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Synthesis, Characterization, and Application of a Highly Hydrophilic Triarylmethyl Radical for Biomedical EPR
journal contribution
posted on 2020-08-06, 22:10 authored by Urikhan Sanzhaeva, Martin Poncelet, Oxana Tseytlin, Mark Tseytlin, Marieta Gencheva, Timothy D. Eubank, Valery V. Khramtsov, Benoit DriesschaertStable tetrathiatriarylmethyl
radicals have significantly contributed to the recent progress in
biomedical electron paramagnetic resonance (EPR) due to their unmatched
stability in biological media and long relaxation times. However,
the lipophilic core of the most commonly used structure (Finland trityl)
is responsible for its interaction with plasma biomacromolecules,
such as albumin, and self-aggregation at high concentrations and/or
low pH. While Finland trityl is generally considered inert toward
many reactive radical species, we report that sulfite anion radical efficiently substitutes the three carboxyl moieties of Finland trityl
with a high rate constant of 3.53 × 108 M–1 s–1, leading to a trisulfonated Finland trityl
radical. This newly synthesized highly hydrophilic trityl radical
shows an ultranarrow linewidth (ΔBpp = 24 mG), a lower affinity for albumin than Finland trityl, and
a high aqueous solubility even at acidic pH. Therefore, this new tetrathiatriarylmethyl
radical can be considered as a superior spin probe in comparison to
the widely used Finland trityl. One of its potential applications
was demonstrated by in vivo mapping oxygen in a mouse
model of breast cancer. Moreover, we showed that one of the three
sulfo groups can be easily substituted with S-, N-, and P-nucleophiles,
opening access to various monofunctionalized sulfonated trityl radicals.