have been performed on this compound. The crystal structure of mebendazole form C is resolved for the first time. Mebendazole form C crystallizes in the triclinic centrosymmetric space group and this drug is practically planar, since the least-squares methyl benzimidazolylcarbamate plane is much fitted on the forming atoms. However, the benzoyl group is twisted by 31(1)° from the benzimidazole ring, likewise the torsional angle between the benzene and carbonyl moieties is 27(1)°. The formerly described bends and other interesting intramolecular geometry features were viewed as consequence of the intermolecular contacts occurring within mebendazole C structure. Among these features, a conjugation decreasing through the imine nitrogen atom of the benzimidazole core and a further resonance path crossing the carbamate one were described. At last, the X-ray powder diffractogram of a form C rich mebendazole mixture was overlaid to the calculated one with the mebendazole crystal structure. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2336–2344, 2009 [ABSTRACT FROM AUTHOR]

Abstract: Cyclization of thiosemicarbazones derived from β-keto esters and β-keto amides (HTSC) in the presence of diphenyllead(IV) acetate was explored in methanol solution at room temperature and under reflux. All β-keto ester TSCs underwent cyclization to give the corresponding pyrazolone (HL), which, except in one case, deprotonated and coordinated the PbPh2 2+ moiety to form homoleptic [PbPh2(L)2] or heteroleptic [PbPh2(OAc)(L)] derivatives. Cyclization did not occur with β-keto amide TSCs and only [PbPh2(TSC)2] or [PbPh2(OAc)(TSC)] thiosemicarbazonates were isolated. The complexes were characterized by IR spectroscopy in the solid state and by 1H, 13C and 207Pb NMR spectroscopy in DMSO–d 6 solution, in which they evolve and decompose with time. Additionally, crystals of p-acetoacetanisidide thiosemicarbazone (HTSC10), [PbPh2(OAc)(L5)]·MeOH (HL5 =2,5-dihydro-3,4-dimethyl-5-oxo-1H-pyrazolone-1-carbothioamide), [PbPh2Cl(L2)] (HL2 =2,5-dihydro-5-oxo-3-phenyl-1H-pyrazolone-1-carbothioamide), [PbPh2(OAc)(TSC8)]·2MeOH (HTSC8 =acetoacetanilide thiosemicarbazone), [PbPh2(OAc)(TSC10)]·H2O and [PbPh2(OAc)(TSC11)]·0.75MeOH (HTSC11 = o-acetoacetotoluidide) were studied by X-ray crystallography. The complexes, monomers or dimers with almost linear C–Pb–C moieties, are compared with the corresponding derivatives of Pb(II). [Copyright &y& Elsevier]

Abstract: Cyclization of n butyl glyoxylate thiosemicarbazone (HBuTSC) under reflux in the presence of Pb(OAc)2 led to the formation of the complex [Pb(HTz)2] (H2Tz=3,4-dihydro-3-thioxo-1,2,4-triazin-5(2H)-one), which after recrystallization from DMSO afforded the polymer [Pb(Tz)] n , the first example of a Tz2− metal complex. [Copyright &y& Elsevier]

Abstract: The reaction of lead(II) acetate in methanol with thiosemicarbazones derived from β-keto esters and β-keto amides (HTSCs) afforded two lead(II) thiosemicarbazonates and numerous homoleptic ([PbL2]) and/or heteroleptic ([Pb(OAc)L]) complexes containing deprotonated pyrazolones L− formed by metal-induced cyclization of the starting HTSC ligands. All the complexes isolated were characterized by IR spectroscopy in the solid state and by 1H and 13C NMR spectroscopy in DMSO solution; in addition, crystals containing [Pb(L6)2] and [Pb(L7)2] were examined by X-ray crystallography. [Pb(L6)2]·0.5H2O·0.3MeOH (HL6 =4-ethyl-2,5-dihydro-3-methyl-5-oxo-1H-pyrazole-1-carbothiamide) showed three types of molecule with significant structural differences that appear to be determined by packing interactions. In all three molecules the Pb⋯Pb distances are very short [3.6096(8)–3.7562(8)Å], but density-functional-theoretic calculations at the B3LYP level do not support the existence of Pb–Pb bonds. In [Pb(L7)2] (HL7 = N-ethyl-2,5-dihydro-3-methyl-5-oxo-1H-pyrazole-1-carbothiamide) all the molecules are of a single type, and they are linked in a three-dimensional network by weak intermolecular Pb⋯O bonds. [Copyright &y& Elsevier]

