Tuning of the copper-thioether bond in tetradentate N₃S(thioether) ligands; O-O bond reductive cleavage via a [Cu(II)₂(μ-1,2-peroxo)]²⁺/[Cu(III)₂(μ-oxo)₂]²⁺ equilibrium.

Current interest in copper/dioxygen reactivity includes the influence of thioether sulfur ligation, as it concerns the formation, structures, and properties of derived copper-dioxygen complexes. Here, we report on the chemistry of {L-Cu(I)}2-(O2) species L = (DMM)ESE, (DMM)ESP, and (DMM)ESDP, which are N3S(thioether)-based ligands varied in the nature of a substituent on the S atom, along with a related N3O(ether) (EOE) ligand. Cu(I) and Cu(II) complexes have been synthesized and crystallographically characterized. Copper(I) complexes are dimeric in the solid state, [{L-Cu(I)}2](B(C6F5)4)2, however are shown by diffusion-ordered NMR spectroscopy to be mononuclear in solution. Copper(II) complexes with a general formulation [L-Cu(II)(X)](n+) {X = ClO4(-), n = 1, or X = H2O, n = 2} exhibit distorted square pyramidal coordination geometries and progressively weaker axial thioether ligation across the series. Oxygenation (-130 °C) of {((DMM)ESE)Cu(I)}(+) results in the formation of a trans-μ-1,2-peroxodicopper(II) species [{((DMM)ESE)Cu(II)}2(μ-1,2-O2(2-))](2+) (1(P)). Weakening the Cu-S bond via a change to the thioether donor found in (DMM)ESP leads to the initial formation of [{((DMM)ESP)Cu(II)}2(μ-1,2-O2(2-))](2+) (2(P)) that subsequently isomerizes to a bis-μ-oxodicopper(III) complex, [{((DMM)ESP)Cu(III)}2(μ-O(2-))2](2+) (2(O)), with 2(P) and 2(O) in equilibrium (K(eq) = [2(O)]/[2(P)] = 2.6 at -130 °C). Formulations for these Cu/O2 adducts were confirmed by resonance Raman (rR) spectroscopy. This solution mixture is sensitive to the addition of methylsulfonate, which shifts the equilibrium toward the bis-μ-oxo isomer. Further weakening of the Cu-S bond in (DMM)ESDP or substitution with an ether donor in (DMM)EOE leads to only a bis-μ-oxo species (3(O) and 4(O), respectively). Reactivity studies indicate that the bis-μ-oxodicopper(III) species (2(O), 3(O)) and not the trans-peroxo isomers (1(P) and 2(P)) are responsible for the observed ligand sulfoxidation. Our findings concerning the existence of the 2(P)/2(O) equilibrium contrast with previously established ligand-Cu(I)/O2 reactivity and possible implications are discussed.

Introduction

<span class="Chemical">Coppern> ion-mediated <span class="Chemical">dioxygen activation studies have focused on understanding the kinetics and thermodynamics of reactive intermediate formation and their subsequent diverse oxidative reactivity.[1] Such work is inspired by the known utility of <span class="Chemical">copper in oxidative transformation of organic substrates. Additionally, the probing of ligand-copper(I)-O2 chemistry is motivated by the presence of copper enzymes which mediate O2-processing.[2] The detailed nature of the copper(s) active site environment (i.e., ligand type, coordination number and geometry, etc.) dictates the observed chemical reactivity, such as functioning as an O2-carrier, an oxygenase incorporating O atom(s) into a substrate, or an oxidase effecting substrate dehydrogenation chemistry.[2] In chemical studies geared toward either practical oxidations or elucidation of fundamental aspects of copper-dioxygen chemistry, it is a chelating polydentate ligand which controls the (L)CuI/O2 reactivity.

The majority of the CuI–<n class="Chemical">span class="Chemical">O2 literature on adduct formation and reactivity involves systems containing all <spn>an class="Chemical">nitrogen ligands, primarily bi-, tri-, or tetradentate entities.[1] However, certain copper metalloproteins utilize sulfur-containing ligand residues, such as cysteine and methionine (Met) in “blue” copper electron-transfer proteins[3] and in certain monooxygenases,[4] (vide infra), (Figure 1).[2]

Figure 1

Copper enzymes/proteins with S-ligands: (a) Peptidylglycine-α-hydroxylating monooxygenase (PHM), C–H oxygenation, (b) Azurin, electron transfer.

<span class="Chemical">Coppern> enzymes/proteins with S-ligands: (a) Peptidylglycine-α-hydroxylating monooxygenase (<span class="Gene">PHM), C–H oxygenation, (b) Azurin, electron transfer.

<span class="Chemical">Thioethern> S-ligation is important in the <span class="Chemical">dioxygen activating monooxygenases peptidylglycine-α-hydroxylating monooxygenase (PHM) (Figure 1a)[4] and dopamine β-monooxygenase (DβM).[2a,4a] These enzymes contain unique “non-coupled” binuclear copper centers, separated by ∼11 Å, one copper center with three histidine ligands (CuH), and the other with two histidines and one methionine (Met)(CuM). The CuM center is where O2-activation and substrate hydroxylation occur, while CuH receives reducing equivalents from ascorbate and is thought to serve as an electron transfer relay source to the CuM center as needed for monooxygenase activity.

Undoubtedly, the <span class="Chemical">thioethern> ligand plays a major role in setting the electronic structure and coordination required for CuM <span class="Chemical">O2-binding and activation leading to peptide pro-hormone (for <span class="Gene">PHM) oxidative N-dealkylation. However, the precise role of Met coordination and the actual PHM reaction mechanism have yet to be fully determined. A crystal structure obtained by Amzel and co-workers[4b] reveals dioxygen bound to CuM in an end-on superoxo fashion as depicted in Figure 1a. Computational or biochemical arguments suggest that this CuII–O2•– intermediate initiates the chemistry via substrate hydrogen-atom abstraction. Other O2-derived species have been suggested as the H atom abstracting intermediate; these include a cupric hydroperoxide (CuII–OOH) complex formed from reduction-protonation of the initially formed CuII–O2•– complex or a cupryl (CuIII=O ↔ CuII–O•) entity generated after even further reduction–protonation.[5]

Inspired by this biochemistry and with the motivation to elucidate the role of the <n class="Chemical">span class="Chemical">Met ligand in <spn>an class="Gene">PHM and DβM, a variety of ligand scaffolds with thioether donors have been synthesized, and their O2-reactivity has been interrogated. Within the N2S(thioether) family of ligands, copper(I) complexes with anionic ligands (Chart 1a)[6] react to give bis-μ-oxo dicopper(III) products, however, thioether ligation was ruled out. CuI complexes with imidazolyl ligands (Chart 1b)[7] were oxidized, but no discrete Cu/O2 intermediates formed. With tertiary amine donors (Chart 1c) we demonstrated that a μ-η2:η2-peroxodicopper(II) complex could be generated.[8]

