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The asymmetric unit of the title compound, C(6)H(9)N(2)OS(2)(+).HSO(4)(-).H(2)O, contains a heterocyclic cation, a hydrogen sulfate anion and a water molecule. There are strong hydrogen bonds between the hydrogen sulfate anions and water molecules, forming an infinite chain along the [010] direction, from which the cations are pendent. The steric, electronic and geometric features are compared with those of similar compounds. In this way, structural relationships are stated in terms of the influence of the sulfate group on the protonation of the heterocycle and on the tautomeric equilibrium in the solid state.

The water‐soluble compound [Ru3O(CH3COO)6(4‐ampy)3]Cl (1, 4‐ampy=4‐aminopyridine) was evaluated in terms of its biologically relevant properties. Compound 1 participates in a hydrogen bonding network which includes the NH2 substituents of the ancillary ligands, methanol molecules, the Cl− counter‐ion, and a non‐conventional hydrogen bond with the neighboring 4‐ampy molecules′ π‐cloud, as determined by X‐ray measurements. One protonation equilibrium was observed at pH values below 2.3. Additionally, the compound exhibited a partition coefficient value of −0.86 (±0.07), indicating that it is highly hydrophilic. At 37 0C and pH=7.4 (phosphate buffer), compound 1 shows moderate (Ksv=2.4 104 M−1) and spontaneous (ΔG=−26.4 kJ mol−1) binding to human serum albumin (HSA) through ground‐state association, which involves formation of hydrogen bonds (ΔH=−35.7 kJ mol−1 and, ΔS=−29.8 J mol−1 K−1). Molecular docking calculations support the formation of hydrogen bonds between 1 and HSA, and suggest subdomain IIA (site I), which contains the Trp‐214 residue, as the primary interactive pocket, in agreement with the experimental static fluorescence quenching mechanism. Furthermore, a preliminary assay reveals that 1 has low cytotoxicity towards human glioblastoma U87‐MG cells. [ABSTRACT FROM AUTHOR]

The chemical reaction of 4-bromo-benzoyl-chloride and 2-amino-thia-zole in the presence of potassium thio-cyanate yielded a white solid formulated as C15H10BrN3OS2, which consists of 4-bromo-benzamido and 2-benzo-thia-zolyl moieties connected by a thio-urea group. The 4-bromo-benzamido and 2-benzo-thia-zolyl moieties are in a trans conformtion (sometimes also called s-trans due to the single bond) with respect to the N-C bond. The dihedral angle between the mean planes of the 4-bromo-phenyl and the 2-benzo-thia-zolyl units is 10.45 (11)°. The thio-urea moiety, -C-NH-C(=S) -NH- fragment forms a dihedral angle of 8.64 (12)° with the 4-bromo-phenyl ring and is almost coplanar with the 2-benzo-thia-zolyl moiety, with a dihedral angle of 1.94 (11)°. The mol-ecular structure is stabilized by intra-molecular N-H⋯O hydrogen bonds, resulting in the formation of an S(6) ring. In the crystal, pairs of adjacent mol-ecules inter-act via inter-molecular hydrogen bonds of type C-H⋯N, C-H⋯S and N-H⋯S, resulting in mol-ecular layers parallel to the ac plane. [ABSTRACT FROM AUTHOR]