Abstract In the present work, the crystal structure of (3b)-3-acetoxy-30-methoxy-30-oxo-olean-12-en-28-oic acid, (Spergulagenic Acid A) is presented. The compound was isolated from Cecropia telenitida roots, employing semi-pilot scale extraction system and automated flash chromatography device. Vapor diffusion of methanol in chloroform yield suitable crystals for X-ray diffraction. The crystal packing of the Spergulagenic Acid A as methanol solvate is formed by strong hydrogen bonds between the SA-A molecule and the methanol. SA-A as well other pentacyclic triterpenes, present interesting potential biological activities. Inasmuch as biological activity is clearly related to molecular structure, the main goal of the present work was the structural elucidation of this molecule by single crystal X-ray diffraction. To the best of our knowledge, there is no previous crystal structure report in the literature for the titled compound or any other with simultaneous substitution at C 2 and C 7. Graphical abstract Image 1 Highlights • Isolation at semi-pilot scale of Spergulagenic Acid A, a pentacyclic triterpene from roots of an endemic Colombian plant. • Several automated flash chromatography procedures were employed in order to guarantee the isolation reproducibility. • First crystal structure of Spergulagenic Acid A is reported. This structure have simultaneous substitution at C 17 and C 20. [ABSTRACT FROM AUTHOR]

In this paper three novel salts of the anti-tuberculosis drug Isoniazid (INH) with the GRAS salt formers (oxalic, maleic and methanesulfonic acids) were supramolecularly synthesized by solvent evaporation method. Aiming to expand the diversity of supramolecular synthons of this drug as well as obtaining new solid forms with enhanced solubility and thermal stability, these salts namely oxalate (INH−OXA), maleate (INH−MAL) and mesylate (INH−MES) were fully characterized by X-ray diffraction (SCXRD, PXRD), spectroscopic (FT-IR) and thermal (TGA, DSC, HSM) techniques. At the same time, salts' solubility was explored. Analysis of the crystal structures and packings were analyzed in details, showing that the INH salts exhibit layered structures stabilized by N H⋯O, C H⋯O and π···π interactions. The salt formations were confirmed from the FT-IR and FT-Raman spectra and their thermal behaviors indicate that INH−OXA and INH−MES are thermally more stable than the corresponding INH. The equilibrium solubilities of these salts, in different buffered media, were evaluated and both INH−MAL and INH−MES were found to be more soluble (∼3 fold) than INH. Therefore, the present study proved that salt formation is an efficient strategy to enhance solubility and thermal stability of INH. [ABSTRACT FROM AUTHOR]

5-Fluorocytosine (5-FC) has been widely used for the treatment of fungal infections and recently was found to exert an extraordinary antineoplastic activity in gene directed prodrug therapy. However, despite of its intense use, 5-FC exhibits tabletability issues due its physical instability in humid environments, leading to transition from the anhydrous to monohydrate phase. By considering that salt formation is an interesting strategy to overcome this problem, in this paper crystal engineering approach was applied to the supramolecular synthesis of new 5-FC salts with sulfuric, hydrobromic and methanesulfonic inorganic acids. A total of four structures were obtained, namely 5-FC sulfate monohydrate (1:1:1), 5-FC hydrogen sulfate (1:1), 5-FC mesylate (1:1) and 5-FC hydrobromide (1:1), the last one being a polymorphic form of a structure already reported in the literature. These novel salts were structurally characterized by single crystal X-ray diffraction and its supramolecular organization were analyses by Hirshfeld surface analysis. The vibrational behavior was evaluated by Raman spectroscopy and it was found to be consistent with the crystal structures. [ABSTRACT FROM AUTHOR]

