Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
Add more filters










Publication year range
1.
J Inorg Biochem ; 203: 110902, 2020 02.
Article in English | MEDLINE | ID: mdl-31770696

ABSTRACT

Seven novel Copper(II) complexes, namely [Cu(Am4DHotaz)(H2O)2](ClO4) (1), [Cu(Am4DHotaz)(NO3)(MeOH)]·H2O (2), [Cu(Am4Motaz)2(H2O)](ClO4)2·0.83H2O (3), [Cu(Am4Motaz)2(NO3)]NO3·MeOH (4), [Cu(Am4Eotaz)2(NO3)]3(NO3)3·2H2O (5), [Cu(Am4Eotaz)2(ClO4)](ClO4) (6) and [Cu(Am4Eotaz)(ClO4)(H2O)](ClO4) (6a) (HAm4DHotaz = N'-(4-oxothiazolidin-2-ylidene)pyridine-2-carbohydrazonamide, Am4Motaz = N'-(3-methyl-4-oxothiazolidin-2-ylidene)pyridine-2-carbohydrazonamide and Am4Eotaz = N'-(3-ethyl-4-oxothiazolidin-2-ylidene)pyridine-2-carbohydrazonamide), have been successfully synthesized and characterized by several physicochemical techniques and, for 1-6 complexes, single crystal X-ray diffraction. Having the structural data as a base, complexes 1, 2 and 3 exhibited square pyramidal to square pyramidal slightly distorted geometry, whereas 4, 5 and 6 an intermediate between square pyramidal and trigonal bipyramidal. The ability of complexes 1-6 to cleave DNA was assayed with the aid of gel electrophoresis on supercoiled pUC18-DNA. Except for [Cu(Am4Motaz)2(H2O)](ClO4)2·0.83H2O (3), the compounds were not able to perform DNA cleavage (data not shown). Since 3 has been shown to behave as a nuclease, its interaction with DNA was studied by means of thermal denaturation and viscosimetry measurements.


Subject(s)
Copper/chemistry , DNA/chemistry , Deoxyribonucleases/chemical synthesis , Organometallic Compounds/chemical synthesis , Thiazoles/chemistry , Hydrolysis
2.
J Inorg Biochem ; 115: 64-71, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22922313

ABSTRACT

Sulfonamides derived from 8-aminoquinoline react with Mn(II) and Mn(III) salts to form Mn(II) complexes; the Mn(III) species are reduced to the divalent state in the presence of 1,10 phenanthroline and bipyridine. Their molecular structure, determined by single crystal X-ray diffraction, show that all the complexes present a distorted octahedral geometry, in which the deprotonated sulfonamide acts as a bidentate ligand. UV-visible spectroscopy and changes in the melting temperature (Tm) of calf thymus DNA show a strong interaction of these complexes with DNA. The significant hypochromicity of the charge transfer transition at 370 nm without an appreciable change in wavelength and the minor changes in the relative viscosity of calf thymus DNA have been attributed to an interaction between the surface of DNA and the complexes. [Mn(qbsa)(2)(MeOH)(2)], [Mn(qbsa)(2)(phen)], [Mn(qtsa)(2)(H(2)O)(2)] and [Mn(qtsa)(2)(phen)] (where qbsa=N-quinolin-8-yl-bencenesulfonamide, qtsa=N-quinolin-8-yl-p-toluenesulfonamide and qnsa=N-quinolin-8-yl-naftalenesulfonamide) exhibit a prominent nuclease activity and the mechanism of DNA cleavage is investigated.


