Polyoxometalatocyclophanes: Synthesis, structure, anti-leukemic activity, and molecular docking

A series of polyoxometalate-based cyclophanes (polyoxometalatocyclophanes) have been successfully synthesized through the covalent linkage of Lindqvist-type hexamolybdate clusters with bis-arylimido ligands incorporating flexible alkyl chains. Single-crystal structure and circular dichroism (CD) spectroscopies confirm that the compound 3 (n-C₄H₉)N)₂[Mo₆O₁₇N(o-phenyl-O(CH₂)₅O-phenyl-o)N] can resolve spontaneously through crystallization. The inhibitory activity results against leukemia K562 cell line indicate that, among this series of compounds—including organoimido ligands, hexamolybdate salt, and other polyoxometalatocyclophanes—the chiral compound 3 exhibits the highest activity against K562 cells. In high concentration, its activity is even better than positive control 5-fluorouracil’s (5-FU). Molecular docking and molecular dynamics simulation results indicate that [Mo₆O₁₇N(o-phenyl-O(CH₂)₅O-phenyl-o)N] (C5-Mo6), adopted a compact conformation, can effectively bind to the key anti-apoptotic protein Bcl-2 of leukemia K562 cell line, with a predicted binding affinity of −27.39 kcal/mol.