Chart 1

A number of N3S(<span class="Chemical">thioethern>) type ligands have also been studied. In the case of two pyridyl and one <span class="Chemical">amine donors (Chart 1d), we showed that CuI/O2 reactivity leads to a μ-1,2-trans-peroxo dicopper(II) species.[9] In addition, evidence for a Cu(II)–S bond in this species was observed in the extended X-ray absorption fine structure (EXAFS) spectra. For a number of N3S(thioether) benzimidazole containing ligands (Chart 1e), Castilla and co-workers tested O2 reactivity with copper(I) derivatives, but no copper-dioxygen intermediates (as might be detected by spectroscopic interrogation) were observed during the complexes’ oxidation to copper(II).[10] Depending on the identity if the Ar and R substituents, superoxide anion could be detected by a radical trapping agent.[10] With guanidine donors (Chart 1f), Schindler and co-workers[11] recently reported the formation of a side-on μ-η2:η2-peroxodicopper(II) complex that subsequently isomerized to an equilibrium mixture with a bis-μ-oxodicopper(III) product.

In the investigations described in this pr<span class="Chemical">esent report, we explored the chemistry of three N3S(<span class="Chemical">thioether) ligands. Salient features of th<span class="Chemical">ese new ligands are that they all contain more electron-rich 4-methoxy-3,5-dimethylpyridyl (DMM) donors (relative to ESE, Chart 1d)[12] and the ethyl linked thioether moieties. The thioether donor was tuned across a series of ligands by using a variety of substituents (either ethyl in DMMESE, phenyl in DMMESP, or 2,4-dimethylphenyl in DMMESDP, Chart 1). As will be detailed in this report, addition of dioxygen to the Cu(I) complex of DMMESE leads to the formation of a μ-1,2-trans-peroxodicopper(II) complex similar to the pyridine containing ESE. Weakening of the Cu–S interaction by substituting a phenyl or dimethylphenyl group (DMMESP and DMMESDP) stabilizes a copper(III) bis-μ-oxo isomer product as determined from UV–vis and resonance Raman (rR) spectroscopy. In the case of DMMESP, both Cu2O2 core isomers are present at equilibrium, the first example of such an equilibrium reaction in the presence of a thioether donor. The results have also been compared to those observed for the N3O ligand DMMEOE (Chart 1) that contains an ether donor, to further assess the effect the thioether donor has on the activation of dioxygen in these complexes.

Experimental Section

General

All materials used were commercially available analytical grade from Sigma-Aldrich chemicals and <span class="Gene">TCI. <span class="Chemical">Acetone was distilled under an inert atmosphere over <span class="Chemical">CaSO4 and degassed under argon prior to use. Diethyl ether was used after being passed through a 60 cm long column of activated alumina (Innovative Technologies) under argon. Acetonitrile was stored under N2 and purified via passage through 2 × 60 cm columns of activated alumina (Innovative Technologies Inc.). Inhibitor free tetrahydrofuran (THF) and 2-methyltetrahydrofuran (MeTHF) were purchased from Sigma-Aldrich and distilled under argon from sodium/benzophenone and degassed with argon prior to use. Pentane was freshly distilled from calcium hydride under an inert atmosphere and degassed prior to use. CuI(CH3CN)4(B(C6F5)4) was synthesized according to literature protocols,[13] and its identity and purity were verified by elemental analysis and/or 1H NMR. Synthesis and manipulations of copper salts were performed according to standard Schlenk techniques or in an MBraun glovebox (with O2 and H2O levels below 1 ppm). Instrumentation: Bench-top low-temperature UV–vis experiments were carried out on a Cary Bio-50 spectrophotometer equipped with a liquid nitrogen chilled Unisoku USP-203-A cryostat using a 1 cm modified Schlenk cuvette. NMR spectroscopy was performed on Bruker 300 and 400 MHz instruments with spectra calibrated either to internal tetramethylsilane (TMS) standard or to a residual protio solvent. EPR measurements were performed on an X-Band Bruker EMX CW EPR controlled with a Bruker ER 041 XG microwave bridge operating at the X-band (∼9 GHz) in 5 mm quartz EPR tubes. ESI-Mass spectra were acquired using a Finnigan LCQDeca ion-trap mass spectrometer equipped with an electrospray ionization source (Thermo Finnigan, San Jose, CA). Single crystal X-ray diffraction was performed on suitable crystals of [{(DMMESE)CuI}2](B(C6F5)4)2 (1), [{(DMMESP)CuI}2](B(C6F5)4)2 (2), [{(DMMESDP)CuI}2](B (C6F5)4)2 (3), [(DMMESE)CuII(ClO4)](ClO4) (1a), [(DMMESP)CuII(H2O)](ClO4)2 (2a), and [(DMMESDP)CuII(H2O)](ClO4)2 (3a), which were mounted either on the tip of a glass fiber or on a loop with a tiny amount of Paratone-N oil and transferred to a N2 cold stream (100 K: 2, 110 K: 1, 3, 3a, 150 K: 1a, and 240 K: 2a). Data were collected with either a Xcalibur3 diffractometer [Mo Kα radiation (λ = 0.71073 Å)] or a SuperNova diffractometer [Cu Kα radiation (mirror optics, λ = 1.54178 Å)] from Agilent Technologies. Also, see the Supporting Information for further details (SI). Resonance Raman (rR) Measurements: A 1.5 mM stock solution of copper(I) complexes was prepared in MeTHF. A 500 μL aliquot of this copper(I) solution was added to the 5 mm NMR sample tube, capped with a septum, and chilled in a pentane/N2(l) bath. Oxygenation of the copper samples was achieved by slowly bubbling an excess of dioxygen through the solution using a Hamilton gastight syringe equipped with a three-way valve and needle outlet. Dioxygen, 16O2 (Airgas OX UHP-300) or 18O2 (Icon 6393), was added to an evacuated Schlenk flask fitted with a septum for the oxygenation reactions described above. Resonance Raman spectra were collected on a triple monochromator (Spex 1877 CP with 1200, 1800, and 2400 grooves/mm holographic spectrograph gratings) with a back-illuminated CCD (Princeton Instruments ST-135). Samples were placed in a liquid nitrogen finger dewar (Wilmad) in a ∼135° backscattering configuration, and excitation was provided by an argon ion laser (Innova Sabre 25/7) and a krypton ion laser (Coherent I90C–K). Data were collected for 5 min at 20 mW of power, and samples were hand spun for data collected at 380 nm. Peak positions were determined from fitting the experimental data with Gaussian transitions using Peakfit Version 4. For the DMMESE rR spectra, the CuI spectrum was subtracted from both the 16O2 and 18O2 spectra, and each transition was constrained to have an identical bandwidth.

