  Sucralose is a commonly employed artificial sweetener that appears to
destabilize protein native structures. This is in direct contrast to the
bio-preservative nature of its natural counterpart, sucrose, which enhances the
stability of biomolecules against environmental stress. We have further
explored the molecular interactions of sucralose as compared to sucrose to
illuminate the origin of the differences in their bio-preservative efficacy. We
show that the mode of interactions of sucralose and sucrose in bulk solution
differ subtly using hydration dynamics measurement and computational
simulation. Sucralose does not appear to disturb the native state of proteins
for moderate concentrations (<0.2 M) at room temperature. However, as the
concentration increases, or in the thermally stressed state, sucralose appears
to differ in its interactions with protein leading to the reduction of native
state stability. This difference in interaction appears weak. We explored the
difference in the preferential exclusion model using time-resolved
spectroscopic techniques and observed that both molecules appear to be
effective reducers of bulk hydration dynamics. However, the chlorination of
sucralose appears to slightly enhance the hydrophobicity of the molecule, which
reduces the preferential exclusion of sucralose from the protein-water
interface. The weak interaction of sucralose with hydrophobic pockets on the
protein surface differs from the behavior of sucrose. We experimentally
followed up upon the extent of this weak interaction using isothermal titration
calorimetry (ITC) measurements. We propose this as a possible origin for the
difference in their bio-preservative properties.
