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Assessment of Nitrones as In Vivo Redox Sensors

机译：体内氧化还原传感器的硝态氮评估

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Spin traps such as 5,5-dimethyl-1-pyrroline N-oxide, alpha-phenyl-tert-butyl nitrone, alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone and newer generation 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide analogs have been known for years. What are the desired properties of good probes for measuring in vivo redox reactions in biological systems? These are specificity, sensitivity, rapid, high yield kinetics, low toxicity, high stability and easy to administer and target. Unfortunately, the nitrones perform poorly in almost all of these categories. Typical in vivo concentrations of spin trap approach 100 mM (assuming solubility and toxicity are not an issue), frequently yield 1% nitroxide or less stoichiometry, are typically unstable with time and frequently lack specificity. In vivo electron paramagnetic resonance (EPR) experiments need to have strong signals that correlate with redox chemistry. The resultant signal should be stable and not rapidly interconvert to other diamagnetic species. Fortunately, some newer probes of in vivo redox reactions in biological systems have come upon the horizon. In fact some have been around for a long time, but their virtues are becoming increasingly appreciated. This paper summarizes the disadvantages of nitrones versus the clear advantages of other probes of free radicals, redox state and the like by EPR. It also expands on the properties of nitroxides and nitrones as therapeutics.
机译：自旋阱，例如5,5-二甲基-1-吡咯啉N-氧化物，α-苯基叔丁基硝酮，α-（4-吡啶基-1-氧化物）-N-叔丁基硝酮和新一代5-（二乙氧基磷酰基）-5-甲基-1-吡咯啉N-氧化物类似物已有多年历史。用于测量生物系统中体内氧化还原反应的优良探针的期望特性是什么？这些是特异性，敏感性，快速，高产率动力学，低毒性，高稳定性并且易于施用和靶向。不幸的是，硝酮在几乎所有这些类别中的性能都较差。自旋阱的典型体内浓度接近100 mM（假设溶解度和毒性不是问题），经常产生1％的一氧化氮或更少的化学计量，通常随时间不稳定，并且经常缺乏特异性。体内电子顺磁共振（EPR）实验需要具有与氧化还原化学相关的强信号。所得信号应稳定并且不能快速互变为其他抗磁性物质。幸运的是，一些新的生物系统中体内氧化还原反应的探针已经问世。实际上，有些已经存在很长时间了，但是它们的优点越来越受到赞赏。本文总结了EPR与其他自由基，氧化还原状态等探针的明显优势相比，硝酮的劣势。它还扩大了氮氧化物和硝酮作为治疗剂的性质。

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