Organic Chemistry

Design of an Antioxidant Nitrone Scaffold Based on Plant Pigments

Abstract

Nitrones derived from natural antioxidants are emerging as highly specific therapeutics for the treatment of 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 precursor. Betalains are nitrogen-containing natural pigments that exhibit marked antioxidant and pharmacological properties and, hence, are ideal candidates for the design of multifunctional nitrones. In this work, we describe the semisynthesis and properties of a biocompatible and antioxidant betalain-nitrone named 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 gives rise to a persistent nitroxide radical, which was studied by electron paramagnetic resonance spectroscopy. 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 analogue of OxiBeet. The findings in this study will enable the development of antioxidant nitrones based on the novel N-oxide 1,7-diazaheptamethinium scaffold and betalain dyes with enhanced hydrolytic stability in aqueous alkaline media.

Version notes

v.1. Manuscript submitted for publication.

Content

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Supplementary material

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Pinheiro SI ChemRxiv