Graduate School of Pharmaceutical Sciences, Nagoya City University.
Chem Pharm Bull (Tokyo). 2023;71(6):447-450. doi: 10.1248/cpb.c23-00146.
Nitric oxide (NO) has multiple physiological activities, including roles in vasorelaxation, neurotransmission, and immune response. Indeed, NO-releasing compounds are utilized as therapeutic agents for cardiovascular diseases based on the potent and rapid vasorelaxation induced by NO. We have developed a series of photoinduced-electron-transfer-driven (PeT-driven) NO releasers composed of a light-harvesting antenna moiety and an NO-releasing N-nitrosoaminophenol moiety, which efficiently release NO upon irradiation with blue (500 nm), green (560 nm), or red (650 nm) light. In this paper, we investigated substituent effects at the 2-position of the N-nitrosoaminophenol moiety by means of spectroscopic, fluorescence, and NO-release measurements. Interestingly, a methyl substituent at this position had no significant effect on the NO-releasing ability, while a nitro group or a methoxy group reduced it. The nitro group may suppress electron transfer to the antenna moiety, while the methoxy group may accelerate electron transfer but suppress deprotonation to afford the phenoxyl radical, which is the key reaction for release of NO. These structure-activity relationships should be helpful for further functionalizing PeT-driven NO releasers.
一氧化氮（NO）具有多种生理活性，包括在血管舒张、神经递质传递和免疫反应中的作用。事实上，基于 NO 诱导的强大而快速的血管舒张作用，释放 NO 的化合物被用作心血管疾病的治疗剂。我们已经开发了一系列光诱导电子转移驱动（PeT 驱动）的 NO 释放剂，由光捕获天线部分和 NO 释放 N-亚硝基氨基苯酚部分组成，在蓝（500nm）、绿（560nm）或红（650nm）光照射下，它们能够有效地释放 NO。在本文中，我们通过光谱、荧光和 NO 释放测量研究了 N-亚硝基氨基苯酚部分 2 位取代基的影响。有趣的是，该位置的甲基取代基对 NO 释放能力没有显著影响，而硝基或甲氧基取代基则降低了其能力。硝基可能会抑制电子向天线部分的转移，而甲氧基可能会加速电子转移，但抑制去质子化以提供苯氧自由基，这是释放 NO 的关键反应。这些结构-活性关系应该有助于进一步功能化 PeT 驱动的 NO 释放剂。