Salt formation approach was taken to improve Mebendazole (MBZ) solubility. MBZ polymorph A was easily recrystallized as a 1:1 nitrate salt (MBZ N) in methanol. Single crystal X-ray diffraction data show that MBZ N crystallizes in the P 1 ¯ space group. By strong intermolecular H- bonding interactions, MBZ is associated with a nitrate anion forming a supramolecular R 2 2 ( 8 ) synthon. Crystal packing is stabilized by these H- bonds, through which each nitrate connects two molecules of MBZ forming chains along the b axis. The vibrational behavior studied by micro FT-Raman and FT-IR spectroscopy is consistent with the crystal structure. Thermal analysis of the salt indicates that the compound is stable up to 150 °C, when an almost simultaneous elimination of HNO 3 and CO 2 occurs. MBZ N equilibrium solubility was evaluated in hydrochloric acid 0.1 M solution and compared with those of MBZ A and C. An improvement in a factor of 5 and 1.22 was found respectively. [ABSTRACT FROM AUTHOR]

Four novel cocrystals of the anti-tuberculosis drug Isoniazid (INH), including two polymorphs, with the aromatic carboxylic acids p -nitrobenzoic (PNBA), p -cyanobenzoic (PCNBA) and p -aminobenzoic (PABA) were rationally designed and synthesized by solvent evaporation. Aiming to explore the possible supramolecular synthons of this API, these cocrystals were fully characterized by X-ray diffraction (SCXRD, PXRD), spectroscopic (FT-IR) and thermal (TGA, DSC, HSM) techniques. The cocrystal formation was found to be mainly driven by the synthons formed by the pyridine and hydrazide moieties. In both INH−PABA polymorphs, the COOH acid groups are H-bonded to pyridine and hydrazide groups giving rise to the acid⋯pyridine and acid⋯hydrazide heterosynthons. In INH−PNBA and INH−PCNBA cocrystals these acid groups are only related to the pyridine moiety. In addition to the structural study, supramolecular and Hirshfeld surface analysis were also performed based on the structural data. The cocrystals were identified from the FT-IR spectra and their thermal behaviors were studied by a combination of DSC, TGA and HSM techniques. [ABSTRACT FROM AUTHOR]

To avoid drug resistance, an adequate tuberculosis treatment should include not only a first-line drug but also at least one second-line drug such as, for example, Ethionamide (ETH). However, the dissolution rate and oral absorption of ETH is highly limited by its low aqueous solubility. Considering that a salt is in general more soluble than its parent compound, herein we depicted a new supramolecular modification of ETH, an Ethionamide nitrate salt (ETHNO 3 ). This salt is the first ETH structure that has been crystallized with four independent ionic pairs (ETH + NO 3 − ) in the asymmetric unit. In addition to the structural study, the salt formation was also identified on the FT-IR and FT-Raman spectra. The thermal behavior of ETHNO 3 was also investigated here together with its solubility profile in three dissolution media (purified water, pH 4.0 and 7.0). [ABSTRACT FROM AUTHOR]

Ethambutol (ETB) is a chiral dibasic compound formulated and marketed as the (S,S)-ethambutol dihydrochloride, (S,S)-EDH, to treat tuberculosis. It is administered orally in a solid formulation composed of isoniazid, rifampicin, and pyrazinamide as a fixed-dose combination tablet. Because of its high hygroscopicity, (S,S)-EDH is known for catalyzing the degradation of isoniazid by rifampicin to yield isonicotinyl hydrazone. In order to avoid or even minimize these mutual drug-drug interactions, in this work we have focused on the development of less hygroscopic multicomponent solid forms of ETB. Four salts of this drug, namely, oxalate (ETBOXA), maleate, terephthalate, and trichloroacetate, were prepared via supramolecular synthesis by the slow evaporation method and characterized by X-ray diffraction (single crystal X-ray diffraction, powder X-ray diffraction), spectroscopic (Fourier transform-infrared), and thermal (thermogravimetric analysis, differential scanning calorimetry, hot stage microscopy) techniques. The hygroscopic nature of these salts, including (S,S)-EDH, were evaluated, and all of them were found to be hygroscopic, with the exception of ETBOXA. [ABSTRACT FROM AUTHOR]

