Antioxidant activity of film forming systems based on melanins from 5,6-dihydroxyindole derivatives

The development of innovative dip-coating technologies for surface functionalization has been a very active issue over the past decade following the discovery of the adhesion properties of polydopamine, a eumelanin-like material. New opportunities have derived from the discovery that hexamethylenediamine (HMDA) markedly enhances film deposition from a variety of catechol, including the key eumelanin precursor 5,6-dihydroxyindole (DHI). The remarkable antioxidant properties of synthetic eumelanins from the other main melanogenic precursor 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and its methyl ester (MeDHICA) have recently been described. In this work the film forming properties of MeDHICA melanin generated in the presence of HMDA or other diamines/monoamines and the antioxidant activity of the resulting films were investigated. Further to a systematic investigation, the most promising results were obtained running the aerobic oxidative polymerization of MeDHICA in aqueous buffers at pH 9.0 at 1 mM in the presence HMDA at 1:1.5 molar ratio. Under these conditions a dark yellow pigment is formed over 24 h exhibiting good film forming properties on different supports. HPLC analysis of the film solubilized in organic solvents indicated a mixture of oligomers of MeDHICA up to hexamers. Further polymerization of the film was obtained by exposure to ammonia vapors. The films showed high antioxidant activities in the 2,2-diphenyl-1-picrylhydrazyl and Ferric Reducing Antioxidant Power assays. Biocompatibility of MeDHICA/HMDA films was assessed on HaCat cells

Properties of melanin pigments for the definition of mechanisms of (photo)toxicity in red hair phenotype and development of strategies of (photo)protection.

In recent years particular attention has been focused on the properties of melanin pigments with regard to their association with some pathological conditions and to their controversial role in the response of skin to solar radiation. This is especially true in the case of pheomelanins, typical of red hair phenotype, with red hair pale skin, blue-green eyes and freckles. People exhibiting this phenotype have poor tanning capacity, exhibit a UV-susceptibility trait with high tendency to sunburn and an increased risk for skin tumors and melanoma. On the other hand, eumelanins are commonly believed to be the most important photoprotective factor, even if evidence accumulating over the last decades highlight a much more controversial role of eumelanins in human pigmentation. On these bases, the research work carried out during the PhD course and reported in this thesis was directed at investigating the light-independent effects of purified human hair melanins on keratinocyte cell cultures with particular attention to their pro-oxidant properties and at defining the origin of the broadband absorption spectrum of eumelanin, which underpins their protective shielding effect. Based on the consideration that, besides eumelanin pigments, the entire melanogenic pathway is relevant to melanocyte function, the effect of carboxyl group substituent of indole precursors on eumelanin properties was evaluated and a suitable derivative of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) was prepared to assess the photoprotective properties for potential application in sunscreen formulations. Local excess of pigmentation is one of the most common pigmentary disorder5 whose aesthetically impact has urged the search for efficient strategies for control of skin pigmentation. As a preliminary approach toward the implementation of a novel skin depigmenting agent a conjugate of caffeic acid with dihydrolipoic acid was prepared and tested for its ability to inhibit mushroom tyrosinase activity