The aim of the present study was to report the crystal structure and spectroscopic, electronic, supramolecular and electrostatic properties of a new polymorph of 4‐(pyridin‐2‐yl)pyrimidin‐2‐amine (C9H8N4). The compound was synthesized under microwave irradiation. The single‐crystal X‐ray structure analysis revealed an angle of 13.36 (8)° between the planes of the rings, as well as molecules linked by Nsp2—H...N hydrogen bonds forming dimers along the crystal. The material was analyzed by FT–IR vibrational spectroscopy, while a computational approach was used to elucidate the vibrational frequency couplings. The existence of Nsp2—H...N hydrogen bonds in the crystal was confirmed spectroscopically by the IR peaks from the N—H stretching vibration shifting to lower wavenumbers in the solid state relative to those in the gas phase. The supramolecular studies confirmed the formation of centrosymmetric R22(8) rings, which correspond to the formation of dimers that stack parallel to the b direction. Other weak C—H...π interactions, essential for crystal growth, were found. The UV–Vis spectroscopic analysis showed a donor–acceptor process, where the amino group acts as a donor and the pyridine and pyrimidine rings act as acceptors. The reactive sites of the molecule were identified and their quantitative values were defined using the electrostatic potential model proposed in the multifunctional wave function analyzer multiwfn. The calculated interaction energies between pairs of molecules were used to visualize the electrostatic terms as the leading factors against the dispersion factors in the crystal‐growth process. The docking results showed that the amino group of the pyrimidine moiety was simultaneously anchored by hydrogen‐bonding interactions with the Asp427 and His407 protein residues. This compound could be key for the realization of a series of syntheses of molecules that could be used as possible inhibitors of chronic myelogenous leukemia. [ABSTRACT FROM AUTHOR]

Two CuII complexes [Cu(C14H13N4O2)Cl]n, I, and [Cu4(C8H10NO2)4Cl4]n, II, have been synthesized. In the structure of the mononuclear complex I, each ligand is coordinated to two metal centers. The basal plane around the CuII cation is formed by one chloride anion, one oxygen atom, one imino and one pyridine nitro­gen atom. The apical position of the distorted square-pyramidal geometry is occupied by a pyridine nitro­gen atom from a neighbouring unit, leading to infinite one-dimensional polymeric chains along the b-axis direction. Each chain is connected to adjacent chains by inter­molecular C—HO and C—HCl inter­actions, leading to a three-dimensional network structure. The tetra­nuclear complex II lies about a crystallographic inversion centre and has one core in which two CuII metal centers are mutually inter­connected via two enolato oxygen atoms while the other two CuII cations are linked by a chloride anion and an enolato oxygen. An open-cube structure is generated in which the two open-cube units, with seven vertices each, share a side composed of two CuII ions bridged by two enolato oxygen atoms acting in a μ3-mode. The CuII atoms in each of the two CuO3NCl units are connected by one μ2-O and two μ3-O atoms from deprotonated hydroxyl groups and one chloride anion to the three other CuII centres. Each of the penta­coordinated CuII cations has a distorted NO3Cl square-pyramidal environment. The CuII atoms in each of the two CuO2NCl2 units are connected by μ2-O and μ3-O atoms from deprotonated alcohol hy­droxy groups and one chloride anion to two other CuII ions. Each of the penta­coordinated CuII cations has a distorted NO2Cl2 square-pyramidal environment. In the crystal, a series of intra­molecular C—H···O and C—H···Cl hydrogen bonds are observed in each tetra­nuclear monomeric unit, which is connected to four tetra­nuclear monomeric units by inter­molecular C—H···O hydrogen bonds, thus forming a planar two-dimensional structure in the (1...01) plane. [ABSTRACT FROM AUTHOR]

In this paper we describe the synthesis of a new family of rare earth compounds of general formula [RE2(dcpz)2(suc)(H2O)8]·(H2O)1.5, where RE = Y (1), La (2), Ce (3), Pr (4), Nd (5), Sm (6), Gd (7), Tb (8), Dy (9), Ho (10), Er (11), Tm (12) and Yb (13); dcpz = 3,5-dicarboxypyrazolate; suc = succinate. Single crystal X-ray diffraction studies showed that all the complexes are isostructural and crystallize in the triclinic system, space group P1̅. They exist as dinuclear discrete molecules in which the metallic centers are linked together by dcpz and suc bridges. Hydrogen bonds between dimers give rise to a 3D bcu supramolecular network with topology (424·64). Solid-state photoluminescence studies revealed that the ligand-to-metal energy transfer mechanism is responsible for the visible emission of Sm (6), Tb (8) and Dy (9) compounds while for (5), near-infrared (1060 nm) emission was obtained by the direct excitation f orbitals in the Nd3+ ion. Magnetization measurements indicated antiferromagnetic interactions between the RE3+ ions, except Y3+ (1) and La3+ (2). [ABSTRACT FROM AUTHOR]

