Reactivity of a heterobinuclear heme-peroxo-Cu complex with -substituted catechols shows a p -dependent change in mechanism.

In biological systems, heme-copper oxidase (HCO) enzymes play a crucial role in the oxygen reduction reaction (ORR), where the pivotal O-O bond cleavage of the (heme)Fe-peroxo-Cu intermediate is facilitated by active-site (peroxo core) hydrogen bonding followed by proton-coupled electron transfer (PCET) from a nearby (phenolic) tyrosine residue. A useful approach to comprehend the fundamental relationships among H-bonding/proton/H-atom donors and their abilities to induce O-O bond homolysis involves the investigation of synthetic, bioinspired model systems where the exogenous substrate properties (such as p and bond dissociation energy (BDE)) can be systematically altered. This report details the reactivity of a heme-peroxo-copper HCO model complex (LS-4DCHIm) toward a series of substituted catechol substrates that span a range of p and O-H bond BDE values, exhibiting different reaction mechanisms.

Dioxygenase Chemistry in Nucleophilic Aldehyde Deformylations Utilizing Dicopper O-Derived Peroxide Complexes.

The chemistry of copper-dioxygen complexes is relevant to copper enzymes in biology as well as in (ligand)Cu-O (or Cu-O) species utilized in oxidative transformations. For overall energy considerations, as applicable in chemical synthesis, it is beneficial to have an appropriate atom economy; both O-atoms of O are transferred to the product(s). However, examples of such dioxygenase-type chemistry are extremely rare or not well documented.

Intramolecular Phenolic H-Atom Abstraction by a NArOH Ligand-Supported (μ-η:η-Peroxo)dicopper(II) Species Relevant to the Active Site Function of oxy-Tyrosinase.

Synthetic side-on peroxide-bound dicopper(II) () complexes are important for understanding the active site structure/function of many copper-containing enzymes. This work highlights the formation of new {Cu(μ-η:η-O)Cu} complexes (with electronic absorption and resonance Raman (rR) spectroscopic characterization) using tripodal NArOH ligands at -135 °C, which spontaneously participate in intramolecular phenolic H-atom abstraction (HAA). This results in the generation of bis(phenoxyl radical)bis(μ-OH)dicopper(II) intermediates, substantiated by their EPR/UV-vis/rR spectroscopic signatures and crystal structural determination of a diphenoquinone dicopper(I) complex derived from ligand -C═C coupling.

Coordination Variations within Binuclear Copper Dioxygen-Derived (Hydro)Peroxo and Superoxo Species; Influences upon Thermodynamic and Electronic Properties.

Copper ion is a versatile and ubiquitous facilitator of redox chemical and biochemical processes. These include the binding of molecular oxygen to copper(I) complexes where it undergoes stepwise reduction-protonation. A detailed understanding of thermodynamic relationships between such reduced/protonated states is key to elucidate the fundamentals of the chemical/biochemical processes involved.

Heme-copper and Heme O-derived synthetic (bioinorganic) chemistry toward an understanding of cytochrome c oxidase dioxygen chemistry.

Cytochrome c oxidase (CcO), also widely known as mitochondrial electron-transport-chain complex IV, is a multi-subunit transmembrane protein responsible for catalyzing the last step of the electron transport chain, dioxygen reduction to water, which is essential to the establishment and maintenance of the membrane proton gradient that drives ATP synthesis. Although many intermediates in the CcO catalytic cycle have been spectroscopically and/or computationally authenticated, the specifics regarding the I intermediate, hypothesized to be a heme-Cu (hydro)peroxo species whose O-O bond homolysis is supported by a hydrogen-bonding network of water molecules, are largely obscured by the fast kinetics of the A (Fe-O/Cu/Tyr) → P (Fe=O/Cu-OH/Tyr) step. In this review, we have focused on the recent advancements in the design, development, and characterization of synthetic heme-peroxo‑copper model complexes, which can circumvent the abovementioned limitation, for the investigation of the formation of I and its O-O cleavage chemistry.

Ligand-Copper(I) Primary O-Adducts: Design, Characterization, and Biological Significance of Cupric-Superoxides.

