Planarizable Push-Pull Probes with Sulfoximine-Bridged Dithienothiophene Acceptors

Contrary to sulfides, sulfoxides or sulfones, sulfoximines have been mostly neglected in the design of fluorescent probes until recently. In this study, we elaborate systematically on sulfoximine acceptors in fluorescent flipper probes. Fluorescent flippers have been introduced as mechanosensitive probes to image membrane order and tension. They consist of twisted dithienothiophene dimers with sulfide and sulfone bridges to produce the essential primary dipole of the coupled push-pull system. The objective of this study was to replace the sulfone acceptor by a series of sulfoximines. This is intriguing as a synthetic challenge and worthwhile because the extra nitrogen substituent offers a variability that is attractive to understand and control the performance of the probes. The new sulfoximine flippers provide corroborative evidence for the importance of the primary dipole of the planarizable push-pull probe. Partitioning into differently ordered membranes and positioning within these different membranes is shown to correlate directly and dramatically with fluorescence lifetimes and mechanosensitivity. Sufficient partitioning into ordered membranes is confirmed as particularly important to image membrane tension by probe compression in the ground state. Compared to the conventional sulfone homolog, the best sulfoximine flipper has more red-shifted absorption and emission maxima, longer fluorescence lifetime in cell membranes, and larger difference in lifetime upon application of membrane tension.