RICERCA ITALIANA     

AN INTEGRATED APPROACH TO THE SYNTHESIS, CHARACTERIZATION AND FUNCTION OF 5,6-DIHYDROXYINDOLE-DERIVED EUMELANIN BIOPOLYMERS AND THEIR BLENDING WITH CONVENTIONAL POLYMERS AND COMPOSITES

Università degli Studi di Napoli "Federico II"

Abstract

The aim of the proposed project is to combine for the first time the complementary expertises of various research groups in the fields of organic natural products and biopolymers, organic physical chemistry, mass spectrometry, electron paramagnetic resonance, electrochemistry and polymer science to address long-lasting issues concerning the structure and mechanism of synthesis of eumelanins, a characteristic group of natural pigments arising by oxidative polymerization of 5,6-dihydroxyindole (DHI), its 2-carboxylic acid (DHICA) and related metabolites, and to assess the potential of these biopolymers for technological applications. The eumelanins occupy a unique position among the numerous pigments found in nature because of their central role in human and mammalian pigmentation, where they provide the dark colourations to skin, hair, eyes and substantia nigra. The social and biomedical importance of eumelanins stems from their relevance to ethnic pigmentation, photoprotection, and certain disorders such as albinism, vitiligo, melanoma and Parkinson’s disease. Recently, eumelanins have also attracted the attention of the soft matter and functional organic materials communities because of their unique physicochemical properties, including broadband monotonic absorption in the UV-visible range; persistent and inducible free radical populations that can be detected by EPR; metal-binding and redox properties; and electrical conductivity. Eumelanins have been suggested to be >>>

Principal Investigator

Marco D'ischia Università degli Studi di NAPOLI "Federico II"

Research Objectives

The long-standing issues of 5,6-dihydroxyindole oxidation and eumelanin structural characterization provide the major focus for the research plan, which will pursue the following specific aims.

Specific aim 1: To elucidate the mode of coupling of 5,6-dihydroxyindoles and their oligomers.
Within this aim, main objectives will be the development of synthetic protocols for the preparation of 5,6-dihydroxyindole derivatives; the synthesis, isolation and structural characterization of higher oligomers of 5,6-dihydroxyindoles, e.g. tetramers from DHI and hexamers from DHICA; the elucidation of the mechanism of coupling of the indole monomers to form the dimers, with special reference to the mechanism of formation of the 2,2’-biindolyl by metal promoted oxidation of DHI; the mechanism of coupling of DHI and DHICA dimers to give higher oligomers; the factors controlling the regiochemistry of the reactions and the effect of different oxidation conditions, e.g. chemical oxidation, enzymatic oxidation, electropolymerization..

Specific aim 2: to determine the mode of assemblage of indole oligomers and the mechanism of growth of the eumelanin particles. Expected outcomes of this specific aim would be the definition of the mode of growth of the melanin particle via oligomer chain extension or p-stacking of short oligomers; the mechanism of interaction of monomer units with growing particles, via physical adsorption or redox exchange with the preformed >>>

Timescale

24 months

National and international background

This research plan is focused on the structural characterisation, mechanism of formation and properties of eumelanins, the principal pigments of man and mammals. It will develop through an integrated approach aimed at addressing the oxidative polymerization of 5,6-dihydroxyindoles, the physicochemical properties of the resulting polymers and their potential for practical applications in material sciences. Human pigmentation is the natural phenomenon that provided the initial stimulus for eumelanin research. In man and non-human mammals, almost all normal pigmentation is due to varying amounts, type and distribution of melanins and related pigments throughout the epidermis (Prota, 1992). Melanin pigments are usually classified into two main classes, the black-to-dark brown, insoluble eumelanins, which are widely distributed in the animal kingdom, and the yellow-to-reddish brown, sulphur-containing variants termed pheomelanins. Besides mammals, eumelanin pigments are found also in lower organisms, e.g. the cephalopods, where they are produced in the characteristic ink gland and form the black ink that the animals discharge when frightened. In mammalian skin, eumelanins, like pheomelanins, are produced by highly specialised cells termed the melanocytes. Within these cells, eumelanin biosynthesis involves the tyrosinase-catalyzed conversion of the amino acid tyrosine to dopaquinone, an unstable orthoquinone (Land et al., 2003). This undergoes oxidative cyclisation to give >>>