Minimalistic ice recrystallisation inhibitors based on phenylalanine.

Ice recrystallisation inhibition (IRI) is typically associated with ice binding proteins, but polymers and other mimetics are emerging. Here we identify phenylalanine as a minimalistic, yet potent, small-molecule IRI capable of inhibiting ice growth at just 1 mg mL-1. Facial amphiphilicity is shown to be a crucial structural feature, with para-substituents enhancing (hydrophobic) or decreasing (hydrophilic) IRI activity. Both amino and acid groups were found to be essential. Solution-phase self-assembly of Phenylalanine was not observed, but the role of self-assembly at the ice/water interface could not be ruled out as a contributing factor.

Ice Recrystallization Inhibition by Amino Acids: The Curious Case of Alpha- and Beta-Alanine.

Extremophiles produce macromolecules which inhibit ice recrystallization, but there is increasing interest in discovering and developing small molecules that can modulate ice growth. Realizing their potential requires an understanding of how these molecules function at the atomistic level. Here, we report the discovery that the amino acid l-α-alanine demonstrates ice recrystallization inhibition (IRI) activity, functioning at 100 mM (∼10 mg/mL). We combined experimental assays with molecular simulations to investigate this IRI agent, drawing comparison to ß-alanine, an isomer of l-α-alanine which displays no IRI activity. We found that the difference in the IRI activity of these molecules does not originate from their ice binding affinity, but from their capacity to (not) become overgrown, dictated by the degree of structural (in)compatibility within the growing ice lattice. These findings shed new light on the microscopic mechanisms of small molecule cryoprotectants, particularly in terms of their molecular structure and overgrowth by ice.