Esterified Dendritic TAM
Radicals with Very High Stability
and Enhanced Oxygen Sensitivity
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Abstract
In this work, we have developed a new class of dendritic
TAM radicals
(TG, TdG, and dTdG) through a convergent method based on the TAM core
CT-03 or its deuterated analogue dCT-03 and trifurcated Newkome-type
monomer. Among these radicals, dTdG exhibits the best EPR properties
with sharpest EPR singlet and highest O<sub>2</sub> sensitivity due
to deuteration of both the ester linker groups and the TAM core CT-03.
Like the previous dendritic TAM radicals, these new compounds also
show extremely high stability toward various reactive species owing
to the dendritic encapsulation. The highly charged nature of these
molecules resulting from nine carboxylate groups prevents concentration-dependent
EPR line broadening at physiological pH. Furthermore, we demonstrate
that these TAM radicals can be easily derivatized (e.g., PEGylation)
at the nine carboxylate groups and the resulting PEGylated analogue
dTdG–PEG completely inhibits the albumin binding, thereby enhancing
suitability for in vivo applications. These new dendritic TAM radicals
show great potential for in vivo EPR oximetric applications and provide
insights on approaches to develop improved and targeted EPR oximetric
probes for biomedical applications