Fast and Versatile Functionalization of Glassy Carbon.

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.

Electrocatalytic alcohol oxidation by covalently immobilized ruthenium complex on carbon.

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.

Phenolate-bonded bis(µ-oxido)-bis-copper(III) intermediates: hydroxylation and dehalogenation reactivities.

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.

Selective Oxidation of Exogenous Substrates by a Bis-Cu(III) Bis-Oxide Complex: Mechanism and Scope.

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.

Exclusive imidazole ligation to CuIII2O2 and CuIIICuII2O2 cores.

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).

Electronic Structure and Reactivity Studies of a Nonsymmetric One-Electron Oxidized CuII Bis-phenoxide Complex.

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 then studied in detail, and Cu K-edge X-ray Absorption Spectroscopy (XAS) measurements confirmed a CuII-phenoxyl radical complex in solution. Subsequent 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 reacted in a similar manner as the oxidized CuII-salen analogue, and does not exhibit a substrate-binding pre-equilibrium as observed for the oxidized bisaminophenoxide CuII-salan derivative.

High-valent copper in biomimetic and biological oxidations.

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.

Simplest Monodentate Imidazole Stabilization of the oxy-Tyrosinase Cu2 O2 Core: Phenolate Hydroxylation through a Cu(III) Intermediate.

Tyrosinases are ubiquitous binuclear copper enzymes that oxygenate to Cu(II) 2 O2 cores bonded by three histidine Nτ-imidazoles per Cu center. Synthetic monodentate imidazole-bonded Cu(II) 2 O2 species self-assemble in a near quantitative manner at -125 °C, but Nπ-ligation has been required. Herein, we disclose the syntheses and reactivity of three Nτ-imidazole bonded Cu(II) 2 O2 species at solution temperatures of -145 °C, which was achieved using a eutectic mixture of THF and 2-MeTHF. The addition of anionic phenolates affords a Cu(III) 2 O2 species, where the bonded phenolates hydroxylate to catecholates in high yields. Similar Cu(III) 2 O2 intermediates are not observed using Nπ-bonded Cu(II) 2 O2 species, hinting that Nτ-imidazole ligation, conserved in all characterized Ty, has functional advantage beyond active-site flexibility. Substrate accessibility to the oxygenated Cu2 O2 core and stabilization of a high oxidation state of the copper centers are suggested from these minimalistic models.

Direct Copper(III) Formation from O2 and Copper(I) with Histamine Ligation.

Histamine chelation of copper(I) by a terminal histidine residue in copper hydroxylating enzymes activates dioxygen to form unknown oxidants, generally assumed as copper(II) species. The direct formation of copper(III)-containing products from the oxygenation of histamine-ligated copper(I) complexes is demonstrated here, indicating that copper(III) is a viable oxidation state in such products from both kinetic and thermodynamic perspectives. At low temperatures, both trinuclear Cu(II)2Cu(III)O2 and dinuclear Cu(III)2O2 predominate, with the distribution dependent on the histamine ligand structure and oxygenation conditions. Kinetics studies suggest the bifurcation point to these two products is an unobserved peroxide-level dimer intermediate. The hydrogen atom reactivity difference between the trinuclear and binuclear complexes at parity of histamine ligand is striking. This behavior is best attributed to the accessibility of the bridging oxide ligands to exogenous substrates rather than a difference in oxidizing abilities of the clusters.

Manganese(II)/Picolinic Acid Catalyst System for Epoxidation of Olefins.

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.

Low temperature syntheses and reactivity of Cu2O2 active-site models.

