Iron Porphyrin Carbenes as Catalytic Intermediates: Structures, Mössbauer and NMR Spectroscopic Properties, and Bonding

Abstract

Iron porphyrin carbenes (IPCs) are thought to be intermediates involved in the metabolism of various xenobiotics by cytochrome P450, as well as in chemical reactions catalyzed by metalloporphyrins and engineered P450s. While early work proposed IPCs to contain Fe II , more recent work invokes a double-bond description of the iron-carbon bond, similar to that found in Fe IV porphyrin oxenes. Reported herein is the first quantum chemical investigation of IPC Mçssbauer and NMR spectroscopic properties, as well as their electronic structures, together with comparisons to ferrous heme proteins and an Fe IV oxene model. The results provide the first accurate predictions of the experimental spectroscopic observables as well as the first theoretical explanation of their electrophilic nature, as deduced from experiment. The preferred resonance structure is Fe II ! {:C(X)Y} 0 and not Fe IV = {C(X)Y} 2À , a result that will facilitate research on IPC reactivities in various chemical and biochemical systems.

Catalytic iron-carbene intermediate revealed in a cytochrome c carbene transferase

“…Although the IPC open shell singlet is similar to the Fe(III)superoxide electronic structure in heme oxygen binding (33), no experimental evidence has been published to support the relevance of an open shell singlet configuration in IPCs. Computational studies from both the Zhang group and the Shaik group suggest that the energy differences between electronic states are small (22)(23)(24)27), and thus, the open shell singlet, closed shell singlet, and triplet states should all be considered plausible ground states for the IPC intermediate in the environment of an enzyme active site.…”

“…By analogy to known transition metal-catalyzed reactions that use diazo reagents as carbene precursors (3)(4)(5), the emerging enzymatic carbene transfer activities of heme proteins are all thought to involve a reactive iron porphyrin carbene (IPC) intermediate; transfer of the carbene to a second substrate and product release regenerate the protein catalyst (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Our current understanding of enzyme-catalyzed carbene transfer reactions comes primarily from experimental characterizations of model IPC compounds (16)(17)(18)(19)(20)(21) and their computational studies (22)(23)(24)(25)(26)(27). Determining the structures and properties of reactive intermediates is central to deciphering how enzymes enhance reaction rates and dictate selectivity (28), and recent mechanistic studies of cyclopropanation enzymes (24,26,27) have also underscored the importance of the IPC intermediate and the need to characterize it within a protein scaffold.…”

Comparative Study of the Electronic Structures of μ-Oxo, μ-Nitrido, and μ-Carbido Diiron Octapropylporphyrazine Complexes and Their Catalytic Activity in Cyclopropanation of Olefins

“…30,40 Several mononuclear iron carbene complexes have been described though their electronic structure is still a matter of debates in the literature. [89][90][91][92][93][94] To get insight into possible involvement of putative carbene species on binuclear diiron platform, we have firstly performed a detailed DFT study of the three diiron porpyrazine complexes differing in the nature of bridging atom (µ-O, µ-N and µ-C) and in the iron oxidation state, Fe III µOFe III , Fe III µNFe IV and Fe IV µCFe IV , respectively (Figure 1). DFT calculations provided useful information on the electronic properties of these complexes.…”

“…Several experimental and theoretical studies published on the olefin cyclopropanation mediated by EDA and mononuclear iron porphyrin-like catalysts point to an active intermediate having carbene axially bonded to the Fe site. 33,36,82,[89][90][91] The observed catalytic activity of the three diiron complexes suggests that related carbene intermediates can be formed at binuclear platforms. We performed theoretical modelling on the putative (FePz)2X-carbene species using the same DFT approach successfully used for the initial (FePz)2X species.…”

“…Previous theoretical studies have been done on carbenic species issued from mononuclear Fe II porphyrins, 89,[92][93][94] while only few studies on Fe III porphyrin carbene species have been described. 36,95 Interestingly, we observe a similar behavior as that of Fe II porphyrin carbene species described by Sharon et al 93 In (FePz)2O and (FePz)2N species, the unpaired electron of carbene is localized on a py orbital which exhibits some delocalization onto the O atoms of the ester group yielding a planar structure of both Fe -C(H)COO moieties.…”