Sowiński Mateusz P, Gahlawat Sahil, Lund Bjarte A, Warnke Anna-Luisa, Hopmann Kathrin H, Lovett Janet E, Haugland Marius M
Department of Chemistry, UiT The Arctic University of Norway, 9037, Tromsø, Norway.
Hylleraas Center for Quantum Molecular Sciences, UiT The Arctic University of Norway, 9037, Tromsø, Norway.
Commun Chem. 2023 Jun 5;6(1):111. doi: 10.1038/s42004-023-00912-7.
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.
氮氧化物在光谱学和成像中被广泛用作探针和极化转移剂。这些应用要求对还原性生物环境具有高稳定性，以及良好的弛豫特性。虽然后者由氮氧化物支架上的螺环基团提供，但此类体系在还原条件下本身并不稳定。在这项工作中，我们引入了一种通过构象调控来增强稳定性的策略，即在氮氧化物环上引入额外的取代基会导致向高度稳定的封闭螺环构象转变，这由X射线晶体学和密度泛函理论（DFT）计算表明。封闭的螺环己基氮氧化物在抗坏血酸还原作用下表现出显著提高的稳定性，同时在电子顺磁共振（EPR）光谱中保持较长的弛豫时间。这些发现对未来新型氮氧化物基自旋标记物和成像剂的设计具有重要意义。
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