To Transfer or Not to Transfer? Development of a Dinitrosyl Iron Complex as a Nitroxyl Donor for the Nitroxylation of an FeIII-Porphyrin Center

A positive myocardial inotropic effect achieved using HNO/NO−, compared with NO⋅, triggered attempts to explore novel nitroxyl donors for use in clinical applications in vascular and myocardial pharmacology. To develop M‐NO complexes for nitroxyl chemistry and biology, modulation of direct nitroxyl‐transfer reactivity of dinitrosyl iron complexes (DNICs) is investigated in this study using a FeIII‐porphyrin complex and proteins as a specific probe. Stable dinuclear {Fe(NO)2}9 DNIC [Fe(μ‐MePyr)(NO)2]2 was discovered as a potent nitroxyl donor for nitroxylation of FeIII‐heme centers through an associative mechanism. Beyond the efficient nitroxyl transfer, transformation of DNICs into a chemical biology probe for nitroxyl and for pharmaceutical applications demands further efforts using in vitro/in vivo studies. A dinitrosyl iron complex, DNIC [Fe(μ‐MePyr)(NO)2]2, was found to be a potent nitroxyl donor for prospective clinical applications in vascular and myocardial pharmacology.