Understanding the copper–phenoxyl radical array in galactose oxidase: contributions from synthetic modeling studies

Jazdzewski, Brian A.; Tolman, William B.

doi:10.1016/s0010-8545(00)00342-8

Cited by 306 publications

(163 citation statements)

References 97 publications

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“…In smallmolecule Cu II -phenoxyl radical complexes, the difference between antiferromagnetic and ferromagnetic coupling arises from differences in the angular overlap of the unpaired spin containing orbitals (27,12,20,24,(36)(37)(38). The orientation of the aromatic ring relative to the Cu coordination basal plane observed in crystal structures of Cu(II)-salen complexes precludes the orbital overlap required for antiferromagnetic coupling (13,16).…”

Section: ½1mentioning

confidence: 99%

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Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase

Verma

Pratt

Storr

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Integrating sulfanyl substituents into copper-bonded phenoxyls significantly alters their optical and redox properties and provides insight into the influence of cysteine modification of the tyrosine cofactor in the enzyme galactose oxidase. The model complexes ½1 SR2 þ are class II mixed-valent Cu II -phenoxyl-phenolate species that exhibit intervalence charge transfer bands and intense visible sulfur-aryl π → π Ã transitions in the energy range, which provides a greater spectroscopic fidelity to oxidized galactose oxidase than non-sulfur-bearing analogs. The potentials for phenolate-based oxidations of the sulfanyl-substituted 1 SR2 are lower than the alkylsubstituted analogs by up to ca. 150 mV and decrease following the steric trend: −S t Bu > −S i Pr > −SMe. Density functional theory calculations suggest that reducing the steric demands of the sulfanyl substituent accommodates an in-plane conformation of the alkylsulfanyl group with the aromatic ring, which stabilizes the phenoxyl hole by ca. 8 kcal mol −1 (1 kcal ¼ 4.18 kJ; 350 mV) through delocalization onto the sulfur atom. Sulfur K-edge X-ray absorption spectroscopy clearly indicates a contribution of ca. 8-13% to the hole from the sulfur atoms in ½1 SR2 þ . The electrochemical results for the model complexes corroborate the ca. 350 mV (density functional theory) contribution of hole delocalization on to the cysteine-tyrosine cross-link to the stability of the phenoxyl radical in the enzyme, while highlighting the importance of the in-plane conformation observed in all crystal structures of the enzyme.Marcus-Hush analysis | density functional theory reduction potentials | noninnocent ligands | magnetic coupling G alactose oxidase (GO) is an enzyme that selectively oxidizes primary alcohols to aldehydes via a unique Cu II -tyrosyl radical with concomitant reduction of dioxygen to hydrogen peroxide (1, 2). The active site of GO contains a Cu center ligated by two histidines, one unmodified tyrosine (axial) and one tyrosine residue (equatorial) that is covalently cross-linked to a cysteine residue in a posttranslational oxidative modification step (3-5) (Fig. 1). The consensus mechanism involves two catalytically relevant forms: the reduced (GO red ), which contains a Cu I -tyrosine unit, and the oxidized (GO oxy ), which contains a Cu II center and a cysteine-modified tyrosyl radical. One-electron reduction of GO oxy generates the inactive semireduced (GO semi ) form, which contains a Cu II -tyrosinate unit. Cysteine-modification of the redox-active tyrosine significantly influences the redox properties of the active oxidant: The potential of the Tyr-Cys/Tyr•-Cys couple estimated from the GO semi ∕ GO oxy interconversion is ca. 400 mV [vs. normal hydrogen electrode (NHE), pH 7.5], which is significantly lower than free tyrosine in solution (ca. 900 mV) and unmodified redox-active tyrosines in other enzymes (ca. 660-1,000 mV) (1, 6). Delocalization of the tyrosyl radical onto the thioether bridge, which is predicted by density functional theory (DFT) compu...

