A Water Soluble Pd₂ L₄ Cage for Selective Binding of Neu5Ac

Area of Science:

• Supramolecular Chemistry
• Carbohydrate Chemistry
• Biomolecular Recognition

Background:

• Sialic acids, like N-acetylneuraminic acid (Neu5Ac), play crucial roles in biological processes such as cell-cell recognition and viral infections.
• Developing molecules that can selectively bind to Neu5Ac in aqueous environments is challenging but essential for monitoring and therapeutic applications.

Purpose of the Study:

• To design and synthesize a water-soluble coordination cage capable of selective Neu5Ac recognition.
• To investigate the binding affinity and selectivity of the synthesized cage for Neu5Ac and other saccharides in water.

Main Methods:

• Synthesis of a water-soluble palladium-based coordination cage ([Pd2L4][NO3]16 cage 7) functionalized with guanidinium dendrons.
• NMR spectroscopy to assess binding interactions between cage 7 and various anionic and neutral monosaccharides.
• Molecular modeling to elucidate the binding mechanism and selectivity.

Main Results:

• Cage 7 demonstrated selective binding to anionic monosaccharides, with the strongest affinity observed for N-acetylneuraminic acid (Neu5Ac) (Ka = 24 M⁻¹).
• The cage exhibited negligible binding to thirteen different neutral saccharides.
• Molecular modeling suggested that charge-assisted hydrogen bonds and salt bridges involving the guanidinium arms contribute to the selective binding of anionic carbohydrates.

Conclusions:

• A simple coordination cage can achieve selective recognition of Neu5Ac in water.
• This work provides a foundation for developing advanced M2L4 cages with enhanced stability, affinity, and selectivity for carbohydrates and other small molecules.
• The developed cage represents a promising tool for biological sensing and intervention strategies targeting Neu5Ac-mediated processes.