Issue 4, 2005

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

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 [1] to high (millimolar) intracellular concentrations through passive incubation with the corresponding acetoxymethyl (AM) ester [2]. In the present study, we show that under physiological conditions aminoxyl [1] 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 [10], 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.

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

Article information

Article type
Paper
Submitted
08 Oct 2004
Accepted
08 Dec 2004
First published
19 Jan 2005

Org. Biomol. Chem., 2005,3, 645-648

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

G. M. Rosen, S. R. Burks, M. J. Kohr and J. P. Y. Kao, Org. Biomol. Chem., 2005, 3, 645 DOI: 10.1039/B415586F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements