Conformational tuning improves the stability of spirocyclic nitroxides with long paramagnetic relaxation times

Mateusz P. Sowiński, Sahil Gahlawat, Bjarte A. Lund, Anna-Luisa Warnke, Kathrin H. Hopmann, Janet E. Lovett, Marius M. Haugland*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Nitroxides are widely used as probes and polarization transfer agents in spectroscopy and imaging. These applications require high stability towards reducing biological environments, as well as beneficial relaxation properties. While the latter is provided by spirocyclic groups on the nitroxide scaffold, such systems are not in themselves robust under reducing conditions. In this work, we introduce a strategy for stability enhancement through conformational tuning, where incorporating additional substituents on the nitroxide ring effects a shift towards highly stable closed spirocyclic conformations, as indicated by X-ray crystallography and density functional theory (DFT) calculations. Closed spirocyclohexyl nitroxides exhibit dramatically improved stability towards reduction by ascorbate, while maintaining long relaxation times in electron paramagnetic resonance (EPR) spectroscopy. These findings have important implications for the future design of new nitroxide-based spin labels and imaging agents.
Original languageEnglish
Article number111
Number of pages8
JournalCommunications Chemistry
Volume6
Issue number1
DOIs
Publication statusPublished - 5 Jun 2023

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