Nature-inspired phenolic systems for technological and biomedical applications

The imitation of Nature’s chemical principles and logics has emerged as a competitive strategy for the design and implementation of functional molecular systems and biomaterials for innovative technological and biomedical applications. A unique source of inspiration in this context is offered by phenols, polyphenols and especially catechols, in view of their disparate biological roles. In the last decades, great interest has been directed to understand structural, physical and chemical properties of melanins, the black or brownish-red insoluble polyphenolic pigments of human skin, hair, eyes and melanomas.However, the extreme heterogeneity of their molecular systems and practical difficulties in their extraction and purification processes from natural sources, made their structural characterization and the definition of structure properties relationships a most difficult task. To this aim, synthetic mimics of natural melanins that can be obtained by oxidative polymerization of dopamine (DA), DOPA, 5-Scysteinyldopamine (CDA), 5,6-dihydroxyindole (DHI) or 5,6- dihydroxyindole carboxylic acid (DHICA) hold much promise for technological applications due to their peculiar properties which include a broad-band UV and visible absorption profile, redox properties, free radical scavenging ability and water-dependent hybrid electronic-ionic semiconduction. Of particular relevance for technological purposes is the black polymer produced by oxidation of dopamine, polydopamine (PDA) and inspired by mussels’ unique ability to strongly adhere to rocks underwater via catechol and amine crosslinks from DOPA and lysine residues. Because of its robustness, universal adhesion properties, biocompatibility, reversible and pH switchable permselectivity for both cationic and anionic redox-active probe molecules, PDA based coating technology has opened up the doorway to novel opportunities in the fields of bioengineering, nanomedicine, biosensing and organic electronics. So far, however, progress in polyphenol-, catecholamine- and melanin-based functional materials and systems has been limited by a number of gaps and issues, including: a) the lack of rational strategies based on structure-property relationships for selectively enhancing functionality or imparting new technologically relevant properties to polydopamine and synthetic melanins tailored to applications. b) the lack of detailed studies on the actual scope of previous observations in the literature on catecholamine oxidation chemistry and the coupling with carbon, nitrogen and sulfur nucleophiles; c) the lack of unambiguous data about the specific structural factors underpinning the universal material independent sticking behavior of polydopamine and other mussel inspired bioadhesives. In the light of the foregoing, specific objectives of the present PhD project include: 1) The definition of key structure-property relationships in synthetic eumelanins for the development of rational strategies to enhance or tailor functionality for specific applications; 2) The synthesis and chemical characterization of innovative molecular systems and functional polymers based on rational manipulation of melanin precursors, including dopamine and 5,6-dihydroxyindole for adhesion, crosslinking and other applications; 3) The development of alternative mussel inspired systems for various applications based on the oxidative chemistry of cheap, easily accessible and non-toxic natural phenolic compounds such as caffeic acid and chlorogenic acid; 4) The rational design of novel fluorescence turn-on systems for sensing applications based on catecholamine oxidation chemistry and coupling with nucleophiles. Main results can be summarized as follows: 1) The origin and structure-dependent differences of the main chromophores generated by oxidative polymerization of DHI and DHICA to melanin-type products have been elucidated by a combined experimental and computational approach based on an unprecedented set of dimeric precursors. An improved model for the origin of eumelanin broadband absorption properties has been proposed; 2) The impact of carboxyl group esterification on the structure and antioxidant activity of DHICA-melanins has been clarified for the first time, providing novel directions for the design of melanin-inspired antioxidants and functional systems; 3) The adhesion and pro-oxidant properties of the polymer deriving from CDA oxidation (pCDA) were reported in comparison with PDA. This material proved capable of accelerating the kinetics of autoxidation of glutathione in its reduced form (GSH), a property potentially useful for sensing applications; 4) Two new sulfur-containing analogs of dopamine and 5,6-dihydroxyindole were synthesized, 3,4- dihydroxyphenilethanethiol (DHPET) and 5,6- dihydroxybenzothiophene (DHBT), their oxidative chemistry was investigated and the spectrophotometric, morphological and electronic properties of the DHBT polymer (thiomelanin) were assessed in the frame of a proof-of-concept project on novel melanin-like materials. Part of this work was carried out during a 3-month stay at the Catalan Institute for Nanoscience and Nanotechnologies (ICN2, Bellaterra, Spain) 5) Novel mussel-inspired adhesive films and biocompatible coatings with good metal chelating and dye adsorbing properties were rationally designed and characterized by the autoxidative coupling of the natural catechol caffeic acid with the long-chain hexamethylenediamine at pH 9. The same coupling chemistry was extended to chlorogenic acid and two amino acids, glycine and lysine, for the synthesis of biocompatible green pigments for food-related applications. 6) A pH-sensitive fluorescent thin film and a fluorescent polymer tag were designed and obtained by suitable optimization of the strongly fluorogenic reaction between dopamine and resorcinols. The reaction is efficient, develops from cheap and easily available compounds and can be extended to a range of resorcinol and catecholamine partners. Possible sensing of volatile amines with this fluorogenic system is disclosed. Overall, these results fulfil the main objectives of the PhD project and expand the current repertoire of functional nature-inspired materials and systems

