Reactivity of molecular oxygen with ethoxycarbonyl derivatives of tetrathiatriarylmethyl radicals

Shijing Xia, Frederick A. Villamena, Christopher M. Hadad, Periannan Kuppusamy, Yunbo Li, Hong Zhu, Jay L. Zweier

Research output: Contribution to journalArticle

Abstract

Tetrathiatriarylmethyl (TAM) radicals are commonly used as oximetry probes for electron paramagnetic resonance imaging applications. In this study, the electronic properties and the thermodynamic preferences for O2 addition to various TAM-type triarylmethyl (trityl) radicals were theoretically investigated. The radicals' stability in the presence of O2 and biological milieu was also experimentally assessed using EPR spectroscopy. Results show that H substitution on the aromatic ring affects the trityl radical's stability (tricarboxylate salt 1-CO2Na > triester 1-CO2Et > diester 2-CO2Et > monoester 3-CO 2Et) and may lead to substitution reactions in cellular systems. We propose that this degradation process involves an arylperoxyl radical that can further decompose to alcohol or quinone products. This study demonstrates how computational chemistry can be used as a tool to rationalize radical stability in the redox environment of biological systems and aid in the future design of more biostable trityl radicals.

Original languageEnglish (US)
Pages (from-to)7268-7279
Number of pages12
JournalJournal of Organic Chemistry
Volume71
Issue number19
DOIs
StatePublished - Sep 15 2006
Externally publishedYes

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ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Xia, S., Villamena, F. A., Hadad, C. M., Kuppusamy, P., Li, Y., Zhu, H., & Zweier, J. L. (2006). Reactivity of molecular oxygen with ethoxycarbonyl derivatives of tetrathiatriarylmethyl radicals. Journal of Organic Chemistry, 71(19), 7268-7279. https://doi.org/10.1021/jo0610560