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Previous issue date: 2016-09-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The superoxide anion is among the reactive oxygen species closely related to physiopathological states associated with oxidative stress. The physiological superoxide levels are controlled in vivo by the superoxide dismutase enzymes (SOD). Pentacationic Mn porphyrins derived from 2-N-alkylpyridylporphyrins have been explored as potent SOD mimics and efficient redox modulators of oxidative stress. The in vivo efficiency of these compounds is related with their intrinsic catalytic activity, lipophilicity, bioavailability, and toxicity. The present study describes the synthesis of two A3B-type neutral porphyrins of low symmetry (A = 2-pyridyl, B = 3-methoxy-4-hydroxyphenyl or 3,4-dimethoxyphenyl), the methylation of these compounds to yield tricationic porphyrins and the preparation of the corresponding tetracationic Mn(III) porphyrins; overall, 8 new compounds are described: 5-(3-methoxy-4-hydroxyphenyl)-10,15,20-tris(2-pyridyl)porphyrin (H2VanTri-2-PyP), 5-(3,4-dimethoxyphenyl)-10,15,20-tris(2-pyridyl)porphyrin (H2MVanTri-2-PyP), 5-(3-methoxy-4-hydroxyphenyl)-10,15,20-tris(N-methylpiridinium-2-yl)porphyrin chloride (H2VanTriM-2-PyPCl3), 5-(3,4-dimethoxyphenyl)-10,15,20-tris(N-methylpiridinium-2-yl)porphyrin chloride (H2MVanTriM-2-PyPCl3), 5-(3-methoxy-4-hydroxyphenyl)-10,15,20-tris(2-pyridyl)porphinatomanganese(III) (MnVanTri-2-PyPCl), 5-(3,4-dimethoxyphenyl)-10,15,20-tris(2-pyridyl)porphinatomanganese(III) chloride (MnMVanTri-2-PyPCl), 5-(3-methoxy-4-hydroxyphenyl)-10,15,20-tris(N-methylpiridinium-2-yl)porphinatomanganese(III) chloride (MnVanTriM-2-PyPCl4) and 5-(3,4-dimethoxyphenyl)-10,15,20-tris(N-methylpiridinium-2-yl)porphinatomanganese(III) chloride (MnMVanTriM-2-PyPCl4). The spectroscopic, electrochemical properties and lipophilicity of all compounds were compared with A4-type 2-N-pyridyl porphyrin analogues. The monocationic compounds MnVanTri-2-PyP+ and MnMVanTri-2-PyP+ showed too low Mn(III)/Mn(II) reduction potential incompatible with superoxide dismuting activity, whereas the tetracationic complexes MnVanTriM-2-PyP4+ and MnMVanTriM-2-PyP4+ showed potential values suitable for the development these compounds as SOD mimics based on structure-activity relationships reported for analogous systems. The lipophilicity of MnVanTriM-2-PyP4+ and da MnMVanTriM-2-PyP4+ suggests promising bioavailability for in vitro and in vivo testing. / O ânion radical superóxido constitui uma das espécies reativas de oxigênio intimamente relacionada a estados fisiopatológicos associados ao estresse oxidativo. Os níveis fisiológicos do superóxido são controlados in vivo pelas enzimas Superóxido Dismutases (SOD). Mn-porfirinas pentacatiônicas derivadas das 2-N-alquilpiridilporfirinas têm se destacado como mímicos potentes das enzimas SOD e, por sua vez, potentes moduladores redox de estresse oxidativo. A eficiência in vivo destes compostos está relacionada à atividade catalítica intrínseca, à lipofilicidade, à biodisponibilidade e à toxicidade. No presente estudo, descreve-se a síntese de 2 porfirinas neutras de baixa simetria do tipo A3B (A = 2-piridil, B = 3-metoxi-4-hidroxifenil ou 3,4-dimetoxifenil), a metilação destes compostos para obtenção de porfirinas tricatiônicas e a preparação das Mn(III) porfirinas tetracatiônicos correspondentes; ao todo são descritos 8 compostos inéditos: 5-(3-metoxi-4-hidroxifenil)-10,15,20-tris(2-piridil)porfirina (H2VanTri-2-PyP), 5-(3,4-dimetoxifenil)-10,15,20-tris(2-piridil)porfirina (H2MVanTri-2-PyP), cloreto de 5-(3-metoxi-4-hidroxifenil)-10,15,20-tris(N-metilpiridinio-2-il)porfirina (H2VanTriM-2-PyPCl3), cloreto de 5-(3,4-dimetoxifenil)-10,15,20-tris(N-metilpiridinio-2-il)porfirina (H2MVanTriM-2-PyPCl3), cloreto de 5-(3-metoxi-4-hidroxifenil)-10,15,20-tris(2-piridil)porfirinatomanganês(III) (MnVanTri-2-PyPCl), cloreto de 5-(3,4-dimetoxifenil)-10,15,20-tris(2-piridil)porfirinatomanganês(III) (MnMVanTri-2-PyPCl), cloreto de 5-(3-metoxi-4-hidroxifenil)-10,15,20-tris(N-metilpiridinio-2-il)porfirinatomanganês(III) (MnVanTriM-2-PyPCl4) e cloreto de 5-(3,4-dimetoxifenil)-10,15,20-tris(N-metilpiridinio-2-il)porfirinatomanganês(III) (MnMVanTriM-2-PyPCl4). As propriedades espectroscópicas, eletroquímicas e de lipofilicidade de todos os compostos foram comparadas com os derivados das 2-N-piridilporfirinas análogas do tipo A4. Os complexos monocatiônicos MnVanTri-2-PyP+ e MnMVanTri-2-PyP+ apresentam potenciais de redução Mn(III)/Mn(II) muito baixos para catalisarem a dismutação do superóxido, enquanto os complexos tetracatiônicos MnVanTriM-2-PyP4+ e MnMVanTriM-2-PyP4+ apresentaram potenciais apropriados para o desenvolvimento de mímicos SOD com base nas relações estrutura-atividade reportadas para sistemas correlatos. A lipofilicidade da MnVanTriM-2-PyP4+ e da MnMVanTriM-2-PyP4+ sugere que os compostos têm biodisponibilidade promissora para testes in vitro e in vivo.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede.biblioteca.ufpb.br:tede/8985 |
| Date | 15 September 2016 |
| Creators | Sarmento Neto, José Ferreira |
| Contributors | Rebouças, Júlio Santos |
| Publisher | Universidade Federal da Paraíba, Programa de Pós-Graduação em Química, UFPB, Brasil, Química |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFPB, instname:Universidade Federal da Paraíba, instacron:UFPB |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1435648362225100898, 600, 600, 600, 600, 9054006085480167889, 1571700325303117195, 2075167498588264571 |
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