A Supramolecular Ice Growth Inhibitor

Safranine
O, a synthetic dye, was found to inhibit growth of ice
at millimolar concentrations with an activity comparable to that of
highly evolved antifreeze glycoproteins. Safranine inhibits growth
of ice crystals along the crystallographic a-axis,
resulting in bipyramidal needles extended along the <0001> directions
as well as and plane-specific thermal hysteresis (TH) activity. The interaction
of safranine with ice is reversible, distinct from the previously
reported behavior of antifreeze proteins. Spectroscopy and molecular
dynamics indicate that safranine forms aggregates in aqueous solution
at micromolar concentrations. Metadynamics simulations and aggregation
theory suggested that as many as 30 safranine molecules were preorganized
in stacks at the concentrations where ice growth inhibition was observed.
The simulations and single-crystal X-ray structure of safranine revealed
regularly spaced amino and methyl substituents in the aggregates,
akin to the ice-binding site of antifreeze proteins. Collectively,
these observations suggest an unusual link between supramolecular
assemblies of small molecules and functional proteins.