First Evidence of Pheomelanin-UVA-Driven Synthesis of Pummerer’s Ketones by Peroxidase-Mediated Oxidative Coupling of Substituted Phenols

Abstract

Photoexcitation of pheomelanin produces high-energy singlet oxygen and the superoxide anion, which are reactive species in damage of cellular targets. In principle, these species can be involved in processes of synthetic utility when adequate experimental conditions are defined. Here, we describe that pheomelanin performs as a selective UVA antenna for the horseradish peroxidase oxidative coupling of substituted phenols to biologically active Pummerer’s ketones under 2-methyltetrahydrofuran/buffer biphasic conditions. In this system, singlet oxygen is scavenged by conversion of 2-methyltetrahydrofuran into the corresponding organic hydroperoxide, while the superoxide anion is dismutated into hydrogen peroxide. Both these intermediates are able to oxidize the active site of horseradish peroxidase triggering the oxidative coupling reaction. Trimer derivatives, produced by addition of phenoxy radicals on preformed Pummerer’s ketones were also isolated, suggesting the possibility to further improve the structural complexity of the reaction products.

Synthesis of Bioactive Hydroxytyrosol Esters via Multienzyme Cascade on Electroactive Melanin Lignin Nanoparticles: A One‐Pot Approach without Extra Reducing Agents

“…The reaction was performed by addition of the appropriate catalyst (150 μg in PBS, 0.15 mL) to substrate in 2‐methyltetrahydrofuran (2‐MeTHF; 5.0 mL) at 50 °C for 48 h in the presence of bubbled dioxygen [14] . 2‐MeTHF was previously used by us as a sustainable organic solvent [67,68] in different bio‐catalytic and photo‐biocatalytic applications [14,35] . The reaction was repeated using a mixture of native MJL (8 U) and Ty (2 U) in the same ratio by which the enzymes were contained in Catalyst I – III as a reference.…”

“…[14] 2-MeTHF was previously used by us as a sustainable organic solvent [67,68] in different biocatalytic and photo-biocatalytic applications. [14,35] The reaction was repeated using a mixture of native MJL (8 U) and Ty (2 U) in the same ratio by which the enzymes were contained in Catalyst I-III as a reference. At the end, the reaction was filtered to recover the catalyst and the filtrate was concentrated under reduced pressure.…”

“…[33] The electrochemical properties of eumelanin and pheomelanin are reviewed, and the capability of these polyphenols to perform as semiconductor in dark conditions discussed in detail. [34][35] The redox potential of hybrid melanin lignin nanoparticles was favourable for the regeneration of the active site of tyrosinase from unproductive met-form to reversible deoxy/oxyform as indicated by optoelectronic and electrochemical analyses. [36] This effect improved the overall activity of tyrosinase in the multienzyme cascade with respect to lignin alone and favoured the reduction of undesired quinones to corresponding catechols.…”

“…Eumelanin and pheomelanin were selected in order to lowering the HOMO‐LUMO energy gap between the aromatic sub‐units of lignin, thus improving the redox properties of the overall platform [33] . The electrochemical properties of eumelanin and pheomelanin are reviewed, and the capability of these polyphenols to perform as semiconductor in dark conditions discussed in detail [34–35] …”

Blue‐LED Synthesis of Pummerer's Ketones by Peroxidase‐Lignin‐Catalyzed Oxidative Coupling of Substituted Phenols

“…In the last years, Horseradish Peroxidase (HRP) received a great attention as an effective and selective catalyst in synthetic transformations. [1][2][3] The enzyme is activated by heterolytic cleavage of H 2 O 2 with the concomitant formation of the ferryl intermediate, which is in turn converted to the resting state by oxygen atom transfer to substrate. [4][5][6] When H 2 O 2 accumulates in the reaction medium, HRP is inhibited due to undesired overoxidation of the iron atom in the prosthetic group.…”