Melanin pigments as antibacterial agents

In this dissertation I investigated the structural properties of melanin biopigment from different sources as an antibacterial and endotoxin bonding agent. I extracted melanin from Equus ferus hair with acid hydrolysis (termed EquusMel) and characterized it by microscopic and spectroscopic techniques. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that EquusMel is mainly elliptical in shape with a mesoporous and layered structure within the individual particles. Wide-angle (WAXS) and small-angle (SAXS) X-ray scattering measurements demonstrated a semicrystalline multilayered structure with order spacing of 45.2 Å. Pore size distribution determined by the Barrett–Joyner–Halenda (BJH) method showed primary pores within the range of 30–50 Å. Nitrogen adsorption–desorption isotherms exhibited a Brunaur–Emmett–Teller (BET) surface area of 3 m2/g. Raman, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR) spectra revealed similar chemical signature between EquusMel and synthetic melanin (SynMel). I investigated the antibacterial effect and its mechanism of action for EquusMel. I found that EquusMel has distinct antibacterial activity due to its potential to generate reactive oxygen species (ROS). ROS generated via oxidation of catechols is considered the main mechanism of antibacterial activity. The simplicity of EquusMel extraction and its antibacterial property allows this biomaterial to be applicable to a variety of areas. Zinc cations (Zn2+) were loaded on melanin structure (Mel-Zn) for rapid and selective separation of gram-negative bacteria and lipopolysaccharide (LPS) from blood. Mel-Zn was characterized by XPS and Raman which revealed the successful Zn2+ loading. I identified that Mel-Zn rapidly captures approximately 90% of Escherichia coli in whole blood and 100% of LPS in PBS, which can reduce bacteremia loads and mitigate the spread of these infectious agents to other tissues and organs. Additionally, simultaneous binding to bacteria and LPS could enhance the efficacy of antibiotic therapy. Adsorption of protein from individual protein model solutions, as well as LPS-spiked protein solutions, was found to be minimal. Hemolysis and coagulation assays demonstrate the blood biocompatibility of Mel-Zn, which could be adapted for clinical use in an extracorporeal membrane to remove pathogens and LPS in acute sepsis patients

Intermolecular interactions in eumelanins: A computational bottom-up approach. I. small building blocks

The non-covalent interactions between pairs of the smallest eumelanins building blocks, 5,6-dihydroxy-indole (DHI) and its redox derivatives, are subjected to a systematic theoretical investigation, elucidating their nature and commenting on some of their possible effects on the layered structure of eumelanin. An accurate yet feasible protocol, based on second order perturbation theory, was set up and validated herein, and thereafter used to sample the intermolecular potential energy surfaces of several DHI related dimers. From the analysis of the resulting local minima, the crucial role of stacking interactions is assessed, evidencing strong effects on the geometrical arrangement of the dimer. Furthermore, the absorption spectra of the considered dimers in their most stable arrangements are computed and discussed in relation to the well known eumelanin broadband features. The present findings may help in elucidating several eumelanin features, supporting the recently proposed geometrical order/disorder model (Chen et al., Nat. Commun. 2014, 5, 3859)

Conducting Polymers and Natural Molecular Materials for Bioelectronics and Energy Storage