In this Account, we overview and highlight synthetic bioinorganic chemistry focused on initial adducts formed from the reaction of reduced ligand-copper(I) coordination complexes with molecular oxygen, reactions that produce ligand-Cu(O) complexes (O ≡ superoxide anion). We provide mostly a historical perspective, starting in the Karlin research group in the 1980s, emphasizing the ligand design and ligand effects, structure, and spectroscopy of these O adducts and subsequent further reactivity with substrates, including the interaction with a second ligand-Cu complex to form binuclear species. The Account emphasizes the approach, evolution, and results obtained in the Karlin group, a synthetic bioinorganic research program inspired by the state of knowledge and insights obtained on enzymes possessing copper ion active sites which process molecular oxygen.

Fenton-like Chemistry by a Copper(I) Complex and HO Relevant to Enzyme Peroxygenase C-H Hydroxylation.

Lytic polysaccharide monooxygenases have received significant attention as catalytic convertors of biomass to biofuel. Recent studies suggest that its peroxygenase activity (i.e.

Reductive Coupling of Nitric Oxide by Cu(I): Stepwise Formation of Mono- and Dinitrosyl Species to a Cupric Hyponitrite Intermediate.

Transition-metal-mediated reductive coupling of nitric oxide (NO) to nitrous oxide (NO) has significance across the fields of industrial chemistry, biochemistry, medicine, and environmental health. Herein, we elucidate a density functional theory (DFT)-supplemented mechanism of NO reductive coupling at a copper-ion center, [(tmpa)Cu(MeCN)] () {tmpa = tris(2-pyridylmethyl)amine}. At -110 °C in EtOH (<-90 °C in MeOH), exposing to NO leads to a new binuclear hyponitrite intermediate [{(tmpa)Cu}(μ-NO)] (), exhibiting temperature-dependent irreversible isomerization to the previously characterized κ-O,O'--[(tmpa)Cu(μ-NO)] () complex.

Concluding remarks: discussion on natural and artificial enzymes including synthetic models.

This paper overviews the final remarks lecture delivered (by K. D. K.

End-On Copper(I) Superoxo and Cu(II) Peroxo and Hydroperoxo Complexes Generated by Cryoreduction/Annealing and Characterized by EPR/ENDOR Spectroscopy.

In this report, we investigate the physical and chemical properties of monocopper Cu(I) superoxo and Cu(II) peroxo and hydroperoxo complexes. These are prepared by cryoreduction/annealing of the parent [LCu(O)] Cu(I) dioxygen adducts with the tripodal, N-coordinating, tetradentate ligands L = tmpa, tmpa, TMGtren and are best described as [LCu(O)] Cu(II) complexes that possess end-on (η-O) superoxo coordination. Cryogenic γ-irradiation (77 K) of the EPR-silent parent complexes generates mobile electrons from the solvent that reduce the [LCu(O)] within the frozen matrix, trapping the reduced form fixed in the structure of the parent complex.

Proton Relay in Iron Porphyrins for Hydrogen Evolution Reaction.

The efficiency of the hydrogen evolution reaction (HER) can be facilitated by the presence of proton-transfer groups in the vicinity of the catalyst. A systematic investigation of the nature of the proton-transfer groups present and their interplay with bulk proton sources is warranted. The HERs electrocatalyzed by a series of iron porphyrins that vary in the nature and number of pendant amine groups are investigated using proton sources whose p values vary from ∼9 to 15 in acetonitrile.

A Thioether-Ligated Cupric Superoxide Model with Hydrogen Atom Abstraction Reactivity.

The central role of cupric superoxide intermediates proposed in hormone and neurotransmitter biosynthesis by noncoupled binuclear copper monooxygenases like dopamine-β-monooxygenase has drawn significant attention to the unusual methionine ligation of the Cu ("Cu") active site characteristic of this class of enzymes. The copper-sulfur interaction has proven critical for turnover, raising still-unresolved questions concerning Nature's selection of an oxidizable Met residue to facilitate C-H oxygenation. We describe herein a model for Cu, [(NS)Cu] ([]), and its O-bound analog [(NS)Cu(O)] ([·O]).

Ferric Heme Superoxide Reductive Transformations to Ferric Heme (Hydro)Peroxide Species: Spectroscopic Characterization and Thermodynamic Implications for H-Atom Transfer (HAT).

