Synthesis, characterization and study of nuclease activity of mono and bimetallic coordinating compounds of Fe(II), Zn(II) and Cu(I)
This thesis presents the synthesis and characterization of a series of both monometallic coordination compounds and homo-nuclear bimetallic helicates, derived from Fe(II), Zn(II) and Cu(I), with bi-coordinating and tetra-coordinating phenanthrolinic ligands, which are structurally related to each ot...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | Chile |
| OAI Identifier: | oai:repositorio.anid.cl:10533/246529 |
| Acceso en línea: | https://hdl.handle.net/10533/246529 |
| Access Level: | acceso abierto |
| Palabra clave: | Ciencias Naturales Ciencias Químicas Otras Especialidades de la Química |
| Sumario: | This thesis presents the synthesis and characterization of a series of both monometallic coordination compounds and homo-nuclear bimetallic helicates, derived from Fe(II), Zn(II) and Cu(I), with bi-coordinating and tetra-coordinating phenanthrolinic ligands, which are structurally related to each other. These compounds have been evaluated as artificial metallonucleases in plasmid DNA by gel electrophoresis experiments, where the nuclease-type activity is dependent on the nature of the metal ion and the nuclearity of the complex. The compounds studied interact with DNA through its minor groove or major groove. In general, bimetallic systems were more effective in inducing DNA cleavage, which is associated with the higher cationic charge and contact surface to interact with the biopolymer. Fe(II) and Cu(I) compounds showed higher nuclease-type activity compared to the Zn(II) compounds, which is related to the mechanism of action of these complexes. Gel electrophoresis and electron paramagnetic resonance experiments indicate that Fe(II) and Cu(I) compounds act through an oxidative mechanism on DNA, where reactive oxygen species (ROS) are generated in the presence of O2 and H2O2. In this regard, hydroxyl radical, •OH, is the main species responsible for DNA oxidation. The lower nuclease-type activity observed for the Zn(II) compounds, is because they operate through a hydrolytic mechanism on DNA. The ability of Zn(II) complexes to hydrolyze bis(p-nitrophenyl) phosphate (BNPP), a molecule analogous to the phosphate group in DNA, was confirmed by 31P-NMR spectroscopy, suggesting the hydrolysis of the phosphate group in DNA as a possible mechanism of action. |
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