Mariano Macchione, Antoine Goujon, Karolina Strakova, Heorhii V. Humeniuk,
Giuseppe Licari, Emad Tajkhorshid, Naomi Sakai, and Stefan Matile.
A chalcogen-bonding cascade switch for planarizable push-pull probes.
Angewandte Chemie - International Edition in English,
58:15752-15756, 2019.
(PMC: PMC7035594)
MACC2019-ET
Planarizable push–pull probes have been introduced to demonstrate physical
forces in biology. However, the donors and acceptors needed to polarize
mechanically planarized probes are incompatible with their twisted resting
state. The objective of this study was to overcome this “flipper dilemma” with
chalcogen-bonding cascade switches that turn on donors and acceptors only
in response to mechanical planarization of the probe. This concept is explored
by molecular dynamics simulations as well as chemical double-mutant cycle
analysis. Cascade switched flipper probes turn out to excel with chemical
stability, red shifts adding up to high significance, and focused
mechanosensitivity. Most important, however, is the introduction of a new,
general and fundamental concept that operates with non-trivial
supramolecular chemistry, solves an important practical problem and opens a
wide chemical space.