Synthesis of Ligands

DMMESE

2-(Chloro<span class="Chemical">metn>hyl)-4-<span class="Chemical">methoxy-3,5-di<span class="Chemical">methylpyridine hydrochloride (5.50 g, 24.76 mmol), 2-(ethylthio) ethylamine (1.24 g, 11.79 mmol), and potassium carbonate (17.10 g, 123.75 mmol) in CH3CN (100 mL) were placed in a 250 mL two-neck-flask. The mixture solvent was stirred for 4 days under Ar at room temperature. After removal of the solvent, crude yellow oil was dissolved in 100 mL dichloromethane and washed with water. After drying over MgSO4, the solution was filtered and removed by rotary evaporation. The resulting yellow oil was purified by column chromatography (silica gel, 100% ethyl acetate, R = 0.28) yielding a pale yellow oil (3.61 g, 76% yield). 1H NMR (400 MHz, CDCl3): δ 8.14 (s, 2H), 3.75 (s, 4H), 3.70 (s, 6H), 2.74–2.70 (t, 2H), 2.57–2.54 (t, 2H), 2.34–2.29 (q, 2H), 2.21(s, 6H), 2.11(s, 6H), 1.12–1.08 (t, 3H). 1H NMR (300 MHz, THF-d8): δ 8.14 (s, 2H), 3.77 (s, 4H), 3.74 (s, 6H), 2.73–2.70 (t, 2H), 2.64–2.58 (t, 2H), 2.37–2.31 (q, 2H), 2.24(s, 6H), 2.15(s, 6H), 1.16–1.12 (t, 3H). ESI-MS, m/z: 404.39 (M + H+).

DMMESP

In a 250 mL round-bottom flask, 2.21 g (20.060 mmol) <span class="Chemical">thiophenoln>, <span class="Chemical">2-chloroethylamine hydrochloride (3.02 g, 26.04 mmol), and <span class="Chemical">potassium carbonate (8.32 g, 60.20 mmol) were stirred in 120 mL methylene chloride at room temperature under Ar. After 48 h, the mixture solution was washed with water and then dried over Na2SO4. All solvent was removed by a reduced vacuum resulting in a crude 2-(phenylthio)ethanamine, and it was used directly for the subsequent reactions.[14] Without further purification, a crude 2-(phenylthio)-ethanamine (3.073 g, 20.05 mmol) and 2-chloromethyl-4-methoxy-3,5-dimethyl-pyridine hydrochloride (8.910 g, 40.12 mmol), and potassium carbonate (11.09 g, 80.21 mmol) in CH3CN (120 mL) were placed in a 250 mL round-bottom flask, and then this mixture was stirred for 4 days under Ar at room temperature. After removal of the solvent, crude yellow oil was dissolved in 100 mL dichloromethane and washed with water. After drying over MgSO4, the solution was filtered and removed by rotary evaporation. The resulting yellow oil was purified by column chromatography (alumina, 25% ethyl acetate with hexane, R = 0.34) yielding a pale yellow oil (4.71 g, 52% yield). 1H NMR (400 MHz, CDCl3): δ 8.11 (s, 2H), 7.16–7.07 (m, 5H), 3.77 (s, 4H), 3.70 (s, 6H), 2.95–2.91 (t, 2H), 2.81–2.79 (t, 2H), 2.21 (s, 6H), 2.13 (s, 6H). ESI-MS, m/z: 452.42 (M + H+).

DMMESDP

Following a similar <n class="Chemical">span class="Chemical">methodology as described above, <spn>an class="Chemical">2,4-dimethylbenzenethiol 2.20 g (15.92 mmol), 2-chloroethylamine hydrochloride 2.40 g (20.70 mmol), and potassium carbonate 6.60 g (60.20 mmol) were stirred in 100 mL methylene chloride in a 250 mL round-bottom flask at room temperature under Ar. After 5 days, the mixture solution was washed with water and then dried over Na2SO4. All solvent was removed by a reduced vacuum resulting in a crude 2-((2,4-dimethylpheny)thio)ethanamine, and it was used directly for the subsequent reactions.[14] Without further purification, a crude 2-((2,4-dimethyl-pheny)-thio)ethanamine 1.52 g (8.38 mmol) and 2-chloromethyl-4-methoxy-3,5-dimethylpyridine hydrochloride (3.73 g, 16.77 mmol), and potassium carbonate (5.80 g, 41.97 mmol) in CH3CN (100 mL) were placed in a 250 mL round-bottom flask, and then this mixture was refluxed for 4 days under Ar. After removal of the solvent, crude yellow oil was dissolved in 100 mL dichloromethane and washed with water three times. After drying over MgSO4, the solution was filtered and removed by rotary evaporation. The resulting yellow oil was purified by column chromatography (alumina, 100% ethyl acetate, R = 0.67) yielding a pale yellow oil (2.36 g, 59% yield). 1H NMR (400 MHz, CDCl3): δ 8.11 (s, 2H), 6.93–6.81(m, 3H), 3.77 (s, 4H), 3.70 (s, 6H), 2.89–2.86 (t, 2H), 2.79–2.75 (t, 2H), 2.25–2.13 (s, 12H), 2.13 (s, 6H). ESI-MS, m/z: 480.50 (M + H+).

DMMEOE

2-(Chloro<span class="Chemical">metn>hyl)-4-<span class="Chemical">methoxy-3,5-di<span class="Chemical">methylpyridine hydrochloride (2.26 g, 10.19 mmol), 2-ethoxyl ethanamine (0.41 g, 4.63 mmol), and K2CO3 (3.22 g, 23.30 mmol) in CH3CN (80 mL) were placed in a 100 mL round flask. The mixture solvent was stirred for 2 days under Ar at room temperature. After removal of the solvent, crude yellow oil was dissolved in 100 mL dichloromethane and washed with water. After drying over MgSO4, the solution was filtered and removed by rotary evaporation. The resulting yellow oil was purified by column chromatography over alumina (ethyl acetate:hexane = 2:1, R = 0.52) yielding a pale oil (1.52 g, 85% yield). 1H NMR (400 MHz, CDCl3): δ 8.14 (s, 2H), 3.77 (s, 4H), 3.70 (s, 6H), 3.47–3.44 (t, 2H), 3.38–3.33 (q, 2H), 2.72–2.70 (t, 2H), 2.16 (s, 6H), 2.08 (s, 6H), 1.20–1.10 (t, 3H). ESI-MS, m/z: 388.42 (M + H+).