Subject(s)
DNA/chemistry , Deoxyribonucleases/chemistry , Deoxyribonucleases/chemical synthesis , Manganese/chemistry , Plasmids/chemistry , Sulfonamides/chemistry , Animals , Cattle , Molecular Structure
3.
J Inorg Biochem ; 103(7): 1067-73, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19515426

ABSTRACT

We report herein the synthesis of a novel tetracationic tris(2,2'-bipyridine) ligand 4. We show that this ligand metalated with copper(II), and in the presence of ascorbate as a reducing agent, strongly damages pUC18 plasmid DNA. Copper complex formation was demonstrated by ESI-MS (electrospray ionization-mass spectrum) at a 1:3 ligand to metal ratio. Binding of both 4 and its copper(II) complex to CT-DNA (calf thymus DNA) was characterized by viscosimetry, thermal denaturation and fluorescence-based competition assays. The viscosimetric data indicated that 4 and its copper(II) complex bind DNA through partial intercalation and thermal denaturation studies revealed a significant increase of duplex DNA stability in the presence of these species (DeltaT(m)=16.4 and 18.3 degrees C, respectively). Moreover, 4 and its copper(II) complex were found to effectively compete with ethidium bromide for the intercalative binding sites of DNA. Overall, the copper(II)-4 complex constitutes a very efficient DNA cleaving agent in the presence of ascorbate. Experiments with scavengers further suggest that the generation of Cu(I), hydrogen peroxide, superoxide, hydroxyl radical and singlet oxygen-like species contributes to the DNA breakage induced by the Cu(II) complex of 4.


Subject(s)
2,2'-Dipyridyl/analogs & derivatives , Copper/chemistry , DNA Cleavage , DNA/chemistry , Deoxyribonucleases/chemistry , 2,2'-Dipyridyl/chemical synthesis , 2,2'-Dipyridyl/chemistry , Animals , Deoxyribonucleases/chemical synthesis , Ligands , Spectrometry, Mass, Electrospray Ionization
4.
J Inorg Biochem ; 103(6): 923-34, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19428113

ABSTRACT

The complex [Cu(N9-ABS)(phen)2].3.6H2O, H2N9-ABS = N-(9H-purin-6-yl)benzenesulfonamide and phen = 1,10-phenanthroline, has been synthesized and then characterized with the aid of X-ray diffraction, analytical, and spectroscopic techniques. The geometry of Cu(II) is distorted square pyramidal with the equatorial positions occupied by three N atoms from two phenantroline molecules and one N atom from the adenine ring of the sulfonamide ligand. The interaction of the complex with DNA was studied by means of viscosity measurements and fluorescence spectroscopy. The results pointed to a classic intercalation of the complex between the DNA base pairs. The complex was found to be a very efficient agent of plasmid DNA cleavage in the presence of ascorbate. Both the kinetics and the mechanism of the cleavage reaction were studied. In addition, the cytotoxic properties of the complex were evaluated in human Jurkat T and Caco-2 cell lines. The cytotoxicity of the compound was higher than that of the reference ([Cu(phen)2]2+). The mechanism and type of cell death induced by the compound was determined by flow cytometry and Hoechst dye staining. The compound demonstrated a significant ability to induce cell death by apoptosis. The apoptosis induced by [Cu(N9-ABS)(phen)2].3.6H2O was associated with an increase in p53 protein levels while those of Bcl-2 were reduced.


Subject(s)
Antineoplastic Agents/chemical synthesis , Copper/chemistry , DNA Cleavage/drug effects , DNA/metabolism , Organometallic Compounds/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Caco-2 Cells , Humans , Jurkat Cells , Organometallic Compounds/chemical synthesis , Phenanthrolines/chemistry , Proto-Oncogene Proteins c-bcl-2/analysis , Sulfonamides/chemistry , Tumor Suppressor Protein p53/analysis , Benzenesulfonamides
5.
J Inorg Biochem ; 103(2): 243-55, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19054567

