Thioether S-ligation in a side-on μ-η²:η²-peroxodicopper(II) complex

Abstract

[(ANS)Cu^I(CH₃CN)]⁺ reacts with O₂ giving [{(ANS)Cu^II}₂(μ-η²:η²-O₂²⁻)]²⁺, ν_O–O = 731 cm⁻¹, shown to possess S-thioether ligation, based on comparisons with analogues having all N-ligands or a –S(Ph) group. The finding is a rare occurrence and new for side-on O₂²⁻ binding.

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Copper(I)–dioxygen adducts or derived species pertinent to copper protein O₂-binding and activation are currently of considerable interest in bioinorganic chemistry.^1–4 The focus of this communication relates to the discovery and influence of thioether sulfur ligation in copper(I)–dioxygen adducts, a topic which has attracted more recent attention. This is due to the existence of important copper monooxygenases, namely dopamine β-monooxygenase (DβM) and peptidyl glycine α-hydroxylating monooxygenase (PHM), which serve important roles in neurotransmitter or regulatory hormone biosynthesis.⁵ The active-site in these proteins, where substrate binding and copper–dioxygen activation occur, is the so-called Cu_M site, which is ligated by two His and one Met ligands.^5–7 Biochemical and chemical evidence suggests that O₂ binds here and that a Cu^II–superoxo (O₂˙⁻) dioxygen adduct or a derived Cu^II–hydroperoxo or cupryl (Cu^II–O˙) entity initiates substrate oxidation chemistry.^5,8–12 In fact, the observance of an X-ray structure on a protein Cu^II–O₂˙⁻ complex,⁷ biochemical evidence^5,8–10 and theoretical calculations^9,10 show that the Cu^II–superoxo species is the one effecting a substrate hydrogen-atom abstraction reaction.

The vast majority of the literature deals with copper(I)–dioxygen chemistry and adducts and reactivity with systems containing all nitrogen ligands, typically bi-, tri-, or tetradentate entities.^1–4,13,14 However, it is clearly important to develop an understanding of how thioether ligation influences the structure(s), spectroscopy, and reactivity of Cu^I_n–(O₂)-derived species.

Some work in this general area has occurred. A dicopper(I) complex with a Met-based ligand was synthesized by Casella and co-workers;^15,16 reaction with O₂ led to hydroxylation of a xylyl spacer group. Tolman and co-workers reported Cu^I–O₂ chemistry with a N₂S β-diketiminate ligand, but the S-donor does not coordinate to copper in the derived O₂-adduct.¹⁷ Quite recently, Nicholas and co-workers synthesized a bis-imidazole-thioether tridentate N₂S ligand while Cu^I-complex oxidation occurs, they did not observe Cu^I–O₂ adducts.^18–20

Recently, we reported the first copper–dioxygen adduct with thioether ligation, an “end-on”μ-1,2-peroxodicopper(II) complex, each copper ion possessing a tetradentate N₃S ligand.^21,22

As DβM and PHM employ N₂S rather than N₃S protein ligand donors, we were interested to look further, at new tridentate ligands. In this report, we describe copper(I)–O₂ reactivity with ANS (Scheme 1), a linear N₂S tridentate ligand. We also had previously studied copper(I)–O₂ chemistry with the N₃ ligand MeAN (Scheme 1), which readily forms a side-on binuclear peroxo complex [{(MeAN)Cu^II}₂(μ-η²:η²-O₂²⁻)]²⁺ (2P), λ_max = 360 nm (ε = 22 000 M⁻¹ cm⁻¹) and 540 nm (ε = 2500 M⁻¹ cm⁻¹).²³ Our hypothesis was that an analogue, ANS, in which one alkylamine arm of MeAN is replaced by a thioether donor, might exhibit related chemistry. This turns out to be true, as we described here.

Scheme 1 Ligands and their Cu₂–O₂ adducts.

The copper(I) complex [(ANS)Cu^I(CH₃CN)]⁺ (1A) (as B(C₆F₅)₄⁻ salt) was generated from [Cu^I(CH₃CN)₄]B(C₆F₅)₄ addition to ANS, and characterized as a greenish white air-sensitive solid. [(ANS)Cu^II(Cl)₂] (1B) was also synthesized. Both of these Cu^I and Cu^II complexes were characterized by X-ray diffraction (Fig. 1).‡ Notably, the S(thioether) coordination to copper ion occurs in both Cu^I and Cu^II complexes.

