Flexibility-Aided Orientational Self-Sorting and Transformations of Bioactive Homochiral Cuboctahedron Pd₁₂L₁₆

Area of Science:

• Supramolecular Chemistry
• Coordination Chemistry
• Materials Science

Background:

• Designing complex coordination assemblies from flexible ligands is challenging.
• Bile acids offer a natural, amphiphilic scaffold for ligand development.
• Unsymmetrical ligands present unique challenges in predictable self-assembly.

Purpose of the Study:

• To achieve selective self-assembly of unsymmetric ligands into large coordination cages.
• To explore the formation of chiral supramolecular structures using bile acid-derived ligands.
• To investigate the biological activity of palladium complexes encapsulated within these cages.

Main Methods:

• Coordination-driven self-assembly using a tris-pyridyl ligand derived from ursodeoxycholic acid.
• Structural characterization via molecular modeling and circular dichroism spectroscopy.
• In vitro studies using 3D spheroids of HepG2 human hepatic cells to assess cellular uptake and anticancer efficacy.

Main Results:

• Selective formation of chiral stellated palladium cages (Pd6L8 and Pd12L16) from an unsymmetric ligand.
• Demonstration of switchable interspecific transformations controlled by reaction conditions.
• Confirmation of orientational self-sorting into homochiral quadruple and octuple right-handed helical species.
• Enhanced cellular uptake and increased anticancer activity of palladium cations mediated by the bile acid-derived cages.

Conclusions:

• The flexibility and adaptivity of the ligand enable selective cage formation.
• Bile acid-derived ligands can be rationally designed for controlled supramolecular assembly.
• The resulting chiral palladium cages show promise for enhanced drug delivery and cancer therapy.