Histidine is among the most versatile amino acids by virtue of its imidazole ring, which is capable of shuttling protons and binding metals at each of its two nitrogen atoms, Nπ (Nδ) and Nτ (Nε). Despite having a tautomeric relationship and similar basicities, the nitrogen atoms used in copper enzymes are differentiated functionally, with near exclusive Nτ-ligation associated with substrate activation sites and exclusive Nπ-ligation with electron-transfer sites. The results herein show that the innate thermodynamic preference is Nτ-ligation to Cu(II) centers, a conclusion drawn from ligand competition experiments at -145 °C between histidine imidazoles within synthetic μ-η2:η2-peroxodicopper(II) cores. The findings from these faithful models of oxygenated binuclear copper sites in tyrosinase enzymes are informed by spectroscopic data from a series of related complexes with monodentate methylated imidazoles. This preference of histidine Nτ-ligation is ascribed enthalpically to greater basicity and entropically to the greater molecular volume of the resulting metal complex compared to its Nπ-ligated isomer. These results support that the Nτ-ligation observed in copper enzymatic sites is the innate thermodynamic form, independent of the protein matrix, while the Nπ-ligation observed in electron transfer sites is presumably entatic in origin─requiring evolved protein structural influences. This structural distinction provides a powerful indicator of function among the biological copper sites.

Imidazole ligation of metals through histidine is extensive among metalloproteins, yet the role of the imidazol ate conjugate base is often neglected, despite its potential accessibility when bonded to an oxidized metal center. Using synthetic models of oxygenated tyrosinase enzymes ligated exclusively by monodentate imidazoles, we find that deprotonation of the μ 2 -η 2 :η 2 -peroxidodicopper(II) species triggers redox isomerization to an imidazol ate -ligated bis(μ 2 -oxido)dicopper(III) species. Formal two-electron oxidation to Cu(III) remains biologically unprecedented, yet is effected readily by addition of base. Spectrophotometric titrations by UV/Visible/near-IR and copper K-edge X-ray absorption spectroscopies are interpreted most simply as two cooperative, 2H + transformations in which the peroxide O−O is cleaved in the first step. Elaboration from simple imidazoles to a protected histidine extends this isomerization into an amino acid environment. The role of phenolate as a base suggests this four-electron reduction of O 2 is energetically viable in a biological context and requires only two copper centers, which act as two-electron shuttles when imidazole deprotonation assists. This existential precedent of viable imidazol ate intermediates invites speculation into an alternative mechanism for phenol hydroxylation not previously considered at Type 3 copper sites such as tyrosinases. Structural biological evidence suggests imidazolate ligation of copper may be more widespread than generally understood.

Exogenous phenolate ortho-hydroxylation by copper oxidants formed from dioxygen is generally thought to occur through one of two limiting mechanisms defined by the structure of the active oxidant: an electrophilic μ-η2:η2-peroxo-bis-copper(II) species as found in the oxygenated form of the binuclear copper enzyme tyrosinase (oxyTyr), or an isomeric bis(μ-oxido)-bis-copper(III) species (O) with ligated phenolate(s) as evidenced by most synthetic systems. The characterization of the latter is limited due to their limited thermal stability. This study expands the scope of an O species with ligated phenolate(s) using N,N'-di-tert-butyl-1,3-propanediamine (DBPD), a flexible secondary diamine ligand. Oxygenation of the [(DBPD)Cu(I)]1+ complex at low temperatures (e.g., 153 K) forms a spectroscopically and structurally faithful model to oxyTyr, a side-on peroxide intermediate, which reacts with added phenolates to form a bis(μ-oxido)-bis-copper(III) species with ligated phenolates, designated as an A species. The proposed stoichiometry of A is best understood as possessing 2 rather than 1 bonded phenolate. Thermal decomposition of A results in regiospecific phenolate ortho-hydroxylation with the ortho-substituent as either a C-H or C-X (Cl, Br) group, though the halogen displacement is significantly slower. DFT and experimental studies support an electrophilic attack of an oxide ligand into the π-system of a ligated phenolate. This study supports a hydroxylation mechanism in which O-O bond cleavage of the initially formed peroxide by phenolate ligation, which precedes phenolate aromatic hydroxylation.

A rapid procedure for the functionalization of glassy carbon surfaces (GCSs) is disclosed. A three-step sequence of bromomethylation, azide displacement, and copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) allows ethynylated molecules to be attached covalently to the carbon surface through a methylene functional group. Redox-active ethynyl ferrocene and [RuII(Cl)(DMSO)(ethynyl-TPA)]1+ (DMSO = dimethylsulfoxide; TPA = tris(2-pyridylmethyl)amine) are attached with high coverages as assessed by cyclic voltammetry, and the elemental composition of the surface is confirmed by X-ray photoelectron spectroscopy. In less than 1 h, surface coverages of 1 × 1014 molecules/cm2 are possible that exhibit good durability in both acidic and basic media. Attached [RuII(Cl)(DMSO)(ethynyl-TPA)]1+ catalytically oxidizes alcohols, yet the currents and potentials are less impressive compared to an attachment without the intervening methylene group. The advantages of this covalent attachment procedure for GCSs are its short reaction times, mild reaction conditions, and the use of standard laboratory reagents and glassware, allowing for many types of ethynylated molecules to be attached rapidly to the surface.