Synthesis of Copper(I) Complexes

[(DMMESE)CuI](B(C6F5)4) (1)

In a 100 mL Schlenk flask in the glovebox, 258 mg (0.285 mmol) of <span class="Chemical">[n class="Chemical">Cu(CH3CN)4](B(C6F5)4) was dissolved in 7 mL of <spn>an class="Chemical">THF. 115 mg (0.285 mmol) of DMMESE ligand dissolved in ∼5 mL of THF was added to the copper solution yielding a pale yellow solution. This yellow solution was allowed to stir for 10 min at which time ∼100 mL of degassed pentane was added to the solution. After 1 h, the supernatant was decanted, and the oil removed from the glovebox and dried under vacuum for 20 min affording 288 mg of a white powder (88% yield). Single crystals were obtained by topping of dry pentane into a solution of the complex in THF. 1H NMR (300 or 400 MHz, THF-d8): δ 8.41 (s, 2H), 4.34–4.28 (d, 2H), 4.10–4.04 (d, 2H), 3.81 (s, 6H), 3.03–3.00 (b, 4H), 2.42–2.37 (q, 2H), 2.29(s, 6H), 2.23(s, 6H), 1.27–1.22 (t, 3H). Elemental analysis: (C46H33BCuF20N3O2S) Calcd: C (48.20), H (2.90), N (3.67); Found: C (48.26), H (2.94), N (3.42).

[(DMMESP)CuI](B(C6F5)4) (2)

1H NMR (300 MHz, <n class="Chemical">span class="Chemical">THF-d8): δ 8.34 (s, 2H), 7.48–7.31 (m, 5H), 4.25 (d, 2H), 4.09 (d, 2H), 3.73 (s, 6H), 3.50 (s, 2H), 2.99 (s, 2H), 2.24 (s, 6H), 2.17(s, 6H). Elemental analysis: (<spn>an class="Chemical">C50H33BCuF20N3O2S) Calcd: C (50.29), H (2.79), N (3.52); Found: C (50.39), H (2.92), N (3.27).

[(DMMESDP)CuI](B(C6F5)4) (3)

1H NMR (300 MHz, <n class="Chemical">span class="Chemical">THF-d8): δ 8.21 (s, 2H), 7.14–6.90 (m, 5H), 4.22 (d, 2H), 4.01 (d, 2H), 3.73 (s, 6H), 3.42 (s, 2H), 3.02 (s, 2H), 2.41–2.18 (m, 18H). Elemental analysis: <spn>an class="Chemical">(C52H37BCuF20N3O2S) Calcd: C (51.10), H (3.05), N (3.44); Found: C (51.06), H (3.08), N (3.34).

[(DMMEOE)CuI](B(C6F5)4) (4)

1H NMR (300 MHz, <n class="Chemical">span class="Chemical">THF-d8): δ 8.28 (s, 2H), 4.17–4.11 (d, 2H), 3.75 (s, 6H), 3.71–3.67 (d, 2H), 3.12–3.03 (m, <spn>an class="Chemical">4H), 2.41–2.35 (d, 2H), 2.25(s, 6H), 2.22(s, 6H), 1.00–0.97 (t, 3H). Elemental analysis: (C46H33BCuF20N3O3) Calcd: C (48.89), H (2.94), N (3.72); Found: C (48.87), H (3.11), N (4.21).

Following a similar <n class="Chemical">span class="Chemical">methodology as described above, dinuclear <spn>an class="Chemical">copper(I) complexes, [(N)Cu](B(C6F5)4)2, and [(XYL-H)Cu]-(B(C6F5)4)2 were synthesized and characterized by NMR analyses (see SI).

Synthesis of Copper(II) Complexes

[(DMMESE)CuII(ClO4)](ClO4) (1a)

In a 100 mL Schlenk flask, 305 mg (0.756 mmol) of <span class="Chemical">DMMESEn> ligand was dissolved in 20 mL dry <span class="Chemical">acetone. 280 mg (0.756 mmol) of <span class="Chemical">CuII(ClO4)2·6H2O was dissolved in 20 mL dry acetone, and then copper solution was added to DMMESE solution. After stirring for 10 min at room temperature, the complex was precipitated as a blue solid upon addition of diethyl ether (100 mL). The supernatant was decanted, and the resulting blue solid was washed two times with diethyl ether and dried under vacuum to afford 411 mg of a copper(II) complex (82% yield). Single crystals were obtained by vapor diffusion of diethyl ether into a solution of the complex in acetone. Elemental analysis: (C22H33Cl2CuN3O10S) Calcd: C (39.67), H (4.99), N (6.31); Found: C (38.95), H (5.09), N (5.98). EPR spectrum (Figure S18): X-band (2 mM, ν = 9.186 GHz) spectrometer in acetone at 70 K: g∥ = 2.263, A∥ = 168 G, g⊥ = 2.036.

[(DMMESP)CuII(H2O)](ClO4)2 (2a)

Elemental analysis: (<span class="Chemical">C2n class="Chemical">6H35Cl2CuN3O11S) Calcd: C (42.66), H (4.82), N (5.74); Found: C (42.69), H (4.98), N (5.69). EPR spectrum (Figure <spn>an class="Gene">S18): X-band (2 mM, ν = 9.186 GHz) spectrometer in acetone at 70 K: g∥ = 2.263, A∥ = 168 G, g⊥ = 2.034.

[(DMMESDP)CuII(H2O)](ClO4)2 (3a)

Elemental analysis: (<span class="Chemical">C28H39Cl2n class="Chemical">CuN3O11S) Calcd: C (44.24), H (5.17), N (5.53); Found: C (44.27), H (5.48), N (5.54). EPR spn>ectrum (Figure <span class="Gene">S18): X-band (2 mM, ν = 9.186 GHz) spectro<span class="Chemical">meter in acetone at 70 K: g∥ = 2.262, A∥ = 168 G, g⊥ = 2.034.

[(DMMEOE)CuII(H2O](ClO4)2 (4a)

Elemental analysis: (<span class="Chemical">C2n class="Chemical">2H35Cl2CuN3O12) Calcd: C (39.56), H (5.28), N (6.29); Found: C (40.03), H (5.43), N (6.00). EPR spectrum (Figure <spn>an class="Gene">S18): X-band (2 mM, ν = 9.186 GHz) spectrometer in acetone at 70 K: g∥ = 2.265, A∥ = 170 G, g⊥ = 2.036.

