Formation and Reactivity of New Isoporphyrins: Implications for Understanding the Tyr-His Cross-Link Cofactor Biogenesis in Cytochrome c Oxidase

Abstract

Cytochrome c oxidase (CcO) catalyzes the reduction of dioxygen to water utilizing a heterobinuclear active site composed of a heme moiety and a mononuclear copper center coordinated to three histidine residues, one of which is covalently cross-linked to a tyrosine residue via a post-translational modification (PTM). Although this tyrosine-histidine moiety has functional and structural importance, the pathway behind this net oxidative C-N bond coupling is still unknown. A novel route employing an iron(III) meso-substituted isoporphyrin derivative, isoelectronic with Cmpd-I ((Por •+ )Fe IV =O), is for the first time proposed to be a key intermediate in the Tyr-His cofactor biogenesis. Newly synthesized iron(III) meso-substituted isoporphyrins were prepared with azide, cyanide, and substituted imidazole functionalities, by adding nucleophiles to an iron(III) π-dication species formed via addition of trifluoroacetic acid to F 8 Cmpd-I (F 8 = (tetrakis(2,6-difluorophenyl)porphyrinate)). Isoporphyrin derivatives were characterized at cryogenic temperatures via ESI-MS and UV-vis, 2 H NMR, and EPR spectroscopies. Addition of 1,3,5-trimethoxybenzene or 4-methoxyphenol to the imidazolesubstituted isoporphyrin led to formation of the organic product containing the imidazole coupled to aromatic substrate via a new C-N bond, as detected via cryo-ESI-MS. Experimental evidence for the formation of an imidazole-substituted isoporphyrin and its promising reactivity to form the imidazole-phenol coupled product yields viability to the herein proposed pathway behind the PTM (i.e., biogenesis) leading to the key covalent Tyr-His cross-link in CcO.

Controlling Oxygen Reduction Selectivity through Steric Effects: Electrocatalytic Two‐Electron and Four‐Electron Oxygen Reduction with Cobalt Porphyrin Atropisomers

“…The 4 e − ORR is required in many energy conversion techniques, [4–7] while the 2 e − ORR makes H 2 O 2 , which is a widely used industrial oxidant and also a promising fuel [8–10] . Recently, many molecular ORR catalysts have been reported [1–5, 11–28] . Although achievements have been made in improving the 4 e − ORR by providing rapid electron and proton transfers, [17, 29, 30] introducing hydrogen‐bonding [31, 32] and electrostatic interactions, [33] and using dinuclear cooperation, [34–38] realizing these functionalities is challenging from both design and synthesis points of view.…”

“…[8][9][10] Recently, many molecular ORR catalysts have been reported. [1][2][3][4][5][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Although achievements have been made in improving the 4 e À ORR by providing rapid electron and proton transfers, [17,29,30] introducing hydrogenbonding [31,32] and electrostatic interactions, [33] and using dinuclear cooperation, [34][35][36][37][38] realizing these functionalities is challenging from both design and synthesis points of view. Unlike 4 e À ORR, few studies have been dedicated to improving the 2 e À ORR.…”

“…Each Co is incorporated by a porphyrin ring through four N atoms. An aqueous molecule axially binds to Co with a long Co•••O distance of 2.331 (15) . The four Co À N bond distances are identical 1.959 (3) .…”

Quest for Zinc Methoxyisoporphyrin Molecules: Experimental and Theoretical Studies

“…1 Fe(III)‐isoporphyrin is iso‐electronic with reactive Fe(IV)‐oxo porphyrin radical and may have potential roles as biomimetic catalysts in organic transformation reactions [18] . Iron(III) isoporphyrin is also proposed as an essential intermediate in the biosynthesis of the cytochrome c oxidase enzyme [19] . A platinum meso ‐spiro[cyclopentadiene‐isoporphyrin] is known [20] .…”

Enzyme‐Inspired Iron Porphyrins for Improved Electrocatalytic Oxygen Reduction and Evolution Reactions

“…[1,3] Inspired by nature, many synthetic Fe porphyrins and other related metal macrocycles have been designed and investigated as catalysts for O 2 reduction. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] From these studies, fundamental knowledge to boost catalyst performance is learned. For example, efficient electron transfer to Fe porphyrin sites and proper hydrogen bonding interactions with Fe-O 2 adducts can facilitate the 4e reduction of O 2 to water.…”