Thermodynamically Driven Multi‐Site Photoswitching in Tetraoxindole Cavitands Controlled by Hydrogen Bonding and Mechanochemistry

Integration of multiple photoswitches into a single multi‐responsive system is a promising strategy toward achieving high information density, complex logic operations, and large‐amplitude motion. However, such systems typically suffer from poor efficiency. In this study, we present a strategy for efficient multi‐site photoswitching that is based on realizing forward and reverse transformations along thermodynamically favorable pathways. We show that tetra‐ E ‐oxindole‐resorcinarene undergoes effective multi‐site photoswitching to form a tetra‐ Z ‐isomer, which is more stable due to the intramolecular hydrogen‐bonding network. To achieve a reverse transformation, modulation of the relative stability of the isomers is required. Here, deprotonation under mechanochemical conditions effectively swaps stability, enabling effective back transformation to the tetra‐ E ‐isomer. Mechanochemistry is indispensable for this transformation, as swapping the stability of isomers is ineffective in solutions. By DFT calculations, we demonstrate that a network of hydrogen bonds is crucial for the modulation of isomers’ stability and multiplication of energetic effects. Finally, gas‐phase ion mobility mass spectrometry provided a complementary picture, confirming the all‐ E ↔ all‐ Z interconversions and their charge‐dependent direction.