The description of experimental procedures for generating and handling the <span class="Chemical">copper-dioxygen adducts in order to carry out UV–vis, IR, CV, ESI-MS, and NMR analyses and the reactivity study where examination of ligand <span class="Chemical">thioether sulfoxidation is probed are further described in the Supporting Information (SI).

Results and Discussion

Synthesis and Characterization of Copper(I) Complexes, 1, 2, and 3

Reaction of ligand <span class="Chemical">DMMESE and <span class="Chemical">[CuI(CH3CN)4](B(C6F5)4) under Ar in <span class="Chemical">THF gives a white powder, formulated as [(DMMESE)CuI](B(C6F5)4), 1, on the basis of elemental analysis. Attempts to grow crystals of 1 in THF/pentane lead to the isolation of a dinuclear complex, [{(DMMESE)CuI}2](B(C6F5)4)2 (designated as compound 1) shown in Figure 2. X-ray data and details of the structure determination for 1 are provided in the SI. Selected bond lengths and bond angles of this complex are listed in Figure 2. Complex 1 is found as a centrosymmetric dimer in the solid state, where each copper ion is coordinated by one ligand via the three N-donors and by the other ligand via its thioether atom, thus giving the overall dinuclear structure. Each copper center is found in a distorted tetrahedral arrangement in which the three nitrogen atoms and one S atom from the adjacent copper site are the vertices of a distorted tetrahedron.

Figure 2

Representations of the dimeric Cu(I) complexes described in the crystal structures of (a) [{(DMMESE)CuI}2](B(C6F5)4)2 (1), (b) [{(DMMESP)CuI}2](B(C6F5)4)2 (2), and (c) [{(DMMESDP)CuI}2](B(C6F5)4)2 (3). Selected bond distances (Å) and bond angles (deg) are also listed. The H atoms and counterions were omitted for clarity.

<span class="Chemical">Copper(n class="Chemical">I) complexes containing at least one <spn>an class="Chemical">thioether ligand reveal Cu–S bond distances between 2.2 and 2.44 Å.[7a,8,9b,15] Accordingly, the Cu–S distance of 2.1891(5) Å in the dimer 1 is fairly typical (but suggesting relatively strong binding of the thioether arm). Following very similar procedures, [{(DMMESP)CuI}2](B(C6F5)4)2 (2) and [{(DMMESDP)CuI}2](B(C6F5)4)2 (3) were also isolated and crystallized (Figure 2). Their coordination environments are quite similar to that of [{(DMMESE)CuI}2](B(C6F5)4)2 (1). In fact, this type of copper(I) complex dimerization in the solid state has been observed previously for a number of three- or four-coordinate complexes, with a thioether donor and even with all nitrogen donor ligands.[6,9b,10,16,17]

Repr<span class="Chemical">esen>ntations of the dimeric <span class="Chemical">Cu(I) complexes described in the crystal structures of (a) <span class="Chemical">[{(DMMESE)CuI}2](B(C6F5)4)2 (1), (b) [{(DMMESP)CuI}2](B(C6F5)4)2 (2), and (c) [{(DMMESDP)CuI}2](B(C6F5)4)2 (3). Selected bond distances (Å) and bond angles (deg) are also listed. The H atoms and counterions were omitted for clarity.

While the three ligand-<span class="Chemical">copper(n class="Chemical">I) complexes are dimeric in the solid state, we postulate that in solution th<spn>an class="Chemical">ese Cu(I) complexes are mononuclear species. Support for this conclusion was obtained from the NMR spectroscopic technique diffusion ordered spectroscopy (DOSY). This utilizes pulsed field gradients to measure the translational diffusion of molecules.[18] Our DOSY measurement gives a log D (diffusion constant) of −9.08 for the [(DMMESE)CuI]+ (1) complex in THF. From this value, we calculate a hydrodynamic diameter of 1.13 × 10–9 m, which agrees closely (1.08 × 10–9 m) with that obtained from X-ray structural parameters for the mononuclear copper(II) complex [(DMMESE)CuII(ClO4)]+ (1a), see SI.[19] Further, our diffusion constant for 1 closely matches that determined via DOSY measurements for the well-known mononuclear Cu species [(TMPA)CuI(CH3CN)](B(C6F5)4),[20] however log D varies considerably from that determined for the discrete dicopper complexes [(N5)(CuI)2](B(C6F5)4)2 and [(XYL-H)CuI2](B(C6F5)4)2, see SI including Table S1.

Additionally, variable-temperature (n class="Disease">VT) 1H NMR experiments on (1) in THF-d8, acetone-d6, or DMF-d7 (25 °C to −60 °C) show minimal temperature dependence resulting from chemical dynamics (see Figures S7–S11 for details). This is in contrast to systems where the dimer is in equilibrium with the monomer, resulting in significant chemical shift changes with temperature.[6,16] Further, DMF and acetone are reasonably good ligands for copper(I),[21] and even weak solvent coordination would be expected to break up any dimeric structure.[22]

Synthesis and Characterization of Copper(II) Complexes

To experimentally probe the effect of the <span class="Chemical">thioethern> substituent on the <span class="Chemical">Cu(II)–S interaction, which would also be expected to occur in <span class="Chemical">copper-dioxygen adducts where the copper is either CuII or CuIII (vide infra), copper(II) perchlorate complexes (Chart 2) were synthesized for each ligand. [(DMMESE)CuII(ClO4)](ClO4) (1a), [(DMMESP)CuII(H2O)](ClO4)2 (2a), and [(DMMESDP)CuII(H2O)](ClO4)2 (3a) were generated by simple combination of ligand and Cu(ClO4)2·6H2O in acetone. The structures of 1a, 2a, and 3a were determined by single crystal X-ray diffraction, which reveals that all three compounds are mononuclear complexes with a distorted square pyramidal (SP) coordination (τ = 0.39 for 1a, τ = 0.38 for 2a, and τ = 0.12 for 3a; τ = 0.00 for idealized SP geometries), see Figure 3.[23] The thioether donor groups are found in an axial position, and the Cu–S bond distances are 2.536 Å in 1a, 2.603 Å in 2a, and 2.691 Å for 3a; similar to the 2.68 Å Cu–S(methionine) bond length observed in an oxidized form of PHM. The shortest Cu–S bond occurs for complex 1a with its donating ethyl S-substituent. For 2a and 3a, the aryl substituent is a poorer donor electronically (then an ethyl group), while steric factors are clearly relevant, even with comparing the Cu–S bond lengths 2a directly with 3a, the latter with its o-methylaryl substituent. We carried out cyclic voltammetry experiments on 1a, 2a, and 3a (see the SI). A slightly more negative E1/2 value observed for 1a compared to 2a and 3a indicates that the ethylthio arm of 1a is at least a marginally better donor than the thiophenyl-type arms in 2a and 3a. Overall, however, it is difficult to tease out the differences in electronic vs steric factors in these and related complexes.[24]

