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.
Rivas
Juan C Mareque
JC
School of Chemistry, The University of Edinburgh, Joseph Black Building, King's Buildings, West Mains Road, Edinburgh, UKEH9 3JJ. Juan.mareque@ed.ac.uk.
Salvagni
Emiliano
E
Prabaharan
Ravi
R
de Rosales
Rafael Torres Martin
RT
Parsons
Simon
S
D000577:Amides / Q000737:chemistry*; D000581:Amidohydrolases / Q000737:chemistry; D018360:Crystallography, X-Ray; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D000577:Amides; D000581:Amidohydrolases; C019665:amidase; D015032:Zinc; D010100:Oxygen