The
permeability of hydrogels for the selective transport of molecular
penetrants (drugs, toxins, reactants, etc.) is a
central property in the design of soft functional materials, for instance
in biomedical, pharmaceutical, and nanocatalysis applications. However,
the permeation of dense and hydrated polymer membranes is a complex
multifaceted molecular-level phenomenon, and our understanding of
the underlying physicochemical principles is still very limited. Here,
we uncover the molecular principles of permeability and selectivity
in hydrogel permeation. We combine the solution–diffusion model
for permeability with comprehensive atomistic simulations of molecules
of various shapes and polarities in a responsive hydrogel in different
hydration states. We find in particular that dense collapsed states
are extremely selective, owing to a delicate balance between the partitioning
and diffusivity of the penetrants. These properties are sensitively
tuned by the penetrant size, shape, and chemistry, leading to vast
cancellation effects, which nontrivially contribute to the permeability.
The gained insights enable us to formulate semiempirical rules to
quantify and extrapolate the permeability categorized by classes of
molecules. They can be used as approximate guiding (“rule-of-thumb”)
principles to optimize penetrant or membrane physicochemical properties
for a desired permeability and membrane functionality.