Chart 2

Figure 3

Representations of the monomeric Cu(II) complexes described in the crystal structures of (a) [(DMMESE)CuII(ClO4)](ClO4) (1a), (b) [(DMMESP)CuII(H2O)](ClO4)2 (2a), and (c) [(DMMESDP)CuII(H2O)](ClO4)2 (3a). Selected bond distances (Å) and bond angles (deg) are also listed. The H atoms (except for those of the water ligands found in 2a and 3a) and noncoordinating counterions were omitted for clarity.

The EPR spectra for all of th<n class="Chemical">span class="Chemical">ese complexes in solution are of the axial type (Figure <spn>an class="Gene">S18) indicating that these mononuclear Cu(II) complexes are found in a distorted SP environment. This observation that the S(thioether) atom binds axially in these copper(II) complexes suggests that such binding can occur in the copper-dioxygen adducts described below.

Repr<span class="Chemical">esen>ntations of the monomeric <span class="Chemical">Cu(II) complexes described in the crystal structures of (a) <span class="Chemical">[(DMMESE)CuII(ClO4)](ClO4) (1a), (b) [(DMMESP)CuII(H2O)](ClO4)2 (2a), and (c) [(DMMESDP)CuII(H2O)](ClO4)2 (3a). Selected bond distances (Å) and bond angles (deg) are also listed. The H atoms (except for those of the water ligands found in 2a and 3a) and noncoordinating counterions were omitted for clarity.

Oxygenation Reactions of Cu(I) complexes. [(DMMESE)CuI]+ (1) + O2(g)

<span class="Chemical">Dioxygenn> reacts with [(<span class="Chemical">DMMESE)CuI]+ (1) in <span class="Chemical">MeTHF at −130 °C, forming the low-temperature stable intense indigo blue species (1)(see Chart 2). The UV–vis spectrum of 1 is characterized by three transitions at 445 (2150 M–1 cm–1), 521 (8640 M–1 cm–1), and 615 nm (10 850 M–1 cm–1, Figure S23) and is similar to other trans-peroxo species such as [{(TMPA)CuII}2(μ-1,2-O22–)]2+.[25] Yet, the lower energy charge transfer (CT) transition at 615 nm for 1 is more intense than the higher energy transition. This intensity ratio was previously observed in [{(ESE)CuII}2(μ-1,2-O22–)]2+ (Chart 1d, Figure 4b) and was ascribed to a geometric distortion from the trigonal bipyramidal coordination environment in TMPA (Figure 4a) toward a SP geometry in ESE. This geometric distortion would increase the overlap of the π*ν orbital with the Cu(II) hole, resulting in a higher intensity CT transition.[9b] The similar intensity ratio of the CT transitions in 1 and [{(ESE)CuII}2(μ-1,2-O22–)]2+ indicate it also possesses a distorted SP geometry, similar to the coordination environment observed in the X-ray structure of [(DMMESE)-CuII(ClO4)](ClO4) (1a) (vide supra).

Figure 4

(a) Structure of [{(TMPA)CuII}2(μ-1,2-O22–)]2+ obtained from X-ray crystallography and (b) low-temperature UV–vis absorption spectra of [{(TMPA)CuII}2(μ-1,2-O22–)]2+ (purple) and [{(ESE)-CuII}2(μ-1,2-O22–)]2+ (blue).[9b,25]

(a) Structure of [{(<span class="Chemical">TMPAn>)CuII}2(μ-1,2-O22–)]2+ obtained from X-ray crystallography and (b) low-temperature UV–vis absorption spectra of [{(<span class="Chemical">TMPA)CuII}2(μ-1,2-O22–)]2+ (purple) and [{(ESE)-CuII}2(μ-1,2-O22–)]2+ (blue).[9b,25]

[(DMMESP)CuI]+ (2) + O2(g)

Upon <span class="Chemical">oxygenn>ation in <span class="Chemical">MeTHF at −130 °C, a trans-<span class="Chemical">peroxodicopper(II) species [{(DMMESP)CuII}2(μ-1,2-O22–)]2+ (2) with UV–vis features at 504 and 644 nm was initially formed. Over time (∼30 min) these features decay, and a new species (2) with an absorption feature at 388 nm forms (Figure 5).

Figure 5

UV–vis spectra and time profile of the equilibrium between 2 and 2 in MeTHF at −130 °C.

However, the absorption features of 2 do not completely convert to 2 (Figure 5), indicating an equilibrium between th<span class="Chemical">ese complexes (Figure 6a, upper), with <span class="Chemical">Keq = [2]/[2] = 2.6 at −130 °C.[26] The rate constant for the <span class="Chemical">trans-peroxo to bis-μ-oxo interconversion can be well estimated from the data in Figure 5, k = 9.6 s–1 (−130 °C). Further evidence that the low-temperature combination of 2 and 2 represents a dynamic equilibrium mixture can be readily seen from examination of a series of spectra we recorded for the 2 + O2 reaction at a variety of temperatures, in some cases then also warming. Those spectra and explanatory comments are given in Figures S19–S20.

Figure 6

Equilibrium between (a) a μ-1,2-trans-peroxodicopper(II) and bis-μ-oxodicopper(III) species; with 1 equiv CH3SO3–, the mixture converts to a pure bis-μ-oxodicopper(III) complex, and (b) Stack and co-workers’ mixture of side-on μ-η2:η2-peroxodicopper(II) and bis-μ-oxodicopper(III) species reacts with chelating anions to give a clean side-on μ-η2:η2-peroxodicopper(II) complex.

