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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Author: Levín Vásquez, Pedro Andrés
Format: doctoral thesis
Status:Published version
Publication Date:2020
Country:Chile
OAI Identifier:oai:repositorio.anid.cl:10533/246529
Online Access:https://hdl.handle.net/10533/246529
Access Level:Open access
Keyword:Ciencias Naturales
Ciencias Químicas
Otras Especialidades de la Química
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dc.title.es_CL.fl_str_mv Synthesis, characterization and study of nuclease activity of mono and bimetallic coordinating compounds of Fe(II), Zn(II) and Cu(I)
Síntesis, caracterización y estudio de la actividad nucleasa de compuestos de coordinación mono y bimetálicos de Fe(II), Zn(II) y Cu(I)
title Synthesis, characterization and study of nuclease activity of mono and bimetallic coordinating compounds of Fe(II), Zn(II) and Cu(I)
spellingShingle Synthesis, characterization and study of nuclease activity of mono and bimetallic coordinating compounds of Fe(II), Zn(II) and Cu(I)
Levín Vásquez, Pedro Andrés
Ciencias Naturales
Ciencias Químicas
Otras Especialidades de la Química
title_short Synthesis, characterization and study of nuclease activity of mono and bimetallic coordinating compounds of Fe(II), Zn(II) and Cu(I)
title_full Synthesis, characterization and study of nuclease activity of mono and bimetallic coordinating compounds of Fe(II), Zn(II) and Cu(I)
title_fullStr Synthesis, characterization and study of nuclease activity of mono and bimetallic coordinating compounds of Fe(II), Zn(II) and Cu(I)
title_full_unstemmed Synthesis, characterization and study of nuclease activity of mono and bimetallic coordinating compounds of Fe(II), Zn(II) and Cu(I)
title_sort Synthesis, characterization and study of nuclease activity of mono and bimetallic coordinating compounds of Fe(II), Zn(II) and Cu(I)
dc.creator.none.fl_str_mv Levín Vásquez, Pedro Andrés
author Levín Vásquez, Pedro Andrés
author_facet Levín Vásquez, Pedro Andrés
author_role author
dc.contributor.advisor.none.fl_str_mv Lemus Chávez, Luis Lemus
Pavez Irrazabal, Jorge Enrique
dc.contributor.institution.es_CL.fl_str_mv UNIVERSIDAD DE SANTIAGO DE CHILE
dc.subject.oecd1n.es_CL.fl_str_mv Ciencias Naturales
topic Ciencias Naturales
Ciencias Químicas
Otras Especialidades de la Química
dc.subject.oecd2n.es_CL.fl_str_mv Ciencias Químicas
dc.subject.oecd3n.es_CL.fl_str_mv Otras Especialidades de la Química
description 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.
publishDate 2020
dc.date.issued.es_CL.fl_str_mv 2020
dc.date.accessioned.none.fl_str_mv 2021-02-18T12:55:22Z
2022-08-16T16:44:33Z
dc.date.available.none.fl_str_mv 2021-02-18T12:55:22Z
2022-08-16T16:44:33Z
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dc.type.tesis.none.fl_str_mv Tesis
format doctoralThesis
status_str publishedVersion
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spelling UNIVERSIDAD DE SANTIAGO DE CHILELevín Vásquez, Pedro Andrés2020https://hdl.handle.net/10533/246529http://purl.org/coar/access_right/c_abf2Otras Especialidades de la QuímicaCiencias QuímicasCiencias NaturalesSynthesis, characterization and study of nuclease activity of mono and bimetallic coordinating compounds of Fe(II), Zn(II) and Cu(I)Lemus Chávez, Luis LemusPavez Irrazabal, Jorge EnriqueUNIVERSIDAD DE SANTIAGO DE CHILEChileLevín Vásquez, Pedro Andrés2021-02-18T12:55:22Z2022-08-16T16:44:33Z2021-02-18T12:55:22Z2022-08-16T16:44:33Z2020This 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.Esta tesis presenta la síntesis y caracterización de una serie de compuestos de coordinación monometálicos y helicatos bimetálicos homo-nucleares de