Despite extensive investigations over the past decade, the chemical basis of the extraordinary underwater adhesion properties of polydopamine (PDA) has remained not entirely understood. The bulk of evidence points to PDA wet adhesion as a complex process based on film deposition, and growth in which primary amine groups, besides catechol moieties, play a central role. However, the detailed interplay of chemical interactions underlying the dynamics of film formation has not yet been elucidated. Herein, we report the results of a series of experiments showing that coating formation from dopamine at pH 9.0 in carbonate buffer: (a) Requires high dopamine concentrations (>1 mM); (b) is due to species produced in the early stages of dopamine autoxidation; (c) is accelerated by equimolar amounts of periodate causing fast conversion to the o-quinone; and (d) is enhanced by the addition of hexamethylenediamine (HMDA) and other long chain aliphatic amines even at low dopamine concentrations (<1 mM). It is proposed that concentration-dependent PDA film formation reflects the competition between intermolecular amine-quinone condensation processes, leading to adhesive cross-linked oligomer structures, and the intramolecular cyclization route forming little adhesive 5,6-dihydroxyindole (DHI) units. Film growth would then be sustained by dopamine and other soluble species that can be adsorbed on the surface.

Eumelanins, the dark variant of skin pigments, are endowed with a remarkable antioxidant activity and well-recognized photoprotective properties that have been ascribed to pigment components derived from the biosynthetic precursor 5,6-dihydroxyindole-2-carboxylic acid (DHICA). Herein, we report the protective effect of a polymer obtained starting from the methyl ester of DHICA (MeDHICA-melanin) against Ultraviolet A (UVA)-induced oxidative stress in immortalized human keratinocytes (HaCaT). MeDHICA-melanin was prepared by aerial oxidation of MeDHICA. At concentrations as low as 10 µg/mL, MeDHICA-melanin prevented reactive oxygen species accumulation and partially reduced glutathione oxidation in UVA-irradiated keratinocytes. Western blot experiments revealed that the polymer is able to induce the translocation of nuclear factor erythroid 2–related factor 2 (Nrf-2) to the nucleus with the activation of the transcription of antioxidant enzymes, such as heme-oxygenase 1. Spectrophotometric and HPLC analysis of cell lysate allowed to conclude that a significant fraction (ca. 7%), consisting mainly of the 4,4′-dimer of MeDHICA (ca. 2 μM), was internalized in the cells. Overall these data point to the potential use of MeDHICA-melanin as an antioxidant for the treatment of skin damage, photoaging and skin cancers.

Design and implementation of functional coatings is a topic of active research in a variety of health‐related applications, most of which require wet adhesion. The powerful wet adhesion of mussel byssus proteins rich in DOPA and lysine residues provided a clue to realize that the combination of a catechol and an amine component has a specific role in the interfacial adhesion. From this natural model, polydopamine (PDA)‐based coatings have been developed that result from the oxidative polymerization of dopamine combining the catechol and amine functionalities in the same molecule. Covalent interactions resulting from Michael‐type addition or Schiff‐base formation of the polymeric products from dopamine oxidation as well as non‐covalent π‐stacking and cation‐π interactions exemplify the diverse mode of catechol/amine interplay that have been identified as responsible of the adhesion and cohesion properties of PDA. In the last decade coatings inspired to the same chemistry but using different starting materials have been explored particularly catechols of natural origin and different amine components, while mechanistic studies with model compounds have allowed to rationalize the structural requirements for adhesion and to expand the potential of these functional coatings.

The activity of natural phenols is primarily associated to their antioxidant potential, but is ultimately expressed in a variety of biological effects. Molecular scaffold manipulation of this large variety of compounds is a currently pursued approach to boost or modulate their properties. Insertion of S/Se/Te containing substituents on phenols may increase/decrease their H-donor/acceptor ability by electronic and stereo-electronic effects related to the site of substitution and geometrical constrains. Oxygen to sulphur/selenium isosteric replacement in resveratrol or ferulic acid leads to an increase in the radical scavenging activity with respect to the parent phenol. Several chalcogen-substituted phenols inspired by Vitamin E and flavonoids have been prepared, which in some cases prove to be chain-breaking antioxidants, far better than the natural counterparts. Conjugation of catechols with biological thiols (cysteine, glutathione, dihydrolipoic acid) is easily achieved by addition to the corresponding ortho-quinones. Noticeable examples of compounds with potentiated antioxidant activities are the human metabolite 5-S-cysteinyldopa, with high iron-induced lipid peroxidation inhibitory activity, due to strong iron (III) binding, 5-S-glutathionylpiceatannol a most effective inhibitor of nitrosation processes, and 5-S-lipoylhydroxytyrosol, and its polysulfides that proved valuable oxidative-stress protective agents in various cellular models. Different methodologies have been used for evaluation of the antioxidant power of these compounds against the parent compounds. These include kinetics of inhibition of lipid peroxidation alkylperoxyl radicals, common chemical assays of radical scavenging, inhibition of the OH• mediated hydroxylation/oxidation of model systems, ferric- or copper-reducing power, scavenging of nitrosating species. In addition, computational methods allowed researchers to determine the Bond Dissociation Enthalpy values of the OH groups of chalcogen modified phenolics and predict the best performing derivative. Finally, the activity of Se and Te containing compounds as mimic of glutathione peroxidase has been evaluated, together with other biological activities including anticancer action and (neuro)protective effects in various cellular models. These and other achievements are discussed and rationalized to guide future development in the field.

Melanins are pigments employed in food, cosmetic, and textile industries, manufactured by extraction from cuttlefishes. Their biotechnological production by Streptomycetes, instead, has been poorly investigated so far. In this paper, for the first time, the strain Streptomyces nashvillensis DSM 40314 was tested as an extracellular melanin producer by investigating the influence of diverse temperatures (26, 28, and 30 °C) and pH values (6.0 and 7.0) on bacterial growth, melanin production, and on the activity of the secreted tyrosinase, the first enzyme of the pigment biosynthetic pathway. In physiological 96-h shake flask experiments, the optimal growth parameters resulted to be 28 °C and pH 7.0, at which a maximum biomass of 8.4 ± 0.5 g_cdw/L, a melanin concentration of 0.74 ± 0.01 g/L (yield on biomass of 0.09 ± 0.01 g/g_cdw and productivity of 0.008 ± 0.001 g/L/h), and a final tyrosinase activity of 10.1 ± 0.1 U/mL were reached. The produced pigment was purified from the broth supernatant with a two-step purification process (75.0 ± 2.0% of purity with 65.0 ± 5.0% of recovery) and tested for its chemical, antioxidant, and photoprotective properties. Finally, characterization by UV-visible and FT-IR spectroscopy, elemental analyses, and mono- and bi-dimensional NMR suggested the eumelanin-like nature of the pigment.