Synthetic Advances Inspired by the Bioactive Dinitrosyl Iron Unit

Abstract

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...

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

“…[7] As ac onsequence, al ong-lasting HNO/ NO À donor derived from steady nitroxyl-releasing compounds with an ON/OFF switch or from stable compounds with dedicated nitroxyl-transfer reactivityt owardt he Fe III centeri nh eme proteins is am uch-neededt arget for pharmaceutical applications.The intrinsic redox propensity of transitionm etals in metalnitrosyl complexes modulates the oxidation state of NO and allowst he potentialu se of MÀNO complexes in nitroxyl chemistry. [8][9][10][11][12][13] In particular, the electronic structure of {M(NO) x } n complexes (M = Fe or Co, x = 1o r2 ,n = 7, 8, 9, or 10) regulates the redoxs witch for the reductiven itrosylation of the Fe III -porphyrinc omplex/protein and controls the proton-induced nitroxyl-release reactivity. [14][15][16][17][18][19] {Fe(NO) 2 } 9 /{Fe(NO) 2 } 10 complexes [Fe(NO) 2 (Ar-nacnac)] 0/1À exhibita ne lectrochemically reversible redoxc ouple at À1.34 V, whereas the reduction potential for [Fe III (TPP)Cl] is À0.90Vv ersus Fc/Fc + (Ar-nacnac = anion of [(2,6-diisopropylphenyl)NC(Me)] 2 CH).…”

A three-coordinate iron–silylene complex stabilized by ligand–ligand dispersion forces

“…1,2 Carbene ligands have also proven to be adept at stabilizing small-molecule models of important iron-containing biological systems, 3 and they have allowed access to rare or unprecedented iron oxidation states and coordination environments. 4 Our work in this area has focused on iron-NHC complexes of the type [(NHC)Fe(N″) 2 ], where the NHC is typically a bulky derivative such as 1,3-di(2,6-diisopropyl)phenylimidazolin-2-ylidene (IPr) and N″ = N(SiMe 3 ) 2 .…”

Structures and Properties of Dinitrosyl Iron and Cobalt Complexes Ligated by Bis(3,5-diisopropyl-1-pyrazolyl)methane

“…The biosynthesis of NO and its physiological reactions reveals some interaction with metalloproteins [2][3][4][5][6][7]. NO has also been implicated in the disassembly of iron-sulfur proteins, leading to the formation of dinitrosyl iron complexes (DNICs) [8][9][10]. DNICs can serve as NO storage and transport in biological systems [8][9][10][11].…”

“…NO has also been implicated in the disassembly of iron-sulfur proteins, leading to the formation of dinitrosyl iron complexes (DNICs) [8][9][10]. DNICs can serve as NO storage and transport in biological systems [8][9][10][11]. In 2005, the protein-bound DNICs structure known as the Fe(NO) 2 unit in the active site of human glutathione transferase (GST P1-1) was reported [5,8,12,13].…”