A structural and conformational study of 3β-acetoxy-17-chloro-16-formyl-5α-androstan-16-ene has been carried out by using X-ray analysis and M06-2X density functional calculations. The compound crystallizes with three independent molecules in the asymmetric unit. Natural Bond Order and Atoms in Molecules methods were used for a better understanding of the key factors that determine the stability of this steroidal molecule, particularly the role of C-H...Cl intramolecular interactions. A detailed investigation of C-H...Cl and C-H...O intermolecular interactions, in addition to the most important van der Waals contribution, are presented by means of Hirshfeld surface analysis. The crystal packing exhibits an unusual intra- and intermolecular hydrogen bond pattern, and shows the importance of non-classical interactions in the construction of the supramolecular assembly. Excellent agreement between the theoretical and experimental data is found. [ABSTRACT FROM AUTHOR]

Cruzain is the major cysteine protease of Trypanosoma cruzi, the infectious agent responsible for Chagas disease, and cruzain inhibitors display considerable antitrypanosomal activity. In the present work we elucidated crystallographic data of fukugetin, a biflavone isolated from Garcinia brasiliensis, and investigated the role of this molecule as cysteine protease inhibitor. The kinetic analyses demonstrated that fukugetin inhibited cruzain and papain by a slow reversible type inhibition with KI of 1.1 and 13.4 µM, respectively. However, cruzain inhibition was about 12 times faster than papain inhibition. Lineweaver-Burk plots demonstrated partial competitive inhibition for cruzain and hyperbolic mixed-type inhibition for papain. Furthermore, the docking results showed that the biflavone binds to ring C′ in the S2 pocket and to ring C in the S3 pocket through hydrophobic interactions and hydrogen bonds. Finally, fukugetin also presented inhibitory activity on proteases of the T. cruzi extract, with IC50 of 7 µM. [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]

The article presents a study about lupeol whose molecule is said to consist four six-membered rings and one five-membered ring, all fused in trans fashion. The structure of lupeol, showing the atom-numbering scheme is provided. It mentions the stabilization of the crystal packing by van der Waals interactions and intermolecular O-H...O hydrogen bonds.

Single crystals of the phenyl­coumarin named mammeigin (or mammea A/AA cycle D) [systematic name: 5-hydroxy-8,8-dimethyl-6-(3-methyl­butanoyl)-4-phenyl-2 H,8 H-pyrano[2,3- f]chromen-2-one], C25H24O5, were obtained in the course of a chemotaxonomic study of the Guttiferae family. Mammeigin was extracted from the fruits of Kilmeyera pumila. The structure reveals an infinite three-dimensional network stabilized by non-classical inter­molecular hydrogen bonds. [ABSTRACT FROM AUTHOR]

In the centrosymmetric molecule of the title compound, [Hg(C12H10O2P)2(C5H5N)2(C12H11O2P)2], the approximately octa­hedral Hg atom is coordinated by two each of phenyl­phosphinate, phosphinic acid and pyridine ligands. Each pair of phosphinic acid and phosphinate ligands features an intra­molecular hydrogen bond, so forming an eight-membered ring. [ABSTRACT FROM AUTHOR]

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]

In the title compound (systematic name: ( )-1-[(cyclo­hex­yloxy)carbonyl­oxy]ethyl 2-ethoxy-1-{[2′-(1 H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1 H-benzimidazole-7-carboxyl­ate), C33H34N6O6, the biphenyl­tetrazole moiety projects almost perpendicularly from the benzimidazole group. The planes of the three rings in the biphenyl­tetrazole moiety are staggered with respect to one another. In the benzimidazole system, the 2-ethoxy group is extended in the opposite direction with respect to the CH(Me)OCOO-c-hexyl double ester chain. An N—H⋯N hydrogen bond joins [010]-translated molecules to form a chain running along the b axis. [ABSTRACT FROM AUTHOR]

The title compound, C7H8N4O5, which is a potential anti-Chagas' derivative, was synthesized using a simple hydroxy­methyl­ation method in a basic medium with formaldehyde. The structure reveals two infinite two-dimensional networks in the ( 02) and (001) planes, stabilized by inter­molecular hydrogen bonds. [ABSTRACT FROM AUTHOR]