A comprehensive solid state study of Paroxetine nitrate hydrate, (PRX + ·NO 3 − )H 2 O, is reported. This salt was characterized by a combination of methods, including Single crystal X-ray diffraction, Thermal analysis, Fourier transform infrared spectroscopy (FTIR) and Solubility measurements. (PRX + ·NO 3 − )H 2 O crystallizes in the monoclinic C2 space group (Z′ = 1) and its packing was analyzed in details, showing that the main supramolecular motif consists in a C 2 2 ( 4 ) chain formed by charge-assisted N + -H⋯O − hydrogen bonds. The salt formation and conformation features were also accuracy established via FTIR spectra. In comparison with the pharmaceutical approved (PRX + ⋅Cl − )⋅0.5H 2 O, (PRX + ⋅NO 3 − )⋅H 2 O showed a decrease of 24 °C in the drug melting peak and a slight reduction in its water solubility value. [ABSTRACT FROM AUTHOR]

Diffractaic acid (DA) is a secondary metabolite of lichens that belongs to the chemical class of depsides, and some relevant pharmacological properties are associated with this natural product, such as antioxidant, antiulcerogenic and gastroprotective effects. Considering the relevant biological activities and taking into account that the activities are intrinsically related to the structure, the main goal of this study was to elucidate the structure of diffractaic acid by single crystal X-ray diffraction as well to characterize its physicochemical properties by powder X-ray diffraction, thermal analysis and vibrational spectroscopy. It was observed that DA belongs to the monoclinic crystal system, crystallizing in the space group P 2 1 / c with the following cell parameters: a = 18.535(7) Å, b = 4.0439(18) Å, c = 23.964(6) Å, β = 91.55(3)°. The crystal packing is characterized by difractaic acid dimers, which are reflected in the vibrational spectrum. These observations were supported by quantum mechanical calculations. [ABSTRACT FROM AUTHOR]

The vibrational and thermal characterizations of four multicomponent molecular crystals of lamivudine, namely, lamivudine hydrochloride anhydrate ( 1 ), lamivudine hydrochloride monohydrate ( 2 ), lamivudine duplex I ( 3 ), with a 8:2:2:1:4 lamivudine:maleic acid:HCl:(CH 3 ) 2 CHOH:H 2 O stoichiometry, being all three more soluble in water than the commercial solid form of lamivudine, and lamivudine maleate ( 4 ), have been performed here by infrared (IR) and Raman spectroscopy, differential scanning calorimetry (DSC), and thermogravimetry (TG). Furthermore, the vibrational spectra of zalcitabine hydrochloride ( 5 ), isostructural to 1 but with a methylene moiety in the 3′-position of the five-membered ring instead of sulfur in lamivudine, have also been measured in order to point out the role of this molecular substitution and conformation in the vibrational modes of the salts. In fact, scattering bands at the high frequency range relative to CH stretching modes are not superimposable in the Raman spectra of 1 and 5, even though these crystal forms are assembled with the same molecular conformation and intermolecular packing. At the same time, the structural similarity between 1 and 5 can be reflected in their IR spectra, as in the carbonyl and iminium stretching bands shifted to lower frequencies as consequence of their hydrogen bonding engagement. Furthermore, a scattering band at 3057 cm −1 is observed only in the Raman spectra of crystal forms present with their 5′-CH 2 OH moiety in– gauche conformation, namely, 2–4. It is absent in the Raman spectra of 1 and 5 whose 5′-CH 2 OH moiety adopts + gauche conformation. In– gauche conformation, the 5′-OH oxygen is pointed toward one of the two aromatic CH hydrogens. Consequently, there is formation of an intramolecular hydrogen bond between them, shifting the aromatic CH stretching band to a lower frequency. The DFT calculations have also revealed in-phase and out-of-phase couplings of the two aromatic CH stretchings in the Raman spectra of 1, which is without intramolecular hydrogen bond due to + gauche conformation of 5′-CH 2 OH moiety. Both coupled vibrational modes are observed in the corresponding experimental spectrum as a single peak because of their similar frequencies. On contrary, aromatic CH stretching modes are not coupled in 2 due to the intramolecular hydrogen bond, resulting in resolution of the Raman bands. Thermal events in DSC and TG curves of 1 and 2 are also in agreement with crystal stoichiometry as observed from single-crystal X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

