MediaChrom: exploring a new family of pyrimidoindolone-based polarity-sensitive dyes

The modern biological research asks for a continuous development of new fluorescent dyes characterized by improved performances and suitable to be used as markers or probes [1]. A particular class of dyes, called polarity-sensitive dyes have the unique features to display a different emission maximum as a function of the polarity of their molecular environment (media). This peculiarity makes polarity-sensitive dyes the ideal probes to monitor the local properties of particular cell districts as well as different type of biomolecular interactions [2]. Since many years, we have been interested in the development of new strategies for the synthesis and the functionalization of indoles and polycyclic indole-based heterocycles. In this context, we reported a domino approach to pyrimidoindolones [3] that displayed interesting fluorescence properties. Starting from these findings, a small library of original polarity-sensitive fluorescent dyes, nicknamed MediaChrom, has been prepared [4]. They are characterized by a pyrimidoindolone core fitted out with a conjugated push-pull system, and a linker for an easy coupling with biomolecules. The synthetic strategy involves a highly chemo- and regioselective gold catalyzed cycloisomerization as key step. The photophysical properties of MediaChrom dyes have been evaluated, and some potential biological applications have been spottily investigated. [1] Lakowicz, J. R. Principles of Fluorescence Spectroscopy, 3rd ed.; Springer: New York, 2006. [2] Klymchenko, A. S.; Mely, Y. In: Progress in Molecular Biology and Translational Science, Morris, M.C. Editor(s), Academic Press, 2013, Vol. 113, Cap. 2, 35. [3] Facoetti, D.; Abbiati, G.; d’Avolio, L.; Ackermann, L.; Rossi, E. Synlett 2009, 2273. [4] Dell'Acqua, M.; Ronda, L.; Piano, R.; Pellegrino, S.; Clerici, F.; Rossi, E.; Mozzarelli, A.; Gelmi, M. L.; Abbiati, G. J. Org. Chem. 2015, 21, 10939. This work has been supported by Fondazione Cariplo, Grant No. 2012-0907.