Francisco González-Vílchez

Study of the biological effects and DNA damage exerted by a new dipalladium-Hmtpo complex on human cancer cells

The new dipalladium complex [Pd(2)(mu-mtpo-N(3),N(4))(2)(phen)(2)](NO(3))(2) (where phen=1,10-phenantroline; Hmtpo=5,7-dihydro-7-oxo-5-methyl[1,2,4]triazolopyrimidine), (Pd(2)-Hmtpo, or complex I), interacts effectively with DNA plasmid (pBS), as studied by circular dichroism spectroscopy (CD), causing large helix distortions, altering the direction of the main DNA helix axis and producing unwinding of the DNA double helix. DNA damage induced by complex I was highly significant at 2.81 microM (ovarian carcinoma TG cell line), as assessed by comet assay, a dose at which all treated nuclei showed more than 30% DNA migration to the comet tail. DNA damage effect is a consequence of genotoxicity and not a false positive response caused by cytotoxicity. In vitro cytotoxic assay on the two human tumor cell lines TG and BT-20 (breast carcinoma), shows that doses of 0.47, 1.41 and 2.81 microM produce significant antiproliferative effects after 4 days of treatment compared with control. Complex I was highly cytotoxic at 2.81 microM causing an inhibition of viable cells of 65.5%. Cisplatin (cis-DDP) exhibits lower cytotoxic activity in TG cells than dipalladium complex (a cisplatin dose of 6.67 microM inhibits 30.3%) and does not cause migration of DNA to comet tail.

The first isolated antineoplastic Ru(IV) complex: Synthesis and structure of [Cl2(1,2-cyclohexanediaminotetraacetate)Ru]·2H2 O

Abstract Treatment of ruthenium(III) chloride with solid cyclohexanediaminetetraacetic acid (H4cdta) affords the water soluble complex [Ru(H2cdta)Cl2]·2H2O (1), the first isolated Ru4+ compound showing cytostatic activity. Complex 1 has been characterized by X-ray diffraction, electronic spectroscopy and magnetic studies. The molecular structure indicates that the chelating ligand acts a tetradentate, showing two free carboxylic groups. The octahedral coordination around the metal ion is completed by two chlorine atoms.

Synthesis, Structure and Antitumour Properties of a New 1,2-Propylenediaminetetraacetate-Ruthenium(III) Compound.

A novel complex formed by ruthenium (III) and the sequestering ligand 1,2-propylenediaminetetraacetic acid (PDTA) has been synthetized and characterized. The structure of the monomeric compound, studied by X-ray diffraction , shows an almost symmetric octahedral geometry around the metal ion, with two chlorine atoms in a cis conformation. The antitumour activity against a variety of murine and human cancers is reported.

The bidentate bonding mode of bis [2-oximinocyanacetamidato(2-)-N,N]nickelate(II) anion towards tetraphenylantimony (V) : unusually long Sb — O contact

Abstract The heteronuclear complex of tetraphenylantimony (V) with anion of bis (oximino-cyanoacetamidato (2-) -N,N) nickelate (II) [ (Ph4Sb) 2 {Ni (NCC (NO) C (O) NH) 2} ] 1 was synthesized and investigated by single crystal X-ray analysis. 1 was isolated as a result of the reaction between tetraphenylantimony (V) chloride and nickel (II) complex with (hydroximino) cyanoacetamide (H2aco) Na2 {Ni (aco) 2} obtained by reaction of Ni (Haco) 2 with NaOH. The crystal comprises heterometal centrosymmetric molecules (Ph4Sb) 2 {Ni (aco) 2} . The Ni atom is in a slightly distorted square planar surrounding formed by the four nitrogen atoms of deprotonated hydroximino and amide groups (Ni — Noxime 1.890 (4) , Ni — Namide 1.862 (4) A) . The ligands are situated in trans positions with respect to each other. The coordination environment of the antimony atom in the Ph4Sb+ cation is somewhat distorted trigonal bipyramidal [SbC4O] , Sb — Ceq 2.084 (5) –2.108 (5) A . All angles Ceq — Sb — Oax are less than 90°. Ph4Sb+ coordinates to the oxygen atom of C = O group (Sb — O 2.647 (3) A ) . The geometrical parameters of the CNO group indicate that it exists in the nitroso-form.

Formation of supramolecules in solution. Interaction between transition-metal complexes and water-soluble porphyrins

The rates of copper(II) insertion into water-soluble porphyrins in the presence of ethylenediamine have been studied near pH 7. Unusual kinetic profiles result which are interpreted as arising from the formation of supramolecular assemblies in solution. Confirmatory evidence for this model is provided by light scattering, conductance and temperature-variation experiments. The influences on assembly formation of reactant concentration, porphyrin charge and basicity, ionic strength, as well as buffer and electrolyte identity are reported.