Nature's facility with dioxygen outmatches modern chemistry in the oxidation and oxygenation of materials and substrates for biosynthesis and cellular metabolism. The Earth's most abundant naturally occurring oxidant is-frankly-poorly understood and controlled, and thus underused. Copper-based enzyme metallocofactors are ubiquitous to the efficient consumption of dioxygen by all domains of life. Over the last several decades, we have joined many research groups in the study of copper- and dioxygen-dependent enzymes through close investigation of synthetically derived, small-molecule active-site analogs. Simple copper-dioxygen clusters bearing structural and spectroscopic similarity to dioxygen-activating enzymes can be probed for their fundamental geometrical, electronic, and reactive properties using the tools available to inorganic and synthetic chemistry. Our exploration of the copper-dioxygen arena has sustained product evaluation of the key dynamics and reactivity of binuclear Cu2O2 compounds. Almost exclusively operating at low temperatures, from -78 °C to solution characterization even at -125 °C, we have identified numerous compounds supported by simple and easily accessed, low molecular weight ligands-chiefly families of bidentate diamine chelates. We have found that by stripping away complexity in comparison to extended protein tertiary structures or sophisticated, multinucleating architectures, we can experimentally manipulate activated compounds and open pathways of reactivity toward exogenous substrates that both inform on and extend fundamental mechanisms of oxygenase enzymes. Our recent successes have advanced understanding of the tyrosinase enzyme, and related hemocyanin and NspF, and the copper membrane monooxygenases, specifically particulate methane monooxygenase (pMMO) and ammonia monooxygenase (AMO). Tyrosinase, ubiquitously distributed throughout life, is fundamental to the copper-based oxidation of phenols and the production of chromophores by dedicated biosynthesis or incidental oxidative browning. The copper membrane monooxygenases are comparatively new entrants to the copper-dioxygen field. While pMMO mediates the synthetically tantalizing transformation of methane to methanol, AMO catalyzes the first metabolic step in deriving chemical energy from ammonia-a reaction massively represented on a global scale and a critical component of chemical homeostasis on Earth. In this Account, we begin by introduction of the synthetic copper-dioxygen chemistry field, from techniques to the differential coordination of dioxygen with copper. Then, we describe the unambiguous self-assembly of an oxygenated tyrosinase mimic from basic constituents (copper, dioxygen, and monodentate-imidazole histidine analogs) and the resulting emergence of intrinsic reactivity, free of any influence due to the protein environment. Next, we discuss the first catalytic oxidation of phenol through a fully characterized tyrosinase mimic, derived from molecular oxygen, and its application to substrates unreactive in the native enzyme system. Finally, we detail evidence for chemical plausibility of dioxygen activation in pMMO (and AMO) through a high-valent species and the thermodynamic criteria that beg introduction of the Cu(III) state to biological redox catalysis.

Chemical Plausibility of Cu(III) with Biological Ligation in pMMO.

The mechanisms of dioxygen activation and methane C-H oxidation in particulate methane monooxygenase (pMMO) are currently unknown. Recent studies support a binuclear copper site as the catalytic center. We report the low-temperature assembly of a high-valent dicopper(III) bis(µ-oxide) complex bearing marked structural fidelity to the proposed active site of pMMO. This unprecedented dioxygen-bonded Cu(III) species with exclusive biological ligation directly informs on the chemical plausibility and thermodynamic stability of the bis(µ-oxide) structure in such dicopper sites and foretells unusual optical signatures of an oxygenation product in pMMO. Though the ultimate pMMO active oxidant is still debated, C-H oxidation of exogenous substrates is observed with the reported Cu(III) complexes. The assembly of a high valent species both narrows the search for relevant pMMO intermediates and provides evidence to substantiate the role of Cu(III) in biological redox processes.

Sequential "click" functionalization of mesoporous titania for energy-relay dye enhanced dye-sensitized solar cells.

Energy relay dyes (ERDs) have been investigated previously as a mean to achieve panchromatic spectral response in dye-sensitized solar cells via energy transfer. To reduced the distance between the ERDs and energy-accepting injection dyes (IDs) on the surface of a mesoporous titanium dioxide electrode, the ERDs were immobilized adjacent to the IDs via a sequential functionalization approach. In the first step, azidobenzoic acid molecules were co-adsorbed on the mesoporous titanium dioxide surface with the ID. In the second step, the highly selective copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition "click" reaction was employed to couple an alkyne-functionalized ERD to the azidobenzoic acid monolayer. The cycloaddition step in the mesoporous electrode was slowed dramatically due to reactants and catalysts forming agglomerates. In solar cell devices, the close proximity between the surface-immobilized ERD and energy-accepting squaraine sensitizer dyes results in energy transfer efficiencies of up to 91%. The relative improvement in device performance due to the additional ERD spectral response was 124%, which is among the highest reported. The sequential functionalization approach described herein is transferrable to other applications requiring the functionalization of electrodes with complex molecules.

Formation of hybrid guanidine-stabilized bis(µ-oxo)dicopper cores in solution: Electronic and steric perturbations.

A series of new hybrid peralkylated-amine-guanidine ligands based on a 1,3-propanediamine backbone and their Cu-O2 chemistry is reported. The copper(I) complexes react readily with O2 at low temperatures in aprotic solvents with weakly coordinating anions to form exclusively bis(µ-oxo) dicopper species (O). Variation of the substituents on each side of the hybrid bidentate ligand highlights that less sterically demanding amine and guanidine substituents increase not only the thermal stability of the formed O cores but enhance inner-sphere phenolate hydroxylation pathways. TD-DFT analysis on selected guanidine-amine O species suggest that the additional visible feature observed is a guanidine π*→ Cu2O2 LMCT, which appears along with the classic oxo-ζu*→Cu(III) and πζ*→ Cu(III) LMCT transitions.

Primary amine stabilization of a dicopper(III) bis(µ-oxo) species: modeling the ligation in pMMO.

