An Air‐Stable, Neutral Phenothiazinyl Radical with Substantial Radical Stabilization Energy
An Air‐Stable, Neutral Phenothiazinyl Radical with Substantial Radical Stabilization Energy
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DOI：
10.1002/chem.201905238
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发表时间：
2020-01
期刊：
影响因子：
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通讯作者：
L. Sigmund;Fabian Ebner;Christoph Jöst;Jonas Spengler;Nils Gönnheimer;D. Hartmann;L. Greb
中科院分区：
文献类型：
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作者：
L. Sigmund;Fabian Ebner;Christoph Jöst;Jonas Spengler;Nils Gönnheimer;D. Hartmann;L. Greb
自由基状态对吩噻嗪类药物药理活性的重要影响早已被推测。虽然N -取代吩噻嗪的阳离子自由基具有很高的稳定性，但N -未取代吩噻嗪的中性自由基从未被分离出来。本文将1,9 -二氨基- 3,7 -二叔丁基- n1,9 -二（2,6 -二异丙基苯基）- 10H -吩噻嗪- 10 -基自由基（SQH2 .）描述为第一种空气稳定的中性吩噻嗪基自由基。通过EPR和紫外/可见/近红外光谱，循环伏安法，光谱电化学分析，单晶XRD和计算研究对晶体深蓝色进行了表征。SQH2。自由基具有令人印象深刻的稳定能量，它的母胺具有已知的最弱的N - H键离解能。除了在药物化学中作为开壳参考外，它的三叉戟结合口袋或氢键供体能力可以作为氧化还原活性配体或质子偶联电子转移试剂进行多种用途。
Abstract The vital effect of radical states on the pharmacological activity of phenothiazine‐based drugs has long been speculated. Whereas cationic radicals of N‐substituted phenothiazines show high stability, the respective neutral radicals of N‐unsubstituted phenothiazines have never been isolated. Herein, the 1,9‐diamino‐3,7‐di‐tert‐butyl‐N 1,N 9‐bis(2,6‐diisopropylphenyl)‐10H‐phenothiazin‐10‐yl radical (SQH2 .) is described as the first air‐stable, neutral phenothiazinyl free radical. The crystalline dark‐blue species is characterized by means of EPR and UV/Vis/near‐IR spectroscopy, as well as cyclic voltammetry, spectro‐electrochemical analysis, single‐crystal XRD, and computational studies. The SQH2 . radical stands out from other aminyl radicals by an impressive radical stabilization energy and its parent amine has one of the weakest N−H bond dissociation energies ever determined. In addition to serving as open‐shell reference in medicinal chemistry, its tridentate binding pocket or hydrogen‐bond‐donor ability might enable manifold uses as a redox‐active ligand or proton‐coupled electron‐transfer reagent.