Salt-Excluding Artificial Water Channels Exhibiting Enhanced Dipolar Water and Proton Translocation

Aquaporins
(AQPs) are biological water channels known for fast
water transport (∼108–109 molecules/s/channel)
with ion exclusion. Few synthetic channels have been designed to mimic
this high water permeability, and none reject ions at a significant
level. Selective water translocation has previously been shown to
depend on water-wires spanning the AQP pore that reverse their orientation,
combined with correlated channel motions. No quantitative correlation
between the dipolar orientation of the water-wires and their effects
on water and proton translocation has been reported. Here, we use
complementary X-ray structural data, bilayer transport experiments,
and molecular dynamics (MD) simulations to gain key insights and quantify
transport. We report artificial imidazole-quartet water channels with
2.6 Å pores, similar to AQP channels, that encapsulate oriented
dipolar water-wires in a confined chiral conduit. These channels are
able to transport ∼106 water molecules/s, which
is within 2 orders of magnitude of AQPs’ rates, and reject
all ions except protons. The proton conductance is high (∼5
H+/s/channel) and approximately half that of the M2 proton
channel at neutral pH. Chirality is a key feature influencing channel
efficiency.