Here we report the formation of the first examples of dicopper(III) bis(µ-oxo) complexes ligated by the primary amines, propylenediamine, and N,N,-dimethyl propylenediamine. Stabilization of these new compounds is effected at -125 °C by "core capture"- introduction of exogenous ligand to a preformed dicopper(III) bis(µ-oxo) complex supported by the peralkylated tetramethyl propylenediamine. Primary amine ligation in these compounds matches the single primary amine coordination of the putative active site of particulate methane monooxygenase (pMMO) and polysaccharide monooxygenase. Reactivity studies presented here show primary amine ligated cores are competent oxidants, capable of activating C-H bonds by an H-atom abstraction mechanism. Trends in spectroscopy, structure, and reactivity provide hints to the potential role of primary amine ligation in pMMO: increased substrate accessibility to the redox active orbitals of the Cu2O2 core and greater stabilization of the oxidant without attenuation of oxidizing power.

Ligand noninnocence of thiolate/disulfide in dinuclear copper complexes: solvent-dependent redox isomerization and proton-coupled electron transfer.

Copper thiolate/disulfide interconversions are related to the functions of several important proteins such as human Sco1, Cu-Zn superoxide dismutase (SOD1), and mammalian zinc-bonded metallothionein. The synthesis and characterization of well-defined synthetic analogues for such interconversions are challenging yet provide important insights into the mechanisms of such redox processes. Solvent-dependent redox isomerization and proton-coupled electron transfer mimicking these interconversions are observed in two structurally related dimeric µ,η(2):η(2)-thiolato Cu(II)Cu(II) complexes by various methods, including X-ray diffraction, XAS, NMR, and UV-vis. Spectroscopic evidence shows that a solvent-dependent equilibrium exists between the dimeric µ-thiolato Cu(II)Cu(II) state and its redox isomeric µ-disulfido Cu(I)Cu(I) form. Complete formation of µ-disulfido Cu(I)Cu(I) complexes, however, only occurs after the addition of 2 equiv of protons, which promote electron transfer from thiolate to Cu(II) and formation of disulfide and Cu(I) via protonation of the coordinating ligand. Proton removal reverses this reaction. The reported unusual reductive protonation/oxidative deprotonation of the metal centers may serve as a new chemical precedent for how related proteins manage Cu ions in living organisms.

L-edge X-ray absorption spectroscopy and DFT calculations on Cu2O2 species: direct electrophilic aromatic attack by side-on peroxo bridged dicopper(II) complexes.

The hydroxylation of aromatic substrates catalyzed by coupled binuclear copper enzymes has been observed with side-on-peroxo-dicopper(II) (P) and bis-µ-oxo-dicopper(III) (O) model complexes. The substrate-bound-O intermediate in [Cu(II)2(DBED)2(O)2](2+) (DBED = N,N'-di-tert-butyl-ethylenediamine) was shown to perform aromatic hydroxylation. For the [Cu(II)2(NO2-XYL)(O2)](2+) complex, only a P species was spectroscopically observed. However, it was not clear whether this O-O bond cleaves to proceed through an O-type structure along the reaction coordinate for hydroxylation of the aromatic xylyl linker. Accurate evaluation of these reaction coordinates requires reasonable quantitative descriptions of the electronic structures of the P and O species. We have performed Cu L-edge XAS on two well-characterized P and O species to experimentally quantify the Cu 3d character in their ground state wave functions. The lower per-hole Cu character (40 ± 6%) corresponding to higher covalency in the O species compared to the P species (52 ± 4%) reflects a stronger bonding interaction of the bis-µ-oxo core with the Cu(III) centers. DFT calculations show that 10-20% Hartree-Fock (HF) mixing for P and ~38% for O species are required to reproduce the Cu-O bonding; for the P species this HF mixing is also required for an antiferromagnetically coupled description of the two Cu(II) centers. B3LYP (with 20% HF) was, therefore, used to calculate the hydroxylation reaction coordinate of P in [Cu(II)2(NO2-XYL)(O2)](2+). These experimentally calibrated calculations indicate that the electrophilic attack on the aromatic ring does not involve formation of a Cu(III)2(O(2-))2 species. Rather, there is direct electron donation from the aromatic ring into the peroxo σ* orbital of the Cu(II)2(O2(2-)) species, leading to concerted C-O bond formation with O-O bond cleavage. Thus, species P is capable of direct hydroxylation of aromatic substrates without the intermediacy of an O-type species.

Squish and CuAAC: additive-free covalent monolayers of discrete molecules in seconds.

A terminal alkyne is immobilized rapidly into a full monolayer by squishing a small volume of a solution of the alkyne between an azide-modified surface and a copper plate. The monolayer is covalently attached to the surface through a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction, and the coverages of the immobilized electroactive alkyne species are quantified by cyclic voltammetry. A reaction time of less than 20 s is possible with no other reagents required. The procedure is effective under aerobic conditions using either an aqueous or aprotic organic solution of the alkyne (1-100 mM).