Theability of the chalcone, C18H18O4, to form solvates was theoretically and experimentally investigated.The unit cell with Z′ > 1, composed of two independent chalconemolecules (α and β), shows the formation of a stable molecularcomplex which is related with the presence of methanol in this crystallattice. Aiming to understand the process of crystal lattice stabilization,a combination of techniques was used, including X-ray diffraction(XRD), computational molecular modeling, and an ab initio moleculardynamic. The results show that α and β molecules are stericallybarred from forming a direct hydrogen bond with one other. In addition,the presence of the methanol molecule stabilizes the crystal structureby a bifurcated OH···O interaction acting asa bridge between them. The theoretical thermodynamic parameter andthe rigid potential energy surface scan describe the role of methanolin the energy stabilization of the crystal. The absence of the methanolcompound in the asymmetric unit destabilizes the crystalline structure,making the formation process of the asymmetric unit nonspontaneous.The energy difference between α and β molecules is around0.80 kcal·mol–1, indicating that both are stableand equally possible in the crystal lattice. The analysis of the energyprofile of the C14–O2···H1–O3 and O2–H1···O3–C17torsion angles in the crystal packing shows that the α and βmolecules are confined in the stable potential region, in agreementwith the two conformers in the asymmetric unit. The Molecular ElectrostaticPotential (MEP) shows that the methanol has no steric effects, whichprevents small motion around the torsion angles. [ABSTRACT FROM AUTHOR]

Highlights: [•] Two solvate forms of fac-[RuCl3(NO)(dppb)] were obtained. [•] Guest acetone and chloroform were identified by XRD and FT-IR analysis. [•] Solvent inclusion affects the molecular structure of the complex. [•] Weak intermolecular interactions kept the solvent caged. [ABSTRACT FROM AUTHOR]

Abstract: The new europium binuclear complex [Eu2(dcpz)2(suc)(H2O)8]·(H2O)1.5 (dcpz=3,5-dicarboxypyrazolate and suc=succinate) has been synthesized and structurally characterized by single crystal X-ray diffraction methods. The binuclear complex crystallizes in the triclinic space group and consists of two lanthanide ions linked by two different bridging organic ligands. 3D supramolecular framework is constructed by hydrogen bonds. The compound shows strong red emission under UV excitation at room temperature associated to IL transitions indicating a ligand to metal energy transfer mechanism since the triplet energy level lies higher than that of europium 5D0 level. Magnetic susceptibility studies showed weak temperature dependence characteristic of the Van Vleck paramagnetism. [Copyright &y& Elsevier]

To optimize solubility of drugs, current strategies mainly focus on engineering and screening of smart crystal phases. Two salts of the anti-human immunodeficiency virus (HIV) drug lamivudine-namely, lamivudine hydrochloride and lamivudine hydrochloride monohydrate, were prepared in the course of screening the crystallization conditions of lamivudine duplex, an uncommon DNA-mimic, double-stranded helical structure made up of partially protonated drug pairs. Here, water solubilities of lamivudine hydrochloride, lamivudine hydrochloride monohydrate, and lamivudine duplex are reported. The aqueous solubility of this anti-HIV drug was significantly increased in both salts and also in lamivudine duplex in relation to the water solubility of lamivudine form II. In comparison with the lamivudine form II incorporated into therapeutic formulations, the drug solubility was increased at a temperature of 299 ± 2 K by factors of 1.2, 3.3, and 4.5 in lamivudine hydrochloride, lamivudine hydrochloride monohydrate, and lamivudine duplex, respectively, demonstrating that this solid-state property of lamivudine can be improved by crystal engineering strategies. Solubility profiles were understood on the basis of structural and solvent-solute interaction approaches. At last, correlations between solubility and crystal structures allowed for a rational approach to understand how this physicochemical feature could be enhanced by engineering new salts of the drug. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2143-2154, 2012 [ABSTRACT FROM AUTHOR]

