Spectroscopic Analysis of Dinitrosyl Iron Complexes of Glutathione (DNIC-GS) During One-Electron Redox Transitions

• Grant number: 25/03508-2
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: August 27, 2025
• End date: February 26, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Daniela Ramos Truzzi
• Grantee: Felipe Alves Garcia
• Supervisor: Nicolai Lehnert
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Michigan, United States
• Associated to the scholarship: 24/08940-7 - Study of the Reactivity of Dinitrosyl Iron Complex of Glutathione (DNIC-GS) toward Superoxide Anion Radical (O2*-)., BP.MS

Abstract

Nitric oxide (NO*) plays key roles in both physiological and pathological processes, with its most abundant metabolite being dinitrosyl iron complexes (DNICs). Studies show that synthetic DNICs mediate functions like vasodilation, platelet aggregation, and carcinogenesis inhibition. In addition, the endogenous generation of DNICs have been correlated to reduction of cellular oxidative stress. In this context, the investigation of DNICs reactions with superoxide is particularly relevant in inflammation process generated during infections since it triggers the overproduction of both NO and superoxide radical. The excess NO leads to DNIC formation, but what exactly are the roles of DNICs in this context is still up for debate. Based on that, Felipe's master's degree project aims to investigate the reactivity of DNICs toward superoxide radical. Early data reveals that DNICs containing glutathione (DNIC-GS) or serum albumin (DNIC-SA) break down when exposed to superoxide radicals, potentially through three pathways: i) the addition of superoxide to DNIC forming a transient intermediate complex containing peroxynitrite as a ligand (Fe(ONOO)); ii) the oxidation of {Fe(NO)2}9 moiety to {Fe(NO)2}8 or iii) the reduction to {Fe(NO)2}10, since superoxide radical can act as reducing or oxidizing agent. Here stands the relevance of studying the spectroscopic properties of biological DNICs during one-electron redox transitions and the identification of byproducts formed in this process - this is the focus of our proposal. To achieve this, we plan to use IR spectroelectrochemistry and UV-Vis Spectroscopy with an immersion probe to track the spectroscopic changes of DNIC-GS during electrochemical and chemical one-electron redox transitions of the {Fe(NO)2}9 moiety at low temperature. The collect data will help lay the groundwork for characterizing the intermediates formed during the reaction between DNICs and superoxide.