RESUMO
DNA condensing agents play a critical role in gene therapy. A tetranuclear nickel(II) complex, [Ni(II)(4)(L-2H)(H(2)O)(6)(CH(3)CH(2)OH)(2)]·6NO(3) (L=3,3',5,5'-tetrakis{[(2-hydroxyethyl)(pyridin-2-ylmethyl)amino]methyl}biphenyl-4,4'-diol), has been synthesized as a nonviral vector to induce DNA condensation. X-ray crystallographic data indicate that the complex crystallizes in the monoclinic system with space group P2(1)/n, a=10.291(9), b=24.15(2), c=13.896(11) Å, and ß=98.175(13)°. The DNA condensation induced by the complex has been investigated by means of UV/Vis spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, dynamic light scattering, atomic force microscopy, gel electrophoresis assay, and zeta potential analysis. The complex interacts strongly with DNA through electrostatic attraction and induces its condensation into globular nanoparticles at low concentration. The release of DNA from its compact state has been achieved using the chelator ethylenediaminetetraacetic acid (EDTA) for the first time. Other essential properties, such as DNA cleavage inactivity and biocompatibility, have also been examined in vitro. In general, the complex satisfies the requirements of a gene vector in all of these respects.
Assuntos
DNA/química , Vetores Genéticos/química , Níquel/química , Compostos Organometálicos/química , Animais , Cristalografia por Raios X , Clivagem do DNA , Eletroquímica , Ligantes , Estrutura Molecular , Espectrofotometria UltravioletaRESUMO
Copper-based artificial metallonucleases are likely to satisfy more biomedical requirements if their DNA cleavage efficiency and selectivity could be further improved. In this study, two copper(II) complexes, [CuL(1)Cl(2)] (1) and [CuL(2)Cl(2)] (2), and two copper(II)-platinum(II) heteronuclear complexes, [CuPtL(1)(DMSO)Cl(4)] (3) and [CuPtL(2)(DMSO)Cl(4)] (4), were synthesized using two bifunctional ligands, N-[4-(2-pyridylmethoxy)benzyl]-N,N-bis(2-pyridylmethyl)amine (L(1)) and N-[3-(2-pyridylmethoxy)benzyl]-N,N-bis(2-pyridylmethyl)amine (L(2)). These complexes have been characterized by elemental analysis, electrospray ionization mass spectrometry, IR spectroscopy, and UV-vis spectroscopy. The DNA binding ability of these complexes follows an order of 1 < 2 < 3 < 4, as revealed by the results of spectroscopy and agarose gel electrophoresis studies. Their cleavage activity toward supercoiled pUC19 plasmid DNA is prominent at micromolar concentration levels in the presence of ascorbic acid. The introduction of a platinum(II) center to the copper(II) complexes induces a significant enhancement in cleavage activity as compared with copper(II) complexes alone. These results show that the presence of a platinum(II) center in copper(II) complexes strengthens both their DNA binding ability and DNA cleavage efficiency.
Assuntos
Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Cobre/química , DNA/metabolismo , Desoxirribonucleases/química , Desoxirribonucleases/metabolismo , Platina/química , Animais , Bovinos , Desenho de Fármacos , Isomerismo , Cinética , Ligantes , Metilaminas/química , Piridinas/química , Espécies Reativas de Oxigênio/metabolismo , Análise EspectralRESUMO
Interaction of DNA with a novel photoactive platinum diimine compound has been studied by electronic absorption spectra, fluorescence spectra and viscosity measurements. The red light-induced DNA cleavage activity of the platinum compound has also been studied by agarose gel electrophoresis. The results suggest that the platinum compound may interact with DNA by intercalation mode. When irradiated with red light, the platinum compound can generate singlet oxygen, resulting in cleavage of DNA.
Assuntos
Iminas/química , Iminas/síntese química , Fármacos Fotossensibilizantes/síntese química , Animais , Bovinos , DNA/química , Substâncias Intercalantes/farmacologia , Cinética , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Conformação de Ácido Nucleico/efeitos dos fármacos , Oxigênio/química , Fotoquímica/métodos , Fármacos Fotossensibilizantes/química , Platina/química , Espectrometria de Fluorescência/métodos , ViscosidadeRESUMO
Terpyridine/benzofurazan conjugation results in a new hybrid fluorophore of the colorimetric sensing ability for Fe(2+) and fluorimetric sensing ability for XII group cations. The improved emission properties and cell imaging ability imply it is a suitable platform to construct a fluorescent sensor for metal imaging in biological systems.