Esterified dendritic TAM radicals with very high stability and enhanced oxygen sensitivity

Yuguang Song, Yangping Liu, Craig Hemann, Frederick A. Villamena, Jay L. Zweier

Research output: Contribution to journalArticle

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 O2 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.

Original languageEnglish (US)
Pages (from-to)1371-1376
Number of pages6
JournalJournal of Organic Chemistry
Volume78
Issue number4
DOIs
StatePublished - Feb 15 2013
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry

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