Proton-Induced Reactivity of NO^– from a {CoNO}⁸ Complex

Abstract

Research on the one-electron reduced analogue of NO, namely nitroxyl (HNO/NO–), has revealed distinguishing properties regarding its utility as a therapeutic. However, the fleeting nature of HNO requires the design of donor molecules. Metal nitrosyl (MNO) complexes could serve as potential HNO donors. The synthesis, spectroscopic/structural characterization, and HNO donor properties of a {CoNO}8 complex in a pyrrole/imine ligand frame are reported. The {CoNO}8 complex [Co(LN4PhCl)(NO)] (1) does not react with established HNO targets such as FeIII hemes or Ph3P. However, in the presence of stoichiometric H+1 behaves as an HNO donor. Complex 1 readily reacts with [Fe(TPP)Cl] or Ph3P to afford the {FeNO}7 porphyrin or Ph3P=O/Ph3P=NH, respectively. In the absence of an HNO target, the {Co(NO)2}10 dinitrosyl (3) is the end product. Complex 1 also reacts with O2 to yield the corresponding CoIII-η1-ONO2 (2) nitrato analogue. This report is the first to suggest an HNO donor role for {CoNO}8 with biotargets such as FeIII-porphyrins.

Overview and New Insights into the Thiol Reactivity of Coordinated NO in {MNO}6/7/8 (M = Fe, Co) Complexes

“…93 Experimental proof for the oxidation state of Co and NO in these complexes has come from X-ray absorption spectroscopy, where a LS Co III d 6 (S = 0) coordinated to 1 NO − (S = 0) assignment has been verified. 104 dinitrosyls tend to exhibit symmetric and asymmetric ν NO stretches that are lower in energy than the more common N-bound and cationic cobalt dinitrosyls. 105 This shift in ν NO is due to the additional electron density in the π* orbital of the NO moiety.…”

“…However, there is strong evidence in ESI-MS of the reaction mixture for {8 − NO} − (calcd m/z: 374.9; found m/z: 374.8; Figure S10 in the SI), and it is common for {M(NO) 2 } n species to lose one or both nitrosyls in MS experiments. 107 104 Separation and isolation of all products were problematic because of similar solubility; however, species present in the equilibrium at t = 24 h were quantified based on NMR integration with an internal standard. The 1 H NMR spectrum provides evidence of unreacted {CoNO} 8 complex 3 (31%) and thiol (45%) as well as {Co(NO) 2 } 10 complex 8 (17%) and the disulfide p-ClPhSSPh-p-Cl (8%), as confirmed by an authentic synthesis.…”

“…93 On the other hand, complex 3 and other {CoNO} 8 complexes with similar imine-pyrrole ligands have been assigned as LS Co III -1 NO − (S = 0). 104 Thus, the kinetic inertness of Co(III) controls the extent to which 3 reacts with thiols or even stronger acids such as HBF 4 . 104 3.4.…”

“…104 Thus, the kinetic inertness of Co(III) controls the extent to which 3 reacts with thiols or even stronger acids such as HBF 4 . 104 3.4. Proposed Reaction Path of 1 with Thiols.…”

Recent advances in the chemical biology of nitroxyl (HNO) detection and generation

“…Harrop reported the first potentially useful MNO complex for HNO delivery. 111 The {CoNO} 8 complex [Co(LN 4 PhCl)(NO)] is relatively stable at physiological pH but addition of stoichiometric amounts of acid releases HNO that is trapped by [Fe(TPP)Cl] or Ph 3 P to afford the {FeNO} 7 complex or Ph 3 P=O/Ph 3 P=NH, providing evidence for HNO release. 111 A ruthenium complex has also been identified as a NO/HNO-donor in aqueous media.…”