Bruno Bruni

Crystal structure and solution chemistry of the cytotoxic complex 1,2-dichloro(o-phenanthroline)gold(III) chloride

Abstract The crystal structure of the cytotoxic complex 1,2-dichloro(o-phenanthroline)gold(III) chloride ([AuphenCl2]Cl) has been solved through single crystal X-ray diffraction methods. The complex is square planar and exhibits a quite regular geometry. Crystals of the compound belong to the space group P21/n with a=12.632(5), b=16.916(3), c=12.902(6) A, β=91.31(3)° and Z=8. The coordination of the two gold(III) ions in the asymmetric unit is completed by two chloride ions at 2.972(3) and 3.043(3) A, respectively, forming a distorted square pyramid. The behavior in solution of [AuphenCl2]Cl was further analyzed through 1H NMR spectroscopy. Results point out that the [Au(III)phen]3+ molecular fragment is stable in solution for several hours, even under physiological conditions, whereas the two chloride ligands are released within approximately 30 min after dissolution in the buffer, at 25°C. The gold(III) chromophore is easily and quickly reduced by addition of stoichiometric amounts of sodium ascorbate; metallic gold is formed and free phenanthroline liberates. The implications of these findings for the biological properties of the [Au(III)phen]3+ species are discussed.

Crystallographic evidence for decomposition of dimethylformamide in the presence of ruthenium(III) chloride

A crystalline product is obtained in high yield when ruthenium(III) chloride is dissolved in dimethylformamide, in the presence of small amounts of hydrochloric acid. The structure of this product has been determined by X-ray diffraction studies. We have found that the obtained product is ionic and may be formulated as (Me 2 NH 2 ) 4 Cl(RuCl 6 ), the structure being formed by dimethylammonium cations, chloride anions and hexachlororuthenate(III) anions. The presence of the dimethylammonium cation in this structure suggests that substantial cleavage of DMF has occurred under the relatively mild experimental conditions used in this study. The implications of these findings are briefly discussed.

Physico-chemical and structural characterization of diacerhein.

The physico-chemical and structural characterization of diacerhein, an anthraquinone with antiinflammatory activity, employed in the symptomatic treatment of inflammatory osteoarthritis, is reported. The combined use of FT-IR, DSC, X-ray powder and single-crystal diffraction has provided a valuable tool to fully characterize the title compound. The X-ray diffraction study has revealed the existence of hydrogen-bond assisted tight packing of the quasi-planar molecules in the solid. The collected results are intended to implement the information required for the compilation of drug master files.

Properly substituted 1,4-dioxane nucleus favours the selective M3 muscarinic receptor activation.

Novel analogues of cis-N,N,N-trimethyl-(6-methyl-1,4-dioxan-2-yl)methanaminium iodide (2a) were synthesized by inserting methyl groups alternatively or simultaneously in positions 5 and 6 of the 1,4-dioxane nucleus in all combinations. Their biological profile was assessed by receptor binding assays at human muscarinic M(1)-M(5) receptors stably expressed in CHO cells and by functional studies performed on classical isolated organ preparations, namely, rabbit electrically stimulated vas deferens, and guinea pig electrically stimulated left atrium, ileum, and lung strips. The results showed that the simultaneous presence of one methyl group in both positions 5 and 6 with a trans stereochemical relationship with each other (diastereomers 4 and 5) or the geminal dimethylation in position 6 (compound 8) favour the selective activation of M(3) receptors. Compounds 4, 5, and 8 might be valuable tools in the characterization of the M(3) receptor, as well as provide useful information for the design and development of novel selective M(3) antagonists.

The dependence of cis-diamminedichloroplatinum(II) binding to DNA upon the GC content: a thermal and spectrophotometrical investigation

Abstract The binding of cis -diamminedichloroplatinum(II) ( cis -DDP) to DNA is investigated as a function of the GC content and of the cis -DDP concentration. Analysis of the melting curves and of the UV and CD spectra shows that binding of cis -DDP to DNA is highly sequence specific, GC rich DNAs being destabilized more effectively. At low levels of platination, stabilization of GC- and destabilization of AT-base pairs can be noted. In AT rich DNA, cis - DDP binding favours the B→ A conformational transition. It is also shown that, in addition to specific interactions between cis -DDP and DNA, several non-specific processes take place.

{2-Hydr-oxy-3-[4-(2-methoxy-ethyl)-phen-oxy]prop-yl}isopropyl-ammonium hemisuccinate.