Leigh Aldous opened the discussion of the paper by Carole Duboc: Since the CoFe has a lower overpotential for H2 production, the current will be much lower than those of NiFe and FeFe (even if they have the same kinetic parameters). So, was there any evidence for electrocatalytic ability, e.g.

A dearth of discrete immobilized metal complexes exist that electrocatalytically oxidize methanol. Reported here is the covalent immobilization of a tris(2-pyridylmethyl)amine ruthenium complex [RuII(Cl)(DMSO)(ethynyl-TPA)]+ (ethynyl-TPA = (5-ethynyl-2-pyridylmethyl)bis(2-pyridylmethyl)amine) to a glassy carbon (GC) electrode through a CuI catalyzed azide-alkyne cycloaddition (click) reaction between the ethynyl-TPA ligand and an azide derivatized carbon surface forming [RuII(Cl)(DMSO)(GC-click-TPA)]+. Following water substitution for DMSO and proton coupled electron transfer, [RuIV(O)(Cl)(GC-click-TPA)]+ electrooxidizes alcohols, including methanol, efficiently relative to other immobilized metal complexes. A primary kinetic isotope effect suggests rate-limiting Cα-H bond cleavage of benzyl alcohol. Approximately 40% of the [RuII(Cl)(DMSO)(GC-click-TPA)]+ undergoes the DMSO for water exchange to form an active oxidant, consistent with the 40% distribution of the more labile Cl-cis-amine isomer before immobilization. Using the benchmark of benzyl alcohol electrocatalytic oxidation, [RuIV(O)(Cl)(GC-click-TPA)]+ operates at ca. 250 mV lower overpotential, with a 15% increase in faradaic efficiency, and at least an order of magnitude increase in average turnover frequency (0.7 s-1 TOFavg) compared to the previously best immobilized discrete ruthenium complexes.

Department of Chemistry, University of California, Davis, California, USA; Department of Chemistry, University of Kansas, Lawrence, Kansas, USA; Department of Chemistry, Boston College, Chestnut Hill, Massachusetts, USA; Department of Chemistry, University of Washington, Seattle, Washington, USA; Department of Chemistry, Stanford University, Stanford, California, USA; Department of Chemistry, Tulane University, New Orleans, Louisiana, USA; Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, USA; Department of Chemistry, Wayne State University, Detroit, Michigan, USA; State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China

Bromomethylation is a mild and convenient synthetic method to modify a carbon surface that can be subsequently derivatized to form a variety of surface groups. Diamine modification yields novel materials that improve the performance of Li–S cathodes.

We disclose herein the synthesis and characterization of L2Cu(iii)2O2 and L3Cu(iii)Cu(ii)2O2 complexes with nitrogen ligation exclusively from imidazoles for the first time. Their accessibility by direct oxygenation of a L-Cu(i) precursor and the resulting Cu(iii) formation inform on the kinetic accessibility and thermodynamic superiority of imidazole in stabilizing Cu(iii).

We disclose herein the synthesis and characterization of L 2 Cu(III) 2 O 2 and L 3 Cu(III)Cu(II) 2 O 2 complexes with nitrogen ligation exclusively from imidazoles for the first time. Their accessibility by direct oxygenation of a L-Cu(I) precursor and the resulting Cu(III) formation inform on the kinetic accessibility and thermodynamic superiority of imidazole in stabilizing Cu(III). Graphical Abstract Direct oxygenation of imidazole-ligated Cu(I) generates dinuclear and trinuclear Cu(III) species with exclusive imidazole ligation. myriad of Cu oxidized to the Cu(I) or oxidation

We disclose herein the synthesis and characterization of L2Cu(iii)2O2 and L3Cu(iii)Cu(ii)2O2 complexes with nitrogen ligation exclusively from imidazoles for the first time. Their accessibility by direct oxygenation of a L-Cu(i) precursor and the resulting Cu(iii) formation inform on the kinetic accessibility and thermodynamic superiority of imidazole in stabilizing Cu(iii).

