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 StructureABSTRACT
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 , BenzenesulfonamidesABSTRACT
New copper(II) complexes with sulfonamide ligands have been prepared and characterized. Sulfonamide ligands were prepared through a reaction between 8-aminoquinoline and either 2-mesitylene (Hqmesa), 4-tert-butylbenzene (Hqtbsa), or alpha-toluene (Halphaqtsa) sulfonyl chlorides. The structural analysis carried out for complex [Cu(alphaqtsa)(2)] indicated that the local environment of the Cu(II) cation is between a square planar and a tetrahedral geometry, with stacking of the benzene rings of the sulfonyl ligands between neighbor molecules. Powder EPR spectra at room temperature gave rhombic spectra for the [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] complexes and an axial spectrum for the [Cu(qtbsa)(2)] complex, probably due to the steric hindrance of the methyl groups. Complexes [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] are artificial chemical nucleases that degrade DNA in the presence of sodium ascorbate. A study of the radical scavengers revealed that the ROS (reactive oxygen species) involved in the DNA damage were hydroxyl, singlet oxygen-like species, and superoxide anion.
Subject(s)
Copper/chemistry , DNA/chemistry , Intercalating Agents/chemistry , Organometallic Compounds/chemistry , Sulfonamides/chemistry , Ascorbic Acid/chemistry , Copper/pharmacology , Crystallography, X-Ray , DNA/drug effects , Intercalating Agents/chemical synthesis , Molecular Conformation , Molecular Structure , Organometallic Compounds/chemical synthesis , Plasmids/drug effects , Reactive Oxygen Species/chemistry , Sulfonamides/chemical synthesisABSTRACT
Mixed coordination compounds of Cu(II) with sulfonamides and 1,10-phenanthroline as ligands have been prepared and characterised. Single crystal structural determination of the complex [Cu(N-quinolin-8-yl-p-toluenesulfonamidate)(2)(phen)] shows Cu(II) ions are located in a highly distorted octahedral environment, probably as a consequence of the Jahn-Teller effect. The FT-IR and electronic paramagnetic resonance (EPR) spectra are also discussed. The mixed complexes prepared undergo an extensive DNA cleavage in the presence of ascorbate and hydrogen peroxide. Two of the complexes have higher nucleolytic efficiency than the bis(o-phenanthroline)copper(II) complex.
Subject(s)
Copper/chemistry , DNA Damage , Organometallic Compounds/chemical synthesis , Crystallization , Hydrolysis/drug effects , Molecular Structure , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Oxidation-Reduction , Phenanthrolines/chemical synthesis , Phenanthrolines/chemistry , Phenanthrolines/pharmacology , Plasmids/drug effects , Plasmids/metabolism , Reactive Oxygen Species/chemistry , Reactive Oxygen Species/metabolism , Sulfonamides/chemical synthesis , Sulfonamides/chemistry , Sulfonamides/pharmacology , Superoxide Dismutase/metabolismABSTRACT
Ofloxacin (oflo) is able to interact with Co(II) and Zn(II) salts to form complexes with the general formula [M(oflo)(2)]. 4H(2)O, (M = Co, Zn). Bonding takes place through one of the oxygen atoms of the carboxylate group (acting as a monodentate) and the oxygen atom of the ketonic group. The IR bands of the carboxylic and ketonic group at 1713 and 1622 cm(-1), respectively, shift to 1615 and 1575 cm(-1) in the complexes. After dissolution in methanol, complex [Co(oflo)(2)]. 4H(2)O crystallizes as [Co(oflo)(2)(MeOH)(2)]. 4MeOH, where Co(II) ion is in an octahedral environment of oxygen atoms. This compound crystallizes in the triclinic system, spatial group P-1, with unit cell dimensions a = 9.3670(12), b = 11.4135(17), c = 11.851(2) A y alpha = 71.999(14), beta = 73.698(12), gamma = 83.528(14) degrees. Magnetic properties (effective magnetic moment 5.02 BM) and visible spectrum (bands at 490, 510, and 1152 nm) are characteristic of such an octahedral geometry. (1)H- and (13)C-NMR spectra of the Zn(II) complex indicate only small structural changes in ofloxacin upon coordination to the metallic site.
Subject(s)
Cobalt/chemistry , Ofloxacin/chemistry , Zinc/chemistry , Chemistry, Pharmaceutical , Crystallization , Crystallography, X-Ray/methodsABSTRACT
A new copper complex with N-quinolin-8-yl-p-toulenesulfonamide has been prepared and characterised. The compound crystallises in the triclinic system, space group P1, with a=13.457(3), b=15.067(5), c=18.589(3) A; alpha=112.05(2), beta=93.92(2), gamma=108.30(2) degrees and Z=4. The geometry of the Cu(II) ion is distorted square planar. The N-quinolin-8-yl-p-toulenesulfonamidate anion behaves as a bidentate ligand through the N(sulfonamidate)and N(quinoline) atoms. The complex does not cleave DNA in the presence of hydrogen peroxide.
