Co-ligand induced chiral recognition of N-thiophosphorylated thioureas in crystalline Ni(II) complexes

The possibility was demonstrated to use metal coordination for the resolution of racemic chiral N-thiophosphorylated thioureas through controlling the stereochemistry of the complex formation and supramolecular chiral recognition during crystallization. A series of new Ni(II) complexes derived from chiral N-thiophosphorylated thioureas with 1,3-N,S-coordination were synthesized in enantiopure and racemic forms and characterized by X-ray single crystal diffraction. It was shown that square-planar centrosymmetric nickel ion coordination results in exclusive formation of meso-complexes from racemic ligands. The symmetry break of the nickel ion coordination by the introduction of pyridine co-ligand into the apical position promotes chiral recognition of the ligands upon complexation with formation of exclusively homochiral complexes. Further supramolecular recognition might be achieved by variation of crystal growth conditions, with racemic crystals being obtained at higher initial concentrations, including two polymorphs with homochiral and heterochiral supramolecular chains formed via intermolecular C-H center dot center dot center dot Ni interactions. Crystal growth from the dilute solutions results in resolution of enantiomers and formation of conglomerates. Crystallization was shown to be determined by the conformational flexibility of the ligands. Racemic Ni(II) complexes showed a notable cytotoxic effect on the M-Hela cancer cell line with absolutely no toxicity on the normal cell line Chang liver.