ABSTRACT

Three doubly-bridged, trinuclear copper(II) compounds with hydroxo and carboxylato bridges, (infinity)(1)[Cu(3)(L1)(2)(mu-OH)(2)(mu-propionato)(2)](1), [Cu(3)(L2)(2)(mu-OH)(2)(mu-propionato)(2)(DMF)(2)] (2) and (infinity)(1){[Cu(3)(L3)(2)(mu-OH)(2)(mu-propionato)(2)]} [Cu(3)(L3)(2)(mu-OH)(2)(mu-propionato)(2)(DMF)(2)]} (3) [HL1=N-(pyrid-2-ylmethyl)benzenesulfonylamide, HL2=N-(pyrid-2-ylmethyl)toluenesulfonylamide, HL3=N-(pyrid-2-ylmethyl)naphthalenesulfonylamide], have been synthesized and characterized. 1 is built from [Cu(3)(L1)(2)(mu-OH)(2)(mu-propionato)(2)] clusters. Each unit contains three copper(II) with two different coordination environments: the terminal centers are square-base pyramidal whereas the central copper is square planar. 2 presents a similar square-base pyramidal geometry in the terminal centers, but the central copper is six-coordinate. 3 shows an unusual 1D coordination polymer comprised of two distinct building blocks: one similar to that found in 1 and the other similar to that found in 2. The magnetic susceptibility measurements (2-300K) reveal a ferromagnetic interaction between the Cu(II) ions with J values of 76.0, 55.0, and 48.0cm(-1) for 1, 2, and 3, respectively. Emission spectroscopy, thermal denaturation, viscosimetry and cyclic voltammetry show an interaction of the complexes with DNA through the sugar-phosphate backbone. All three Cu(II) complexes were found to be very efficient agents of plasmid DNA cleavage in the presence of ascorbato or mercaptopropionic acid. Both the kinetics and the mechanism of the cleavage reaction have also been examined.


Subject(s)
Copper/chemistry , DNA Cleavage , Deoxyribonucleases/chemistry , Organometallic Compounds/chemistry , Benzene/chemistry , Crystallography, X-Ray , DNA/chemistry , Drug Design , Ferric Compounds/chemistry , Kinetics , Molecular Structure , Naphthalenes/chemistry , Organometallic Compounds/chemical synthesis , Oxidation-Reduction , Toluene/chemistry
6.
J Biol Inorg Chem ; 13(8): 1249-65, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18651184

ABSTRACT

Two copper(II) complexes with a benzothiazolesulfonamide ligand, [Cu(L)2(py)2] (1) and [Cu(en)2(L)2] (2) [HL is N-2-(4-methylbenzothiazole)toluenesulfonamide, py is pyridine, en is ethylenediamine], were prepared and then characterized with the aid of X-ray crystallography and spectroscopy. Whereas the copper(II) ion in 1 presents a square-planar geometry, in 2 it has a distorted octahedral environment. In addition, although the ligand is monodentate in both complexes, it exhibits different coordination behavior in each, interacting through the benzothiazole nitrogen atom in 1 and through the sulfonamide nitrogen atom in 2. The propensity for binding of 1 and 2 to calf thymus DNA was studied by thermal denaturation, viscosimetry, and cyclic voltammetry. The ability of the complexes to cleave DNA was studied in vitro through ascorbate activation and was tested by monitoring the expression of the yEGFP gene containing the RAD54 reporter. Moreover, their antiproliferative activity was verified in two cellular models: yeast and human tumor cells in culture. While 1 was found to be the more active cleaving agent in vitro, 2 showed a higher propensity for inflicting DNA damage at the cellular level. The biological studies carried out with human tumor cells, namely, colon adenocarcinoma Caco-2 cells (HTB-37) and leukemia Jurkat T lymphocytes (TIB-152), confirmed that both compounds inhibit the growth of these cell lines, although 2 is more effective. This difference is associated with the latter compound's greater ability to induce cell death by apoptosis.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Benzothiazoles/chemistry , Benzothiazoles/pharmacology , Copper/chemistry , Sulfonamides/chemistry , Sulfonamides/pharmacology , T-Lymphocytes/drug effects , Antineoplastic Agents/chemistry , Binding Sites , Caco-2 Cells , Cations, Divalent , Cell Proliferation/drug effects , Copper/pharmacology , Crystallography, X-Ray , DNA/chemistry , DNA/metabolism , Humans , Jurkat Cells , Mutagenicity Tests , Spectrum Analysis , T-Lymphocytes/cytology
7.
Bioorg Med Chem Lett ; 18(11): 3286-90, 2008 Jun 01.
Article in English | MEDLINE | ID: mdl-18479917