We have previously characterized a similn class="Chemical">ar trans-peroxo/bis-μ-oxo equilibrium with the all nitrogen tetradentate donor (BQPA) ligand (BQPA = bis(2-quinolylmethyl)(2-pyridylmethy1)-amine). Similarly, [(BQPA)CuI]+ reacts with dioxygen to first form a [CuII2(μ-1,2-O22–)]2+ species that converts to a [CuIII2(μ-O)2]2+ complex, k = 0.16 s–1 (−90 °C); Keq =3.2 (−90 °C).[27] The observation of a trans-peroxo/bis-μ-oxo equilibrium in these systems differs from what has typically been presumed, that only a side-on μ-η2:η2-peroxodicopper(II) could be in (rapid) equilibrium with a bis-μ-oxodicopper(III) complex (Figure 6b, upper).[1]

UV–vis spectra and time profile of the equilibrium between 2 and 2 in <n class="Chemical">span class="Chemical">MeTHF at −130 °C.

Equilibrium between (a) a μ-1,2-trans-<span class="Chemical">peroxodicoppern>(II) and bis-μ-oxodi<span class="Chemical">copper(III) species; with 1 equiv <span class="Chemical">CH3SO3–, the mixture converts to a pure bis-μ-oxodicopper(III) complex, and (b) Stack and co-workers’ mixture of side-on μ-η2:η2-peroxodicopper(II) and bis-μ-oxodicopper(III) species reacts with chelating anions to give a clean side-on μ-η2:η2-peroxodicopper(II) complex.

The [CuIII2(μ-O)2]2+/[n class="Chemical">CuII2(μ-1,2-O22–)]2+ equilibrium with DMMESP (Figure 5 and 6a) is also sensitive to the addition of the coordinating anion methylsulfonate. A spectroscopically pure (UV–vis) bis-μ-oxo species 2-(CH3SO3–), λmax = 386 nm (13 000) (Figure S22), is obtained with one equiv of (nBu4N+)(CH3SO3–) (Figure 6a, lower part).[28] Stack and co-workers[29] previously demonstrated that addition of methylsulfonate or other chelating anions converts a mixture of side-on μ-η2:η2-peroxodicopper(II) and bis-μ-oxodicopper(III) species with bidentate ligands to an anion bridged side-on peroxo species (Figure 6b). Masuda and co-workers[30] also observed conversion of a [CuIII2(μ-O2–)2]2+ complex to a side-on peroxo species bridged by a benzoate donor with addition of the latter, indicating coordinating anions stabilize the side-on peroxo isomer relative to the bis-μ-oxo.

[(DMMESDP)CuI]+ (3) + O2(g)

The reaction of <span class="Chemical">[(DMMESDP)n class="Chemical">CuI](B(C6F5)4) (3) with <spn>an class="Chemical">O2 only gives a bis-μ-oxodicopper(III) species (UV–vis criterion), [{(DMMESDP)CuIII}2-(O2–)2]2+ (3) (λmax = 388 nm, 13 000 M–1 cm–1), see Figure S23. This species (3) is stable for hours at −130 °C with only minimal decomposition occurring (UV–vis criterion). The increased size of the dimethylphenyl group weakens the Cu–S interaction (as evident from the longer Cu(II)–S bond in the structure of 3a) with the result that DMMESP acts like as a tridentate ligand, which favors the bis-μ-oxo dicopper(III) isomer. A steric clash due to the dimethylphenyl substituent likely also contributes to a destabilization of a trans-μ-1,2-peroxo dicopper(II) analogue; in the structure of [{(TMPA)CuII}2(μ-1,2-O22–)]2+ (Figure 4), the ligand arms are interdigitated.

The influence of the Cu–S interaction on the <span class="Chemical">oxygenated products was further probed in comparison to a ligand lacking the <span class="Chemical">thioether donor atom. Oxygenation of the Cu(I) complex (4) of DMMEOE, possessing the same three N-donors but having an ether O atom replacing the sulfur (Charts 1 and 2), leads to the formation of a new species with prominent optical absorption at 382 nm (20 000 M–1 cm–1, Chart 2), nearly identical in λmax and absorptivity to the bis-μ-oxo complexes 2 and 3. The further comparison of the UV–vis spectrum of 4 with those of 2 and 3 and other literature examples[15e,31] clearly shows this is a bis-μ-oxodicopper(III) complex, [{(DMMEOE)CuIII}2(O2–)2}2+ (4). This suggests that as the fourth donor is weakened, the bis-μ-oxo isomer is stabilized, and the ligand behaves like a N3 donor. Since the oxygen atom of the ether arm in DMMEOE has an extremely weak to nonexistent interaction with the copper, this also strongly suggests that the thioether is coordinated to the Cu(II) trans-peroxo complexes 1 and 2, similar to [{(ESE)CuII}2(μ-1,2-O22–)]2+ where a Cu(II)–S bond was characterized by EXAFS spectroscopic data.[9a]

Resonance Raman Spectroscopic Characterization of 1, 2, 2, 2-(CHSO–), and 3

Resonance Raman spectroscopy confirms the assignment of 1 and 2 as <span class="Chemical">trans-peroxo isomers and 2, 2-(CHSO), and 3 as bis-μ-oxo isomers. Laser excitation of <span class="Chemical">oxygenated samples of 2 that were frozen after ∼1 min contains mostly 2 and yields rR spectra (Figure 7a) with four isotope sensitive bands that are consistent in energy and isotope shift with the νO–O (16O2: 830 and 810 cm–1; 18O2: 784 and 772 cm–1) and the symmetric νCu–O (16O2: 545 and 531 cm–1; 18O2: 518 and 500 cm–1) of previously characterized end-on peroxo species.[1a] The presence of two νO–O is similar to the rR spectra of [{(BQPA)CuII}2(O22–)]2+ and results from two end-on peroxo isomers in both systems.[27] These two species likely arise from the asymmetric coordination environment present in DMMESP, which yields two different arrangements of the ligand around the CuII2(O22–) core in the interdigitated dimer. In one isomer, the thioether ligands would be anti to each other and in the other syn (Scheme 1). Also present in the rR spectra is an isotope insensitive vibration at 415 cm–1. A band at similar energy and intensity is observed in the rR spectra of [{(TMPA)CuII}2(O22–)]2+ and has been previously assigned as the Cu–Namine stretch.[25b] The rR spectra of 1 are also characteristic of an end-on peroxo species (Figure S24) and are consistent with the presence of both syn and anti trans-peroxo isomers.

Figure 7

Resonance Raman spectra of 2 (a) with 647 nm excitation and 2 (b) with 380 nm excitation in MeTHF collected at 77 K; see text.

Scheme 1

Resonance Raman spectra of 2 (a) with 647 nm excitation and 2 (b) with 380 nm excitation in <n class="Chemical">span class="Chemical">MeTHF collected at 77 K; see text.

