Synthesis of Co^II–NO^– Complexes and Their Reactivity as a Source of Nitroxyl

Metal-nitroxyl (M–HNO/M–NO–) coordination units are found in denitrification enzymes of the global nitrogen cycle, and free HNO exhibits pharmacological properties related to cardiovascular physiology that are distinct from nitric oxide (NO). To elucidate the properties that control the binding and release of coordinated nitroxyl or its anion at these biological metal sites, we synthesized {CoNO}8 (1, 2) and {CoNO}9 (3, 4) complexes that contain diimine–dipyrrolide supporting ligands. Experimental (NMR, IR, MS, EPR, XAS, XRD) and computational data (DFT) support an oxidation state assignment for 3 and 4 of high spin CoII (SCo = 3/2) coordinated to 3NO– (SNO = 1) for Stot = 1/2. As suggested by DFT, upon protonation, a spin transition occurs to generate a putative low spin CoII–1HNO (SCo = Stot = 1/2); the Co–NO bond is ∼0.2 Å longer, more labile, and facilitates the release of HNO. This property was confirmed experimentally through the detection and quantification of N2O (∼70% yield), a byproduct of the established HNO self-reaction (2HNO → N2O + H2O). Additionally, 3 and 4 function as HNO donors in aqueous media at pH 7.4 and react with known HNO targets, such as a water-soluble MnIII-porphyrin ([MnIII(TPPS)]3–; TPPS = meso-tetrakis­(4-sulfonatophenyl)­porphyrinate) and ferric myoglobin (metMb) to quantitatively yield [Mn­(TPPS)­(NO)]4– and MbNO, respectively.金属-亚硝酰基（Metal-nitroxyl，M–HNO/M–NO–）配位单元存在于全球氮循环的脱氮酶中，而游离态HNO具有不同于一氧化氮（nitric oxide，NO）的心血管生理学相关药理学特性。为阐明调控这些生物金属位点上配位亚硝酰基或其阴离子结合与释放的特性，我们合成了含二亚胺-二吡咯支撑配体的{CoNO}₈（1、2）与{CoNO}₉（3、4）配合物。实验数据（核磁共振波谱NMR、红外光谱IR、质谱MS、电子顺磁共振波谱EPR、X射线吸收光谱XAS、X射线衍射XRD）与计算数据（密度泛函理论DFT）证实，3和4的氧化态归属为：高自旋Co²⁺（S_Co = 3/2）与3个NO⁻（S_NO = 1）配位，总自旋S_tot = 1/2。正如密度泛函理论（DFT）所预测，质子化后会发生自旋跃迁，生成推定的低自旋Co²⁺-1HNO（S_Co = S_tot = 1/2）；该配合物的Co–NO键长增加约0.2 Å，且更易解离，进而促进HNO的释放。这一特性通过对N₂O的检测与定量分析得到了实验验证：其产率约为70%，而N₂O是已知HNO自反应（2HNO → N₂O + H₂O）的副产物。此外，3和4在pH 7.4的水溶液中可作为HNO供体，能够与已知的HNO靶标发生反应，例如水溶性Mn³⁺-卟啉（[MnⅢ(TPPS)]³⁻；TPPS = 间-四(4-磺酰苯基)卟啉酸根）与高铁肌红蛋白（ferric myoglobin，metMb），最终分别定量生成[Mn(TPPS)(NO)]⁴⁻与MbNO。