Alessandra Napolitano

Chemical and structural diversity in eumelanins : unexplored bio-optoelectronic materials

Eumelanins, the characteristic black, insoluble, and heterogeneous biopolymers of human skin, hair, and eyes, have intrigued and challenged generations of chemists, physicists, and biologists because of their unique structural and optoelectronic properties. Recently, the methods of organic chemistry have been combined with advanced spectroscopic and imaging techniques, theoretical calculations, and methods of condensed-matter physics to gradually force these materials to reveal their secrets. Herein we review the latest advances in the field with a view to showing how the emerging knowledge is not only helping to explain eumelanin functionality, but may also be translated into effective strategies for exploiting their properties to create a new class of biologically inspired high-tech materials.

Kinetic and chemical assessment of the UV/H2O2 treatment of antiepileptic drug carbamazepine

The UV/H2O2-induced degradation of carbamazepine, a worldwide used antiepileptic drug, recently found as contaminant in many municipal sewage treatment plant (STP) effluents and other aquatic environments, is investigated. The oxidation treatment caused an effective removal of the drug. At complete abatement of the substrate after 4 min treatment, a 35% value of removed total organic carbon (TOC) was obtained. A kinetic constant of (2.05+/-0.14) x 10(9) lmol(-1)s(-1) was determined for OH radical attack to carbamazepine in the UV/H2O2 process. Preparative TLC of the reaction mixture led to the isolation of acridine-9-carboxaldehyde as a reaction intermediate. HPLC and GC/MS analysis indicated formation of small amounts of acridine, salicylic acid, catechol and anthranilic acid among the reaction products. Under the same reaction conditions, synthetically prepared 10,11-epoxycarbamazepine was easily degraded to acridine as main product, suggesting that this epoxide is a likely intermediate in the oxidative conversion of carbamazepine to acridine. Under sunlight irradiation, carbamazepine in water underwent slow degradation to afford likewise acridine as main product. In view of the mutagenic properties of acridine, these results would raise important issues concerning the possible environmental impact of carbamazepine release through domestic wastewaters and support the importance of prolonged oxidation treatments to ensure complete degradation of aromatic intermediates.

Polydopamine and Eumelanin: From Structure–Property Relationships to a Unified Tailoring Strategy

CONSPECTUS: Polydopamine (PDA), a black insoluble biopolymer produced by autoxidation of the catecholamine neurotransmitter dopamine (DA), and synthetic eumelanin polymers modeled to the black functional pigments of human skin, hair, and eyes have burst into the scene of materials science as versatile bioinspired functional systems for a very broad range of applications. PDA is characterized by extraordinary adhesion properties providing efficient and universal surface coating for diverse settings that include drug delivery, microfluidic systems, and water-treatment devices. Synthetic eumelanins from dopa or 5,6-dihydroxyindoles are the focus of increasing interest as UV-absorbing agents, antioxidants, free radical scavengers, and water-dependent hybrid electronic-ionic semiconductors. Because of their peculiar physicochemical properties, eumelanins and PDA hold considerable promise in nanomedicine and bioelectronics, as they are biocompatible, biodegradable, and exhibit suitable mechanical properties for integration with biological tissues. Despite considerable similarities, very few attempts have so far been made to provide an integrated unifying perspective of these two fields of technology-oriented chemical research, and progress toward application has been based more on empirical approaches than on a solid conceptual framework of structure-property relationships. The present Account is an attempt to fill this gap. Following a vis-à-vis of PDA and eumelanin chemistries, it provides an overall view of the various levels of chemical disorder in both systems and draws simple correlations with physicochemical properties based on experimental and computational approaches. The potential of large-scale simulations to capture the macroproperties of eumelanin-like materials and their hierarchical structures, to predict the physicochemical properties of new melanin-inspired materials, to understand the structure-property-function relationships of these materials from the bottom up, and to design and optimize materials to achieve desired properties is illustrated. The impact of synthetic conditions on melanin structure and physicochemical properties is systematically discussed for the first time. Rational tailoring strategies directed to critical control points of the synthetic pathways, such as dopaquinone, DAquinone, and dopachrome, are then proposed, with a view to translating basic chemical knowledge into practical guidelines for material manipulation and tailoring. This key concept is exemplified by the recent demonstration that varying DA concentration, or using Tris instead of phosphate as the buffer, results in PDA materials with quite different structural properties. Realizing that PDA and synthetic eumelanins belong to the same family of functional materials may foster unprecedented synergisms between research fields that have so far been apart in the pursuit of tailorable and marketable materials for energy, biomedical, and environmental applications.