Abstract: The Gedunin compound (C28H34O6) is a natural product extracted from Trichilia pallida that has shown a wide activity. The crystallographic structure shows two conformers in the asymmetric unit, which differ in a rotation of the furan group. To understand this molecular arrangement, the density functional calculations, Molecular Electrostatic Potential (MEP) and thermodynamic function calculation have been performed at the B3LYP/6-311++g(d,p) level. Both conformers were optimized and the agreement with the experimental structure was very good, making possible further theoretical analysis of the structure. The inter-conversion between two conformers depends on the energy barrier. This process is studied in the vacuum and shows two transition states with a low energetic barrier for a potential energy curve scanning rigid around furan group: 4.37kcal/mol and 16.52kcal/mol. As the first transition state has a notably lower energetic barrier, the preferred inter-conversion pathway between the conformers involves the first rather than the second transition state. Understanding this transition state in detail led us to perform its optimization, showing an energetic barrier around 3.66kcal/mol. The negative free energy and low enthalpy confirm that the process is spontaneous and exothermic. The results show that this requirement makes the existence of the two conformers in the asymmetric unit possible. The structure of molecules in the asymmetric unit is better understood when the MEP is used on the interaction between molecules. For Gedunin, both molecules have shown MEP with well-defined regions, and this behavior contributes to the observed link between molecules and for the negative regions complementing positive regions of another molecule. [Copyright &y& Elsevier]

A new family of compounds is presented as potential carbon monoxide releasing molecules (CORMs). These compounds, based on tetrachlorocarbonyliridate(III) derivatives, were synthesized and fully characterized by X-ray diffraction, electrospray mass spectrometry, IR, NMR, and density functional theory calculations. The rate of CO release was studied via the myoglobin assay. The results showed that the rate depends on the nature of the sixth ligand, trans to CO, and that a significant modulation on the release rate can be produced by changing the ligand. The reported compounds are soluble in aqueous media, and the rates of CO release are comparable with those for known CORMs, releasing CO at a rate of 0.03−0.58 μM min−1 in a 10 μM solution of myoglobin and 10 μM of the complexes. [ABSTRACT FROM AUTHOR]

A novel bisthiazole ligand and its copper(II) complex were synthetized. Single crystal X-ray diffraction of complex evidence a pentacoordinated copper center forming 5 and 7 membered rings. Structure packing was analyzed by means of Hirshfeld surfaces and FTIR frequencies were calculated. Antimicrobial activity was determined against bacteria and C. albicans. [Display omitted] In the search of antimicrobial agents a novel bisthiazole ligand containing a methylamine linker (ethyl 2-((2-methylthiazole-4-yl)methylamino)thiazole-4-carboxylate (BTa) and its copper(II) complex [CuCl 2 BTa]·2H 2 O were synthetized. Both compounds were characterized by analytical and spectroscopic methods. Single crystal X-ray diffraction of copper complex evidence a pentacoordinated copper(II) center of intermediate geometry forming 5 and 7 membered chelate rings with BTa acting as a tridentate ligand leaving the amine N H group in the thiazole linker available for participation in intermolecular interactions. Structure packing was analyzed by means of Hirshfeld surfaces, 2D fingerprint plots and lattice interaction energies were assessed. In order to deepen the understanding of the coordination to the flexible ligand DFT studies were carried out at the B3LYP/LANL2DZ level of theory. Calculated FTIR frequencies were used to perform a Vibrational Energy Distribution Analysis (VEDA) where potential energy distribution of vibrational was determined. Minimum inhibitory concentrations for BTa and CuBTa on E. coli ATCC 25922, S. aureus ATCC 25923, P. aeruginosa ATCC 9027 and C. albicans ATCC 10231 were determined. [ABSTRACT FROM AUTHOR]

