Study of the Reactivity of Dinitrosyl Iron Complex of Glutathione (DNIC-GS) toward Superoxide Anion Radical (O2*-).

• Grant number: 24/08940-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2024
• End date: February 28, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Daniela Ramos Truzzi
• Grantee: Felipe Alves Garcia
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/17483-0 - Dinitrosyl iron complexes (DNICs): formation, reactivity, and implications for the physiopathology of nitric oxide, AP.JP
• Associated scholarship(s): 25/03508-2 - Spectroscopic Analysis of Dinitrosyl Iron Complexes of Glutathione (DNIC-GS) During One-Electron Redox Transitions, BE.EP.MS

Abstract

Nitric oxide (NO) is an inorganic neutral radical molecule produced endogenously through reaction catalyzed by the nitric oxide synthase (NOS) family of enzymes. In cells, NO participates in pathophysiological processes by reacting selectively with other radicals and transition metals. Among the main NO biological targets are superoxide anion radical (O2*-) and iron metal centers. The reaction between NO* and O2*- takes place at high speed ((0.4-1.9)109M-1s-1) generating peroxynitrite anion (ONOO) as product while the reaction between NO* and non-heme iron (present in iron-sulfur clusters and in labile iron pool, LIP), leads to the formation of dinitrosyl iron complexes (DNIC). These last are the most abundant NO* metabolites intracellularly (0.5-0.9 nmol/mg protein). Under inflammatory conditions, high levels of NO* and O2*- generate ONOO which decays through different mechanisms forming cytotoxic and pro-inflammatory radicals. In parallel, DNIC are also abundantly generated in inflammatory conditions. Based on that, this project aims to study the reaction between DNIC-GS and superoxide radical in an aqueous medium, determine the rate constant and characterize the products of this reaction. In addition, we intend to verifying whether the formation of DNIC results in the attenuation of oxidative damage via peroxynitrite in macrophages.