Fig. 1 ORTEP diagram view (50% probability ellipsoids) of 1A and 1B. Left: X-ray structure of 1A: Cu1–N1, 2.056 Å; Cu1–N2, 2.122 Å; Cu1–N3, 1.935 Å; Cu1–S1, 2.292 Å. Right: X-ray structure of 1B: Cu1–N1, 2.071 Å; Cu1–N2, 2.136 Å; Cu1–S1, 2.387 Å, τ = 0.61.²⁴

In order to describe the electronic environment of the ligand copper coordination complexes, while also comparing the environment of sulfur containing ANS (N₂S) with MeAN (N₃), CO adducts of [(ANS)Cu^I(CH₃CN)]⁺ (1A) and [(MeAN)Cu^I]⁺ (2A) were generated and the electrochemistry via cyclic voltammetry of 1A and 2A were evaluated (Table 1). The IR spectrum of [(ANS)Cu^I-CO]⁺ (1-CO) shows that ν_CO = 2092 cm⁻¹, significantly higher than that observed for [(MeAN)Cu^I-CO]⁺ (2-CO, 2079 cm⁻¹). It is notable that ν_CO for the Cu_M sites in PHM and DβM (Table 1)^25,26 are essentially the same as that of [(ANS)Cu^I-CO]⁺ (1-CO), indicating that 1A possesses a chemical environment reasonably mimicking that of protein active sites.

Table 1 IR data for Cu^I–CO adducts and E_1/2 values of Cu^I complexes

	MeAN	ANS	PHM^a	DβM^a
a Data for the protein CuM site with His2Met coordination.
Cu–CO νCO (cm^−1), THF solution	2079	2092	2093	2089
E1/2/mV (vs. Fe(Cp)2^+^/0)	−195	−180	—	—
DMF solution under Ar	—	—	—	—

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As for the ligand comparison, the results clearly indicate that MeAN is a better donor to copper(I) which then back-donates to its CO ligand to a greater extent, lowering ν_CO. The electrochemical behavior for 1Avs. 2A is consistent with findings for CO ligation and ν_CO values, as the strong donor ligand MeAN better stabilizes the higher oxidation state, giving a more negative E_1/2 value (Table 1).

Oxygenation of 1A at −94 °C in acetone gives a dark orange species, λ_max = 375 nm (ε = 10 000 cm⁻¹ M⁻¹) and 495 nm (ε = 1000 cm⁻¹ M⁻¹) (Fig. 2), features consistent with those of an μ-η²:η²-peroxodicopper(II) species.¹ Thus, the complex is formulated as [{(ANS)Cu^II}₂(μ-η²:η²-O₂²⁻)]²⁺ (1P). Confirmation derives from resonance Raman spectroscopic data with λ_ex = 379.5 nm employing either ¹⁶O₂ or ¹⁸O₂ for complex generation: ν_Cu–Cu = 273 cm⁻¹ (Fig. 3A) and ν_O–O = 731 cm⁻¹ (Δν(¹⁸O₂) = −40 cm⁻¹) (Fig. 3B). These vibrations are characteristic of a μ-η²:η²-peroxodicopper(II) species.^1,27

Fig. 2 UV-Vis changes upon reaction of O₂ with [(ANS)Cu(CH₃CN)]⁺ (1A) (yellow) in acetone at −94 °C giving [{(ANS)Cu^II}₂(μ-η²:η²-O₂²⁻)]²⁺ (1P) (red); warming to RT leads to a decomposition product (green).

Fig. 3 rR spectra of [{(ANS)Cu^II}₂(μ-η²:η²-O₂²⁻)]²⁺ (1P) in acetone with ¹⁶O₂ (red) and ¹⁸O₂ isotopic substitution (blue) in the region of ν_Cu–Cu (A) and ν_O–O (B) (λ_ex = 379.5 nm, 77 K, 5 mW power).

These values are also similar to those observed for [{(MeAN)Cu^II}₂(μ-η²:η²-O₂²⁻)]²⁺ (2P) (ν_O–O = 721 cm⁻¹ and ν_Cu–Cu = 268 cm⁻¹),²³ however the higher ν_O–O vibrational frequency of [{(ANS)Cu^II}₂(μ-η²:η²-O₂²⁻)]²⁺ (1P) (731 cm⁻¹), compared to that for MeAN complex 2P (721 cm⁻¹), indicates that the O–O bond in 1P is stronger. Compared to MeAN, ANS is a weaker donor to copper resulting in increased peroxo π*_σ donation to Cu and less back-bonding into the peroxo σ* resulting in a stronger peroxo O–O bond.²⁸

The supposition that S(thioether) ligation occurs in [{(ANS)Cu^II}₂(μ-η²:η²-O₂²⁻)]²⁺ (1P) derives from observations discussed above and the following argument. If the thioether donor did not bind to copper in 1P and was dangling, (as seen in Tolman’s N₂S system),¹⁷ the remaining “bidentate amine” ligand (N₂ portion of ANS) would result in formation of a bis-μ-oxo dicopper(III) species. As is already known, the copper(I) complex with N,N,N′,N′-tetramethyl-(1,3)-propanediamine (TMPD), [(TMPD)Cu^I(CH₃CN)]⁺ (4A), which was described by Stack and co-workers,²⁹ does exactly this (Scheme 1); ν_Cu–O = 609 cm⁻¹: Δν(¹⁸O₂) = −28 cm⁻¹. We also note that for a copper(I) complex with TMPD, E_1/2 is very negative (−393 mV, vs. Fe(Cp)₂^+/0), consistent with it’s ability to form a bis-μ-oxo complex, stabilizing a high oxidation state copper(III) environment.