A new end-on low-spin ferric heme peroxide, [(P )Fe -(O )] (P -P), and subsequently formed hydroperoxide species, [(P )Fe -(OOH)] (P -HP) are generated utilizing the iron-porphyrinate P with its tethered axial base imidazolyl group. Measured thermodynamic parameters, the ferric heme superoxide [(P )Fe -(O )] (P -S) reduction potential (E°') and the P -HP pK value, lead to the finding of the OO-H bond-dissociation free energy (BDFE) of P -HP as 69.5 kcal mol using a thermodynamic square scheme and Bordwell relationship.

Kβ X-ray Emission Spectroscopy as a Probe of Cu(I) Sites: Application to the Cu(I) Site in Preprocessed Galactose Oxidase.

Cu(I) active sites in metalloproteins are involved in O activation, but their O reactivity is difficult to study due to the Cu(I) d closed shell which precludes the use of conventional spectroscopic methods. Kβ X-ray emission spectroscopy (XES) is a promising technique for investigating Cu(I) sites as it detects photons emitted by electronic transitions from occupied orbitals. Here, we demonstrate the utility of Kβ XES in probing Cu(I) sites in model complexes and a metalloprotein.

Heme-Fe Superoxide, Peroxide and Hydroperoxide Thermodynamic Relationships: Fe-O Complex H-Atom Abstraction Reactivity.

Establishing redox and thermodynamic relationships between metal-ion-bound O and its reduced (and protonated) derivatives is critically important for a full understanding of (bio)chemical processes involving dioxygen processing. Here, a ferric heme peroxide complex, [(F)Fe-(O)] () (F = tetrakis(2,6-difluorophenyl)porphyrinate), and a superoxide complex, [(F)Fe-(O)] (), are shown to be redox interconvertible. Using Cr(η-CH), an equilibrium state where and are present is established in tetrahydrofuran (THF) at -80 °C, allowing determination of the reduction potential of as -1.

Copper(I) Complex Mediated Nitric Oxide Reductive Coupling: Ligand Hydrogen Bonding Derived Proton Transfer Promotes NO Release.

A cuprous chelate bearing a secondary sphere hydrogen bonding functionality, [(PV-tmpa)Cu], transforms NO to NO in high-yields in methanol. Ligand derived proton transfer facilitates N-O bond cleavage of a putative hyponitrite intermediate releasing NO, underscoring the crucial balance between H-bonding capabilities and acidities in (bio)chemical NO coupling systems.

Impact of Intramolecular Hydrogen Bonding on the Reactivity of Cupric Superoxide Complexes with O-H and C-H Substrates.

The dioxygen reactivity of a series of TMPA-based copper(I) complexes (TMPA=tris(2-pyridylmethyl)amine), with and without secondary-coordination-sphere hydrogen-bonding moieties, was studied at -135 °C in 2-methyltetrahydrofuran (MeTHF). Kinetic stabilization of the H-bonded [( TMPA)Cu (O )] cupric superoxide species was achieved, and they were characterized by resonance Raman (rR) spectroscopy. The structures and physical properties of [( TMPA)Cu (N )] azido analogues were compared, and the O reactivity of ligand-Cu complexes when an H-bonding moiety is replaced by a methyl group was contrasted.

Enhanced Rates of C-H Bond Cleavage by a Hydrogen-Bonded Synthetic Heme High-Valent Iron(IV) Oxo Complex.

Secondary coordination sphere interactions are critical in facilitating the formation, stabilization, and enhanced reactivity of high-valent oxidants required for essential biochemical processes. Herein, we compare the C-H bond oxidizing capabilities of spectroscopically characterized synthetic heme iron(IV) oxo complexes, FCmpd-II (F = tetrakis(2,6-difluorophenyl)porphyrinate), and a 2,6-lutidinium triflate (LutH) Lewis acid adduct involving ferryl O-atom hydrogen-bonding, FCmpd-II(LutH). Second-order rate constants utilizing C-H and C-D substrates were obtained by UV-vis spectroscopic monitoring, while products were characterized and quantified by EPR spectroscopy and gas chromatography (GC).