Conformational Tuning Improves the Stability of Spirocyclic Nitroxides with Long Paramagnetic Relaxation Times

Overview

Journal Commun Chem

Publisher Springer Nature

Specialty Chemistry

Date 2023 Jun 5

PMID 37277501

Authors

Mateusz P Sowinski

Sahil Gahlawat

Bjarte A Lund

Anna-Luisa Warnke

Kathrin H Hopmann

Janet E Lovett

Marius M Haugland

Affiliations

Soon will be listed here.

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.

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

Sowinski M, Gahlawat S, Lund B, Warnke A, Hopmann K, Lovett J Commun Chem. 2023; 6(1):111.

PMID: 37277501 PMC: 10241799. DOI: 10.1038/s42004-023-00912-7.

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