Iacomino, Mariagrazia (2017) Nature-inspired phenolic systems for technological and biomedical applications. [Tesi di dottorato]

Iacomino Mariagrazia-PhD thesis2.pdf

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Item Type: Tesi di dottorato
Lingua: English
Title: Nature-inspired phenolic systems for technological and biomedical applications
Iacomino, Mariagraziamariagrazia.iacomino@unina.it
Date: 10 April 2017
Number of Pages: 175
Institution: Università degli Studi di Napoli Federico II
Department: Scienze Chimiche
Dottorato: Scienze chimiche
Ciclo di dottorato: 29
Coordinatore del Corso di dottorato:
Paduano, Luigilpaduano@unina.it
d' Ischia, MarcoUNSPECIFIED
Date: 10 April 2017
Number of Pages: 175
Uncontrolled Keywords: catechol; melanin; dopamine; fluorescence; mussel; caffeic acid; chlorogenic acid; organic polymers; coating; phenol; biocompatibility; smart materials; food dye; thiols; benzothiophene; eumelanin; pheomelanin; cysteinyldopamine
Settori scientifico-disciplinari del MIUR: Area 03 - Scienze chimiche > CHIM/06 - Chimica organica
Date Deposited: 03 May 2017 17:23
Last Modified: 14 Mar 2018 10:04
URI: http://www.fedoa.unina.it/id/eprint/11756
DOI: 10.6093/UNINA/FEDOA/11756


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.

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