Abiraterone acetate is a first choice prodrug to treat prostate cancer. New higher-solubility multicomponent crystal forms of the active compound abiraterone could substitute for the commonly used acetate prodrug. Here we prepare abiraterone hydrochloride monohydrate, which is the first multicomponent crystal form of this striking prostate anticancer agent. Its solid state characterization by single-crystal X-ray diffraction (SCXRD), infrared (IR) spectroscopy and thermogravimetry (TG) was performed. The only conformational difference in the molecular backbone common to the literature related crystal forms (abiraterone acetate and the free base abiraterone) and our salt resides in the 3-pyridil rotation upon protonation. If the neutral molecules found in the two literature structures are taken as references, this motif is rotated by almost exactly 180° in our protonated abiraterone. Crystal packing also follows the protonation pattern. While in both prodrug and free base there is formation of head-to-tail fashioned one-dimensional chains as the main supramolecular entities, hydrogen bonded sheets are the main supramolecular motifs of abiraterone hydrochloride monohydrate. In addition, the IR spectrum and the TG thermogram of the hydrochloride salt monohydrate are present with characteristics absorption bands and thermal events, being therefore useful as analytical data for control quality purposes of this promising active pharmaceutical ingredient. Image 1 • Abiraterone hydrochloride monohydrate prepared from the prodrug abiraterone acetate. • There is a 180° rotation of 3-pyridil in its first multicomponent crystal form. • Infrared and thermogravimetric data for this promising alternative drug source. [ABSTRACT FROM AUTHOR]

Isobenzofuran-1( 3H )-ones (phtalides) are heterocycles that present a benzene ring fused to a γ-lactone functionality. This structural motif is found in several natural and synthetic compounds that present relevant biological activities. In the present investigation, the 3-(2-hydroxy-4,4-dimethyl-6-oxocyclohexen-1-yl)isobenzofuran-1( 3H )-one was characterized by single-crystal X-ray analysis. In the crystal structure, there are two molecules per asymmetric unit. One of them exhibits resonance assisted hydrogen bonds (RAHBs). Semi-empirical and DFT calculations were performed to obtain electronic structure and π-delocalization parameters, in order to better understand the energy stabilization of RAHBs in the crystal packing of the studied molecule. The structural parameters showed good agreement between theoretical and experimental data. The theoretical investigation revealed that the RAHBs stabilization energy is directly related to the electronic delocalization of the enol form fragment. In addition, RAHBs significantly affected the HOMO and charge distribution around the conjugated system. [ABSTRACT FROM AUTHOR]

• Novel drug-drug cocrystal of AAS-5FC is synthesized by solvent evaporation. • DDC production is also achieved by neat and solvent-drop grinding. • Crystal structure is characterized by XRD, DSC, TGA, RAMAN, IR, and HSM. Mechanochemistry approach is addressed herein for the green formation of a novel 1:1 drug–drug cocrystal (DDC) involving the antifungal prodrug Flucytosine (5FC) and the non-steroidal anti-inflammatory acetylsalicylic acid (AAS). This DDC was designed considering the huge market demand for new antifungal agents and the antifungal activity reported for some non–steroidal anti–inflammatory drugs, including AAS. The structure-properties characterization of the 5FC-AAS cocrystal was determined by X–ray diffraction (single crystal and powder), differential scanning calorimetry, thermogravimetric analysis, spectroscopic techniques (Raman and Fourier transform infrared), and hot–stage microscopy. The strong O–H...O and N–H...O hydrogen bonds formed between the hydroxyl group of AAS and the carbonyl and amine groups of two symmetry–related 5FC molecules maintain the crystalline packing, together with the same classical R 2 2 (8) homodimers observed in other 5FC cocrystals. The direct exposure under accelerated conditions (75% relative humidity/40 °C for 7 days) and at 12–months at room condition were also evaluated. Although the hygroscopicity addressed to 5FC was observed in the cocrystal during the stability studies, nevertheless this property discrepancy can easily be handled with the use of appropriate excipients and packing. DDC production was interestingly achieved by solvent evaporation, neat, and solvent-drop grinding (manually and in a ball-milling), resulting in a very fast production with suitable yield. In this sense, it is believed that this new model DDC will serve as a potential binary base cocrystal system for further developments of related higher dimensional cocrystals in this field, alongside other important drug molecules or in relation to the feasibility of using it therapeutically. [Display omitted] A new drug–drug cocrystal is reported in this work, characterized by X–ray diffraction, infrared/Raman spectroscopies and thermal techniques. It proved be hygroscopic under 75% relative humidity after one week at 40 °C and less stable than the parent APIs after one year storage at room conditions. However, with appropriate choice of excipients it is believed these issues might be overcome. [ABSTRACT FROM AUTHOR]

