Stereoelectronic Insight Into Heme Carbene Catalysis: Bridging Enzymatic and Synthetic Systems

Abstract Iron porphyrin carbenes (IPCs), pivotal intermediates in enzymatic carbene transfer reactions, adopt diverse bonding modes and electronic configurations that govern their catalytic functions. This review systematically compares three IPC isomers—terminal carbenes, bridged carbenes, and N‐alkyl derivatives—isolated from enzymatic systems with synthetic analogues. X‐ray crystal structure analysis, which reveals protein‐induced structural adaptations and isomer‐specific distortions, also facilitates Mössbauer and electron paramagnetic resonance (EPR) spectroscopic studies. Besides ground state assignments on the bridged carbene [Fe(TPP){C═C( p ‐ClPh) 2 }C1] ((d xy ) 2 (d xz ,d yz ) 2 (d z 2 ) 1 ) and the N‐alkyl Mb( N ‐CH 2 COBzyl)(His) ((d xy ) 2 (d xz ) 1 (d yz ) 1 (d z 2 ) 1 (d x 2 − y 2 ) 1 ), Mössbauer studies also reveal that alongside carbene fragment migration, the bridged carbene, which show shorter Fe─C(R) distance than the σ type Fe─C(sp 2 /sp 3 ) bond, retains strong π acceptor capability, in contrast to the stronger σ donor and π acceptor capability of the terminal carbene and the N‐alky derivative which nearly loses the bonding to iron. Accordingly, very large tetragonalities (|Δ/λ| > 16) are observed for the bridged carbene Mb(CHCO 2 Et)(NMH) ((d xy ) 2 (d xz ,d yz ) 3 ) which exhibited rhombic EPR pattern under the near parallel ligand orientation. This work establishes critical connections between synthetic porphyrin and enzymatic systems, highlighting the adjustable scaffolds of engineered proteins in stabilizing various intermediates and advancing the mechanistic understanding of carbene transfer reactions.