Net hydrogen bond interaction driven supramolecular deep eutectic solvent formation: The case of cyclodextrins

Supramolecular deep eutectic solvents (SUPRADESs) as green designer solvents can be applied to facilitate key steps of separation, extraction, catalysis, and drug transport processes. However, so far, the details concerning the formation mechanism of SUPRADESs are still not clear, thus hindering full development. The present study is dedicated to the theoretical exploration of the structural properties of co-formers that can form SUPRADESs with cyclodextrins (CDs) to design better-performing task-specific SUPRADESs and further structural modifications. Firstly, a series of aliphatic organic acids (AOAs) with similar structures were screened for forming the SUPRADESs. The structure-property relationship showed that co-formers with a higher hydrogen-bond donating ability were found to favor the propensity to form SUPRADESs. Based on this finding, an empirical rule originating from molecular surface electrostatic potential (ESP) descriptors was proposed that can preliminarily predict the formation possibility of SUPRADESs. Density functional theory (DFT) calculations in conjunction with molecular dynamics (MD) simulations further demonstrated that the formation of SUPRADESs mainly depends on the net hydrogen donating ability of co-formers, which is affected by the electron-withdrawing substituent, the carbon chain length, and the molecular self-association degree. Overall, this study provides important guidance to develop novel and green functional SUPRADESs, which will greatly simplify the SUPRADES manufacturing process and reduce the time cost.