Resulting from biochemical iron-NO interactions, dinitrosyl iron complexes (DNICs) are small organometallic-like molecules, considered to serve as vehicles for NO transport and storage in vivo. Formed by the interaction of NO with cellular iron sulfur clusters or with the cellular labile iron pool, DNICs have been documented to be the largest NO-derived adduct in cells, even surpassing the well-known nitrosothiols (RSNOs). Continuing efforts in biological chemistry are aimed at understanding the movement of DNICs in and out of cells, and their important role in NO-induced iron efflux leading to apoptosis in cells. Intrigued by the integrity of the unique dinitrosyl iron unit (DNIU) and the possibility of roles for it in human physiology or medicinal applications, the understanding of fundamental properties such as ligand effects on its ability to switch between two redox levels has been pursued through biomimetic complexes. Using metallodithiolates and N-heterocyclic carbenes (NHCs) as ligands to Fe(NO)2, the synthesis of a library of novel DNICs, in both the oxidized, {Fe(NO)2}(9), and reduced, {Fe(NO)2}(10), forms (Enemark-Feltham notation), offers opportunity to examine structural, reactivity, and spectroscopic features. The raison d'etre for the MN2S2·Fe(NO)2 synthesis development is for the potential to exploit the ease of accessing two redox levels on two different metal sites, a property presumably required for achieving two electron redox processes in base metals. Hence such molecules may be viewed as synthetic analogues of [NiFe]- or [FeFe]-hydrogenase active sites in nature, both of which use bridging thiolates for connection of the two centers. A particular success was the development of an Fe(NO)N2S2·Fe(NO)2(+/0) redox pair for proton reduction electrocatalysis. Monomeric, reduced NHC-DNICs of the L2Fe(NO)2 type are synthesized via the Fe(CO)2(NO)2 precursor, and oxidized thiolate-containing forms are derived from the dimeric (μ-RS)2[Fe(NO)2]2. Monomeric NHC-DNICs are four coordinate, pseudotetrahedral compounds with planar Fe(NO)2 units in which the slightly bent Fe-NO groups are directed symmetrically inward at both redox levels. They serve as stable analogues of biological histidine binding sites. In agreement with IR data, Mössbauer spectroscopic parameters, and DFT computations, the prototypic NHC-DNICs indicate extensive delocalization of the electron density of iron via π-backbonding. Such π-delocalization presents an unusual reaction path for the one electron process of RS(-)/RSSR interconversion. Comparisons with imidazole-DNICs find NHCs to be the "better" ligands to Fe(NO)2 and prompted investigations in (a) possible relationships between such imidazole- and NHC-containing DNICs, (b) systems that might mimic the reactivity of DNICs with the endogenous gaseotransmitter CO, and (c) mechanistic details of such processes. In a broader context, these studies aim to further describe the behavior of the {Fe(NO)2} unit as a single molecular entity when subjected to various ligand environments and r...

Dinitrosyliron complexes (DNICs) are organometallic-like compounds of biological significance in that they appear in vivo as products of NO degradation of iron-sulfur clusters; synthetic analogues have potential as NO storage and releasing agents. Their reactivity is expected to depend on ancillary ligands and the redox level of the distinctive Fe(NO)2 unit: paramagnetic {Fe(NO)2}(9), diamagnetic dimerized forms of {Fe(NO)2}(9) and diamagnetic {Fe(NO)2}(10) DNICs (Enemark-Feltham notation). The typical biological ligands cysteine and glutathione themselves are subject to thiolate-disulfide redox processes, which when coupled to DNICs may lead to intricate redox processes involving iron, NO, and RS(-)/RS•. Making use of an N-heterocyclic carbene-stabilized DNIC, (NHC)(RS)Fe(NO)2, we have explored the DNIC-promoted RS(-)/RS• oxidation in the presence of added CO wherein oxidized {Fe(NO)2}(9) is reduced to {Fe(NO)2}(10) through carbon monoxide (CO)/RS• ligand substitution. Kinetic studies indicate a bimolecular process, rate = k [Fe(NO)2](1)[CO](1), and activation parameters derived from kobs dependence on temperature similarly indicate an associative mechanism. This mechanism is further defined by density functional theory computations. Computational results indicate a unique role for the delocalized frontier molecular orbitals of the Fe(NO)2 unit, permitting ligand exchange of RS• and CO through an initial side-on approach of CO to the electron-rich N-Fe-N site, ultimately resulting in a 5-coordinate, 19-electron intermediate with elongated Fe-SR bond and with the NO ligands accommodating the excess charge.

Both monomeric and dimeric tetraacetylglucose-containing {Fe(NO)} dinitrosyl iron complexes (DNICs) were prepared and examined for NO release in the presence of both chemical NO-trapping agents and endothelial cells.

An N-alkyl imidazole bearing a neutral {Fe(NO)2}(10) dinitrosyliron complex (DNIC) when treated with sodium t-butoxide undergoes base-promoted conversion to the N-heterocyclic carbene (NHC)-DNIC, while maintaining the Fe(NO)2 unit intact. Subsequent alkylation led to the isolation of the NHC-DNIC product; further nitrosylation led to trinitrosyl (NHC)Fe(NO)3(+). Both were isolated and structurally characterized.

The displacement of RSc from [(NHC)(SPh)Fe(NO) 2 ] (NHC ¼ N-heterocyclic carbene) by carbon monoxide follows associative kinetics, rate ¼ k [CO] 1 [(NHC)(SPh)Fe(NO) 2 ] 1 , resulting in reduction of the oxidized form of the dinitrosyliron unit, {Fe(NO) 2 } 9 (Enemark-Feltham notation) to {Fe(NO) 2 } 10 . Thermodynamically driven by the release of PhS-SPh concomitant with formation of [(NHC)(CO)Fe(NO) 2 ], computational studies suggested the reactant dinitrosyliron unit serves as a nucleophile in the initial slanted interaction of the p* orbital of CO, shifting into normal linear Fe-CO with weakening of the Fe-SPh bond. The current study seeks to experimentally test this proposal. A series of analogous {Fe(NO) 2 } 9 [(NHC)(p-S-C 6 H 4 X) Fe(NO) 2 ] complexes, with systematic variation of the para-substituents X from electron donor to electron withdrawing groups was used to monitor variation in electron density at the Fe(NO) 2 unit via Hammett analyses. Despite the presence of non-innocent NO ligands, data from n(NO) IR spectroscopy and cyclic voltammetry showed consistent tracking of the electron density at the {Fe(NO) 2 } unit in response to the aryl substituent. The electronic modifications resulted in systematic changes in reaction rates when each derivative was exposed to CO. A plot of the rate constants and the Hammett parameter s p is linear with a negative slope and a r value of À0.831; such correlation is indicative of rate retardation by electron-withdrawing substituents, and provides experimental support for the unique role of the delocalized frontier molecular orbitals of the Fe(NO) 2 unit. † Electronic supplementary information (ESI) available: Experimental methods, additional spectroscopic, cyclic voltammetric and kinetic details, X-ray crystallographic data (CIF) from the structure determination and full list of metric parameters for complexes 1a-1e. CCDC 1004078-1004081. For crystallographic data in CIF or other electronic format see a Average distance or angles. The maximum deviations from the average distances and angles are shown in the table. Full lists of metric parameters are available in the ESI.This journal is