Fe(II), Zn(II) y Cu(I) con ligandos bi-coordinantes y tetra-coordinantes derivados de fenantrolina, los cuales son estructuralmente relacionados entre sí. Estos compuestos han sido evaluados como metalonucleasas artificiales frente a ADN plasmidial mediante experimentos de electroforesis en gel, siendo la actividad del tipo nucleasa dependiente de la naturaleza del ión metálico y la nuclearidad del complejo. Los compuestos estudiados interactúan con ADN a través de su surco menor o surco mayor, y en general, los sistemas bimetálicos fueron más eficaces para inducir la ruptura del ADN, lo cual está asociado a la mayor carga catiónica y superficie de contacto para interactuar con el biopolímero. Los compuestos de Fe(II) y Cu(I) presentaron mayor actividad del tipo nucleasa en comparación a los compuestos de Zn(II), lo que está asociado al mecanismo de acción de los complexos. Experimentos de electroforesis en gel y de resonancia paramagnética electrónica, indican que los compuestos de Fe(II) y Cu(I) actúan mediante un mecanismo oxidativo sobre el ADN, donde especies reactivas de oxígeno (ERO) son generadas en presencia de O2 y H2O2. Respecto a esto, radical hidroxilo, •OH, es la principal especie responsable de la oxidación del ADN. La menor actividad del tipo nucleasa observada en los compuestos de Zn(II) se debe a que estos operan mediante un mecanismo hidrolítico sobre el ADN. La capacidad que presentaron los compuestos de Zn(II) para hidrolizar bis(p-nitrofenil) fosfato (BNPP), una molécula análoga al grupo fosfato en el ADN, fue confirmado mediante espectroscopia de RMN-31P, lo que sugiere la posible hidrólisis del grupo fosfato en el ADN como mecanismo de acción.21160546https://hdl.handle.net/10533/246529instname: Conicytreponame: Repositorio Digital RI2.0info:eu-repo/grantAgreement//21160546info:eu-repo/semantics/dataset/hdl.handle.net/10533/93488info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivs 3.0 Chilehttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/Ciencias NaturalesCiencias QuímicasOtras Especialidades de la QuímicaSynthesis, characterization and study of nuclease activity of mono and bimetallic coordinating compounds of Fe(II), Zn(II) and Cu(I)Síntesis, caracterización y estudio de la actividad nucleasa de compuestos de coordinación mono y bimetálicos de Fe(II), Zn(II) y Cu(I)info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionTesisTesishttps://hdl.handle.net/10533/246529adb2b395-d39b-42f4-a63d-e7eb6f6767abvirtual::48869-1adb2b395-d39b-42f4-a63d-e7eb6f6767abvirtual::48869-1THUMBNAILLevin_Vasquez_Pedro_Andres.pdf.jpgIM Thumbnailimage/jpeg3315https://repositorio.anid.cl/bitstreams/a85755e0-4d06-4007-b600-875a8cfc42a2/download4e9e37505efdf58f5e6da49968c01ffeMD51TEXTLevin_Vasquez_Pedro_Andres.pdf.txtExtracted texttext/plain298222https://repositorio.anid.cl/bitstreams/4e151359-7be0-4912-bb6b-1ef28f223836/download2a1530eb6ddb346b268bbb4d7288a546MD52CC-LICENSElicense_rdfapplication/octet-stream1232https://repositorio.anid.cl/bitstreams/c5a38af5-f278-481f-b000-d0e76bf9c423/downloadf97bcfdf58f3e17b5cec231112dab5b1MD53LICENSElicense.txttext/plain1779https://repositorio.anid.cl/bitstreams/a166b125-8d1f-4ba8-a935-2d7cfdb58c92/download593a6e7305c66c56041a9f9e15a649c1MD54ORIGINALLevin_Vasquez_Pedro_Andres.pdfTesisapplication/pdf6622493https://repositorio.anid.cl/bitstreams/901d706c-79cc-4922-a4d2-e19da5fba778/download54772a2f311a7545a15f93eef26d193dMD5510533/246529oai:repositorio.anid.cl:10533/2465292023-07-24 08:47:35.565http://creativecommons.org/licenses/by-nc-nd/3.0/cl/info:eu-repo/semantics/openAccesshttps://repositorio.anid.clRepositorio ANIDaletelier@anid.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