Melanins and melanogenesis: methods, standards, protocols

Despite considerable advances in the past decade, melanin research still suffers from the lack of universally accepted and shared nomenclature, methodologies, and structural models. This paper stems from the joint efforts of chemists, biochemists, physicists, biologists, and physicians with recognized and consolidated expertise in the field of melanins and melanogenesis, who critically reviewed and experimentally revisited methods, standards, and protocols to provide for the first time a consensus set of recommended procedures to be adopted and shared by researchers involved in pigment cell research. The aim of the paper was to define an unprecedented frame of reference built on cutting‐edge knowledge and state‐of‐the‐art methodology, to enable reliable comparison of results among laboratories and new progress in the field based on standardized methods and shared information.

Melanins and melanogenesis: from pigment cells to human health and technological applications

During the past decade, melanins and melanogenesis have attracted growing interest for a broad range of biomedical and technological applications. The burst of polydopamine‐based multifunctional coatings in materials science is just one example, and the list may be expanded to include melanin thin films for organic electronics and bioelectronics, drug delivery systems, functional nanoparticles and biointerfaces, sunscreens, environmental remediation devices. Despite considerable advances, applied research on melanins and melanogenesis is still far from being mature. A closer intersectoral interaction between research centers is essential to raise the interests and increase the awareness of the biomedical, biomaterials science and hi‐tech sectors of the manifold opportunities offered by pigment cells and related metabolic pathways. Starting from a survey of biological roles and functions, the present review aims at providing an interdisciplinary perspective of melanin pigments and related pathway with a view to showing how it is possible to translate current knowledge about physical and chemical properties and control mechanisms into new bioinspired solutions for biomedical, dermocosmetic, and technological applications.

Phaeomelanin versus eumelanin as a chemical indicator of ultraviolet sensitivity in fair-skinned subjects at high risk for melanoma: a pilot study

It is now generally agreed that solar exposure is a major external factor in the causation of cutaneous melanoma in light skinned populations with red hair and a marked susceptibility to the acute effects of ultraviolet (UV) radiation. In the present study, we investigated the existence of a possible relationship between hair melanin composition and minimal erythema dose (MED), as an indicator of UV sensitivity, in a group of 15 healthy red-haired subjects aged 20-46 years. In spite of comparable skin and hair colour, marked variations were observed in the MED values as well as in the hair melanin composition. Phaeomelanin levels varied in the range 0.026-0.53% w/w and were generally comparable to or higher than eumelanin levels (0.042-0.17% w/w). No significant relationship was found between MED values and phaeomelanin, eumelanin or total melanin (eumelanin plus phaeomelanin) content. Notably, however, a gross positive correlation was found between the eumelanin/phaeomelanin ratio and the MED values. These results would suggest that a high UV sensitivity is associated with high phaeomelanin and low eumelanin levels, and point to the eumelanin/phaeomelanin ratio as a novel chemical parameter that could be used for predicting individuals at high risk for skin cancer and melanoma.

Oxidation Chemistry of Catecholamines and Neuronal Degeneration: An Update

Aberrant oxidative pathways of catecholamine neurotransmitters, i.e. dopamine and norepinephrine, are an important biochemical correlate of catecholaminergic neuron loss in some disabling neurodegenerative diseases of the elderly, notably Parkinsons disease. In an oxidative stress setting, under conditions of elevated lipid peroxidation, iron accumulation, impaired mitochondrial functioning and antioxidant depletion, catecholamines are oxidatively converted to the corresponding o-quinones, which may initiate a cascade of spontaneous reactions, including intramolecular cyclization, aminoethyl side chain fission and interaction with molecular targets. The overall outcome of the competing pathways may vary depending on contingent factors and the biochemical environment, and may include formation of nitrated derivatives, neuromelanin deposition, generation of chain fission products, conjugation with L-cysteine leading eventually to cytotoxic responses and altered cellular function. In addition, catecholamines may interact with products of lipid peroxidation and other species derived from oxidative breakdown of biomolecules, notably glyoxal and other aldehydes, leading e.g. to tetrahydroisoquinolines via Pictet-Spengler chemistry. After a brief introductory remark on oxidative stress biochemistry, the bulk of this review will deal with an overview of the basic chemical pathways of catecholamine oxidation, with special emphasis on the analogies and differences between the central neurotransmitters dopamine and norepinephrine. This chemistry will form the basis for a concise discussion of the latest advances in the mechanisms of catecholamine-associated neurotoxicity in neuronal degeneration.

