New method for the synthesis of a mononucleating cyclic peptide ligand, crystal structures of its Ni, Zn, Cu, and Co complexes, and their inhibitory bioactivity against urease

A novel cyclic peptide complex, NiL 1 (H2L = 12,24-dihydroxy-1,6-dioxo-2,5,14,17-tetraaza[6* 6] metacyclophane-13,17-diene has been synthesized for the first time under solvothermal conditions through a one-pot synthetic procedure using nickel ion as the template reagent. It was found that other metal ions were not suitable for the direct template reagent in this reaction. The nickel ion was eliminated from the complex and the metal-free cyclic peptide ligand H2L was obtained through a series of reactions. Then, Zn-II, Cu-II, and Co-II were coordinated with H2L under the same solvothermal conditions to produce three isomorphous complexes ZnL 2, CuL 3, and CoL 4. Their inhibitory bioactivities against urease were then studied. The copper(II) complex 3 was the strongest inhibitor against jack bean urease, while H2L, 2, and 4 showed weak or no inhibitory activity against this enzyme.