RESUMO
Four coordinate copper(II) complexes 1, 2 and 3 of ligands based on thiophenemethylamine containing imidazole, benzimidazole and pyridine moiety have been synthesized and characterized. Complex 1 has also been crystallographically characterized. The three complexes bind to DNA non-intercalatively, though partial intercalation in the case of complex 2 cannot be ruled out. All the three complexes bring about hydroxyl radical mediated DNA cleavage in the presence of H2O2. Binding of the three copper(II) complexes to BSA lead to changes in the helicity of the protein. Among the three complexes, 2 and 3 are more effective in inhibiting the growth of cancerous MG63 cells than normal NIH3T3 cells. These two complexes promote apoptosis in MG 63 cells.
Assuntos
Antineoplásicos/farmacologia , Cobre/química , DNA/efeitos dos fármacos , Metilaminas/química , Compostos Organometálicos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Bovinos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , DNA/química , Clivagem do DNA , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Peróxido de Hidrogênio/farmacologia , Camundongos , Modelos Moleculares , Estrutura Molecular , Células NIH 3T3 , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Proteólise/efeitos dos fármacos , Soroalbumina Bovina/química , Relação Estrutura-AtividadeRESUMO
We report two fluorophores with open coordination sites for specific sensing of Ni(2+) and Cu(2+) ions via a simple synthetic route. The fluorescence activity was completely quenched on coordination of the metal ions with the phenanthroline ring present in the fluorophore as is clearly evident from the photophysical studies.
Assuntos
Técnicas de Química Analítica/instrumentação , Cobre/análise , Corantes Fluorescentes/química , Níquel/análise , Fenantrolinas/química , Cobre/química , Diaminas/química , Modelos Moleculares , Conformação Molecular , Níquel/químicaRESUMO
A chromium(III) complex [Cr(DPPZ)(2)Cl(2)](+), where DPPZ is a planar bidentate ligand with an extended aromatic system, has been found to bind strongly to CT DNA with an apparent binding constant of (1.8+/-0.5)x10(7) M(-1). The effects of [Cr(DPPZ)(2)Cl(2)](+) on the melting temperature and the viscosity of DNA clearly show that the chromium(III) complex interacts with DNA intercalatively. Competitive binding study shows that the enhancement in emission intensity of ethidium bromide (EthBr) in the presence of DNA was quenched by [Cr(DPPZ)(2)Cl(2)](+) indicating that the Cr(III) complex displaces EthBr from its binding site in DNA. The binding of this complex has been found to bring about B to Z conformational transition in CT DNA as well as poly(dG-dC).poly(dG-dC). Molecular modeling study also shows that binding energy of the complex with d(GC)(12) is much higher than Dickerson model and d(AT)(12). Modeling studies show that [Cr(DPPZ)(2)Cl(2)](+) brings about twist in the DNA base pairs as well as phosphate ester backbone resulting in conformational transition in DNA.
Assuntos
Cromo/química , DNA/química , Substâncias Intercalantes/química , Compostos Organometálicos/química , Compostos Organometálicos/síntese química , Ligação Competitiva , Dicroísmo Circular , Modelos Moleculares , Desnaturação de Ácido Nucleico , Termodinâmica , ViscosidadeRESUMO
[Co(bzimpy)(2)], where bzimpy is 2,6-bis(benzimidazol-2-yl)pyridine was synthesized and characterized by ESI-MS (electrospray ionization mass spectrometry), UV-visible and fluorescence spectra. Absorption titration and thermal denaturation experiments indicate that the complex binds to DNA with moderate strength. Viscosity measurement shows that the mode of binding could be surface binding. Fluorescence study shows that the fluorescence intensity of the complex decreases with increasing concentrations of DNA, which is due to the photoelectron transfer from guanine base to excited MLCT (metal to ligand charge transfer) state of the complex. Photoexcitation of the complex in the MLCT region in the presence of plasmid DNA has been found to give rise to nicking of DNA.
Assuntos
Cobalto/química , DNA/química , Compostos Organometálicos/química , Hidrólise , Desnaturação de Ácido Nucleico , Oxirredução , Fotoquímica , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , ViscosidadeRESUMO
Copper (II) complex 1 having planar tridentate ligand, bzimpy, where bzimpy is 2,6-bis(benzimidazo-2-yl) pyridine was synthesized and characterized by UV-visible, FAB (fast atom bombardment) mass and infrared spectroscopy. From absorption titration data, the binding constant of Cu(II) with DNA was calculated to be (1.8+/-0.02)x10(4) M(-1). Thermal denaturation study of DNA with 1 revealed deltaT(m) of 5+/-0.5 degrees C. Viscosity measurement showed that complex binds with DNA through intercalative mode. Copper (II) complex induces cleavage in plasmid DNA in the presence of coreductants such as ascorbic acid or glutathione.
Assuntos
Cobre/química , DNA/metabolismo , Compostos Organometálicos/química , DNA/química , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Ligantes , Espectrometria de Massas , Desnaturação de Ácido Nucleico/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Oxirredução , Plasmídeos/química , Plasmídeos/metabolismo , Análise Espectral , TemperaturaRESUMO
[Ru(bzimpy)(2)]Cl(2), where bzimpy is 2,6-bis(benzimidazol-2-yl) pyridine was synthesized and characterized by ESI-MS, UV-Visible, (1)H NMR and fluorescence spectra. Absorption titration and thermal denaturation experiments indicate that the complex binds to DNA with moderate strength. Viscosity measurement shows that the mode of binding could be surface binding. Fluorescence study shows that the fluorescence intensity of the complex decreases with increasing concentrations of DNA, which is due to the photoelectron transfer from guanine base to (3)MLCT of the complex. Photoexcitation of the complex in the MLCT region in the presence of plasmid DNA has been found to give rise to nicking of DNA.