Mebendazole mesylate monohydrate, a new stable salt of mebendazole ( MBZ), has been synthesized and fully characterized. It was obtained from recrystallization of MBZ forms A, B, or C in diverse solvents with the addition of methyl sulfonic acid solution. The crystal packing is first organized as a two-dimensional array consisting of rows of alternating MBZ molecules linked to columns of mesylate ions by hydrogen bonds. The three-dimensional structure is further developed by classical intermolecular interactions involving water molecules. In addition, nonclassical contacts are also found. The vibrational behavior is consistent with the crystal structure, the most important functional groups showing shifts to lower or higher frequencies in relation to the MBZ polymorphs. Thermal analysis indicates that the compound is stable up to 50° C. Decomposition occurs in five steps. Solubility studies show that the title compound presents a significant higher performance than polymorph C. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3528-3538, 2013 [ABSTRACT FROM AUTHOR]

In the title compound, C12H7BrN6, the dihedral angle between the bromo­phenyl ring and planar pyrazolopyrimidine skeleton is 46.9 (8)°. The crystal packing is stabilized by N—H⋯N, C—H⋯N, N—H⋯Br and C—H⋯Br inter­actions. [ABSTRACT FROM AUTHOR]

We report on chemistry and cytotoxic studies of four new ruthenium (II) complexes containing uracil derivatives. All compounds are neutral, presenting the formula [Ru(PPh 3) 2 (2TU) 2 ] (1), [Ru(PPh 3) 2 (6m2TU) 2 ] (2), [Ru(dppb)(2TU) 2 ] (3) and [Ru(dppb)(6m2TU) 2 ] (4), where PPh 3 = triphenylphosphine; dppb = 1,4- bis (diphenylphosphino)butane, 2TU = 2-thiouracil and 6m2TU = 6-methyl-2-thiouracil. They were characterized using NMR, UV–vis and IR spectroscopies, microanalytical analysis and mass spectrometry. Furthermore, the crystal structures of 1 – 4 were determined by single-crystal X-ray diffraction. The coordination of 2-thiouracil derivatives with ruthenium increases regions able to carry out hydrogen bonds with the biological targets, such as DNA. We evaluated the interaction of the complexes with DNA by UV/Vis spectrophotometric titration, and as a result, the values of DNA-binding constants are in the range of 0.8–1.8 × 104 M−1. Moreover, the interaction of the complexes with BSA was investigated. In vitro , activities against B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), HL-60 (human promyelocytic leukemia) and K562 (human chronic myelocytic leukemia) and non-tumor cells: PBMC (human peripheral blood mononuclear cells activated with concanavalin A – human lymphoblast) were carried out. Cytotoxicity assays revealed that complexes (2) and (4) present biological activity against tumor cells comparable with oxaliplatin, the reference platinum drug, revealing that they are promising molecules for developing new antitumor compounds. Uracil nucleobase analogs were used as key building blocks to form new cytotoxic agents based on Ru(II). These compounds are promising for anticancer treatment. Unlabelled Image • Synthesis of four Ru(II) complexes with thiouracil • The compounds are bioactives against tumor cells. • The complexes present ability to form strong hydrogen bonds. • The internucleosomal DNA fragmentation and cell cycle distribution was studied. [ABSTRACT FROM AUTHOR]