ABSTRACT

We have focused our interest on the tetrapyridoacridine ligand tetrapyrido[3,2-a:2',3'-c:3'',2''-h: 2''',3'''-j]acridine (tpac), as a model system for the preparation of novel copper-based artificial nucleases. The complex of copper(II)-tpac cleaves supercoiled pUC18 plasmid DNA in an oxidative manner by photoactivation with visible light, exhibiting maximum cleaving efficiency at 1:2 metal-ligand stoichiometric ratio. We propose an interaction of the copper-tpac complex with DNA through both major and minor grooves and a photocleavage mechanism via the formation of hydroxyl radicals and singlet oxygen or singlet oxygen-like species.


Subject(s)
Acridines/chemistry , Copper/chemistry , DNA/metabolism , DNA/radiation effects , Deoxyribonucleases/metabolism , Models, Molecular , Phenanthrolines/chemistry , Copper/metabolism , Ligands , Light , Molecular Structure , Photochemistry , Singlet Oxygen/chemistry
8.
Inorg Chem ; 46(17): 7178-88, 2007 Aug 20.
Article in English | MEDLINE | ID: mdl-17630687

ABSTRACT

A new dinuclear copper(II) complex has been synthesized and structurally characterized: [Cu(mu-ade)(tolSO3)(phen)]2.2H2O (Hade = adenine, tolSO3- = toluenesulfonate anion). Its magnetic properties and electronic paramagnetic resonance (EPR) spectra have been studied in detail. The compound has two metal centers bridged by two adeninate NCN groups. The coordination geometry of the copper(II) ions in the dinuclear entity is distorted square pyramidal, with the four equatorial positions occupied by two phenanthroline N atoms and two N atoms from different adenine molecules. The axial position is occupied by one sulfonate O atom. Magnetic susceptibility data show antiferromagnetic behavior with an estimated exchange constant of -2J = 65 cm-1. The EPR spectrum has been obtained at both X- and Q-band frequencies; a study at different temperatures has been carried out at the latter. Above 20 K, the Q-band spectra are characteristic of S = 1 species with a small zero-field splitting parameter (D = 0.0970 cm-1). A detailed study of the DNA-complex interaction has been performed. The title complex efficiently cleaves the pUC18 plasmid in the presence of reducing agents. Both the kinetics and the mechanism of the cleavage reaction are examined and described herein.


Subject(s)
Adenine/chemistry , Copper/chemistry , DNA/chemistry , Magnetics , Organometallic Compounds/chemistry , Crystallography, X-Ray , Electron Spin Resonance Spectroscopy , Hydrogen Bonding , Kinetics , Ligands , Molecular Structure , Organometallic Compounds/chemical synthesis , Spectrum Analysis
9.
J Inorg Biochem ; 100(7): 1208-18, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16527356

ABSTRACT

A flavonol iron(III) complex, [Fe(flavonolato)(2)Cl(MeOH)], has been prepared. The compound has been characterized by X-ray crystallography, spectroscopy, magnetism and electronic paramagnetic resonance (EPR) at X- and Q-band. The geometrical environment around the metal is best described as rhombic distorted octahedral. This distortion has also been inferred from the magnetic measurements and from the EPR spectra at different temperatures, E/D(rhombicity parameter) approximately 0.06. The DNA cleavage activity of the iron(III) complex with and without ascorbate/hydrogen peroxide is reported. Mechanisms of the oxidative cleavage have been proposed when DNA strand scission is performed both with and without ascorbate/hydrogen peroxide activation.


