Synthesis of New Chelating Agents Potentially Useful as Markers for Neurodegenerative Diseases Through Cross-coupling and Metal-halogen Exchange Reactions Using Lithium or Magnesium Zincate Species in Unconventional Solvents

In recent years, several evidence suggesting the implication of transition bio-metals in the etiopathogenesis of neurodegenerative diseases have been highlighted. In particular, as for Alzheimer’s disease, it has been recently discovered the influence of the so-called ‘nonbound ceruloplasmin copper’ (that is the fraction that circulates freely in the blood) on the onset and on the progression of the disease. Thus, methods have been developed in order to measure its blood level to predict Alzheimer's risk1. In the last decade, a new type of bimetallic compounds known as “alkali metal zincate species” has emerged in the organometallic field, partly due to their unique chemical characteristics which cannot be replicated by their monometallic counterparts2. In this project, we will evaluate the possibility to use these organometallic compounds in metal-halogen exchange and cross-coupling reactions3 in unconventional solvents such as Deep Eutectic Solvents4 to synthesise new fluorescent chelating agents based on a flavonoid structure as molecular scaffold. 1 R. Squitti, R. Ghidoni, M. Siotto, M. Ventriglia, L. Benussi, A. Paterlini, M. Magri, G. Binetti, E. Cassetta, D. Caprara, F. Vernieri, P. M. Rossini and P. Pasqualetti, ANNALS of Neurology, 2014, 75, 574-580. 2 D. R. Armstrong, C. Dougan, D. V. Graham, E. Hevia and A. R. Kennedy, Organometallics, 2008, 27, 6063– 6070. 3 K. Hirano and M. Uchiyama, TCIMAIL No. 171, 2016, 2-20. 4 J. García-Álvarez, E. Hevia and V. Capriati, Eur. J. Org. Chem. 2015, 6779–6799.