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Photoinduced electron transfer of sensitizers under nitrosyl ruthenium complexes to nitric oxide production: photochemical, photophysical studies and citotoxic activity measurements

Grant number: 07/06704-9
Support type:Regular Research Grants
Duration: April 01, 2008 - March 31, 2010
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Roberto Santana da Silva
Grantee:Roberto Santana da Silva
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

AbstractNitric oxide (NO) is a multipurpose biological agent that shows important role in brain, arteries, immunological system, liver and lungs. The NO basal level alterations have correlation with several diseases as hypertension, cancer, Raymond's disease and platelet aggregation. Aiming to supply the NO deficiency that becomes important to produce compounds that can release NO in a controlled way. Among several different possibilities are nitrosyl ruthenium complexes a system that can deliver NO by external stimulation once those complexes seems to be thermodynamically stable but labile by light irradiation or electrochemical reduction. Compounds that can absorb light on the therapeutic window and permit photoinduced electron transfer could induce nitric oxide release from nitrosyl ruthenium complexes. Based on this that we are suggest to use [Ru(pz)(Pc)(pz)Ru(bpy)2NO]+, [Ru(pz)(Pc)(pz){Ru(bpy)2NO}2]4+ e [RuCl(dcbpy)2(NO)]2[Tb(TsPc)(acac)] (pz = pirazine, pc = ftalocyanine; bpy = 2,2 bipiridine as precursor agents of reactive oxygen and nitrogen species by light irradiation on 500 nm to 700 nm. Studies involving electron and energy transfer between the nitrosyl and chromophore specie will be developed by UV-visible spectrum, phluorescence and the NO release will be evaluated by a amperometric sensor (ISO-NO), developed by World Precision Intruments.AbstractNitric oxide (NO) is a multipurpose biological agent that shows important role in brain, arteries, immunological system, liver and lungs. The NO basal level alterations have correlation with several diseases as hypertension, cancer, Raymond's disease and platelet aggregation. Aiming to supply the NO deficiency that becomes important to produce compounds that can release NO in a controlled way. Among several different possibilities are nitrosyl ruthenium complexes a system that can deliver NO by external stimulation once those complexes seems to be thermodynamically stable but labile by light irradiation or electrochemical reduction. Compounds that can absorb light on the therapeutic window and permit photoinduced electron transfer could induce nitric oxide release from nitrosyl ruthenium complexes. Based on this that we are suggest to use [Ru(pz)(Pc)(pz)Ru(bpy)2NO]+, [Ru(pz)(Pc)(pz){Ru(bpy)2NO}2]4+ e [RuCl(dcbpy)2(NO)]2[Tb(TsPc)(acac)] (pz = pirazine, pc = ftalocyanine; bpy = 2,2 bipiridine as precursor agents of reactive oxygen and nitrogen species by light irradiation on 500 nm to 700 nm. Studies involving electron and energy transfer between the nitrosyl and chromophore specie will be developed by UV-visible spectrum, phluorescence and the NO release will be evaluated by a amperometric sensor (ISO-NO), developed by World Precision Intruments.After that the cytotoxic activity by a photodynamic therapy viewpoint will be evaluated based on the fact that those species produce nitric oxide and singlet oxygen at the same time. Also photochemical and photophysical studies will be developed in relation to production of reactive oxygen and nitrogen species in aqueous solution and also in lipossomal conditions. (AU)