Neutron Diffraction Study of Indole Solvation in Deep Eutectic Systems of Choline Chloride, Malic Acid, and Water

Deep eutectic systems are currently under intense investigation to replace traditional organic solvents in a range of syntheses. Here, indole in choline chloride‐malic acid deep eutectic solvent (DES) was studied as a function of water content, to identify solute interactions with the DES which affect heterocycle reactivity and selectivity, and as a proxy for biomolecule solvation. Empirical Potential Structure Refinement models of neutron diffraction data showed [Cholinium](+) cations associate strongly with the indole π‐system due to electrostatics, whereas malic acid is only weakly associated. Trace water is sequestered into the DES and does not interact strongly with indole. When water is added to the DES, it does not interact with the indole π‐system but is exclusively in‐plane with the heterocyclic rings, forming strong H‐bonds with the ‐NH group, and also weak H‐bonds and thus prominent hydrophobic hydration of the indole aromatic region, which could direct selectivity in reactions.