Laser excitation of an <span class="Chemical">oxygenated sample of [(<span class="Chemical">DMMESP)CuI]+ (2) that was frozen after ∼90 min and contains mostly 2 produces one isotope sensitive stretch (16<span class="Chemical">O2: 597 cm–1; 18O2: 570 cm–1, Figure 7b) that is similar to the rR spectra of the structurally characterized [{Me2tpaCuIII}2(μ-O2–)2]2+ complex[34] and the bis-μ-oxo isomer of BQPA.[27] This vibration has been previously assigned as the symmetric Cu2(μ-O2–)2 core-breathing mode. The addition of dioxygen and 1 equiv of tetrabutylammonium methanesulfonate (CH3SO3–) (per copper dimer) to a solution of the CuI salt 2 results in an absorption spectrum that only contains features arising from a bis-μ-oxo species (vide infra). The rR spectra of this complex is indistinguishable (2 cm–1 resolution) from the rR spectrum of 2, which was synthesized with a B(C6F5)4– counterion (Figure S25). Additionally, similar rR spectra were observed for 3 (Figure S26). This further indicates that while 1 and 3 are pure trans-peroxo and bis-μ-oxo species, respectfully, the oxygenated products of 2 in the presence of B(C6F5)4– (and not CH3SO3–) are an equilibrium mixture of these two isomers.

The combination of the absorption and rR data indicate that the coordination environment of 1 and 2 is distorted toward SP (Scheme 1). Not only is this coordination geometry observed in the <span class="Chemical">perchlorate crystal structures 1a and 2a but also the lower energy π*v CT transition in both 1 and 2 is more intense than the higher energy π*σ CT transition. This is in contrast to the structure of [{(TMPA)CuII}2(μ-1,2-O22–)]2+ (Figure 4a) where a trigonal bipyramidal coordination geometry (τ = 0.9) is observed.[25a,32] The ligand environment is rather flexible since 2 can readily equilibrate to give bis-μ-oxo species (2), adopting a CuIII2(μ-O)2 core with a square planar geometry (Scheme 1) analogous to the crystallographically characterized complex [{(Me2tpa)CuIII}2(O2–)2]2+ where Me2tpa has two of the three pyridyl donors (of TMPA) possessing ortho (6-position) methyl groups.[33] In this case, the methylpyridines are axial (Cu···N = 2.5 Å). By analogy, the apical amine and one pyridyl ligand arm are equatorial in 2 and 3, with the other pyridyl and thiophenyl arms interacting axially with the Cu(III) ion. However, due to the potential lability of this interaction, it is possible that 2 and 3 do not possess even a weak, axial thioether–Cu(III) interaction as we have depicted in Scheme 1.

Ligand Substrate Reactivity of 1, 2, and 3 Species

To seek further insight into <span class="Chemical">n class="Chemical">Cu-dioxygen bonding and reactivity in the pr<spn>an class="Chemical">esence of a thioether donor, the copper(I) complexes were oxygenated at slightly warmer temperatures to probe for the possibility of ligand sulfoxidation chemistry. [(DMMESP)CuI](B(C6F5)4) (2) was bubbled with dioxygen gas in MeTHF at −120 °C, forming as described above a mixture of [{(DMMESP)CuII}2(μ-1,2-O22–)]2+ (2) and [{(DMMESP)CuIII}2(μ-O2–)2]2+ (2). Further hour-long incubation at −120 °C led to decomposition of both intermediates resulting in a color change from dark indigo blue to green. Workup of this reaction product solution at low temperature (see SI) and analysis of the organic products, the ligands, and any oxidized species showed that approximately one out of two DMMESP thioether-amine (N3S) ligands had undergone sulfoxidation as determined by TLC, NMR spectroscopy, and ESI-MS spectrometry, with a ∼ 40% measured yield obtained (Scheme 2).

Scheme 2

Th<span class="Chemical">esen> results suggest that a mono<span class="Chemical">oxygenase-type reaction occurred with the 2/2 mixture, as we previously observed in the room temperature <span class="Chemical">oxygenation of [(ESE)CuI]+.[9b] Here, two electrons provided by two copper(I) complexes lead to a peroxo or bis-μ-oxodicopper product which is capable of only one oxo-transfer (net) reaction, giving a sulfoxide; the theoretical yield is a maximum of 50%. By comparison, under identical conditions, similar reactivity studies were carried out for the trans-peroxo species, [{(DMMESE)CuII}2(O22–)]2+ (1) and bis-μ-oxo species, [{(DMMESDP)CuIII}2(O2–)2}2+ (3). The same behavior was observed for 3 leading to ∼43% ligand sulfoxidation. However, 1 showed no ligand sulfoxidation at −120 °C (Scheme 2) indicating that the bis-μ-oxodicopper(III) isomer is responsible for the ligand sulfoxidation, as we had previously hypothesized with ESE (Chart 1d).[9b] Interestingly, when an excess of triphenylphosphine (PPh3) was added to the 2/2 mixture and allowed to stand for 2–3 h, low-temperature work-up showed that no sulfoxidation occurred and rather O=PPh3 formed. Thus, the ligand (intramolecular) sulfoxidation was suppressed in favor of a more facile intermolecular oxidation of PPh3.

Summary and Conclusion

The <span class="Chemical">oxygenn>ation of <span class="Chemical">copper(I) salts of a series of N3S <span class="Chemical">DMM derivatized ligands indicates that the nature of the oxygenated product can be tuned by modulating the Cu–S interaction. While a trans-peroxo isomer is favored for DMMESE, an increase in steric bulk (and/or decrease in donor strength) at the thioether donor causes a weakening of the Cu–S interaction resulting in the stabilization of the bis-μ-oxo isomer observed for DMMESP and DMMESDP with their S-aryl substituents. In the case of DMMESP, an equilibrium mixture of the two species is observed, the first example supported by a ligand with a thioether donor. The addition of the coordinating anion CH3SO3– stabilized the bis-μ-oxo, relative to the trans-peroxo isomer, in contrast to the effect of coordinating anions on the side-on peroxo/bis-μ-oxo equilibrium observed in other systems. Additionally, only ligands with an accessible bis-μ-oxo isomer oxidize the thioether to the corresponding sulfoxide at low temperatures indicating this isomer is the oxidant responsible for this electrophilic reactivity. The observation of this trans-peroxo/bis-μ-oxo equilibrium in the present N3S and a previous N4 system[27] shifts a previous paradigm which assumed that a bis-μ-oxo dicopper(III) complex generation occurs from initially formed side-on μ-η2:η2-peroxodicopper(II) species. These systems demonstrate a new strategy to reversibly cleave an O–O bond, which has new potential implications for the development of a synthetic, copper-based water splitting catalyst.[34]