Subject(s)
DNA/drug effects , Ferric Compounds/chemistry , Ferric Compounds/pharmacology , Oxidative Stress , Crystallography, X-Ray , DNA/chemistry , Electron Spin Resonance Spectroscopy , Ferric Compounds/chemical synthesis , Models, Molecular , Molecular Structure , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet
10.
Inorg Chem ; 44(25): 9424-33, 2005 Dec 12.
Article in English | MEDLINE | ID: mdl-16323929

ABSTRACT

Copper(II) complexes of N-benzothiazolesulfonamides (HL1=N-2-(4-methylphenylsulfamoyl)-6-nitro-benzothiazole, HL2=N-2-(phenylsulfamoyl)-6-chloro-benzothiazole, and HL3=N-2-(4-methylphenylsulfamoyl)-6-chloro-benzothiazole) with ammonia have been synthesized and characterized. The crystal structures of the [Cu(L1)2(NH3)2].2MeOH, [Cu(L2)2(NH3)2], and [Cu(L3)2(NH3)2] compounds have been determined. Compounds and present a distorted square planar geometry. In both compounds the metal ion is coordinated by two benzothiazole N atoms from two sulfonamidate anions and two NH3 molecules. Complex is distorted square-pyramidal. The Cu(II) ion is linked to the benzothiazole N and sulfonamidate O atoms of one of the ligands, the benzothiazole N of another sulfonamidate anion, and two ammonia N atoms. We have tested the superoxide dismutase (SOD)-like activity of the compounds and compared it with that of two dinuclear compounds [Cu2(L4)2(OCH3)2(NH3)2] and [Cu2(L4)2(OCH3)2(dmso)2] (HL4=N-2-(phenylsulfamoyl)-4-methyl-benzothiazole). In vitro indirect assays show that the dimeric complexes are better SOD mimics than the monomeric ones. We have also assayed the protective action provided by the compounds against reactive oxygen species over Deltasod1 mutant of Saccharomyces cerevisiae. In contrast to the in vitro results, the mononuclear compounds were more protective to SOD-deficient S. cerevisiae strains than the dinuclear complexes.


Subject(s)
Benzothiazoles/chemistry , Copper/chemistry , Organometallic Compounds/pharmacology , Reactive Oxygen Species/antagonists & inhibitors , Saccharomyces cerevisiae/drug effects , Sulfonamides/chemistry , Crystallization , Crystallography, X-Ray , Free Radicals/antagonists & inhibitors , In Vitro Techniques , Models, Molecular , Molecular Structure , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Reactive Oxygen Species/chemistry , Saccharomyces cerevisiae/chemistry , Saccharomyces cerevisiae/metabolism , Structure-Activity Relationship , Superoxide Dismutase/chemistry , Superoxide Dismutase/drug effects , Superoxide Dismutase/metabolism
11.
J Inorg Biochem ; 98(8): 1436-46, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15271522

ABSTRACT

Three new monomeric Cu(II) complexes of 5-amino-3-pyridin-2-yl-1,2,4-triazole (Hapt), [Cu(Hapt)(H(2)O)(2)(SO(4))] (1), [Cu(Hapt)(2)(H(2)O)(NO(3))](NO(3)) (2), and [Cu(Hapt)(2)(NCS-N)](NCS).H(2)O (3), have been prepared and characterized by single crystal X-ray diffraction. One distorted [CuN(2)O(2)+O(')] square-pyramidal (1), one distorted [CuN(3)O+N(')+O(')] octahedral (2), and one distorted [CuN(4)+N(')] intermediate between square-pyramidal and trigonal-bipyramidal (3) coordination configuration were found and are suggested to be due to the chelating nature of the ligand, which interacts with Cu(II) through the N4(triazole) and N(pyridine) atoms. Spectral properties of these chelates are in accordance with the X-ray structural data. With ascorbate and H(2)O(2) activation, compound 2 exhibits higher nuclease activity than compound 1. The influence on the DNA cleavage process of different scavengers of reactive oxygen species: dimethyl sulfoxide (DMSO), tert-butyl alcohol, sodium azide, 2,2,6,6-tetramethyl-4-piperidone and superoxide dismutase enzyme (SOD), and of the minor groove binder distamycin, is also studied.


