Methyl Scanning for Mechanochemical Chalcogen-Bonding Cascade Switches.

Chalcogen-bonding cascade switching was introduced recently to produce the chemistry tools needed to image physical forces in biological systems. In the original flipper probe, one methyl group appeared to possibly interfere with the cascade switch. In this report, this questionable methyl group is replaced by a hydrogen. The deletion of this methyl group in planarizable push-pull probes was not trivial because it required the synthesis of dithienothiophenes with four different substituents on the four available carbons. The mechanosensitivity of the resulting demethylated flipper probe was nearly identical to that of the original. Thus methyl groups in the switching region are irrelevant for function, whereas those in the twisting region are essential. This result supports the chalcogen-bonding cascade switching concept and, most importantly, removes significant synthetic demands from future probe development.