Synthesis and reactivity of new phenolic and/or heteroaromatic systems of potential practical interest

My research project has been directed to the synthesis and characterization of a number of selected phenolic and/or heteroaromatic systems and their derivatives for preparation of new molecular scaffolds of potential practical interest. Most of the activity has therefore been directed to the preparation of new derivatives from 5,6-dihydroxyindole (DHI), the fundamental monomer precursors of eumelanins, and 17β-estradiol, an important human and mammal steroidal hormone, selected as biologically relevant building blocks. In particular Chapter 1 of this thesis is devoted to the synthesis of 5,6-dihydroxyindole oligomers, Chapter 2 to the synthesis and reactivity of new alkynyl-derivatives of DHI, Chapter 3 to the synthesis of new alkynyl-derivatives of 17β-estradiol. The last chapter of this thesis, Chapter 4, concerns the results of experiments started during my Master thesis and regarding the synthesis and reactivity of 9- and 10-nitrolinoleic acids, two important nitrated derivatives of linoleic acid, under physiologically relevant conditions

First synthetic entry to the trimer stage of 5,6-dihydroxyindole polymerization: ortho-alkynylaniline-based access to the missing 2,7':2',7''-triindole

5,6-Dihydroxyindole oligomers are valuable synthetic targets for the structural characterization of eumelanin biopolymers as well as for the realization of bioinspired functional materials. An ortho-alkynylaniline-based strategy allowed the first access to a trimer, the missing 5,5',5'',6,6',6''-hexaacetoxy-2,7':2',7''-triindole, and its detection as a minor intermediate en route from 5,6-dihydroxyindole to eumelanin-like polymers

p-Electron Manipulation of the 5,6-Dihydroxyindole/Quinone System by 3-Alkynylation: Mild Acid-Mediated Entry to (Cross)-Conjugated Scaffolds and Paradigms for Medium-Tunable Chromophores

5,6-Dihydroxyindole-based systems engender increasing interest for the design and implementation of new functional arom. scaffolds and eumelanin-like materials with tailored absorption and electronic properties. However, studies aimed at elucidating the influence of external ??-conjugating groups on the redox properties and acid-induced reactivity of these highly oxidizable indolic platforms are lacking. We report herein the synthesis (as acetyl derivs.) and chem./quantum chem. characterization of the first ??-extended 5,6-dihydroxyindole derivs., 3-ethynyl-5,6-dihydroxyindole (1) and 3,3'-(1,2-ethynediyl)bis-5,6-dihydroxyindole (2), to understand whether and how ?? extension of the enamine-like pyrrole sector affects the absorption properties, redox behavior, and protonation equil. at both the o-diphenol and quinone levels. Oxidn. of 1 and 2 proceeded smoothly to generate dark insol. materials with eumelanin-like UV properties. On exposure to phosphate buffer at pH 3, 1 was rapidly converted to 3-acetyl-5,6-dihydroxyindole (5) and, in the presence of 5,6-dihydroxyindole, to the cross-conjugated 3,3'-ethenylidenebis-5,6-dihydroxyindole (6). DFT calcns. on 1 and 2 and their quinones in their pristine states and after protonation provided a mechanistic frame to rationalize the unusual acid-mediated chem. of 1 and disclosed 2-quinone as the prototype of a novel class of medium-dependent chromophores. The ethynyl(ene) structural motif is thus proposed as the key to new tunable ??-electron extended 5,6-dihydroxyindole/5,6-indolequinone paradigms for the rational design of alkyne-contg. hybrid eumelanin-type polymers

Towards the development of a novel bioinspired functional material: Synthesis and characterization of hybrid TiO 2/DHICA-melanin nanoparticles

A large number of recent literature data focus on modification/modulation of surface chemistry of inorganic materials in order to improve their functional properties. Melanins, a wide class of natural pigments, are recently emerging as a powerful organic component for developing bioinspired active material for a large number of applications from organoelectronics to bioactive compounds. Here we report the use of the approach referred as "chimie douce", involving in situ formation of the hybrids through reactions of precursors under mild conditions, to prepare novel hybrid functional architectures based on eumelanin like 5,6 dihydroxyindole-2-carboxylic acid (DHICA) polymer and TiO 2. Two synthesis procedures were carried out to get DHICA-melanin coated TiO 2 nanoparticles as well as mixed DHICA/TiO 2 hybrid nanostructures. Such systems were characterized through EPR, FT-IR and fluorescence spectroscopy, thermogravimetric analysis (TGA), X-ray diffraction (XRD), and TEM microscopy in order to assess the effect of synthesis path as well as of DHICA content on structural, morphological and optical properties of TiO 2 nanostructures. In particular, EPR, FT-IR spectra and TGA analysis confirmed the presence of DHICA-melanin in these samples. TEM measurements indicated the formation of the nanoparticles having relatively narrow size distribution with average particle size of about 10 nm. DHICA-melanin does act as a morphological agent affecting morphology of hybrid nanostructures. XRD analysis proved that TiO 2 hybrid nanoparticles kept anatase structures for DHICA-melanin contents within the range of investigated compositions, i.e. up to 50% wt/wt. © 2012 Elsevier B.V. All rights reserved