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

Fingerprint

Molecular oxygen
Derivatives
Paramagnetic resonance
Substitution reactions
Computational chemistry
Biological systems
Carbon Monoxide
Electronic properties
Salts
Alcohols
Spectroscopy
Thermodynamics
Imaging techniques
Degradation

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

Reactivity of molecular oxygen with ethoxycarbonyl derivatives of tetrathiatriarylmethyl radicals. / Xia, Shijing; Villamena, Frederick A.; Hadad, Christopher M.; Kuppusamy, Periannan; Li, Yunbo; Zhu, Hong; Zweier, Jay L.

In: Journal of Organic Chemistry, Vol. 71, No. 19, 15.09.2006, p. 7268-7279.

Research output: Contribution to journalArticle

Xia, S, Villamena, FA, Hadad, CM, Kuppusamy, P, Li, Y, Zhu, H & Zweier, JL 2006, 'Reactivity of molecular oxygen with ethoxycarbonyl derivatives of tetrathiatriarylmethyl radicals', Journal of Organic Chemistry, vol. 71, no. 19, pp. 7268-7279. https://doi.org/10.1021/jo0610560
Xia, Shijing ; Villamena, Frederick A. ; Hadad, Christopher M. ; Kuppusamy, Periannan ; Li, Yunbo ; Zhu, Hong ; Zweier, Jay L. / Reactivity of molecular oxygen with ethoxycarbonyl derivatives of tetrathiatriarylmethyl radicals. In: Journal of Organic Chemistry. 2006 ; Vol. 71, No. 19. pp. 7268-7279.
@article{78b9e4c84061414fae1fd9ff13d736f9,
title = "Reactivity of molecular oxygen with ethoxycarbonyl derivatives of tetrathiatriarylmethyl radicals",
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.",
author = "Shijing Xia and Villamena, {Frederick A.} and Hadad, {Christopher M.} and Periannan Kuppusamy and Yunbo Li and Hong Zhu and Zweier, {Jay L.}",
year = "2006",
month = "9",
day = "15",
doi = "10.1021/jo0610560",
language = "English (US)",
volume = "71",
pages = "7268--7279",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "19",

}

TY - JOUR

T1 - Reactivity of molecular oxygen with ethoxycarbonyl derivatives of tetrathiatriarylmethyl radicals

AU - Xia, Shijing

AU - Villamena, Frederick A.

AU - Hadad, Christopher M.

AU - Kuppusamy, Periannan

AU - Li, Yunbo

AU - Zhu, Hong

AU - Zweier, Jay L.

PY - 2006/9/15

Y1 - 2006/9/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33749003177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749003177&partnerID=8YFLogxK

U2 - 10.1021/jo0610560

DO - 10.1021/jo0610560

M3 - Article

VL - 71

SP - 7268

EP - 7279

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 19

ER -