To provide further support for thioether ligation in 1P, we separately synthesized the ligand ANSPh (Scheme 1) and its Cu(I) complex [(ANSPh)Cu^I(CH₃CN)]⁺ (3A). The large phenyl group of the ANSPh ligand, directly on the sulfur atom, inhibits sulfur coordination to copper ion in a Cu₂–O₂ adduct. This in fact is the case. The reaction of dioxygen with 3A at −94 °C in acetone gives a yellow bis-μ-oxo dicopper(III) species (3O), λ_max = 409 nm (ε = 9000 cm⁻¹ M⁻¹) similar to typical bis-μ-oxo dicopper(III) species. Resonance Raman data for 3O (ESI†) show only a characteristic core vibration, ν_Cu–O = 606 cm⁻¹ (Δν (¹⁸O₂) = −28 cm⁻¹), suggesting a structure just like Stack’s TMPD complex (Scheme 1)²⁹ and indicating the –SPh moiety does not coordinate. By inference, these results indicate that the S(thioether) donor in ANS must be able to coordinate to Cu(II) in [{(ANS)Cu^II}₂(μ-η²:η²-O₂²⁻)]²⁺ (1P).

In summary, a side-on μ-η²:η²-peroxodicopper(II) species has been generated from the oxygenation of LCu(I) complex with N₂S thioether ligand ANS. By comparison to the nature of the Cu₂–O₂ species generated with closely related ligands where either the S(thioether) is unable to coordinate or is absent (a bis-μ-oxo dicopper(III) complex), we can conclude that coordination of the S(thioether) donor within [{(ANS)Cu^II}₂(μ-η²:η²-O₂²⁻)]²⁺ (1P) occurs. This is the first case of thioether coordination within a μ-η²:η²-peroxodicopper(II) structural type. This advance in copper–dioxygen chemistry further indicates that it is possible to study systems with S(thioether) ligation. Future investigations will focus on the effect of S(thioether) on reactivity of derived copper–dioxygen complexes,³⁰ and on the design and study of systems where only one copper ion is present.

We are grateful to the NIH (K.D.K., GM28962; E.I.S., DK31450) for research support.

Notes and references

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27. rR spectra of 1P obtained with λ_ex = 406.7 nm revealed the presence of a small fraction (∼15%) of a bis-μ-oxo dicopper(III) (ν_Cu–O = 603 cm⁻¹ (Δν(¹⁸O₂) = −29 cm⁻¹), explaining the small shoulder (near 410 nm) observed in the absorption spectrum (Fig. 2).
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30. Following thermal decomposition of [{(ANS)Cu^II}₂(O₂²⁻)]²⁺ (1P) and [{(ANSPh)Cu^III}₂(O²⁻)₂]²⁺ (3O) and work-up including demetallation, oxygenated ligand products, i.e., sulfoxides of ANS and ANSPh, were isolated in moderate yield. Further details and expanded studies will be the subject of a future report.

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Footnotes

† Electronic supplementary information (ESI) available: Experimental details of the structure determinations. CCDC 738906 and 738907. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/b918616f

‡ Suitable single crystals of [(ANS)Cu^I(CH₃CN)]B(C₆F₅)₄ (1A) and [(ANS)Cu^II(Cl)₂] (1B) were mounted in Paratone-N oil on the end of a glass fiber and transferred to the N₂ cold stream of an Oxford Diffraction Xcalibur3 system equipped with Enhance optics and a CCD detector. The frames were integrated and a face indexed absorption correction and an interframe scaling correction were also applied with the Oxford Diffraction CrysAlisRED software package (CrysAlis CCD, Oxford Diffraction Ltd., Version 1.171.27p5 beta). The structures were solved using direct methods and refined using the Bruker SHELXTL (v6.1) software package (Sheldrick, G.M. 2000). [(ANS)Cu^I(CH₃CN)]B(C₆F₅)₄ (1A): crystal data. C₁₉H₃₃CuN₃S·C₂₄BF₂₀, M = 1078.13, orthorhombic, Pbca, T = 110 K, a = 20.3371(4) Å, b = 16.4920(3) Å, c = 6.8598(6) Å, V/ų = 9008.8(3), Z = 8, μ(Mo-Kα) = 0.65 mm⁻¹, crystal size/mm = 0.78 × 0.25 × 0.12, 55 908 reflections measured, 10 274 unique (R_int = 0.083). The final R₁ (I > 2σ(I)) was 0.091. CCDC 738906. [(ANS)Cu^II(Cl)₂] (1B): crystal data. C₁₇H₃₀Cl₂CuN₂S, M = 428.93, monoclinic, P2₁/n, T = 110 K, a = 14.4850(6) Å, b = 9.3727(3) Å, c = 16.0378(6) Å, β = 115.278(5)°, V/ų = 1968.86 (15), Z = 4, μ(Mo-Kα) = 1.47 mm⁻¹, crystal size/mm = 0.77 × 0.18 × 0.08, 12 886 reflections measured, 4653 unique (R_int = 0.031). The final R₁ (I > 2σ(I)) was 0.032. CCDC 738907.

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