Metoprolol, a widely used adrenoreceptor blocking drug, is commonly administered as the succinate or tartrate salt. The structure of metoprolol succinate, C15H26NO3 +·0.5C4H4O4 2−, is characterized by the presence of ribbons in which cations, generated by N-protonation of the metoprolol molecules, are hydrogen bonded to succinate anions. The dicarboxylic acid transfers its H atoms to two metoprolol molecules; the asymmetric unit contains one cation and half an anion, the latter possessing twofold rotational symmetry. There are localized nets of O—H⋯O and N—H⋯O hydrogen bonds along a ribbon, within centrosymmetric arrangements formed by pairs of metoprolol cations and pairs of anions, each of the latter contributing with one of its carboxyl groups to the localized net. This arrangement is repeated along the ribbon by the operation of the twofold axis bisecting the anion, as well as by the lattice translation.

4-(3-Methyl­anilino)-N-[N-(1-methyl­ethyl)carbamo­yl]pyridinium-3-sulfon­amidate (torasemide T–N): a low temperature redetermination

The structure [Danilovski et al. (2001 ▶). Croat. Chim. Acta 74, 103–120] of the T–N (non-solvated) polymorph of torasemide, C16H20N4O3S, a diuretic drug used in the treatment of hypertension, has been redetermined at low temperature. The zwitterionic form of the molecule is confirmed, although GAUSSIAN03 calculations suggest that this form is less stable in the gas phase. The unit-cell contraction between 298 and 100 K is approximately isotropic and the largest structual change is in a C—N—C—C torsion angle, which differs by 11.4 (3)° between the room-temperature and low-temperature structures. There are two molecules in the asymmetric unit, both of which contain an intramolecular N—H⋯N hydrogen bond. In the crystal structure, both molecules form inversion dimers linked by pairs of N—H⋯N hydrogen bonds. Further N—H⋯N and N—H⋯O hydrogen bonds lead to a three-dimensional network. The different hydrogen-bond arrangements and packing motifs in the polymorphs of torasemide are discussed in detail.

A multi-technique approach to predicting the molecular structure of cuprizone in the gas phase and in the crystalline state

Cuprizone (oxalic acid bis(cyclohexylidene hydrazide)) is a potent neurotoxin that is known to induce the destruction of the myelinic sheath which covers the cells of the central nervous system (CNS). The mechanism of action has not yet been elucidated due to lack of structural information. We have performed an ab initio prediction of the molecular structure by high-level quantum chemical methods, leading to two possible conformers of a nearly identical energy: A, for which an analysis of the electron density distribution shows more propensity for intermolecular bonding, and B, with stronger intramolecular liaison. Having obtained suitable single crystals, we report a detailed study of the crystal and molecular structure, which reveals that the molecular and crystal centers of symmetry coincide, and that the actual conformer is A, as expected, and in agreement with the ab initio prediction. Further information is gained by optimization of the crystal structure by Car-Parrinello molecular dynamics, yielding good agreement with observation. Infrared and Raman spectra show mutual exclusion, suggesting a centrosymmetric molecule with carbonylic bonds in trans configuration; moreover, vibrational frequencies calculated ab initio also show excellent agreement with observations. We thus present a multi-technique approach to the prediction and interpretation of various aspects of the complex interplay between intra- and intermolecular forces.

4-(3-Methyl­anilino)-N-[N-(1-methyl­ethyl)carbamo­yl]pyridinium-3-sulfon­amidate (torasemide) methanol 0.25-solvate 0.25-hydrate

The title compound, C16H20N4O3S·0.25CH4O·0.25H2O, is a hydrate/methanol solvate of torasemide, a diuretic drug used in the treatment of hypertension. The asymmetric unit contains two torasemide molecules and half-occupied methanol and water molecules. It is isomorphous with the previously reported nonsolvated T–II form of torasemide. The water molecules contribute to the stability of the structure by participating in an extensive system of O—H⋯O hydrogen bonds; N—H⋯N and N—H⋯O hydrogen bonds are also present. Both asymmetric molecules of torasemide form inversion dimers in the crystal.

4-Amino-N-(3-meth­oxy­pyrazin-2-yl)benzene­sulfonamide

The overall molecular geometry of the title compound, C11H12N4O3S, is bent, with a dihedral angle of 89.24 (5)° between the best planes through the two aromatic rings. Each molecule behaves as a hydrogen-bond donor toward three different molecules, through its amidic and the two aminic H atoms, and it behaves as a hydrogen-bond acceptor from two other molecules via one of its sulfonamidic O atoms. In the crystal, molecules linked by N—H⋯N and N—H⋯O hydrogen bonds form kinked layers parallel to (001), adjacent layers being connected by van der Waals interactions.