La découverte de la conduction électronique dans les matériaux organiques, dans les années 70, est à l’origine du développement des technologies optoélectroniques organiques. La remarquable propriété que présentent les semiconducteurs organiques de conduire les ions, en plus des porteurs de charge électroniques, a permis l’émergence d’un nouveau domaine de l’optoélectronique organique, c’est à dire la bioélectronique. La bioélectronique organique ouvre de nouvelles opportunités d’interface entre l’électronique organique et la biologie, avec la promesse d’applications dans des domaines aussi variés que les biocapteurs, la livraison de médicament, l’enregistrement et la stimulation neural. Combiner un transport ionique et électronique dans les semiconducteurs organiques utilisés pour les transistors représente une tentative intéressante pour parvenir à des dispositifs bioélectroniques efficaces. Ces dispositifs opèrent à faible polarisation de l’électrode de grille, grâce à la formation d’une double couche électrique au niveau de l’interface électrode/électrolyte. Les capacitances de double couches résultantes ont des valeurs qui dépassent de plusieurs ordres de grandeurs celles typiques des interfaces métal/diélectrique, en raison de la faible épaisseur (ca. 3nm) des doubles couches électriques. Par conséquent, les capacitances de double couche peuvent mener à de plus fortes modulations en courant pour des différences de potentiel de grille plus faibles (~1 V), compatibles avec les milieux aqueux. Le coeur de cette thèse de doctorat est dévoué à une meilleure compréhension des mécanismes d’opération d’une classe importante de dispositifs bioélectroniques organiques, c’est-à-dire les transistors électrochimiques organiques (OECTs), dans le but d’optimiser leurs performances et de concevoir de nouveaux dispositifs bioélectroniques. Les OECTs sont formés d’un canal en polymère conducteur ainsi que d’une électrode de grille mis en contact avec le canal au travers d’un électrolyte. L’application d’une différence de potentiel électrique au niveau de la grille entraîne l’inclusion d’ions de l’électrolyte à l’intérieur de la couche mince en polymère en qui changent sa conducitvité initiale. Dans cette thèse, nous nous sommes concentrés sur le poly(3,4- éthylènedioxythiophène) dopé avec du poly(styrène sulfonate) (PEDOT:PSS) en tant que matériau actif dans le canal de OECTs. Nous avons utilisé différentes épaisseurs de canal ainsi que deux électrolytes différents : le bromure de cétyltriméthyl-ammonium (CTAB), un surfactant apte à former des micelles, et du NaCl. Les rapports ON/OFF les plus élevés ont été obtenus pour de transistors utilisant de faibles épaisseurs (~ 50 nm) de la couche mince et le CTAB comme électrolyte. La voltammétrie cyclique suggère qu’une réaction rédox entre les molécules d’oxygène dissoutes dans l’électrolyte et le PEDOT:PSS mène à de faibles ratios ON/OFF quand le NaCl est utilisé comme électrolyte. La voltammétrie cyclique et la spectroscopie d’impédance électrochimique révèlent que le dopage/dédopage du canal devient plus lent à des épaisseurs relativement élevés de la couche mince et en présence d’ions de plus grande taille. Les caractéristiques de l’électrode de grille ont des effets significatifs sur le comportement des OECTs. Dans cette thèse, du carbone activé (AC) avec une importante surface spécifique a été utilisé comme matériau pour l’électrode de grille dans les OECTs basés sur le PEDOT:PSS. L’utilisation d’électrodes de grille en AC de grande surface, a mené à une importante modulation en courant drain-source dans les OECTs et à la limitation des réactions électrochimiques indésirables. La biocompatibilité et la biodégradabilité des matériaux utilisés en bioélectronique organique sont essentiels. Ces propriétés sont importantes même pour des dispositifs alimentant les dispositifs bioélectroniques. La mélanine est un biopigment abondant en nature et doté d’activité redox. Ce biopigment peut être mis en forme à température ambiante et est donc un matériau extrêmement intéressant pour le développement de dispositifs de stockage de l’énergie biocompatibles et « verts ». L’eumélanine est une des formes de la mélanine qui est particulièrement étudiée par les chercheurs en science de matériaux. Celle-ci se retrouve dans de nombreuses parties du corps humain, dont la peau, les cheveux, l’oreille interne et le cerveau. L’eumélanine réalise de nombreuses fonctions dans le corps humain comme l’absorption dans une large bande du spectre UV-visible ou encore la chélation métallique. Dans cette thèse, nous rapportons les propriétés de stockage d’énergie électrochimique de la part d’électrodes basées sur l’eumélanine, en configuration supercondensateur. L’eumélanine est formée de monomères faits de 5,6-dihydroxyindole (DHI) et d’acide 5,6-dihydroxyindole carboxylique (DHICA), présents sous différentes formes redox (hydroxyquinone, semiquinone et quinone). La synergie entre l’activité redox des monomères et la capacité de plusieurs de leurs fonctionnalités à lier des cations de façon réversible permet l’utilisation de l’eumélanine dans des dispositifs de stockage d’énergie fonctionnant en mode pseudocapacitif. En partant de la démonstration des supercondensateurs basés sur l’eumélanine, nous avons utilisé une approche non-conventionnelle pour fabriquer des micro-condensateurs flexibles sur substrats plastiques. ---------- The discovery of electronic conduction in carbon-based materials, in the 1970s, is the basis of the development of organic optoelectronics technologies. The remarkable property of organic semiconductors to conduct ions, in addition to electronic charge carriers, has recently offered a new emerging direction in organic optoelectronics, called organic bioelectronics. Organic bioelectronics opens the opportunity to interface organic electronics with biology with promising applications such as biosensing, drug delivery, neural recording and stimulation. Combining ionic and electronic transport in organic semiconductors into transistor architectures represents an interesting attempt to achieve efficient bioelectronics devices. These devices operate at low gate biases, due to the formation of electrical double layers at electrode/electrolyte interfaces. The resultant double layer capacitances are a few orders of magnitude higher compared to capacitances typical of metal/dielectric interfaces, due to the low thickness (ca. 3 nm) of the electrical double layers, which consequently leads to higher current modulations at lower gate voltage (~1 V). The core of this Ph.D. thesis is devoted to a better understanding of the operational mechanism of an important class of organic bioelectronics devices, i.e. organic electrochemical transistors (OECTs), to optimize their performance and to design novel bioelectronics devices. OECTs consist of a conducting polymer channel and a gate electrode in contact with an electrolyte. The application of a gate electrical bias triggers the inclusion of electrolyte ions into the polymer film thus changing its initial conductivity. In this thesis we focus on poly(3,4-ethylenedioxythiophene) doped with polystyrenesulfonate (PEDOT:PSS) as the active material in OECTs. We employed various channel thicknesses and two different electrolytes: the micelle-forming surfactant cetyltrimethyl ammonium bromide (CTAB) and NaCl. The highest transistor ON/OFF ratios were achieved at low film thicknesses (~ 50 nm), using CTAB as the electrolyte. Cyclic voltammetry suggested that a redox reaction between molecular oxygen dissolved in the electrolytes and PEDOT:PSS leads to low ON/OFF ratios when NaCl was used as the electrolyte. Cyclic voltammetry and electrochemical impedance spectroscopy revealed that doping/dedoping of the channel becomes slower at relatively high film thickness and in the presence of bulky ions. The characteristics of the gate electrode have significant effects on the behavior of OECTs. In this thesis, high specific surface area activated carbon (AC) was used as gate electrode material in OECTs based PEDOT:PSS. The use of high surface area carbon gate electrodes led to the high drain-source current modulation in OECT and limited undesirable electrochemical processes. The biocompatibility and biodegradability property of the materials used in organic bioelectronics is of course of primary importance. These features are important even for devices powering the bioelectronics devices. Melanin is a redox active biopigment abundant in nature. The biopigment can be processed at room temperature and, as such, it is an extremely attractive material for environmentally and human friendly energy storage solutions. A form of melanin highly investigated by materials scientists is eumelanin, found in many parts of the human body including skin, hair, inner ear and brain. Eumelanin has many functions in the human body, such as strong broad-band UV-visible absorption and metal chelation. In this thesis, we report the ion storage property of eumelanin-based electrodes assembled in supercapacitors. Eumelanin is based on 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole carboxylic acid (DHICA) building blocks, present in different redox forms (hydroxyquinone, semiquinone and quinone). The synergy between the redox activity of the building blocks and the capability of several of their functionalities to reversibly bind cations constitutes the foundation for the use of melanin in pseudocapacitive energy storage systems. Capitalizing on the demonstration of eumelanin-based supercapacitors, we used an unconventional patterning approach to fabricate binder-free flexible micro-supercapacitors on plastic substrates