Subject(s)
Copper/chemistry , DNA/metabolism , Deoxyribonucleases , Triazoles/chemistry , Copper/metabolism , Crystallography, X-Ray , Deoxyribonucleases/chemistry , Deoxyribonucleases/metabolism , Free Radical Scavengers/chemistry , Free Radical Scavengers/metabolism , Models, Molecular , Molecular Sequence Data , Molecular Structure , Oxidation-Reduction , Spectrum Analysis , Triazoles/metabolism
12.
J Inorg Biochem ; 98(2): 189-98, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14729299

ABSTRACT

Copper(II) complexes of N-benzothiazolsulfonamides, [Cu(N-2-(5,6-dimethylbenzothiazole)toluenesulfonamidate)(2)(dmso)(2)] (1), [Cu(N-2-(6-chlorobenzothiazole)benzenesulfonamidate)(2)(dmso)(2)] (2) and [Cu(N-2-(6-chlorobenzothiazole)toluenesulfonamidate)(2)(dmso)(2)] (3) with interesting protective properties against superoxide radicals have been prepared. The compounds have been characterized by X-ray diffraction and their chemical properties have been studied by spectroscopic methods. The crystal structure of 1 shows that the copper(II) is surrounded by two benzothiazole N atoms from the sulfonamide ligands and two O atoms from the dimethylsulfoxide molecules in a square planar arrangement. The coordination polyhedron around copper(II) in 2 and 3 is distorted square pyramidal being the metal ion linked to benzothiazole N and sulfonamidate O atoms of the ligand and to two dimethylsulfoxide O atoms. The three complexes have a strong protective action over Delta sod1 mutant of Saccharomyces cerevisiae against reactive oxygen radicals derived from respiration and against those generated by hydrogen peroxide and menadione.

13.
J Inorg Biochem ; 96(4): 443-51, 2003 Sep 01.
Article in English | MEDLINE | ID: mdl-13678809

ABSTRACT

Two new mu-methoxo-bridged dinuclear copper(II) complexes with a N-substituted sulfonamide, [Cu(mu-OMe)(L)(NH(3))](2) (1) and [Cu(mu-OMe)(L)(DMSO)](2) (2) [HL, N-2-(4-methylbenzothiazole)benzenesulfonamide], have been prepared and characterized by single-crystal X-ray difraction analyses. Compound 1 crystallizes in the monoclinic space group C(2)/c with a=22.0678(18), b=7.9134(7), c=21.1186(18)A, beta=113.788(4) degrees and Z=8. Compound 2 crystallizes in the monoclinic space group C(2)/c with a=18.0900(10), b=9.5720(10), c=24.2620(10) A, beta=98.7120(10) degrees and Z=8. In both complexes the copper atoms have square-planar environments bridged by two oxygen atoms from methoxide groups. Magnetic susceptibility measurements indicate a very strong antiferromagnetic coupling between the copper(II) ions in both complexes (2J<-1000 cm(-1)). Electronic Paramagnetic Resonance (EPR) spectra of the two complexes both in solid and in solution are silent. 13C NMR spectra of the complexes in solid state have been studied. The complexes have been evaluated as model systems for the catechol oxidase enzyme using 3,5-di-tert-butylcatechol as the test substrate. Complex 2 is slightly more active than complex 1.


Subject(s)
Catechol Oxidase/chemistry , Catechol Oxidase/metabolism , Copper/metabolism , Electron Spin Resonance Spectroscopy , Sulfonamides/metabolism , Binding Sites , Catalysis , Catechol Oxidase/biosynthesis , Crystallography, X-Ray , Ligands , Magnetic Resonance Spectroscopy , Magnetics , Models, Molecular , Structure-Activity Relationship , Sulfonamides/chemistry
14.
J Biol Inorg Chem ; 8(6): 644-52, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12739108

