Controlling Water Flow through a Synthetic Nanopore with Permeable Cations

[Image: see text] There is presently intense interest in the development of synthetic nanopores that recapitulate the functional properties of biological water channels for a wide range of applications. To date, all known synthetic water channels have a hydrophobic lumen, and while many exhibit a comparable rate of water transport as biological water channels, there is presently no rationally designed system with the ability to regulate water transport, a critical property of many natural water channels. Here, we describe a self-assembling nanopore consisting of stacked macrocyclic molecules with a hybrid hydrophilic/hydrophobic lumen exhibiting water transport that can be regulated by alkali metal ions. Stopped-flow kinetic assays reveal a non-monotonic-dependence of transport on cation size as well as a strikingly broad range of water flow, from essentially none in the presence of the sodium ion to as high a flow as that of the biological water channel, aquaporin 1, in the absence of the cations. All-atom molecular dynamics simulations show that the mechanism underlying the observed sensitivity is the binding of cations to defined sites within this hybrid pore, which perturbs water flow through the channel. Thus, beyond revealing insights into factors that can modulate a high-flux water transport through sub-nm pores, the obtained results provide a proof-of-concept for the rational design of next-generation, controllable synthetic water channels.