Tuning the Type 1 Reduction Potential of Multicopper Oxidases: Uncoupling the Effects of Electrostatics and H-Bonding to Histidine Ligands.

In multicopper oxidases (MCOs), the type 1 (T1) Cu accepts electrons from the substrate and transfers these to the trinuclear Cu cluster (TNC) where O is reduced to HO. The T1 potential in MCOs varies from 340 to 780 mV, a range not explained by the existing literature. This study focused on the ∼350 mV difference in potential of the T1 center in Fet3p and laccase (TvL) that have the same 2His1Cys ligand set.

Oxygen Reduction by Iron Porphyrins with Covalently Attached Pendent Phenol and Quinol.

Phenols and quinols participate in both proton transfer and electron transfer processes in nature either in distinct elementary steps or in a concerted fashion. Recent investigations using synthetic heme/Cu models and iron porphyrins have indicated that phenols/quinols can react with both ferric superoxide and ferric peroxide intermediates formed during O reduction through a proton coupled electron transfer (PCET) process as well as via hydrogen atom transfer (HAT). Oxygen reduction by iron porphyrins bearing covalently attached pendant phenol and quinol groups is investigated.

Resonance Raman Spectroscopy and Density Functional Theory Calculations on Ferrous Porphyrin Dioxygen Adducts with Different Axial Ligands: Correlation of Ground State Wave Function and Geometric Parameters with Experimental Vibrational Frequencies.

A dioxygen adduct of ferrous porphyrin is an important chemical species in nature as it is a common intermediate in all oxygen transfer, storage, reducing, and activating heme enzymes. The ground state (GS) wave function of this complex has been investigated using several techniques like resonance Raman (rR), Mossbauer, and X-ray absorption spectroscopies. The Fe-O and O-O vibrations of these six-coordinated diamagnetic species show a positive correlation with each other in contrast to analogous ferrous carbonyl complexes where the Fe-CO vibration correlates negatively with the C-O vibration due to a synergistic effect.

Hydrogen atom abstraction by synthetic heme ferric superoxide and hydroperoxide species.

To date, artificial dioxygen adducts of heme have not been demonstrated to be able to oxidize organic substrates in sharp contrast to their non-heme analogues and naturally occurring enzymes like heme dioxygenases. To address this apparent anomaly, an iron porphyrin complex is synthesized which includes a pendant quinol group. The corresponding dioxygen bound iron porphyrin species is demonstrated to perform hydrogen atom transfer (HAT) from the quinol group appended to the porphyrin ligand.

Effect of hydrogen bonding on innocent and non-innocent axial ligands bound to iron porphyrins.

Most known heme enzymes utilize hydrogen bonding interactions in their active sites to control electronic and geometric structures and the ensuing reactivity. The details of these weak 2nd sphere interactions are slowly unravelling through spectroscopic and theoretical investigations in addition to biochemical studies. In synthetic Fe porphyrins, nature of hydrogen bonding by iron bound hydroxide ligand (H bond acceptor or donor) is found to alter the spin state of Fe in a series of iron hydroxide complexes.

Interplay of Electronic Cooperativity and Exchange Coupling in Regulating the Reactivity of Diiron(IV)-oxo Complexes towards C-H and O-H Bond Activation.

Activation of inert C-H bonds such as those of methane are extremely challenging for chemists but in nature, the soluble methane monooxygenase (sMMO) enzyme readily oxidizes methane to methanol by using a diiron(IV) species. This has prompted chemists to look for similar model systems. Recently, a (μ-oxo)bis(μ-carboxamido)diiron(IV) ([Fe O(L) ] L=N,N-bis-(3',5'-dimethyl-4'-methoxypyridyl-2'-methyl)-N'-acetyl-1,2-diaminoethane) complex has been generated by bulk electrolysis and this species activates inert C-H bonds almost 1000 times faster than mononuclear Fe =O species and at the same time selectively activates O-H bonds of alcohols.

Mechanism of Reduction of Ferric Porphyrins by Sulfide: Identification of a Low Spin Fe-SH Intermediate.

The reaction of Fe porphyrin complexes bearing distal hydrogen bonding residues with sulfide/hydrosulfide is kinetically monitored to reveal the presence of an intermediate and a k/k of 3.0. This intermediate is trapped at low temperatures and investigated with resonance Raman and electron paramagnetic resonance spectroscopy.

Iron porphyrins with a hydrogen bonding cavity: effect of weak interactions on their electronic structure and reactivity.

The electronic structure and reactivity of iron porphyrin complexes bearing 2 sphere hydrogen bonding residues have been investigated over the last few years. The presence of these weak interactions alters the spin ground state, and axial ligand bonding and provides a proton translocation pathway into the active site. Mechanistic investigations in organic as well as aqueous media demonstrate how controlled delivery of protons is fundamental in dictating the selectivity of a multi-electron multi-proton process like the reduction of dioxygen to water.

Second sphere control of spin state: Differential tuning of axial ligand bonds in ferric porphyrin complexes by hydrogen bonding.

An iron porphyrin with a pre-organized hydrogen bonding (H-Bonding) distal architecture is utilized to avoid the inherent loss of entropy associated with H-Bonding from solvent (water) and mimic the behavior of metallo-enzyme active sites attributed to H-Bonding interactions of active site with the 2nd sphere residues. Resonance Raman (rR) data on these iron porphyrin complexes indicate that H-Bonding to an axial ligand like hydroxide can result in both stronger or weaker Fe(III)-OH bond relative to iron porphyrin complexes. The 6-coordinate (6C) complexes bearing water derived axial ligands, trans to imidazole or thiolate axial ligand with H-Bonding stabilize a low spin (LS) ground state (GS) when a complex without H-Bonding stabilizes a high spin (HS) ground state.