ABSTRACT

Copper-based transition metal complexes performing single- and double-strand scission of DNA have been studied. The dinuclear complexes [Cu(2)(L)(2)(OCH(3))(2)(NH(3))(2)] and [Cu(2)(L)(2)(OCH(3))(2)(DMSO)(2)] are more active than the corresponding mononuclear [Cu(L)(2)(py)(2)] (where HL= N-(4-methylbenzothiazol-2-yl)benzenesulfonamide), suggesting that the dinuclearity is an important factor in the oxidative cleavage of DNA. The cleavage efficiency of the complexes depends on the reducing agent used in the process, the tandem ascorbate/H(2)O(2) being the most efficient. PAGE analyses have shown that these complexes cleave DNA without sequence selectivity. The DNA degradation process takes place mainly by C1' oxidation, but C4' and C5' oxidations cannot be ruled out as minor pathways. These copper complexes preferably oxidize guanine under mild conditions, but under more drastic conditions the oxidation reactivity appears to be T>G>C>A, suggesting the intervention of hydroxyl radicals as active species.


Subject(s)
Copper/metabolism , DNA/metabolism , Organometallic Compounds/metabolism , Sulfonamides/metabolism , Thiazoles/metabolism , Chromatography, High Pressure Liquid , Copper/chemistry , Deoxyribonucleases/antagonists & inhibitors , Deoxyribonucleases/metabolism , Deoxyribose/metabolism , Electrophoresis, Polyacrylamide Gel , Free Radical Scavengers/pharmacology , Ligands , Models, Molecular , Organometallic Compounds/chemistry , Oxidation-Reduction , Reactive Oxygen Species/metabolism , Reducing Agents/pharmacology , Sulfonamides/chemistry
15.
J Biol Inorg Chem ; 8(1-2): 112-20, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12459905

ABSTRACT

Copper(II) ternary complexes based on the novel benzothiazole- N-sulfonamides, HL1 ( N-2-(4-methylbenzothiazole)benzenesulfonamide) and HL2 ( N-2-(6-nitrobenzothiazole)naphthalenesulfonamide) ligands, and pyridine have been synthesized and characterized. Complexes [Cu(L1)(2)(py)(2)] (1). and [Cu(L2)(2)(py)(2)] (2). were chemically characterized and their structures determined by means of single crystal X-ray analysis. In both compounds the Cu(II) ion is coordinated to four N atoms in a nearly square planar arrangement. The Cu-N bond distances are similar to those of Cu(2)Zn(2)SOD. The SOD mimetic activity of the complexes was determined both in vitro and in vivo. For determining the SOD-like activity of the complexes in vivo, we have developed a new method based on the complexes' protective effect on a delta sod1mutant of Saccharomyces cerevisiae against free radicals generated by hydrogen peroxide and menadione as well as free radicals produced in the cellular respiration process. The results have shown that complex 1 presents a protective action against oxidative stress induced by menadione or H(2)O(2) and that both complexes 1 and 2 protect against free radicals generated in cellular respiration.


Subject(s)
Antioxidants/chemistry , Copper/chemistry , Sulfonamides/chemistry , Superoxides/antagonists & inhibitors , Thiazoles/chemistry , Antioxidants/pharmacology , Benzothiazoles , Cell Respiration/drug effects , Crystallization , Crystallography, X-Ray , Models, Molecular , Molecular Mimicry , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Oxidative Stress , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/metabolism , Sulfonamides/pharmacology , Superoxide Dismutase/chemistry , Superoxide Dismutase/metabolism , Vitamin K 3/pharmacology
16.
Inorg Chem ; 41(22): 5821-30, 2002 Nov 04.
Article in English | MEDLINE | ID: mdl-12401089

