Schiff Base-Wrapped Co, Zn-Based Clusters with Hierarchical Chiral Structures for Therapeutic Application in Parkinson’s Disease

Hierarchical chiral structures have wide applications in materials science and biomedicine. The synthesis of multilevel chiral structures with specific functions is a key issue. In this work, we have successfully designed and synthesized R/S-Co₄Zn₅L₁₀ (L = C₁₆H₁₅O₃N) quinary chiral helix, in which the chirality transfers from the chiral carbon atoms of ligands to octahedral stereochirality, then to a single helix, further to a supramolecular helical chain, and ultimately to the chiral crystal structure. R/S-Co₄Zn₅L₁₀ consists of two chiral building units, R/S-Zn₃L₂ and R/S-CoL₂. R/S-CoL₂ can also agglomerate into R/S-Co₄L₆. The evaluation of the biocompatibility and bioactivity for three pairs of enantiomers reveals that R-Co₄Zn₅L₁₀ and R-CoL₂ effectively restore dopaminergic neuron loss and improve dopamine-dependent locomotion deficits in nematodes. Additionally, these compounds inhibit α-synuclein aggregation during nematode development. These findings suggest that elaborately designed cobalt-based chiral structures have potential as novel therapeutic candidates for Parkinson's disease.