Hydroxylation of p-substituted phenols by tyrosinase: Further insight into the mechanism of tyrosinase activity

Muñoz‐Muñoz, José Luis; Berná, José; García-Molina, Maria del Mar; García‐Molina, Francisco; Garcı́a-Ruiz, Pedro Antonio; Varón, R.; Rodríguez-López, José Neptuno; Garcı́a-Cánovas, Francisco

doi:10.1016/j.bbrc.2012.06.074

Cited by 24 publications

(20 citation statements)

References 38 publications

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“…In 2012, Garcia‐Canovas et al. reported on kinetic measurements of the hydroxylation under physiological pH (without borate and hydroxylamine) and they obtained a ρ value of −1.75 . Both results showed that tyrosinase hydroxylates phenolic substrates also with an electrophilic substitution mechanism.…”

Section: Resultsmentioning

confidence: 99%

“…determined with a bis(pyridinyl)benzylamine ligand a hydroxylation constant k ox of 0.083 s −1[15] which is considerably slower than our systems. With natural tyrosinase the hydroxylation reactions are five to ten times faster but it has to be taken into account that the enzyme works at ambient temperatures and most of the model systems are cooled at least to −80 °C.…”

Section: Resultsmentioning

confidence: 99%

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Record Broken: A Copper Peroxide Complex with Enhanced Stability and Faster Hydroxylation Catalysis

Liebhäuser

Keisers

Hoffmann

et al. 2017

Chemistry A European J

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Tyrosinase model systems pinpoint pathways to translating Nature's synthetic abilities for useful synthetic catalysts. Mostly, they use N-donor ligands which mimic the histidine residues coordinating the two copper centres. Copper complexes with bis(pyrazolyl)methanes with pyridinyl or imidazolyl moieties are already reported as excellent tyrosinase models. Substitution of the pyridinyl donor results in the new ligand HC(3-tBuPz) (4-CO MePy) which stabilises a room-temperature stable μ-η :η -peroxide dicopper(II) species upon oxygenation. It reveals highly efficient catalytic activity as it hydroxylates 8-hydroxyquinoline in high yields (TONs of up to 20) and much faster than all other model systems (max. conversion within 7.5 min). Stoichiometric reactions with para-substituted sodium phenolates show saturation kinetics which are nearly linear for electron-rich substrates. The resulting Hammett correlation proves the electrophilic aromatic substitution mechanism. Furthermore, density functional theory (DFT) calculations elucidate the influence of the substituent at the pyridinyl donor: the carboxymethyl group adjusts the basicity and nucleophilicity without additional steric demand. This substitution opens up new pathways in reactivity tuning.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Record Broken: A Copper Peroxide Complex with Enhanced Stability and Faster Hydroxylation Catalysis

Liebhäuser

Keisers

Hoffmann

et al. 2017

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…Under these conditions, the rate-limiting step of the hydroxylation reaction is slowed by electron deficient substrates (Hammett ρ = −2.4), in line with an electrophilic oxidation mechanism. The KIE of 1.1 for mushroom Ty with deuterium substitution on the oxidized carbon of the phenol suggests that the C-H(D) bond cleavage is not rate limiting [61,112]. …”

Section: Monooxygenase Reactivity Of O Speciesmentioning

confidence: 99%

High-valent copper in biomimetic and biological oxidations

2016

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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 (i) that Cu(I) should be considered as either a one or two electron reductant reacting with O2, (ii) that Cu(III) reduction potentials of these formed complexes are modest and well within the limits of a protein matrix and (iii) 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.

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“…Such at rend has been found in the literaturef or other enzyme-catalyzed reactions involving nucleophilic centers in the aromatic ring:i n, for example, tyrosinase-catalyzed hydroxylations [14] and bromoperoxidase-catalyzed brominations. Such at rend has been found in the literaturef or other enzyme-catalyzed reactions involving nucleophilic centers in the aromatic ring:i n, for example, tyrosinase-catalyzed hydroxylations [14] and bromoperoxidase-catalyzed brominations.…”

Section: Effect Of Substituents On the Initial Ratesmentioning

confidence: 99%

“…[6,10] Even though reasonably depicted scenarios have been regarded as exceptions, successful examples exist. tyrosinase), [14,15] hydrolases (aryl sulfatase, epoxide hydrolase, and lipase) [16] and lyases (benzoyl formate decarboxylase). [12] Electronic (s)a nd hydrophobic (p)c onstants have been shown to be very useful to describe the reactivity observed in enzyme-catalyzed reactions, in terms of mechanism and structural requirements; [13] examples include systems based on monooxygenases and dioxygenases( cytochromeP 450 and The enzymatic carboxylation of phenolic compounds hasb een attracting increasingi nterest in recent years, owing to its regioselectivity and technical potential as ab iocatalytic equivalent for the Kolbe-Schmitt reaction.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Substrate Scope of Benzoic Acid (De)carboxylases According to Chemical and Biochemical Parameters

2016

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The enzymatic carboxylation of phenolic compounds has been attracting increasing interest in recent years, owing to its regioselectivity and technical potential as a biocatalytic equivalent for the Kolbe-Schmitt reaction. Mechanistically the reaction was demonstrated to occur through electrophilic aromatic substitution/water elimination with bicarbonate as a cosubstrate. The effects of the substituents on the phenolic ring have not yet been elucidated in detail, but this would give detailed insight into the substrate-activity relationship and would provide predictability for the acceptance of future substrates. In this report we show how the kinetic and (apparent) thermodynamic behavior can be explained through the evaluation of linear free energy relationships based on electronic, steric, and geometric parameters and through the consideration of enzyme-ligand interactions. Moreover, the similarity between the benzoic acid decarboxylases and the amidohydrolases superfamily is investigated, and promiscuous hydrolytic activity of the decarboxylase in the context of the hydrolysis of an activated ester bond has been established.

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Hydroxylation of p-substituted phenols by tyrosinase: Further insight into the mechanism of tyrosinase activity

Cited by 24 publications

References 38 publications

Record Broken: A Copper Peroxide Complex with Enhanced Stability and Faster Hydroxylation Catalysis

Record Broken: A Copper Peroxide Complex with Enhanced Stability and Faster Hydroxylation Catalysis

High-valent copper in biomimetic and biological oxidations

Evaluation of the Substrate Scope of Benzoic Acid (De)carboxylases According to Chemical and Biochemical Parameters

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