Formation of a Reactive, Alkyl Thiolate-Ligated Fe^III-Superoxo Intermediate Derived from Dioxygen

Abstract

Herein, we describe an alkyl thiolate-ligated iron complex that reacts with dioxygen to form an unprecedented example of an iron superoxo (O2•−) intermediate, [FeIII(S2Me2N3(Pr,Pr))(O2)] (4), which is capable of cleaving strong C–H bonds. A cysteinate-ligated iron superoxo intermediate is proposed to play a key role in the biosynthesis of β-lactam antibiotics by isopenicillin N-synthase (IPNS). Superoxo 4 converts to a metastable putative Fe(III)–OOH intermediate, at rates that are dependent on the C–H bond strength of the H atom donor, with a kinetic isotope effect (kH/kD = 4.8) comparable to that of IPNS (kH/kD = 5.6). The bond dissociation energy of the C–H bonds cleaved by 4 (92 kcal/mol) is comparable to C–H bonds cleaved by IPNS (93 kcal/mol). Both the calculated and experimental electronic absorption spectra of 4 are comparable to those of the putative IPNS superoxo intermediate, and are shown to involve RS− → Fe–O2•− and O2•− → Fe charge transfer transitions. The π-back-donation by the electronrich alkyl thiolate presumably facilitates this reactivity by increasing the basicity of the distal oxygen. The frontier orbitals of 4 are shown to consist of two strongly coupled unpaired electrons of opposite spin, one in a superoxo π*(O–O) orbital, and the other in an Fe(dxy) orbital.

A Facially Coordinating Tris-Benzimidazole Ligand for Nonheme Iron Enzyme Models

“…All DFT calculations were performed in ORCA 4.o 14 using the B3LYP functional with atom-pairwise dispersion correction with Becke-Johnson damping 15,16 and def2-SVP 17…”

“…3 Modelling the 3-His coordination has been attempted through various nitrogen donor ligands such as 1,4,7triazacyclononane (tacn), 4 tris(2-pyridyl)methane (Tpym), 5 trispyrazolyl variants namely trispyrazolylborates (Tp), 6 trispyrazolylmethanes (Tpm) 7 and trisimidazolylphosphines (TIP), 8 and other ligands. 9,10 Some of these facially coordinating ligands have been used to prepare Fe-based O2 derived oxidants, such as superoxo and oxo species, [11][12][13][14][15][16] and there are a few catalytic examples. 17,18 In our pursuit to prepare structurally faithful 3-His mononuclear nonheme iron model complexes, we noted that despite similar coordination geometry, most of the ligands contain donor groups that are not representative of those in nature (Figure 1).…”

A Facially Coordinating Tris‐Benzimidazole Ligand for Nonheme Iron Enzyme Models

“…Modelling of the facial 3‐His coordination has been accomplished through various nitrogen donor ligands such as 1,4,7‐triazacyclononane ( tacn ), [4] tris(2‐pyridyl)methane, [5] trispyrazolyl variants namely trispyrazolylborates, [6] trispyrazolylmethanes [7] and trisimidazolylphosphines ( TIP ) [8] . Some of these facially coordinating ligands have been used to prepare Fe‐based O 2 derived oxidants, such as superoxo and oxo species [9,10,11,12,13,14] and in catalysis [15,16] …”

The Properties of Hydrotris(3‐mesitylpyrazol‐1‐yl) Borate Iron(II) Complexes with Aryl Carboxylate Co‐ligands – Stabilization of an Iron(III) Alkylperoxide

“…Attempts to synthesize complexes that model superoxide and peroxide intermediates have met with limited success. Only one iron(III) superoxide so far has been isolated and characterized structurally but it was prepared from KO 2 ; [14] in other cases superoxides were generated in‐situ from O 2 and identified as such by spectroscopic methods [15–17] . Several synthetic iron(III) organoperoxides have been reported, though, and in this context particularly representatives with tris(2‐pyridylmethyl)amine (TPA), 1,4,8,12‐tetraazacyclopentadecane ([15]aneN 4 ) and related spectator ligands are worth mentioning, which were extensively studied in the past [18–22] …”