Novel Ruthenium‐based Nitrosyl Complexes: NO Donation and Vasorelaxant Potentials for Cardiovascular Therapeutics

Author:

Gouveia Júnior Florêncio S.1ORCID,de Sousa Allandeiverson S.1ORCID,da Silva Renally B.2,Rocha Danilo G.34,Teixeira Edson H.2ORCID,Odorico de Moraes Filho Manoel34,Jamacaru Francisco Vagnaldo F.34,Serra Azul Monteiro Helena34ORCID,Jorge Roberta Jeane B.34ORCID,Wink David A.5ORCID,de Sousa Eduardo Henrique S.1,de F. Lopes Luiz Gonzaga1ORCID

Affiliation:

1. Department of Organic and Inorganic Chemistry Federal University of Ceara Campus do Pici 60455-760 Fortaleza CE Brazil

2. Departament of Pathology and Legal Medicine Federal University of Ceara Campus do Porangabussu 60430-270 Fortaleza CE Brazil

3. Department of Physiology and Pharmacology Federal University of Ceara Coronel Nunes de Melo St., 1127 60.430-275 Fortaleza CE Brazil.

4. Drug Research and Development Center Federal University of Ceara Coronel Nunes de Melo St., 1000 60.430-275 Fortaleza CE Brazil.

5. Cancer and Inflammation Program National Cancer Institute Ft. Detrick Frederick MD 21702 United States

Abstract

AbstractNitrosyl ruthenium complexes have emerged as promising platforms for the controlled delivery of nitric oxide (NO) and nitroxyl (HNO), both of which possess significant therapeutic implications. Considering this scenario, we synthesized and characterized the metal complex cis‐[RuNO(phen)2(2MIM)]3+ and its precursors, where phen and 2MIM correspond to 1,10‐phenantroline and 2‐methylimidazole, respectively. Comprehensive structural elucidation was undertaken using a combination of spectroscopic and electrochemical methodologies, including XANES/EXAFS experiments. This structural data was further validated through DFT computational analyses. We demonstrated that such compound can release NO and HNO in the presence of thiol‐based substrates. Not only this, but the same metal complex can also delivery nitric oxide under irradiation with visible light (λ=460 nm). The nitrosyl complex and its derivatives displayed marked vasodilatory capabilities as evidenced in assays involving isolated rat aorta rings. They also exhibited commendable antioxidant activity in free radical scavenging assays. Collectively, based on these data, this nitrosyl ruthenium compound is a potential therapeutic candidate, especially in the field of cardiovascular pathology like atherosclerosis, thereby deserving further in‐depth investigations.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico

Publisher

Wiley

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