Synthesis and Characterization of Ester-Derivatized Tetrathiatriarylmethyl Radicals as Intracellular Oxygen Probes

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.