ABSTRACT

New copper(II) complexes of the cyclic trinuclear type with 1,2,4-triazole ligands, [Cu(3)(mu(3)-OH)(aaat)(3)(H(2)O)(3)](NO(3))(2).H(2)O [Haaat = 3-acetylamino-5-amino-1,2,4-triazole] (1) and ([Cu(3)(mu(3)-OH)(aat)(3)(mu(3)-SO(4))].6H(2)O)(n) [Haat = 3-acetylamino-1,2,4-triazole] (2), have been prepared and characterized by X-ray crystallography and magnetic measurements. Compound 1, the first reported with the ligand (H)aaat, consists of discrete trinuclear cations, associated NO(3)(-) anions and lattice water molecules. Compound 2 consists of unusual chains of trinuclear units with a tridentate sulfato group linking the trimeric units and water molecules stabilizing the crystal lattice. In both complexes, 1 and 2, the trinuclear [Cu(3)(OH)L(3)] unit contains a pyramidal Cu(3)-mu(3)OH core, and an almost flat Cu(3)N(6) ring formed by the N,N-bridging triazolato groups. The Cu...Cu' intratrimeric distances are 3.35-3.37-3.39 A in 1 and 3.34-3.34-3.36 A in 2. The copper atoms are five-coordinated with a distorted square-pyramidal geometry. Magnetic measurements have been performed in the 1.9-300 K temperature range. In the high-temperature region (T > 90 K), experimental data could be satisfactorily reproduced by using an isotropic exchange model, H = -J(S(1)S(2) + S(2)S(3) + S(1)S(3)), with J = -194.6 cm(-1) and g = 2.08 for 1, and J = -185.1 cm(-1) and g = 2.10 for 2. The magnitude of the antiferromagnetic exchange in both complexes is discussed on the basis of their structural features by comparison with reported N,N-pheripherically bridged trinuclear systems. In order to fit the experimental magnetic data at low temperature, an antisymmetric exchange term, H(AS) = G(S(1)xS(2) + S(2)xS(3) + S(1)xS(3)), had to be introduced, with G = 27.8 (1) and 31.0 (2) cm(-1). Crystal data: C(12)H(27)Cu(3)N(17)O(14) (1) (MW = 824.13) crystallizes in the triclinic space group, P(-)1, Z = 2, with the cell dimensions a = 8.852(2) A, b = 11.491(3) A, c = 15.404(3) A, alpha = 70.43(3) degrees, beta = 75.11(2) degrees, gamma = 88.43(2) degrees, and V = 1423.8(5) A(3), D(calcd) = 1.922 g cm(-)(3); the final agreement values were R1 = 0.0822 and wR2 = 0.2300 for 4989 unique reflections. C(12)H(28)Cu(3)N(12)O(14)S (2) (MW = 787.14) crystallizes in the triclinic space group, P(-)1, Z = 2, with the cell dimensions a = 7.146(6) A, b = 14.26(1) A, c = 15.35(2) A, alpha = 109.0(9) degrees, beta = 93.6(9) degrees, gamma = 99.5(7) degrees, and V = 1448(2) A(3), D(calcd) = 1.806 g cm(-3); the final agreement values were R1 = 0.0628 and wR2 = 0.1571 for 3997 "observed" reflections.

17.
Inorg Chem ; 36(10): 2052-2058, 1997 May 07.
Article in English | MEDLINE | ID: mdl-11669823

ABSTRACT

A copper(II) complex of formula Cu(2)(stz)(4) (stz(-) = sulfathiazolato) has been synthesized and characterized by single-crystal X-ray diffraction. The compound crystallizes in the orthorhombic system, space group P2(1)cn with a = 10.595(7) Å, b = 14.274(3) Å, c = 29.65(1) Å, and Z = 4. The structure consists of dinuclear copper(II) units which contain four sulfathiazolato ligands bridging the metal ions through a nonlinear NCN group. The copper atoms are four-coordinated, the chromophore being CuN(4). The Cu.Cu bond distance is 2.671(2) Å. Magnetic susceptibility data in the temperature range 7-300 K show the occurrence of intramolecular antiferromagnetic coupling with 2J = -61.5 cm(-1). This low exchange energy value has been analyzed and rationalized through extended Hückel calculations. EPR spectra at X- and Q-band frequencies show the signals corresponding to a dinuclear entity, being the zero-field splitting parameter, D = 0.230 cm(-1).

SELECTION OF CITATIONS
SEARCH DETAIL
...