Synthesis and characterization of ester-derivatized tetrathiatriarylmethyl radicals as intracellular oxygen probes

Yangping Liu; Frederick A. Villamena; Jian Sun; Yingkai Xu; Ilirian Dhimitruka; Jay L. Zweier

doi:10.1021/jo7022747

Synthesis and characterization of ester-derivatized tetrathiatriarylmethyl radicals as intracellular oxygen probes

Yangping Liu, Frederick A. Villamena, Jian Sun, Yingkai Xu, Ilirian Dhimitruka, Jay L. Zweier

Research output: Contribution to journal › Article › peer-review

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Abstract

(Chemical Equation Presented) Electron paramagnetic resonance (EPR) spectroscopy using paramagnetic probes has been employed as an important tool for the accurate determination of oxygen (O₂) concentrations in biological systems. However, paramagnetic probes are still limited by their intracellular penetrability. Various esterified trityl derivatives were synthesized and characterized, and an X-ray structure of one of the triyl radicals was determined. The ester-derivatized trityls exhibited higher sensitivity to O₂ concentration compared to the trityl tricarboxylate CT-03. Cyclic voltammetry was also carried out to assess the susceptibility of the trityl radicals to oxidation and reduction. Among all of the ester-derivatized trityls studied, facile hydrolysis of the acetoxymethoxy esters to the respective carboxylate was observed using porcine liver esterase. This study demonstrates that cellular permeability of the trityl radicals can be achieved by varying the type and number of ester groups. Therefore, ester-derivatized trityl radicals show great potential as intracellular EPR oximetry probes and imaging agents.

Original language	English (US)
Pages (from-to)	1490-1497
Number of pages	8
Journal	Journal of Organic Chemistry
Volume	73
Issue number	4
DOIs	https://doi.org/10.1021/jo7022747
State	Published - Feb 15 2008
Externally published	Yes

ASJC Scopus subject areas

Organic Chemistry

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title = "Synthesis and characterization of ester-derivatized tetrathiatriarylmethyl radicals as intracellular oxygen probes",

abstract = "(Chemical Equation Presented) Electron paramagnetic resonance (EPR) spectroscopy using paramagnetic probes has been employed as an important tool for the accurate determination of oxygen (O2) concentrations in biological systems. However, paramagnetic probes are still limited by their intracellular penetrability. Various esterified trityl derivatives were synthesized and characterized, and an X-ray structure of one of the triyl radicals was determined. The ester-derivatized trityls exhibited higher sensitivity to O2 concentration compared to the trityl tricarboxylate CT-03. Cyclic voltammetry was also carried out to assess the susceptibility of the trityl radicals to oxidation and reduction. Among all of the ester-derivatized trityls studied, facile hydrolysis of the acetoxymethoxy esters to the respective carboxylate was observed using porcine liver esterase. This study demonstrates that cellular permeability of the trityl radicals can be achieved by varying the type and number of ester groups. Therefore, ester-derivatized trityl radicals show great potential as intracellular EPR oximetry probes and imaging agents.",

author = "Yangping Liu and Villamena, {Frederick A.} and Jian Sun and Yingkai Xu and Ilirian Dhimitruka and Zweier, {Jay L.}",

year = "2008",

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doi = "10.1021/jo7022747",

language = "English (US)",

volume = "73",

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T1 - Synthesis and characterization of ester-derivatized tetrathiatriarylmethyl radicals as intracellular oxygen probes

AU - Liu, Yangping

AU - Villamena, Frederick A.

AU - Sun, Jian

AU - Xu, Yingkai

AU - Dhimitruka, Ilirian

AU - Zweier, Jay L.

PY - 2008/2/15

Y1 - 2008/2/15

N2 - (Chemical Equation Presented) Electron paramagnetic resonance (EPR) spectroscopy using paramagnetic probes has been employed as an important tool for the accurate determination of oxygen (O2) concentrations in biological systems. However, paramagnetic probes are still limited by their intracellular penetrability. Various esterified trityl derivatives were synthesized and characterized, and an X-ray structure of one of the triyl radicals was determined. The ester-derivatized trityls exhibited higher sensitivity to O2 concentration compared to the trityl tricarboxylate CT-03. Cyclic voltammetry was also carried out to assess the susceptibility of the trityl radicals to oxidation and reduction. Among all of the ester-derivatized trityls studied, facile hydrolysis of the acetoxymethoxy esters to the respective carboxylate was observed using porcine liver esterase. This study demonstrates that cellular permeability of the trityl radicals can be achieved by varying the type and number of ester groups. Therefore, ester-derivatized trityl radicals show great potential as intracellular EPR oximetry probes and imaging agents.

AB - (Chemical Equation Presented) Electron paramagnetic resonance (EPR) spectroscopy using paramagnetic probes has been employed as an important tool for the accurate determination of oxygen (O2) concentrations in biological systems. However, paramagnetic probes are still limited by their intracellular penetrability. Various esterified trityl derivatives were synthesized and characterized, and an X-ray structure of one of the triyl radicals was determined. The ester-derivatized trityls exhibited higher sensitivity to O2 concentration compared to the trityl tricarboxylate CT-03. Cyclic voltammetry was also carried out to assess the susceptibility of the trityl radicals to oxidation and reduction. Among all of the ester-derivatized trityls studied, facile hydrolysis of the acetoxymethoxy esters to the respective carboxylate was observed using porcine liver esterase. This study demonstrates that cellular permeability of the trityl radicals can be achieved by varying the type and number of ester groups. Therefore, ester-derivatized trityl radicals show great potential as intracellular EPR oximetry probes and imaging agents.

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Synthesis and characterization of ester-derivatized tetrathiatriarylmethyl radicals as intracellular oxygen probes

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