A bioinspired nitrone precursor to a stabilized nitroxide radical

Author(s)

Pinheiro, Amanda Capistrano ^[1] ; Fazzi, Rodrigo Boni ^[1] ; Esteves, Larissa Cerrato ^[1] ; Machado, Caroline Oliveira ^[1] ; Dorr, Felipe Augusto ^[2] ; Pinto, Ernani ^[2] ; Hattori, Yocefu ^[3] ; Sa, Jacinto ^{[4, 3]} ; Ferreira, Ana Maria da Costa ^[1] ; Bastos, Erick Leite ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Quim, Dept Quim Fundamental, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, BR-05508000 Sao Paulo, SP - Brazil

^[3] Uppsala Univ, Dept Chem, Phys Chem Div, Angstrom Lab, S-75120 Uppsala - Sweden

^[4] Polish Acad Sci, Inst Phys Chem, PL-01224 Warsaw - Poland

• Document type: Journal article
• Source: Free Radical Biology and Medicine; v. 168, p. 110-116, MAY 20 2021.
• Web of Science Citations: 0

Abstract

Nitrones derived from natural antioxidants are emerging as highly specific therapeutics against various human diseases, including stroke, neurodegenerative pathologies, and cancer. However, the development of useful pseudo-natural nitrones requires the judicious choice of a secondary metabolite as the precursor. Betalains are nitrogen-containing natural pigments that exhibit marked antioxidant capacity and pharmacological properties and, hence, are ideal candidates for designing multifunctional nitrones. In this work, we describe the semisynthesis and properties of a biocompatible and antioxidant betalain-nitrone called OxiBeet. This bio-based compound is a better radical scavenger than ascorbic acid, gallic acid, and most non-phenolic antioxidants and undergoes concerted proton-coupled electron transfer. The autoxidation of OxiBeet produces a persistent nitroxide radical, which, herein, is studied via electron paramagnetic resonance spectroscopy. In addition, femtosecond transient absorption spectroscopy reveals that excited state formation is not required for the oxidation of OxiBeet. The results are compared with those obtained using betanin, a natural betalain, and pBeet, the imine analog of OxiBeet. The findings of this study will enable the development of antioxidant and spin-trap nitrones based on the novel N-oxide 1,7-diazaheptamethinium scaffold and betalain dyes with enhanced hydrolytic stability in aqueous alkaline media. (AU)

• FAPESP's process: 19/06391-8 - Photophysical characterization and anti-inflammatory potential of betalains
• Grantee: Erick Leite Bastos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/18474-4 - Functionalization of polysaccharides with photoresponsive betalains
• Grantee: Amanda Capistrano Pinheiro
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/15412-9 - Conjugates of flower pigments and silica: smart and biocompatible hybrid materials
• Grantee: Erick Leite Bastos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/22136-4 - Use of green solvents and their mixtures for optimizing chemical processes
• Grantee: Omar Abou El Seoud
• Support Opportunities: Research Projects - Thematic Grants