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Section: ½1mentioning

confidence: 99%

“…150 mV lower than 1 tBu2 . An ortho-methylsulfanyl group lowers this potential by a lesser amount in the range of 10-50 mV (20 mV for 2 SMe2 ) (24,33,36,44,45). For para substituted 1 R2 , the potential for the first oxidation varies linearly with the σ þ Hammett constant (see SI Appendix, Fig.…”

Section: Sr2mentioning

confidence: 99%

Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase

Verma

Pratt

Storr

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Such a trend is also applied to the salen-type complexes, and most of the Cu(II) and group 10 metal(II) salen-type complexes exhibited two reversible redox waves in the range of 0 to 1.5 V vs NHE, due to having two phenolate moieties [29][30][31][39][40][41][42][43][44][45][46][47]. On the other hand, the metal centered one-and two-electron oxidized complexes may possibly be generated in the similar potential range.…”

Section: Scheme 1 Proposed Mechanism Of Galactose Oxidase (Go)mentioning

confidence: 91%

“…For understanding the detailed mechanism of GO and the properties of the metal complexes with the coordinated phenoxyl radical, many metal−phenolate complexes have been synthesized, and their oxidation behavior and properties of the oxidized forms have been characterized in [12,13,[29][30][31][32][33][34][35][36]. Salen (Salen = di(salicylidene)ethylenediamine) and its family are one of the most important and famous ligands having two phenol moieties (Figure 3) [37,38].…”

Section: Scheme 1 Proposed Mechanism Of Galactose Oxidase (Go)mentioning

confidence: 99%

“…In general, Cu(III) complexes have a square-planar geometry and are diamagnetic and EPR silent due to the low-spin d 8 configuration [12,13]. The Cu(II)-phenoxyl radical complex, on the other hand, has two electron spins on different nuclei, and therefore the spin-spin interaction should be considered in [29][30][31]. In the case of the oxidized Cu(II) salen-type complexes, since correlation between ligand p-orbital and the copper dx2-y2 orbital having an unpaired electron is close to orthogonal, the d-electron spin of copper ion coupled with radical electron spin ferromagnetically [60].…”

Section: Magnetic Properties Of One-electron Oxidized Metal Salen-typmentioning

confidence: 99%

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Oxidation Chemistry of Metal(II) Salen-Type Complexes

Shimazaki¹

2013

Electrochemistry

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Metal Coordinated Phenoxyl Radicals

Thomas

2010

Stable Radicals

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The term "phenoxyl" radical was first introduced in 1914 by Pummerer 1 to designate species involved in the oxidation of naphthols and phenanthroles. It was not until the 1960s that the existence of phenoxyls was demonstrated by Electron Paramagnetic Resonance (EPR). The term "stable" is commonly used to designate radicals such as nitroxides, trityls, and so on. Although the term "stable" had been associated with some phenoxyl radicals in 1967, 2 it must be realized that phenoxyl radicals exhibiting stabilities comparable to those of nitroxides were rather rare at this time. During the 1970s, Reichard et al . 3 demonstrated that radicals related to phenoxyls could also arise from mono-electronic oxidation of the phenolic side chain of tyrosines in some proteins, and thus could be involved in biological processes. The new term "tyrosyl" was then introduced to designate these residues, and many other biological systems involving such radicals have been described. 4,5 One of the more important recent advances in tyrosyl radical history was achieved in the 1990s with the characterization of the galactose oxidase (GO) active site. 6 -8 For the first time it was demonstrated that tyrosyls could exist coordinated to a metal ion. To better understand this association, chemists have subsequently developed many complexes involving coordinated phenoxyl radicals. 9 -13 Elucidation of the properties of coordination compounds involving redox active ligands, especially those involving sterically hindered phenolates, is one of the most recent and fascinating topics of interest in bioinorganic chemistry. The challenge in this kind of chemistry is the right description of the electronic structure of the M n+ -OPh entity (where OPh represents a phenolate group) once it has been oxidized by one electron. In principle, either the M (n+1)+ -OPh, that is the oxidation is metal based, or the M n+ -• OPh form, that is the oxidation is ligand based, could be obtained. The right description is thus not obvious and, as will be shown below, it strongly depends on the nature of the metal ion, the denticity of the ligand, the substituents of the phenolate precursor and even the temperature. Coordination is also found to improve the radical stability, and exerts an extraordinary control on their magnetic properties and reactivity (regio-and stereoselective oxidations are promoted by a radical). Stable Radicals: Fundamentals and Applied Aspects of Odd-Electron CompoundsEdited by Robin G. Hicks

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Understanding the copper–phenoxyl radical array in galactose oxidase: contributions from synthetic modeling studies

Cited by 306 publications

References 97 publications

Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase

Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase

Oxidation Chemistry of Metal(II) Salen-Type Complexes

Metal Coordinated Phenoxyl Radicals

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