Abstract: The chemistry of Ru(III) complexes containing dmso as a ligand has become an interesting area in the cancer treatment field. Because of this, structural knowledge and chemistry of the moiety Ru(III)–dmso have become important to cancer research. The crystal structures of the compounds mer-[RuCl3(dms)3] (1) and mer-[RuCl3(dms)2(dmso)]:mer-[RuCl3(dms)3] (2) were determined by X-ray crystallography and a speciation of the presence of intramolecular hydrogen bond in these structures has been studied. Compound (1) crystallizes in the orthorhombic space group, Pna21; a =16.591(8)Å, b =8.724(2)Å, c =10.547(3)Å; Z =12 and (2) crystallizes in the space group, P21/C; a =11.9930(2)Å, b =7.9390(2) Å, c =15.8700(3)Å, β =93.266(1)°, Z =2. From the X-ray structures solved in this work, were possible to suggest an interpretation for the broad lines observed in the EPR spectra of the Ru(III) compounds explored here. Also, the exchange interactions detected by EPR spectroscopy in solid state and in solution, confirm the presence of van der Waals interactions such as C–H…Cl in the compounds (1), (2) and (3). The use of techniques such as IR, UV–vis, 1H NMR and EPR Spectroscopy and Cyclic Voltammetry were applied in this work to analyze the behavior of these metallocompounds. [Copyright &y& Elsevier]

Abstract: The biological activity and crystal structure of (±)-1,2:4,5-di-O-isopropylidene-3,6-di-O-(2-propylpentanoyl)-myo-inositol have been investigated. This compound shows better anticonvulsant activity than valproic acid (VPA) in the MES test as measured in mice. Its structure, determined from single-crystal X-ray diffraction measurements, shows that the inositol ring deviates from the ideal chair conformation and that the two 2-propylpentanoyl groups are located on opposite ring positions. This molecular conformation lets carbonyl and hydroxyl oxygen atoms to be available for hydrogen-bonding interactions, hinders carbonyl carbon atoms, preventing metabolic enzymatic hydrolysis, and helps to rationalize the observed inactive profile in the PTZ test. The anticonvulsant activity profile suggests a mechanism different from that of VPA. [Copyright &y& Elsevier]

Abstract: Complex fac-[RuCl3(NO)(P–N)] was synthesized from [RuCl3(H2O)2(NO)] in methanol solution under reflux. The orange solid obtained was characterized by NMR (31P{1H}, 1H, 13C) and, cyclic voltammetry, ESI-MS, IR, elemental analysis and X-ray diffraction structure determination. The 31P{1H} reveals the presence of singlet at 36ppm. IR N–O stretching as KBr pellets or CH2Cl2 solution presented 1866cm−1 and 1872cm−1, respectively. [Copyright &y& Elsevier]

Two polymorphs of Leflunomide were found and studied (form I and II). Both of them were characterized by X-ray powder diffraction and thermal analysis. Single crystals were obtained and both structures were solved. Forms I and II crystallize in the space group P21/c with two and one independent molecules per asymmetric unit, respectively. Thermodynamic stability of the two forms is assessed by differential scanning calorimetry. The cohesion in the crystal of form I (the more stable) is provided by both by H bonding as well as π ... π interactions, while in form II it is given only by the former. The independent molecules in form I adopt different conformations thus allowing for a larger number of intermolecular interactions. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:1075–1083, 2006 [ABSTRACT FROM AUTHOR]