The Biopigment Eumelanin in the Sustainability Challenge: Interfaces With Metal Electrodes, UV-Absorption Enhancement of Plastics and its Biodegradability

L’Organisation des Nations Unies (ONU) définit le développement durable comme la capacité d’une génération de satisfaire ses propres besoins « sans compromettre la possibilité des générations suivantes de satisfaire les leurs ». Le domaine de l’électronique est marqué par la croissance effrénée des déchets d’équipements électriques et électroniques (DEEE) et par l’épuisement des ressources nécessaires à la fabrication des EEE. L’utilisation de matériaux organiques (constitués de carbone) naturels (biosourcés), biodégradables et traités à l’aide de solvants non toxiques, est alors une solution à considérer pour réduire l’empreinte écologique de l’électronique. L’eumélanine, sous-catégorie noire/marron de la mélanine (pigment omniprésent dans la faune et la flore), présente une absorption optique étendue sur les spectres ultraviolet (UV) et visible, une réponse électrique dépendante du niveau d’hydratation, des propriétés de chélation des métaux et de piégeage des radicaux ainsi qu’une structure moléculaire qui comporte des groupements fonctionnels redox. L’eumélanine est donc un matériau prometteur dans l’électronique organique verte. L’électronique organique utilise des matériaux conducteurs ou semiconducteurs à base de carbone, qui présentent une alternance de liaisons simples et doubles carbone-carbone (systèmes conjugués). Ces matériaux, outre leur flexibilité mécanique, peuvent être traités en solution. Les dispositifs à base de matériaux organiques se distinguent, par conséquent, par leur faible énergie intrinsèque (l’énergie consommée pendant leur fabrication), comparés à la majorité des dispositifs à base de matériaux inorganiques pour lesquels le processus de fabrication implique de hautes températures et des très baisses pressions (vide élevé). Les efforts pour rendre le développement plus durable concernent aussi les matériaux organiques isolants (plastiques) pour les emballages et leurs additifs nécessaires pour améliorer certaines propriétés telles que la stabilité thermique et l’absorption des rayons UV. Le coeur de cette thèse est consacré à l’étude de plusieurs propriétés fonctionnelles de l’eumélanine dans le cadre d’une utilisation potentielle dans les technologies liées à l’électronique organique verte ainsi que dans le domaine des additifs plus respectueux de l’environnent pour les plastiques. Le Chapitre 1 présente la mélanine, avec une attention particulière portée à l’eumélanine et ses propriétés.----------Abstract The United Nations define sustainability as the ability to meet one generation’s needs “without compromising the ability of future generations to meet their own needs”. The field of electronics features a dramatic increase of waste electrical and electronic equipment (WEEE) and the depletion of key elements necessary for EEE fabrication. The use of biodegradable organic (carbon-based) materials extracted from natural sources (bio-sourced) and processed with non-toxic solvents represents a valuable option to alleviate the environmental footprint of the electronic sector. Eumelanin, a dark-brown subcategory of melanins (a ubiquitous biopigment in flora and fauna), features broad ultraviolet-visible absorption, hydration-dependent electrical response as well as metal chelation, radical scavenging and redox activity. Eumelanin is a promising candidate in the field of green (sustainable) organic electronics. Organic (plastic) electronics is based on carbon-based conducting and semiconducting polymers and small molecules that feature conjugation (alternance of single and double carbon-carbon bonds) in their molecular structure. In addition of being mechanically flexible, devices based on organic electronic materials can be solution-processable and thus stand for their lower embodied energy (i.e. “energy spent in the production phase and stored in the inner constituents”) with respect to most inorganic ones, which are processed at high-temperature and under high-vacuum conditions. Sustainability is an issue also in the field of (non-conducting) plastics for packaging, where it concerns not only the packaging polymers but also the additives needed to enhance certain properties, such as thermal stability or ultraviolet (UV) radiation absorption. The core of this PhD thesis is devoted to the study of a number of functional properties of eumelanin in view of its use in sustainable organic electronic technologies as well as a greener additive for plastic packaging. Chapter 1 gives an overview on melanins, with a focus on the subcategory eumelanin and its properties. Chapter 2 provides a review of the state of the art of the potential applications of eumelanin demonstrated in the literature. Chapter 3 details the targets of the research: the investigation of eumelanin-metal interfaces under bias, the study of eumelanin as an additive for plastics and the assessment of eumelanin’s biodegradability. Chapter 4 briefly explains the characterization techniques used

