Zinc(II) complexes with intramolecular amide oxygen coordination as models of metalloamidases.

Polydentate ligands (6-R1-2-pyridylmethyl)-R2(R1= NHCOtBu, R2= bis(2-pyridylmethyl)amine L1, bis(2-(methylthio)ethyl)amine L2 and N(CH2CH2)2S L3) form mononuclear zinc(II) complexes with intramolecular amide oxygen coordination and a range of coordination environments. Thus, the reaction of Zn(ClO4)2.6H2O with L1-3 in acetonitrile affords [(L)Zn](ClO4)2(L=L1, 1; L2, 2) and [(L3)Zn(H2O)(NCCH3)](ClO4)2 3. The simultaneous amide/water binding in resembles the motif that has been proposed to be involved in the double substrate/nucleophile Lewis acidic activation and positioning mechanism of amide bond hydrolysis in metallopeptidases. X-ray diffraction, 1H and 13C NMR and IR data suggests that the strength of amide oxygen coordination follows the trend 1>2 >3. L1-3 and undergo cleavage of the tert-butylamide upon addition of Me4NOH.5H2O (1 equiv.) in methanol at 50(1)degrees C. The rate of amide cleavage follows the order 1> 2>> 3, L1-3. The extent by which the amide cleavage reaction is accelerated in 1-3 relative to the free ligands, L1-3, is correlated with the strength of amide oxygen binding and Lewis acidity of the zinc(II) centre in deduced from the X-ray, NMR and IR studies.

[1]  T. Rana,et al.  Iron chelate mediated proteolysis: Protein structure dependence , 1991 .

[2]  William N. Lipscomb,et al.  Recent Advances in Zinc Enzymology. , 1996, Chemical reviews.

[3]  W. Tolman,et al.  INDEPENDENT SYNTHESIS AND STRUCTURAL CHARACTERIZATION OF A MONONUCLEAR COPPER-HYDROXIDE COMPLEX PREVIOUSLY ASSIGNED AS A COPPER-SUPEROXIDE SPECIES , 1996 .

[4]  Judith N. Burstyn,et al.  Toward the development of metal-based synthetic nucleases and peptidases: a rationale and progress report in applying the principles of coordination chemistry , 1998 .

[5]  L. Sayre,et al.  Metal ion catalysis of amide hydrolysis. Very large rate enhancements by copper(II) in the hydrolysis of simple ligand-functionalized tertiary amides , 1992 .

[6]  N. Kostić,et al.  New Selectivity and Turnover in Peptide Hydrolysis by Metal Complexes. A Palladium(II) Aqua Complex Catalyzes Cleavage of Peptides Next to the Histidine Residue , 1996 .

[7]  J. Chin,et al.  Determination of the equilibrium constant for coordination of an amide carbonyl to a metal complex in water , 1993 .

[8]  Dewain K. Garner,et al.  Mononuclear nitrogen/sulfur-ligated zinc methoxide and hydroxide complexes: investigating ligand effects on the hydrolytic stability of zinc alkoxide species. , 2002, Journal of the American Chemical Society.

[9]  W. Lipscomb,et al.  Comparison of the structures of three carboxypeptidase A-phosphonate complexes determined by X-ray crystallography. , 1994, Biochemistry.

[10]  R. Wolfenden,et al.  Cytidine deaminase. The 2.3 A crystal structure of an enzyme: transition-state analog complex. , 1994, Journal of molecular biology.

[11]  L. A. Baron,et al.  Models of zinc-containing proteases. Catalysis of cobalt(III)-mediated amide hydrolysis by a pendant carboxylate , 1989 .

[12]  R. Blessing,et al.  An empirical correction for absorption anisotropy. , 1995, Acta crystallographica. Section A, Foundations of crystallography.

[13]  E. Hegg,et al.  Hydrolysis of unactivated peptide bonds by a macrocyclic copper(II) complex: Cu([9]aneN3)Cl2 hydrolyzes both dipeptides and proteins , 1995 .

[14]  A. Arif,et al.  Amide Alcoholysis in Mononuclear Zinc and Cadmium Complexes Ligated by Thioether Sulfur and Nitrogen Donors , 2000 .

[15]  L. Sayre.  Metal ion catalysis of amide hydrolysis , 1986 .

[16]  P. Rajagopalan,et al.  Crystal structure of the Escherichia coli peptide deformylase. , 1997, Biochemistry.

[17]  D. Buckingham,et al.  Cobalt(III)-promoted hydrolysis of amino acid esters and peptides and the synthesis of small peptides , 1987 .