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A Chalcogen-Bonding Cascade Switch for Planarizable Push-Pull Probes.

Mariano Macchione1, Antoine Goujon1, Karolina Strakova1

  • 1Department of Organic Chemistry, University of Geneva, Geneva, Switzerland.

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Summary
This summary is machine-generated.

This study introduces novel cascade switches to overcome the "flipper dilemma" in mechanical probes. These probes enable precise detection of physical forces in biology by activating donors and acceptors upon planarization.

Keywords:
chalcogen bondsfluorescent probesforce imaginglipid bilayer membranespush-pull fluorophores

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Area of Science:

  • Supramolecular Chemistry
  • Chemical Biology
  • Biophysics

Background:

  • Mechanable push-pull probes are used to study physical forces in biological systems.
  • Existing probes face challenges due to incompatible donor and acceptor groups with their resting state.

Purpose of the Study:

  • To resolve the "flipper dilemma" in mechanically planarized probes.
  • To develop probes that activate donor and acceptor groups only upon mechanical planarization using chalcogen-bonding cascade switches.

Main Methods:

  • Molecular dynamics simulations.
  • Chemical double-mutant cycle analysis.

Main Results:

  • Cascade switched flipper probes demonstrate excellent chemical stability.
  • Significant red shifts were observed, indicating successful probe activation.
  • Probes exhibit focused mechanosensitivity, responding specifically to mechanical planarization.

Conclusions:

  • A new, general concept utilizing non-trivial supramolecular chemistry is introduced.
  • This approach solves a key challenge in developing mechanical probes.
  • The developed probes open new avenues for studying mechanobiology and offer a wide chemical space for future applications.