Design concept for α-hydrogen-substituted nitroxides
Design concept for α-hydrogen-substituted nitroxides
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DOI：
10.1038/ncomms7070
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发表时间：
2015-02-01
影响因子：
16.6
通讯作者：
Szpilman, Alex M.
中科院分区：
文献类型：
--
作者：
Amar, Michal;Bar, Sukanta;Szpilman, Alex M.
稳定的硝基氧（硝酰自由基）在化学、生物学和医学中具有许多重要且独特的应用。然而，影响其稳定性的因素仍在研究中，这阻碍了新型硝基氧的设计和开发。具有叔烷基的氮氧化物通常是稳定的，但显然是高度阻碍的。相反，α-氢取代的硝基氧通常本质上不稳定并迅速分解。本文描述了一种设计稳定的环状α-硝基氢的新颖概念，并提出了两个不同系列的稳定α-硝基氧的简单合成和表征形式的概念验证。这些独特的α-氮氧氢的稳定性归因于空间和立体电子效应的结合，通过这种效应在动力学上阻止了歧化。这些稳定效果是通过在硝基氧主链的γ位使用硝基氧共面取代基来实现的。这一前提得到了计算研究的支持，该研究提供了对α-氮氧自由基歧化途径的深入了解。
Stable nitroxides (nitroxyl radicals) have many essential and unique applications in chemistry, biology and medicine. However, the factors influencing their stability are still under investigation, and this hinders the design and development of new nitroxides. Nitroxides with tertiary alkyl groups are generally stable but obviously highly encumbered. In contrast, alpha-hydrogen- substituted nitroxides are generally inherently unstable and rapidly decompose. Herein, a novel, concept for the design of stable cyclic alpha-hydrogen nitroxides is described, and a proof-of-concept in the form of the facile synthesis and characterization of two diverse series of stable alpha-hydrogen nitroxides is presented. The stability of these unique alpha-hydrogen nitroxides is attributed to a combination of steric and stereoelectronic effects by which disproportionation is kinetically precluded. These stabilizing effects are achieved by the use of a nitroxide co-planar substituent in the gamma-position of the backbone of the nitroxide. This premise is supported by a computational study, which provides insight into the disproportionation pathways of alpha-hydrogen nitroxides.