C-1007: The design of small molecule ice recrystallization inhibitors for use as cryopreservatives

Abstract

Ice recrystallization inhibition (IRI) activity is a desirable property for a cryoprotectant. Recently, small molecules having potent IRI activity have been reported by our laboratory ( Chem. Sci. , 2012, 3, 1408). These small molecules are amphiphilic and can form micelles due to their polar carbohydrate-based head and aliphatic tail ( Chem. Sci. , 2012, 3, 1408). We have previously described a correlation between monosaccharide hydrate and IRI activity ( J. Am. Chem. Soc., 2008, 130 (10), 2928) and therefore the effect of adding hydrophobic atoms or functional groups to small molecules on IRI activity was investigated. Fluorine is of particular interest because it possesses what’s known as the ‘hydrophobic hydration effect’, in which water molecules tend to order around fluorine atoms in solution ( ChemBioChem , 2004, 5, 622). Interestingly, the location of a fluorine atom or other hydrophobic functional groups on the aliphatic tail greatly affects the IRI activity of the molecule. During the course of this investigation, several very potent inhibitors of ice recrystallization were discovered and their use as cryoprotectants for Tf-1 α cells, used as a model for stem cells derived from human umbilical cord blood, was explored. Post-thaw cell viability and apoptosis of Tf-1 α cells cryopreserved with these IRI active molecules will be presented.