Nitric oxide (NO) and nitroxyl (HNO) have gained broad attention due to their roles in several physiological and pathophysiological processes. Remarkably, these sibling species can exhibit opposing effects including the promotion of angiogenic activity by NO compared to HNO, which blocks neovascularization. While many NO donors have been developed over the years, interest in HNO has led to the recent emergence of new donors. However, in both cases there is an expressive lack of iron-based compounds. Herein, we explored the novel chemical reactivity and stability of the trans-[Fe(cyclam)(NO)Cl]Cl₂ (cyclam = 1,4,8,11-tetraazacyclotetradecane) complex. Interestingly, the half-life (t_1/2) for NO release was 1.8 min upon light irradiation, vs 5.4 h upon thermal activation at 37 °C. Importantly, spectroscopic evidence supported the generation of HNO rather than NO induced by glutathione. Moreover, we observed significant inhibition of NO donor- or hypoxia-induced HIF-1α (hypoxia-inducible factor 1α) accumulation in breast cancer cells, as well as reduced vascular tube formation by endothelial cells pretreated with the trans-[Fe(cyclam)(NO)Cl]Cl₂ complex. Together, these studies provide the first example of an iron-nitrosyl complex with anti-angiogenic activity as well as the potential dual activity of this compound as a NO/HNO releasing agent, which warrants further pharmacological investigation.

一氧化氮 (NO) 和硝酰 (HNO) 因其在多种生理和病理生理过程中的作用而受到广泛关注。值得注意的是，这些同胞物种可以表现出相反的作用，包括与 HNO 相比，NO 促进血管生成活性，而 HNO 会阻止新血管形成。虽然多年来已经开发了许多 NO 供体，但对 HNO 的兴趣导致最近出现了新的供体。然而，在这两种情况下，铁基化合物都缺乏表现力。在此，我们探索了反式-[Fe(cyclam)(NO)Cl]Cl ₂ (cyclam = 1,4,8,11-四氮杂环十四烷)配合物的新型化学反应性和稳定性。有趣的是，光照射后 NO 释放的半衰期 (t _1/2 ) 为 1.8 分钟，而在 37 °C 下热激活 5.4 小时。重要的是，光谱证据支持生成 HNO 而不是谷胱甘肽诱导的 NO。此外，我们观察到显着抑制 NO 供体或缺氧诱导的 HIF-1α（缺氧诱导因子 1α）在乳腺癌细胞中的积累，以及用反式-[Fe(cyclam)预处理的内皮细胞减少血管形成(NO)Cl]Cl ₂络合物。总之，这些研究提供了具有抗血管生成活性的铁-亚硝基复合物的第一个例子，以及该化合物作为 NO/HNO 释放剂的潜在双重活性，值得进一步的药理学研究。