Miriam Rossi

Ruthenium-arene complexes of curcumin: X-ray and density functional theory structure, synthesis, and spectroscopic characterization, in vitro antitumor activity, and DNA docking studies of (p-cymene)Ru(curcuminato)chloro.

The in vitro antiproliferative activity of the title compound on five tumor cell lines shows preference for the colon-rectal tumor HCT116, IC(50) = 13.98 μM, followed by breast MCF7 (19.58 μM) and ovarian A2780 (23.38 μM) cell lines; human glioblastoma U-87 and lung carcinoma A549 are less sensitive. A commercial curcumin reagent, also containing demethoxy and bis-demethoxy curcumin, was used to synthesize the title compound, and so (p-cymene)Ru(demethoxy-curcuminato)chloro was also isolated and chemically characterized. The crystal structure of the title compound shows (1) the chlorine atom linking two neighboring complexes through H-bonds with two O(hydroxyl), forming an infinite two-step network; (2) significant twist in the curcuminato, 20° between the planes of the two phenyl rings. This was also seen in the docking of the Ru-complex onto a rich guanine B-DNA decamer, where a Ru-N7(guanine) interaction is detected. This Ru-N7(guanine) interaction is also seen with ESI-MS on a Ru-complex-guanosine derivative.

The crystal and molecular structure of quercetin: A biologically active and naturally occurring flavonoid

Abstract The crystal and molecular structure of quercetin, one of the bioflavonoids found in plants, is described. The structure is of interest because of the variety of biological systems affected by it. It is known to be an antitumor agent and to exhibit antiallergenic and anti-inflammatory activity. it is an antioxidant and a cardiostimulant. These biological functions are governed by a number of enzymes and so quercetins interactions with these enzymes are well studied. Crystals suitable for X-ray diffraction were difficult to obtain. Crystal data are as follows: a = 13.060(5), b = 16.564(7), c = 3.725(2) A , α = 92.05(4), β = 94.39(3), γ = 120.55(3), V = 689.4(5) A 3 , z = 2, space group P 1 , Dc = 1.63 g cm−3, Dm = 1.69(1) g cm−3. Quercetin crystallizes with two waters of crystallization that participate in an extended hydrogen bonding network through the crystal lattice. There are intramolecular hydrogen bonds between two hydroxyl groups and the exocyclic oxygen, O4. Quercetin, in the crystal structure, exists as hydrogen-bonded dimers packing almost perpendicular to c. These dimers form a two-dimensional net, mostly in the ab plane, connected via water molecules. Additionally, the waters provide for hydrogen bonding in the z direction. The exocyclic oxygen appears to be the focal point of cohesive forces in the crystal structure. Its electron-withdrawing effects are stabilized by the high degree of hydrogen bonding. This, in turn, leads the exocyclic phenyl ring to exist in an almost planar conformation with respect to the rest of the molecule. The torsion angle between the phenyl ring and the pyrone ring is only 7°. As expected, from an analysis of the atomic charges, it is clear that quercetin has more polar groups than similar flavonoid compounds. Comparison with these structures is made.

Muscle MRI in adult-onset acid maltase deficiency

We report the spectrum of muscle involvement on magnetic resonance imaging in 11 patients with a molecularly confirmed diagnosis of adult-onset acid maltase deficiency at different clinical stages. Muscle magnetic resonance imaging showed a selective progressive pattern of muscle involvement with a constant involvement of the adductor magnus and semimembranosus at the early stage of the disease and a later fatty infiltration of the long head of the biceps femoris, semitendinosus and of the anterior thigh muscles. In the advanced phases a selective sparing of sartorius, rectus, and gracilis muscles and peripheral portions of the vastus lateralis was also evident. Muscle strength and magnetic resonance imaging findings were positively correlated. The results suggest that muscle magnetic resonance imaging may provide valuable diagnostic guidance for the assessment of accurate selective muscular involvement in acid maltase deficiency and may help monitor the progression of the disorder. Further control studies in a larger cohort are needed to evaluate the specificity of these findings.

New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: potential anti-trypanosomal agents

In the search for new therapeutic tools against neglected diseases produced by trypanosomatid parasites, and particularly against African Trypanosomiasis, whose etiological agent is Trypanosoma brucei, organoruthenium compounds with bioactive nitrofuran containing thiosemicarbazones (L) as co-ligands were obtained. Four ruthenium(II) complexes with the formula [Ru(2)(p-cymene)(2)(L)(2)]X(2), where X = Cl or PF(6), were synthesized and the crystal structures of two of them were solved by X-ray diffraction methods. Two of the complexes show significant in vitro growth inhibition activity against Trypanosoma brucei brucei and are highly selective towards trypanosomal cells with respect to mammalian cells (J774 murine macrophages). These promising results make the title organoruthenium compounds good lead candidates for further developments towards potential antitrypanosomal organometallic drugs.

