A thermally stable {FeNO}⁸complex: properties and biological reactivity of reduced MNO systems

Abstract

Reduced nitrogen oxide ligands such as NO-/HNO or nitroxyl participate in chemistry distinct from nitric oxide (NO). Nitroxyl has been proposed to form at heme centers to generate the Enemark-Feltham designated {FeNO} 8 system. The synthesis of a thermally stable {FeNO} 8 species namely, [Co(Cp*)2][Fe(LN4)(NO)] (3), housed in a heme-like ligand platform has been achieved by reduction of the corresponding {FeNO} 7 complex, [Fe(LN4)(NO)] (1), with decamethylcobaltocene [Co(Cp*)2] in toluene. This complex readily reacts with metMb resulting in formation of MbNO via reductive nitrosylation by the coordinated HNO/NO-, which can be inhibited with GSH. These results suggest 3 could serve as a potential HNO therapeutic. The spectroscopic, theoretical, and structural comparisons are made to 1 and the {CoNO} 8 complex, [Co(LN4)(NO)] (2), an isoelectronic analogue of 3.

Synthesis, properties, and reactivity of a series of non-heme {FeNO}7/8 complexes: Implications for Fe-nitroxyl coordination

“…Coordination of HNO or its anion to Fe has been proposed in several heme and non-heme systems as described previously [31,32,34,35,[41][42][43][44]59]. Although the list is sparse, the collective use of porphyrin and cyclam N-ligands has been a popular choice in the construction of {FeNO} 8 complexes.…”

“…These values were largely in agreement with theoretical calculations for small molecules with diamagnetic ground states. Non-heme examples of {FeNO} 8 are even rarer with a total of three such reported complexes [41,42] to date and only one being isolable [43]. The extensive spectroscopic studies by Wieghardt on [Fe(cyclam-ac)(NO)] represent the first reported non-heme derivative [42].…”

“…These results contrast those obtained for [Fe(cyclam-ac)(NO)] due to the triplet ground state of TauD-{FeNO} 8 that has been assigned as a highspin (HS) Fe(II) (S = 2) antiferromagnetically coupled to triplet 3 NO − (S = 1). This small collection of reported {Fe(H)NO} 8 complexes has led to some general properties of {FeNO} 8 : (i) the preference of S = 0 (diamagnetic) ground states (TauD being the only outlier) suggestive of a coordinated singlet nitroxyl or nitroxyl anion ( 1 HNO or 1 NO − ); (ii) ν NO values of~1500 cm −1 for heme; 1300 cm −1 for non-heme with the exception of MbHNO (ν NO : 1385 cm −1 ) [38,45] [43]. Seeking to add to the list of isolable {FeNO} 8 complexes, we describe in this paper new {FeNO} 8 complexes based on similar ligand backbones with subtle electronic/structural differences as a logical extension of our previous study.…”

Three Redox States of Metallonitrosyls in Aqueous Solution

“…A series of 5C Fe-nitroxyl heme-complexes have been obtained by reducing the corresponding n ¼ 7 compounds with cobaltocene derivatives in nonaqueous medium (154,161). The diamagnetic TFPBr 8 -compound (Table 3) has been isolated and characterized by UV-vis, FTIR, 1 H, 15 N NMR spectroscopies and DFT calculations and is very stable in CH 2 Cl 2 , in the absence of oxygen (155).…”

“…This species was obtained by reaction of the corresponding Co(II)-(TPP) with NO, and it is a representative example of a number of well-defined Co(III)-(NO À ) porphyrinate systems, which are all diamagnetic and square-pyramidal (18,53), as is also the recently prepared Co(III)-LN 4 complex with four asymmetrically bound basal N-ligands in a nonmacrocyclic heme platform (161). The Co(III)-tropocoronand (TCC) derivatives show a distinctive behavior: the diamagnetic 4,4-complex shows a bent nitrosyl in the equatorial position of a trigonal bypyramid, while the 3,3-complex is a paramagnetic square-pyramid (153).…”