Synthesis and X-ray structural study of a novel ruthenium(III)-ethylenediaminetetraacetate complex. The first compound showing an unusual coordination site for a carboxylic (glycine) group

Reaction of hydrated ruthenium trichloride in HCl and ethylenediaminetetraacetic acid (H4edta) gives the antitumour complex [Ru(H3edta)Cl2]·4H2O whose X-ray structure shows the first example of a stable Ru–OCOHR (glycine) bond; this type of linking has been confirmed by IR and X-ray photoelectron spectroscopy.

New coordination compounds of palladium(II) with iminodiacetic acid

SummaryIminodiacetic acid (IDA) forms 1:1 or 1:2 complexes with Pdll at room temperature and pH 6.0. The solid compounds have been characterized by elemental analysis, titrimetry, magnetic measurements, i.r. spectroscopy and thermal studies. The far i.r. spectra show peaks that can be assigned to Pd-Cl, Pd-N and Pd-O vibrations. On the basis of these studies tentative structures for the isolated substances are proposed.

Synthesis, Structure, Properties And Biological Behaviour Of The Complex [RuIV (H2L) Cl2].2H2O(H4L= 1,2-Cyclohexanediamminetetraacetic Acid)

The highly water-soluble ruthenium complex [Ru(H2L)Cl2]2H2o, in which H4L is the sequestering ligand trans-l, 2-cyclohexanediamminetetraacetic acid (cdta) has been synthesized, structurally characterized and its properties studied. The X-ray crystallographic study shows that the chelating coordinated ligand is tetradentate while the ruthenium environment is octahedral and slightly distorted, with two chloride anions coordinated in cis positions. Potentiometric, conductimetric and infrared studies confirm the presence of two free carboxylic groups, while electronic and voltammetric studies show that the central ion is Ru(IV). The testing of the cytotoxic activity of this complex against three different human cancer cell lines indicates that [Ru(H2L)Cl2].2H2O shows a remarkable and selective antiproliferative effect against the human uterine neck carcinoma HeLa and the malign adenocarcinoma ADLD, showing only a discrete turnout cell inhibition activity against colon adenocarcinoma HT-29. The important antiprotiferative behaviour of complex 1 against the human adenocarcinoma ADLD, indicates that [Ru(H2L)Cl2].2H2O might be considered as potential antineoplastic compound.

Nitrate/nitrite reductase activity of sulfido/selenido bridged dinuclear ruthenium(III) complexes.

Series of dinuclear species [Ru(2)(L)(2)(LH)(2)-mu-S(2)Cl(2)], [Ru(2)(L)(2)(LH)(4)-mu-Se(2)Cl(2)] (L=L(1)H and L(3)H) and [Ru(2)(L(2))(2)(L(2)H)-mu-Se(2)Cl(2)].2H(2)O, where L(1)H, L(2)H and L(3)H represent for 2-mercapto-5-phenyl-1,3,4-oxadiazole, 2-mercapto-benzimidazole and 2-mercapto-benzothiazole, respectively, have been prepared and characterized by their elemental analyses and spectral (IR, UV-visible, 1H NMR and FAB mass) data. The diamagnetism of these complexes are indicative of an exchange coupled dinuclear ruthenium(III) species containing S(2)(2-) and Se(2)(2-) bridges. The complexes along with free heterocycles (L(1)H-L(3)H) as well as RuCl(3) x 3H(2)0 were tested for their nitrate and nitrite reductase activities. The electrochemical behaviour of the complexes showed irreversible oxidation peaks at +(1.04-1.40) V quite comparable to those reported for sulphido bridged complexes.

Physicochemical properties of the soluble porphyrin tetrakis-(4-N-methylpyridyl)-porphine encapsulated in large unilamellar vesicles

Abstract Large unilamellar vesicles (LUV) formed by egg phosphatidylcholine (PC) and cholesterol (CL), and containing encapsulated soluble porphyrin H 2 TMpyP-4 were characterized and studied by light-scattering, freeze-fracture electron microscopy and fluorescence spectroscopy. The inclusion of CL produces a remarkable increase in LUV size (average size about 120 nm) and the number of porphyrin molecules entrapped by vesicles. Relaxation effects observed in porphyrin-loaded LUV have been attributed to the interaction between encapsulated H 2 TMpyP-4 molecules and the liposome membrane, a finding confirmed by fluorescence-emission spectroscopy. This technique also demonstrates the stability and integrity of LUV subjected to electrical discharges. Porphyrin-loaded LUV scatter light four times less than empty vesicles, a phenomenon attributed to a disturbance in lipid bilayer structure.