Risedronate metal complexes potentially active against Chagas disease.

In the search for new metal-based drugs for the treatment of Chagas disease, the most widespread Latin American parasitic disease, novel complexes of the bioactive ligand risedronate (Ris, (1-hydroxy-1-phosphono-2-pyridin-3-yl-ethyl)phosphonate), [M(II)(Ris)(2)]·4H(2)O, where M═Cu, Co, Mn and Ni, and [Ni(II)(Ris)(2)(H(2)O)(2)]·H(2)O were synthesized and characterized by using analytical measurements, thermogravimetric analyses, cyclic voltammetry and infrared and Raman spectroscopies. Crystal structures of [Cu(II)(Ris)(2)]·4H(2)O and [Ni(II)(Ris)(2)(H(2)O)(2)]·H(2)O were solved by single crystal X-ray diffraction methods. The complexes, as well as the free ligand, were evaluated in vitro against epimastigotes and intracellular amastigotes of the parasite Trypanosoma cruzi, causative agent of Chagas disease. Results demonstrated that the coordination of risedronate to different metal ions improved the antiproliferative effect against T. cruzi, exhibiting growth inhibition values against the intracellular amastigotes ranging the low micromolar levels. In addition, this strong activity could be related to high inhibition of farnesyl diphosphate synthase enzyme. On the other hand, protein interaction studies showed that all the complexes strongly interact with albumin thus providing a suitable means of transporting them to tissues in vivo.

Solution and solid state studies on the interactions of protonated cytosine salts. III. Interpyrimidine base stacking and asymmetric interbase hydrogen bonding in the structure of 1-methylcytosine hemihydroiodide hemihydrate

Abstract Structural and spectroscopic data are presented on the compound 1-methylcytosine hemihydroiodide hemihydrate. In the solid, a 1:1 triply hydrogenbonded complex consisting of one protonated and one neutral 1-methylcytosine base is observed. The hydrogen bonding in this complex is asymmetric, and the asymmetry in the interbase hydrogen bonding is stimulated, at least in part, by base stacking considerations. The hydrogen-bonded base pairs associate into dimers about a crystallographic center of symmetry; the base-base stacking mode is strong [mean stacking distance = 3.22A] and is such that the molecular overlap is between protonated and neutral 1-methylcytosine molecules. The asymmetric, interbase hydrogen bonding and the protonated over neutral base stacking mode coexist in a synergistic interrelationship which maximizes molecular association and crystal packing. Intermolecular hydrogen bonds involving the 1-methylcytosine bases, the water of crystallization and the iodide anion also contribute to the overall crystal stability. Infra-red and 1H nmr data are also presented.

Tin(IV) and organotin(IV) derivatives of novel β-diketones. III Diorgano- and dihalotin(IV) complexes of 1,3-dimethyl-4-R(CO)-pyrazol-5-one (R=CH3, C6H5) and the crystal structure of trans-dicyclohexylbis(1,3-dimethyl-4-acetylpyrazolon-5-ato)tin(IV)

Abstract Several diorgano- and dihalotin(IV) derivatives of new β-diketonate donors, 1,3-dimethyl-4-R(CO)pyrazol-5-ones (R=Me, QDH; R=Ph, QMH) have been synthesized and characterized with analytical and spectroscopic methods. They are stable monomeric species, very soluble not only in aromatic and chlorohydrocarbon solvents, but also in alcohols and hydroalcoholic solutions. In the solid state, the diorganotin(IV) derivatives adopt a skewed trapezoidal bipyramidal geometry. The X-ray structure of bis(1,3-dimethyl-4-acetylpyrazolon-5-ato)dicyclohexyltin(IV) shows marked distortion of the organometallic C–Sn–C angle (155°) and two different sets of Sn–O distances. The factors affecting the distortion of this type of complex are discussed. The dihalotin(IV) derivatives (Q)2SnX2 (X=F, Cl, Br and I) are likely cis octahedral in the solid state, whereas in solution they exist as a mixture of cis and trans isomers. 119Sn-NMR solution data are discussed and related to electronic and steric properties of the β-diketonate donor, and also to the nature of the halo and organic groups bound to tin.

