To understand the behaviour and the features of biological cellular membranes, mechanosensitive¹ fluorescent “flipper” probes have been developed. Combining the chromophore polarization and ground state planarization is the key to determine and visualize the lateral organization.² Improvement on chemical stability have been fully achieved through head group engineering using copper-catalyzed alkyne–azide cycloaddition (CuAAC) approach in a way to have probes ready for use in biology.³ Introducing “bulky” lateral chains on dithienothiophene (DTT) moyeties that affects the molecule’s twisted state, such as isobutyl groups, strongly hinders the planarization in the first excited state producing a probe that fails to respond to changes in membrane order.⁴ However the new more effective synthetic approach introduced, has been highly useful to develop DTT units as privileged motif to study anion transport⁵ and catalysis⁶ with chalcogen bonding. Expanding the length of the current flipper to “trimer” and “tetramer” units is now in progress with the aim to create a new generation of fluorescent membrane probes.

[1] Dal Molin, M.; Verolet, Q.; Soleimanpour S.; Matile, S. Chem. Eur. J. 2015, 21, 6012–6021.
[2] Dal Molin, M.; Verolet, Q.; Colom, A.; Letrun, R.; Derivery, E.; Gonzalez-Gaitan, M.; Vauthey, E.; Roux, A.; Sakai, N.; Matile, S. J. Am. Chem. Soc. 2015, 137, 568–571.
[3] Soleimanpour, S.; Colom, A.; Derivery, E.; Gonzalez-Gaitan, M.; Roux, A.; Sakai, N.; Matile, S. Chem. Commun. 2016, 52, 14450–14453.
[4] Macchione, M.; Chuard, N.; Sakai, N.; Matile, S. ChemPlusChem 2017, DOI: 10.1002/cplu.201600634.
[5] Benz, S.; Macchione, M.; Verolet, Q.; Mareda, J.; Sakai, N.; Matile, S. J. Am. Chem. Soc. 2016, 138, 9093–9096.
[6] Benz, S.; López-Andarias, J.; Mareda, J.; Sakai, N.; Matile, S. Angew. Chem. Int. Ed. 2017, 56, 812–815.