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, ZnII, CuII, and CoII 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.

[1]  O. Wolfbeis,et al.  Disposable cuvette test with integrated sensor layer for enzymatic determination of heavy metals , 1996 .

[2]  J. P. Michael,et al.  Marine Metaboliten und die Komplexierung von Metall-Ionen: Tatsachen und Hypothesen , 1993 .

[3]  Kui Cheng,et al.  Syntheses and Characterizations of Two Novel Silver Polymers from Assembly 5‐Bromosalicylic Acid and 2‐Aminobenzoic Acid, with High Inhibitory Activities against Jack Bean Urease , 2006 .

[4]  D. V. Slyke,et al.  Manometrie, titrimetric, and colorimetric methods for measurement of urease activity. , 1944 .

[5]  Li‐Min Zheng,et al.  Synthesis, structure and magnetic behavior of a di-μ-chloro-di-μ-imidazolato-tetracopper(II) complex with two dinucleating macrocycles , 1999 .

[6]  George M. Sheldrick,et al.  SADABS, Program for Empirical Absorption Correction of Area Detector Data , 1996 .

[7]  Chen Xu,et al.  Synthesis, crystal structure and urease inhibitory activities of Schiff base metal complexes , 2007 .

[8]  Li‐Min Zheng,et al.  Molecular structure and characterization of a pair of hydrate isomers for dinuclear copper(II) complexes with a 26-membered hexaazamacrocycle , 1998 .

[9]  Toru Tanaka,et al.  Urease inhibitory activity of simple α,β-unsaturated ketones , 2003 .

[10]  B. Krajewska,et al.  Heavy Metal Ions Inhibition of Jack Bean Urease: Potential for Rapid Contaminant Probing , 2004, Journal of enzyme inhibition and medicinal chemistry.

[11]  Michael Rosen,et al.  Naturstoffe als Sonden zum Studium zellulärer Funktionen-Untersuchungen von Immunophilinen , 1992 .

[12]  R. Hausinger,et al.  70 Years of Crystalline Urease: What Have We Learned? , 1997 .

[13]  R. Hausinger,et al.  Copyright � 1995, American Society for Microbiology Molecular Biology of Microbial Ureases , 1995 .

[14]  InazuTakahiko,et al.  New dinucleating macrocycle 12,24-dihydroxy-1,6-dioxo-2,5,14,17-tetraaza [6.6] metacyclophane-13,17-diene and its metal complexes , 1987 .

[15]  B. Krajewska.  Urease immobilized on chitosan membrane. Inactivation by heavy metal ions , 2007 .

[16]  F. Dahan,et al.  Synthesis, crystal structures, and nonlinear optical (NLO) properties of new Schiff-base nickel(II) complexes. Toward a new type of molecular switch? , 2005, Inorganic chemistry.

[17]  R. Hausinger,et al.  Fluoride inhibition of Klebsiella aerogenes urease: mechanistic implications of a pseudo-uncompetitive, slow-binding inhibitor. , 2000, Biochemistry.

[18]  Z. You,et al.  The inhibition of xanthine oxidase by the Schiff base zinc(II) complex , 2006 .

[19]  N. Dixon,et al.  Letter: Jack bean urease (EC 3.5.1.5). A metalloenzyme. A simple biological role for nickel? , 1975, Journal of the American Chemical Society.

[20]  I. Goldberg,et al.  Equilibrium studies in solution involving nickel(II) complexes of flexidentate Schiff base ligands: isolation and structural characterization of the planar red and octahedral green species involved in the equilibrium. , 2003, Inorganic chemistry.

[21]  H. Hirota,et al.  Orbiculamide A: a novel cytotoxic cyclic peptide from a marine sponge Theonella sp , 1991 .

[22]  F. Belaj,et al.  Synthesis, characterization and spectroscopic and electrochemical studies of new axially coordinated cobalt(III) salen (salen = N,N'-bis(salicylidene)-1,2-ethylenediamine) complexes. The crystal structure of [CoIII(salen)(aniline)2]ClO4 , 2006 .

[23]  M. Salamone,et al.  Synthesis and Characterization of a Novel Heteroditopic Macrocyclic System – Monometallic Nickel(II) and Uranyl Complexes and Their Corresponding Heterobimetallic Carbonylrhodium(I) Complexes , 2006 .

[24]  K. Wilson,et al.  Molecular details of urease inhibition by boric acid: insights into the catalytic mechanism. , 2004, Journal of the American Chemical Society.

[25]  Toru Tanaka,et al.  α-Hydroxyketones as inhibitors of urease , 2004 .