Cold‐Captured Dynamic Hydration Networks in Oxime‐Based Photoswitches: A Theoretical Challenge Uncovered by Rotational Spectroscopy

Abstract

Abstract With the goal of manipulating (bio)chemical processes, photoswitches emerge as important assets in molecular nanotechnology. To guide synthetic strategies toward increasingly more efficient systems, conformational dynamics studies performed with atomic rigor are in demand, particularly if this information can be extracted with control over the size of a perturbing solvation layer. Here, we use jet‐cooled rotational spectroscopy and quantum chemistry calculations to unravel the structure and micro‐hydration dynamics of a prototype photoswitch. Camphorquinone‐oxime has a switching function enabled by the oxime moiety, and a chiral subspace generated by camphor, ensuring motion directionality. Although it may seem a relatively simple molecule, several popular levels of theory disagree on the energy ordering of the two switch states. We find that the oxime moiety integrates cooperatively into linear water chains captured for the dimer and trimer topologies, as well as into more exotic three‐dimensional structures created for the complex with the water tetramer. Evidence for concerted hydration dynamics emerges from a comparison between theory and experimental isotopic information. We evaluate the balance of intermolecular forces at play during the hydration network build up and discuss how a flexible first solvation layer may affect the switching dynamics of this class of systems.