Bioinspired catecholic polymers for functional materials design

Melanins and Polydopamine (PDA) are bioinspired catecholic polymers that are well known for their intriguing chemical structure and physiological functions. Indeed, PDA has a suite of properties that are uncommon to many known organic materials and over the last decade researchers have endeavored to exploit those properties in technologically relevant materials. Those efforts notwithstanding, PDAs’ chemical structures have yet to be revealed in their entirety and their useful properties yet to be fully explored. In addition, given the natural presence of melanins and dopamine in many animals (including humans), along with their versatile functional features, these materials can serve as non-toxic additives to common polymers and thereby enhance their properties. Or they could, on their own, serve as eco-friendly functional organic films to be used in a variety of useful applications. To this end, we suggest first the potential of melanins as thermal stabilizers for common polymers by evaluating the addition of melanin to several model polymers with well-known degradation pathways. Small loadings of natural and synthetic melanins significantly alter the radical-initiated chain scission behavior of conventional polymers. Such loadings cause a dramatic increase in its onset decomposition temperature, indicating potential benefits for high temperature processing or increasing their upper use temperature in demanding applications. Second, we suggest thin films of synthetic melanin and poly(allylamine hydrochloride) be deposited layer-by-layer from dilute aqueous solutions in ambient conditions. The multilayer films show superior UV-protection performance and substantially extend the useful life of a conductive polymer film under UV light, demonstrating the utility of melanin films in high-tech applications. Third, we establish a synthetic approach to prepare block copolymers of poly(methyl methacrylate) (PMMA) and PDA using a modified atom transfer radical polymerization (ATRP) technique. These copolymers display very good solubility in a range of organic solvents and the spin cast thin films of the copolymers show a sharp reduction (by up to 50%) in protein adsorption compared to those of neat PMMA. The enhanced solvent processability, thermal stability, and low protein adsorption characteristics of this copolymer make it an attractive choice for antifouling coatings on large surfaces. Fourth, we exploit PDA to achieve block copolymer (BCP) lithography on a variety of soft-material surfaces. This biomimetic film serves as a reactive platform for subsequently grafting a surface neutral layer to chemically guide the perpendicular orientation of BCP lamellae. BCP nanopatterning may now be achieved over a large area on cheap, rough, and commercially available roll-to-roll flexible polymer substrates having a wide range of surface energies, surfaces that are of interest to be adapted for patterning. Fifth, we develop an efficient, environmentally friendly, and water-based flame-retardant surface nanocoating for highly flammable foamed materials such as flexible polyurethane (PU) foams. Upon exposure to flame, a PDA coating remains intact on the surface, completely stopping the melting and interrupting foam collapse. In addition, given the reported radical-scavenging capability of catechols, the PDA layer is hypothesized to remove flammable radicals which further retards flame spread during a fire. From cone calorimeter data, peak heat release rate of PDA-coated foams shows a sharp reduction, of up to 67%, relative to a control foam. This represents much better performance than many conventional additives for flexible PU foams that have been reported in the literature. We additionally investigated the effect of catechol functionality on the flammability of PU foams through the comparison of cone calorimetric analysis between PDA-coated flexible PU foams with pristine catechol functionality and LD-containing rigid PU foams with mostly depleted catechols. This new knowledge will be potentially useful in the design of flame-resistant foams and surface coatings.Chemical Engineerin

Biomedical overview of melanin. 2. Updating molecular modeling, synthesis mechanism, and supramolecular properties regarding melanoma therapy

Melanins represent one of the most ancient and important group of natural macromolecular pigments. They have multiple biological roles in almost all organisms across the Phyla, examples being photoprotection, anti-oxidative action, radical scavenger activity, and heavy metal removal. From the biomedical point of view, melanocytes are involved in the origin of melanoma tumors, and the main therapeutic advances for their treatment have been revised in Part 1 of this review. The chemical structure of eumelanin is a biological concern of great importance, and therefore, exploring theoretical molecular models and synthesis mechanisms will be here described, as well as molecular orbital features and supramolecular organization, which are responsible for the key properties that make these biological pigments so important, and so fascinating. Ultimately, this updated overview is devoted to describe present structural models and physico-chemical characteristics of eumelanin, in order to explain and utilize melanin properties on which new photothermal and ultrasonic protocols for melanoma treatment can be devised and applie

