title: Calix[6]arene-based cuprous "funnel complexes": a mimic for the substrate access channel to metalloenzyme active sites.
abstract: Two calixarene-based model systems (a and b) for monocopper enzymes are compared. Both present a tris(pyridine) coordination site for Cu that mimics the imidazole-rich neutral binding site in enzymes. Upon reaction with 1 equiv of copper(I), the tridentate ligands gave rise to ill-defined unsymmetrical complexes. However, in the presence of an organonitrile RCN (R = Me, Et, Ph), tetrahedral species were obtained, with the nitrilo ligand included in the calixarene hydrophobic cone. System b presents a larger cavity than system a, with a wider opening thanks to the removal of three tBu groups from the calixarene structure. As a result, the recognition pattern for MeCN vs PhCN is inverted, and the relative affinity constants differ by 3 orders of magnitude. The mechanism of the acetonitrile exchange at the cuprous centers was studied by (1)H NMR spectroscopy. Thermodynamic and kinetic data show that it follows a dissociative pathway in both cases. The main differences between systems a and b stem from the presence of a door that entraps the guest in case a. In system b indeed, the removal of three calixarene tBu groups led to a 100-fold acceleration of the MeCN exchange rate. Hence, these supramolecular systems provide a rare and interesting model for the hydrophobic substrate channel giving access to a metalloenzyme active site.
authors.affiliation: Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS UMR 8601, Université René Descartes, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Rondelez
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Rager
authors.forename: Arthur
authors.initials: A
authors.lastname: Duprat
authors.forename: Olivia
authors.initials: O
authors.lastname: Reinaud
mesh_terms: D047250:Calixarenes; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D046911:Macromolecular Substances; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism; D018716:Molecular Mimicry; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D013816:Thermodynamics
chemical_list: D004798:Enzymes; D008024:Ligands; D046911:Macromolecular Substances; D008667:Metalloproteins; D047250:Calixarenes; D003300:Copper