Synthesis and biological testing of aminoxyls designed for long-term retention by living cells

Gerald M. Rosen, Scott R. Burks, Mark J. Kohr, Joseph P.Y. Kao

Research output: Contribution to journalArticlepeer-review

Abstract

Owing to recent advances in electron paramagnetic resonance (EPR) imaging methodologies, it is now potentially possible to track and image, in real time in vivo, cells that had been tagged with aminoxyl spin probes. We had previously reported that living cells can accumulate 3-carboxy-2,2,5,5-tetramethyl-1- pyrrolidinyloxyl to high (millimolar) intracellular concentrations through passive incubation with the corresponding acetoxymethyl (AM) ester. In the present study, we show that under physiological conditions aminoxyl is rapidly extruded by cells through an organic anion transport mechanism, resulting in an intracellular exponential lifetime (t1/e or τ) of just 9.84 min at 37°C. Through successive rational structural modifications, we arrived at (2,2,5,5-tetramethylpyrrolidin-1-oxyl-3-ylmethyl)amine-N,N-diacetic acid, which can still be accumulated by cells to high intracellular concentrations, but which, with an intracellular exponential lifetime of τ = 114 min, is well retained by cells for long periods of time, where one expects 14% retention even after 5 h. These results suggest that it should be feasible to use EPR imaging to perform in vivo tracking of populations of cells that have accumulated high intracellular levels of aminoxyls.

Original languageEnglish (US)
Pages (from-to)645-648
Number of pages4
JournalOrganic and Biomolecular Chemistry
Volume3
Issue number4
DOIs
StatePublished - Feb 21 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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