Sampling of the hydration landscape of a benchmark aza-crown ether macrocycle by high resolution rotational spectroscopy

Aza-crown ethers are common building blocks of functional materials with ionophoric properties. The tuning of ion binding selectivity demands a careful control of the three-dimensional conformation of the macrocycle moiety and its solvation environment. In this study, broadband high-resolution microwave rotational spectroscopy is employed to assess the most stable configurations of the macrocycle 1-aza-12-crown-4 and of some of its hydrated clusters with up to three water molecules, generated in a supersonic jet. Nine rotamers are identified, which allows us to lay out a chart of hydration pathways that are consistent with the sequential incorporation of water molecules to the most stable conformations of the bare macrocycle during the early stages of the jet expansion. The preference of water binding on the amine moiety over the ether groups is observed in all the detected hydrates, highlighting the broad impact of N-substitution on the chemical behavior of macrocycles. In contrast to analogous non-substituted crown ethers, the aza-crown ether retains its conformation upon hydration, aided by a preorganized intramolecular N-H⋯O hydrogen bond that facilitates microsolvation without structural rearrangement.