Cu(III)2(μ-O)2 bis-oxides (O) form spontaneously by direct oxygenation of nitrogen-chelated Cu(I) species and constitute a diverse class of versatile 2e-/2H+ oxidants, but while these species have attracted attention as biomimetic models for dinuclear Cu enzymes, reactivity is typically limited to intramolecular ligand oxidation, and systems exhibiting synthetically useful reactivity with exogenous substrates are limited. O tmpd (TMPD = N 1 , N 1 , N 3 , N 3 -tetramethylpropane-1,3-diamine) presents an exception, readily oxidizing a diverse array of exogenous substrates, including primary alcohols and amines selectively over their secondary counterparts in good yields. Mechanistic and DFT analyses suggest substrate oxidation proceeds through initial axial coordination, followed by rate limiting rotation to position the substrate in the Cu(III) equatorial plane, whereupon rapid deprotonation and oxidation by net hydride transfer occurs. Together, the results suggest the selectivity and broad substrate scope unique to O tmpd are best attributed to the combination of ligand flexibility, limited steric demands, and ligand oxidative stability. In keeping with the absence of rate limiting C-H scission, O tmpd exhibits a marked insensitivity to the strength of the substrate Cα-H bond, readily oxidizing benzyl alcohol and 1 octanol at near identical rates.

The tetradentate mixed imino/amino phenoxide ligand (N-(3,5-di-tert-butylsalicylidene)-N′-(2-hydroxyl-3,5-di-tert-butylbenzyl))-trans-1,2-cyclohexanediamine (salalen) was complexed with CuII, and the resulting Cu complex (2) was characterized by a number of experimental techniques and theoretical calculations. Two quasi-reversible redox processes for 2, as observed by cyclic voltammetry, demonstrated the potential stability of oxidized forms, and also the increased electron-donating ability of the salalen ligand in comparison to the salen analogue. The electronic structure of the one-electron oxidized [2]+ was studied in detail, and Cu K-edge X-ray Absorption Spectroscopy (XAS) measurements confirmed a CuII-phenoxyl radical complex in solution. Resonance Raman (rR) and variable temperature 1H NMR studies, coupled with theoretical calculations, showed that [2]+ is a triplet (S=1) CuII-phenoxyl radical species, with localization of the radical on the more electron-rich aminophenoxide. Attempted isolation of X-ray quality crystals of [2]+ afforded [2H]+, with a protonated phenol bonded to CuII, and an additional H-bonding interaction with the SbF6− counterion. Stoichiometric reaction of dilute solutions of [2]+ with benzyl alcohol showed that the complex reacts in a similar manner as the oxidized CuII-salen analogue, and does not exhibit a substrate-binding pre-equilibrium as observed for the oxidized bis-aminophenoxide CuII-salan derivative.

A long-standing debate in the Cu-O2 field has revolved around the relevance of the Cu(III) oxidation state in biological redox processes. The proposal of Cu(III) in biology is generally challenged as no spectroscopic or structural evidence exists currently for its presence. The reaction of synthetic Cu(I) complexes with O2 at low temperature in aprotic solvents provides the opportunity to investigate and define the chemical landscape of Cu-O2 species at a small-molecule level of detail; eight different types are characterized structurally, three of which contain at least one Cu(III) center. Simple imidazole or histamine ligands are competent in these oxygenation reactions to form Cu(III) complexes. The combination of synthetic structural and reactivity data suggests (1) that Cu(I) should be considered as either a one or two electron reductant reacting with O2, (2) that Cu(III) reduction potentials of these formed complexes are modest and well within the limits of a protein matrix and (3) that primary amine and imidazole ligands are surprisingly good at stabilizing Cu(III) centers. These Cu(III) complexes are efficient oxidants for hydroxylating phenolate substrates with reaction hallmarks similar to that performed in biological systems. The remarkable ligation similarity of the synthetic and biological systems makes it difficult to continue to exclude Cu(III) from biological discussions.

The catalytic activity of discrete metal complexes can be dictated by the local ligand environment. By covalently immobilizing ligands on a surface, the ability of a single metal to engage multiple ligands is controlled by the overall surface loading and distribution. Using an azide functionalized mesoporous silica prepared via co-condensation, the surface loading of 1,10-phenanthroline (phen), a bidentate chelating ligand, can be varied systematically to form preferentially mono-, bis-, or tris-phen ligated metal complexes. Solvent refractive index matching enables in situ transmissive spectroscopic quantification of intense metal-to-ligand charge transfer bands of the immobilized copper(I) bis-phen and iron (II) tris-phen complexes. Metal complex formation agrees well with a random distribution model of the phen ligands on the surface, providing a means to quantitatively correlate immobilized species interactions and overall catalytic performance. Rapid epoxidation catalysis is obtained with surface distributions that maximize mono- or bis-phen ligated manganese centers. (C) 2015 Elsevier Inc. All rights reserved.

An in situ generated catalyst system based on Mn(CF3SO3)2, picolinic acid, and peracetic acid converts an extensive scope of olefins to their epoxides at 0 °C in <5 min, with remarkable oxidant efficiency and no evidence of radical behavior. Competition experiments indicate an electrophilic active oxidant, proposed to be a high-valent Mn = O species. Ligand exploration suggests a general ligand sphere motif contributes to effective oxidation. The method is underscored by its simplicity and use of inexpensive reagents to quickly access high value-added products.