Tin(IV) and organotin(IV) derivatives of novel β-diketones I. Dialkyltin(IV) complexes of 1-phenyl-3-methyl-4-R′(CO)-pyrazol-5-one (R′ = CCl3, OCH3, OC2H5, OiC3H7, OC7H7). Crystal and molecular structure of trans-dimethylbis]1-phenyl-3-methyl- 4-i-propoxycarbonyl-pyrazolon-5-ato]tin(IV)

Abstract Stable six-coordinate tin(IV) and organotin(IV) derivatives R2SnQ∗*2 (R = Me, Et, Bun, Bu1) ( HQ ∗* = 1- phenly -3- methyl -4- trichloracetyl-pyrazol -5- one ) have been synthesized in basic (triethylamine0 solution of chloroform. These complexes have been characterized by elemental analysis and spectroscopic (IR and far-IR, 1H, 13C and 119Sn NMR) data. In basic (KOH) alcoholic R′OH solutions (R′ = Me, Et, Pri, benzyl), the tin acceptor induces cleavage of the CCCl3 bond in the donor (Q∗*)− and the new derivatives bis(1-phenyl-3-methyl-4-alkoxycarbonyl-pyrazolon-5-ato)R2Sn(IV) (R = Me, Et, Bu1 or Bua) and (1-phenyl-3-methyl-4-ethoxycarbonyl-pyrazolon-5-ato)-Me2Sn(IV)Cl have been obtained. Structural information has been derived from 119Sn NMR parameters such as 1 J( 119 Sn  13 C ), 2 J( 119 Sn  1 H ) and δ(119Sn). The diffraction study of the complex [Me2Sn(1-phenyl-3-methyl-4(COOPr1)-pyrazolon-5-ato)2] shows the metal to be six-coordinate in a skewed trapezoidal bipyramidal (STB) geometry; SnO distances are 2.10(1) and 2.39(1) A in one ligand, and 2.09(1) and 2.39(1) A in the other ligand, and the MeSnMe bond angle is 157.0(8)°. The title compound crystals are monoclinic, space group P21/c, cell parameters: a = 11.489(4), b = 14. 558(7), c = 18.973(8) A , β = 77.14(3)° .

Anticancer titanium agents

Most antitumour Ti compounds act on tumours in the gastrointestinal tract. Some species with increased water solubility also show activity towards breast, lung and melanoma cancers. These compounds are structurally and chemically diverse, ranging from complex salts to coordination complexes. In the former, the oxidative state can be either Ti(III) or Ti(IV); while in the latter the co-ordination number can be 4 or 6. Active 6 coordinate species can be mono- or tetranuclear compounds. This review focuses on recent progress in this promising area including clinical studies and their related patents. Additional features of this non-toxic metal, not yet described in patents, are also mentioned along with perspectives for application in cancer therapy.

Organotin(IV) derivatives of novel β-diketones ☆: Part V. Synthesis and characterization of di- and triorganotin(IV) derivatives of 4-acyl-5-pyrazolones modified in position 3 of the pyrazole. Crystal structure of (1,3-diphenyl-4-benzoyl-pyrazolon-5-ato)triphenyltin(IV)

Abstract The interaction between R 3 SnCl, (R 3 Sn) 2 O, R 2 SnO or R 2 SnCl 2 acceptors (R=Me, n Bu or Ph) and the two novel β-diketone proligands (LH=1,3-diphenyl-4-R 4 (CO)-pyrazol-5-one: L 1 H, R 4 =Ph; L 2 H, R 4 =Me) yields complexes [SnR 3 (L)(H 2 O)] (R=Me or n Bu, L=L 1 or L 2 ), [SnPh 3 (L)] and [SnR 2 (L) 2 ] (L=L 1 or L 2 ). The phenyl substituent on position 3 induces instability of the triorganotin derivatives in solution with the formation of SnR 2 (L) 2 and SnR 4 compounds. Moreover, diorganotin derivatives partially dissociate in solution yielding [SnR 2 (L)(solvent)] 2+ species. When compared with the related 3-methyl species, the crystal structure of (1,3-diphenyl-4-benzoyl-pyrazolon-5-ato)triphenyltin(IV) is not modified by the 3-phenyl substitution. The chemical instability generated by the Ph in position 3 is greater than in positions 1 and 4. In addition, the Ph in position 3 of the pyrazole influences the solution behavior of the free neutral 4-acyl-5-pyrazolones stabilizing a novel amino-diketo tautomeric form.