INTEGRATED COMPUTATIONAL/EXPERIMENTAL APPROACHES TO THE STUDY OF THE OXIDATIVE CHEMISTRY OF PHENOLIC SYSTEMS

5,6-Dihydroxyindole belongs to a unique group of naturally occurring indole compounds which have intrigued generations of organic and natural product chemists because of their central role in the biosynthesis of eumelanins, the major determinants of human skin, hair and eye pigmentation. The unique status of eumelanins among natural pigments is due to their socio-economic and biomedical relevance, encompassing racial pigmentation, skin photoprotection, sun tanning and pigmentary disorders such as albinism, vitiligo and melanoma. Despite many decades of work within the organic chemistry, biophysics and pigment cell communities, eumelanin structure remains virtually unknown, because of the marked chemical heterogeneity and the lack of well defined physicochemical properties, preventing successful application of spectroscopic techniques. In the present thesis, the chemistry of 5,6-dihydroxyindole has been investigated by combining and integrating the information provided by computational and experimental methodologies. This approach has proved useful to address and settle many open issues concerning the mechanisms of oxidative polymerization of 5,6-dihydroxyindoles and the basic features of eumelanin builiding blocks.