A Water Soluble Pd₂L₄ Cage for Selective Binding of Neu5Ac

The sialic acid N-acetylneuraminic acid (Neu5Ac) and its derivatives are involved in many biological processes including cell-cell recognition and infection by influenza. Molecules that can recognize Neu5Ac might thus be exploited to intervene in or monitor such events. A key obstacle in this development is the sparse availability of easily prepared molecules that bind to this carbohydrate in its natural solvent; water. Here, we report that the carbohydrate binding pocket of an organic soluble [Pd₂L₄]⁴⁺ cage could be equipped with guanidinium-terminating dendrons to give the water soluble [Pd₂L₄][NO₃]₁₆ cage 7. It was shown by means of NMR spectroscopy that 7 binds selectively to anionic monosaccharides and strongest to Neu5Ac with K_a=24 M^-1. The cage had low to no affinity for the thirteen neutral saccharides studied. Aided by molecular modeling, the selectivity for anionic carbohydrates such as Neu5Ac could be rationalized by the presence of charge assisted hydrogen bonds and/or the presence of a salt bridge with a guanidinium solubilizing arm of 7. Establishing that a simple coordination cage such as 7 can already selectively bind to Neu5Ac in water paves the way to improve the stability, affinity and/or selectivity properties of M₂L₄ cages for carbohydrates and other small molecules.