Deceleration of Proton Exchange between Monosaccharides and Water by Metallocryptand and Related Compounds

We report an unexpected yet powerful ability of a tris(salen) nickel(II) metallocryptand LNi₃ to dramatically decelerate proton exchange between monosaccharides and water. In the presence of only 0.025 equiv of LNi₃, the exchange rates of glucose hydroxy protons with water decreased by up to 74-fold. Similar deceleration effects were also observed for mannose, fructose, galactose, and methanol. Comparative studies using a mononuclear analogue (L^mNi) and a metal-free analogue (H₆L) suggest that the salen framework itself reorganizes the local hydrogen-bonding network. These findings identify salen-based molecules as a new class of proton exchange modulators under nonphysiological conditions and provide a conceptual basis for new opportunities to study hydration and for molecular-level control of dynamic processes in glycobiology.