An integrated approach to the structure of Sepia melanin. Evidence for a high proportion of degraded 5,6-dihydroxyindole-2-carboxylic acid units in the pigment backbone

Abstract The relative proportion of 5,6-dihydroxyindole (DHI) versus 5,6-dihydroxyindole-2-carboxylic acid (DHICA) units in Sepia melanin and their degree of structural integrity were assessed by an integrated approach involving quantitative determination of pyrrole-2,3-dicarboxylic acid (PDCA) and pyrrole-2,3,5-tricarboxylic acid (PTCA), specific degradation products of DHI- and DHICA-derived units; carboxyl content; rate of ferricyanide consumption; and absorption spectrum. Analyses of both intact and surfactant-solubilised pigment samples, in comparison with synthetic DHI and DHICA melanins, revealed that Sepia melanin consists of a mixture of oligomeric structures incorporating over 75% of DHICA-derived units and only 20% of DHI-derived units, occurring for the most part in an irreversibly degraded form, possibly as pyrrolecarboxylic acids.

Tris buffer modulates polydopamine growth, aggregation, and paramagnetic properties.

Despite the growing technological interest of polydopamine (dopamine melanin)-based coatings for a broad variety of applications, the factors governing particle size, shape, and electronic properties of this bioinspired multifunctional material have remained little understood. Herein, we report a detailed characterization of polydopamine growth, particle morphology, and paramagnetic properties as a function of dopamine concentration and nature of the buffer (pH 8.5). Dynamic Light Scattering data revealed an increase in the hydrodynamic radii (Rh) of melanin particles with increasing dopamine concentration in all buffers examined, especially in phosphate buffer. Conversely, a marked inhibition of particle growth was apparent in Tris buffer, with Rh remaining as low as <100 nm during polymerization of 0.5 mM dopamine. Small angle neutron scattering data suggested formation of bidimensional structures in phosphate or bicarbonate buffers, while apparently three-dimensional fractal objects prevailed in Tris buffer. Finally, electron paramagnetic resonance spectra revealed a broader signal amplitude with a peculiar power saturation decay profile for polydopamine samples prepared in Tris buffer, denoting more homogeneous paramagnetic centers with respect to similar samples obtained in phosphate and bicarbonate buffers. Overall, these results disclose Tris buffer as an efficient modulator of polydopamine buildup and properties for the rational control and fine-tuning of melanin aggregate size, morphology, and free radical behavior.

Role of Solvent, pH, and Molecular Size in Excited-State Deactivation of Key Eumelanin Building Blocks : Implications for Melanin Pigment Photostability

Ultrafast time-resolved fluorescence spectroscopy has been used to investigate the excited-state dynamics of the basic eumelanin building block 5,6-dihydroxyindole-2-carboxylic acid (DHICA), its acetylated, methylated, and carboxylic ester derivatives, and two oligomers, a dimer and a trimer in the O-acetylated forms. The results show that (1) excited-state decays are faster for the trimer relative to the monomer; (2) for parent DHICA, excited-state lifetimes are much shorter in aqueous acidic medium (380 ps) as compared to organic solvent (acetonitrile, 2.6 ns); and (3) variation of fluorescence spectra and excited-state dynamics can be understood as a result of excited-state intramolecular proton transfer (ESIPT). The dependence on the DHICA oligomer size of the excited-state deactivation and its ESIPT mechanism provides important insight into the photostability and the photoprotective function of eumelanin. Mechanistic analogies with the corresponding processes in DNA and other biomolecules are recognized.