Electrochemical Studies on the Biopigment Eumelanin

Pour répondre à la demande énergétique mondiale croissante, nous devons fabriquer des dispositifs de stockage d'énergie pour de multiples besoins futurs. La durabilité motive la recherche de matériaux / produits chimiques abondants, non toxiques et bon marché pour des dispositifs de stockage d'énergie à faible consommation d'énergie et dont l’utilisation n’a pas d’impact négatif sur l'environnement. Les matières organiques actives redox extraites de sources naturelles (bio-sourcées) sont intrigantes pour de tels dispositifs de stockage d'énergie. L'eumélanine qui est un bio-pigment brun-noir à base de quinone est un candidat prometteur pour les électrodes organiques conçus à partir de matériaux provenant des bio-sources. L'eumélanine présente des propriétés fonctionnelles intéressantes, notamment l'absorption optique à large bande, l'activité redox (propriétés de transfert d'électrons) et des propriétés antioxydantes (par chélation des ions métalliques et piégeage des radicaux). Parmi ces propriétés fonctionnelles, le transfert d'électrons est essentiel pour le stockage d'énergie ainsi que pour exploiter les propriétés anti-oxydantes du biopigment. L'eumélanine naturelle est composée de deux éléments de base, le 5,6-dihydroxyindole (DHI) et l'acide 5,6-dihydroxyindole-2-carboxylique (DHICA). Cependant, son hétérogénéité chimique est reconnue comme le principal défi pour l'étude de ses propriétés redox. Dans cette thèse de doctorat, nous avons fabriqué des eumélanines contrôlées chimiquement à partir leurs éléments constitutifs, à savoir DHI-mélanine, DHICA-mélanine et DHI-DHICA-mélanine dans des rapports contrôlés. L'objectif principal de ce travail est de faire la lumière sur les propriétés redox de l'eumélanine à l'aide de méthodes électrochimiques. Dans l'article 1 et l'article 3, nous avons caractérisé l’eumélanine par les techniques de voltampérométrie et une microscopie électronique à balayage (SEM) dans le but de comprendre et de contrôler davantage ses propriétés électrochimiques basées sur l'effet des ions métalliques, les valeurs de pH des électrolytes, etc. À l'article 2, nous avons étudié l'effet de l'irradiation lumineuse sur les propriétés de stockage d'énergie de l'eumélanine, dans le but d'améliorer lesdites propriétés par la lumière solaire qui est considérée comme source d’énergie durable. En effet, une augmentation de la capacité / capacité d'environ 50% de l'eumélanine est observée sous irradiation lumineuse.----------Abstract To meet the growing global energy demand, we need to fabricate energy storage devices for multiple future needs. Sustainability motivates the search for abundant, non-toxic, low-cost materials/chemicals for low-embedded energy and eco-friendly energy storage devices. Redox active organic materials extracted from natural sources (bio-sourced) are intriguing for such energy storage devices. The quinone-based brown-black biopigment eumelanin is a promising candidate for bio-sourced organic electrode materials. Eumelanin features interesting functional properties including broadband optical absorption, redox activity (electron transfer properties), and antioxidant properties (through metal ion chelation and radical scavenging). Among these functional properties, electron transfer is essential for energy storage as well as to exploit the antioxidant properties of the biopigment. Natural eumelanin is composed of two building blocks, 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA). Natural eumelanin features chemical heterogeneity, which is recognized as the main challenge for studying its redox properties. In this work, we fabricated chemically controlled eumelanins from the building blocks, i.e. DHI-melanin, DHICA-melanin, and DHI-DHICA-melanin in controlled ratios. The main goal of this work is to shed light on the redox properties of eumelanin using electrochemical methods. In Article 1 and Article 3, we conducted cyclic voltammetry and scanning electron microscopy (SEM) on eumelanin, aiming at understanding and further controlling its electrochemical properties based on the effect of metal ions, pH values of the electrolytes, etc. In Article 2, we studied the effect of light irradiation on the energy storage properties of eumelanin, aiming at enhancing its energy storage properties by the sustainable source solar light. Indeed, ca 50% enhanced capacity/capacitance of eumelanin is observed under light irradiation. In Article 3, the antioxidant/prooxidant dual properties of eumelanin are studied by exposing the samples to reactive oxygen species (ROS) and transition metal ions. Cyclic voltammetry, X-ray photoelectron spectroscopy (XPS) and SEM are used to characterize such effects. Article 3 aims at understanding the dual properties of eumelanin and proposing possible methods to suppress the prooxidant properties of eumelanin, which is reported to be the main cause of neurondegeneration-related diseases