• Two new bi and tri thiazolyl derivatives were synthesized and characterized. • The corresponding Cu(II) complexes were synthesized and characterized. • The crystal structure of both complexes is shown. • The cytotoxicity of ligands and complexes was evaluated on breast cancer cell lines. • The complexes show higher cytotoxicity than the free ligands and cisplatin. • Both complexes interact with DNA. New thiazolyl derivatives (BT and TT) and their copper (II) complexes [Cu 2 Cl 2 (BT) 2 (Cu-BT) and [Cu 4 ClO 2 (TT) 2 PF 6 ⋅3.5H 2 O (Cu-TT) were synthesized and characterized by elemental analysis, 1H NMR and 13C NMR, HRMS, X-ray diffraction, IR and UV–Vis spectroscopies. The crystal structure of Cu-BT shows the formation of a dinuclear complex where each copper(II) center is bonded to two thiazol N atoms, from different BT ligands, one deprotonated amide N atom, an O atom from the ester terminal groups and a chlorine atom. The structure found for Cu-TT is a positively charged tetranuclear moiety containing two deprotonated TT ligands, a chlorine anion, two hydroxide anions acting as bridges between the copper centers and a water molecule. The cytotoxic activity of both copper complexes was evaluated on metastatic breast cancer cell lines, characterized for its rapidly dividing behavior. Both, Cu-BT and Cu-TT, show higher cytotoxic activity against these tumor cells than free BT and TT and also than cisplatin. In addition, we found that both complexes interact with DNA. Consistently, they also show cytotoxicity against a rapidly dividing non-tumor cell line, although with higher IC 50, being such interaction and selectivity an indicator of the possible coexistence of more than one mechanism of action. [ABSTRACT FROM AUTHOR]

This work presents the synthesis and characterization of eight copper complexes [Cu(L-dipeptide)(neo)]·nH 2 O (neo = neocuproine) and their cytotoxic activities against tumor cell lines. The crystalline structure of [Cu(gly-val)(neo)]·3H 2 O, [Cu(gly-leu)(neo)]·H 2 O, [Cu(ala-gly)(neo)]·4H 2 O, [Cu(val-phe)(neo)]·4.5H 2 O and [Cu(phe-phe)(neo)]·3H 2 O were determined by single crystal X-ray diffraction. In all of them, the Cu(II) is pentacoordinated, in a square pyramidal environment. The coordination observed in solid state was retained in the major species in aqueous solution, as suggested by Electronic Paramagnet Resonance and UV–vis spectroscopies. The complexes were shown to have affinity for isolated DNA, as determined by Circular Dichroism experiments. Furthermore, biological experiments showed that all the complexes present high cytotoxic activity against the cell lines: MDA-MB-231, MCF-7 (human metastatic breast adenocarcinomas, the first triple negative), MCF-10A (human normal breast cells), A549 (human lung epithelial carcinoma) and MRC-5 (human lung epithelial cells). Together, these results suggest that these compounds are promising steps towards new effective drugs to treat cancer. Eight new Cu-dipeptide-neocuproine complexes were synthesized and characterized both in solid state, including new crystalline structures, and in aqueous solution. The complexes bind to DNA possible as groove binders and are highly cytotoxic to cancer cells. Unlabelled Image • Eight copper-dipeptide-neocuproine complexes were synthesized. • Five new crystalline structures are presented. • The complexes bind to DNA possible as groove binders. • The complexes present high cytotoxic activity on cancer cell lines. [ABSTRACT FROM AUTHOR]

• Three novel Cu(II) complexes containing β-diketone were prepared. • The X-ray structural analysis was performed. • A Cu(II) complex was active and selective toward cancer cell lines. • A Cu(II) complex and its ligand exhibited good activity against T. cruzi. Three novel copper(II) complexes were synthesized: [Cu(tfa) 2 (I), [Cu(tfa)(dmb)(NO 3)].1.5H 2 O (II) and [Cu(tfa)(nphen)(NO 3)] (III), where tfa = 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione, nphen = 5-nitro-1,10-phenanthroline and dmb = 4,4-dimethoxy-2,2-bipyridine. They were characterized by elemental analysis, conductivity measurements, FT-IR, UV–Vis and single-crystal X-ray diffraction. The X-ray crystal structures of I , II and III reveal that the β-diketone coordinates via the oxygen atoms, while the heterocyclic bases coordinate via their two nitrogen atoms. The cytotoxic activity of I , II and III was investigated in two tumor cell lines (Ehrlich tumor and sarcoma 180) and in a non-tumor cell line (myoblast C2C12). Complex III exhibited good activity (IC 50 Ehrlich = 15.75 μM and IC 50 sarcoma 180 = 16.90 μM) and selectivity (SI > 4) in both tumor cell lines. Subsequently, it was found that III also present good activity against Trypanosoma cruzi. [ABSTRACT FROM AUTHOR]