Electrochemically Switchable Fluorescence in Rhodamine Derivatives

Monitoring therapeutic-agent translocation to the cell interior represents one of the significant problems in drug development. Carrier-mediated transport across cellular membranes is frequently executed by fluorophore-labelled cell-penetrating peptides (CPPs),[1] and the process is routinely studied with fluorescence microscopy. Nevertheless, since fluorescence cannot discriminate membrane-bound and bulk-solution peptides in the internal compartment, misleading false positive results may be introduced into the interpretation of translocation processes.[2] Also, classical fluorescent probes currently used are not reversibly switchable. In this context, the development of electrochemically switchable fluorescent probes is of high interest.[3] Therefore, we designed original rhodamine derivative and investigated its spectroelectrochemical properties (Figure 1), which were compared with spectroelectrochemical properties of a commercially available analogue rhodamine 101. The combination of cyclic voltammetry and UV-Vis absorbance and fluorescence spectroelectrochemical experiments showed that the starting fluorescent cationic rhodamine derivatives can be reversibly reduced into the corresponding non-fluorescent radical compounds. Importantly, the stability of electrogenerated radical species allowed reversible activation/deactivation of fluorescence as a function of time and potential values. Figure 1. a) Reversible electrochemical reduction of the new rhodamine derivative. b) UV-Vis spectra of the original cationic compound and species formed after the first and second reduction. c) Electrochemically mediated fluorescence decrease.   Acknowledgement The financial support from the EU Research and Innovation programme Horizon 2020 through the Marie Skłodowska-Curie action (H2020-MSCA-IF-2014, ID 656519) is gratefully acknowledged References [1] a) Frankel, A. D.; Pabo, C.O. Cell 1988, 55, 1189; b) Järver, P.; Langel, Ü. Biochim. Biophys. Act. 2006, 1758, 260; c) Trabulo, S.; Cardoso, A. L.; Mano, M.; Pedroso de Lima, M. C. Pharmaceuticals 2010, 3, 961; d) Dietz, G. P. H.; Bahr, M. Mol. Cell. Neurosci. 2004, 27, 85. [2] Richard, J. P.; Meliko, K.; Vives, E.; Ramos, C.; Verbeure, B.; Gait, M. J.; Chernomordik, L. V.; Lebleu, B. J. Biol. Chem. 2003, 278, 585. [3] Audebert, P.; Miomandre, F. Chem. Sci. 2013, 4, 575. Figure 1