title: Complex formation and stability of westiellamide derivatives with copper(II).
abstract: The CuII coordination chemistry of three synthetic analogues of westiellamide (H3Lwa) with an [18]azacrown-6 macrocyclic structure and imidazole (H3L1), oxazole (H3L2), or thiazole (H3L3) heterocyclic donors in addition to the peptide groups, is reported. The Nheterocycle-Npeptide-N(heterocycle) binding sites are highly preorganized for the coordination to CuII ions. The stability constants of mono- and dinuclear CuII complexes of H3L1, H3L2, and H3L3, obtained by isothermal titration microcalorimetry, are reported. EPR and NMR spectroscopy as well as electrospray ionization mass spectrometry (ESI-MS) were used to characterize the complexes formed in solution. The stabilities of the mononuclear and dinuclear CuII complexes of the three ligands are in the range of 10(5) M(-1), but there are subtle differences; specifically the oxazole-derived ligand has, in contrast to the other two macrocycles, a negative formation entropy for coordination to the first CuII ion and a higher stability for complexation to a second CuII center in comparison with the first CuII center (cooperativity). Differences between the three ligands are also apparent in terms of the formation mechanism. With the oxazole-based ligand H3L2, NMR spectroscopy, EPR spectroscopy, and ESI-MS indicate the formation of a ligand-CuII 2:1 intermediate, and this may explain the differences in the formation entropy as well as the cooperativity.
authors.affiliation: Anorganisch-Chemisches Institut, Universität Heidelberg, 69120, Heidelberg, Germany. peter.comba@aci.uni-heidelberg.de
authors.forename: Peter
authors.initials: P
authors.lastname: Comba
authors.forename: Nina
authors.initials: N
authors.lastname: Dovalil
authors.forename: Gebhard
authors.initials: G
authors.lastname: Haberhauer
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Hanson
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kato
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Taura
mesh_terms: D000818:Animals; D003300:Copper / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000235:genetics
chemical_list: D010455:Peptides; D010456:Peptides, Cyclic; C074972:westiellamide; D003300:Copper