title: Remarkable inertness of copper(II) chelates of cyclen-based macrobicycles with two trans-N-acetate arms.
abstract: Two cross-bridged cyclen-based macrocycles with two trans-N-acetic acid arms, one having a dibenzofuran (DBF) moiety as the bridge, H2L1, and the other a diphenyl ether (DPE) one, H2L2, were synthesized. Both compounds behave as "proton sponges." The thermodynamic stability constants for the Cu(2+), Zn(2+), Al(3+), and Ga(3+) complexes of both compounds were determined. They exhibit an excellent thermodynamic selectivity for copper(II), ensuring that metal ions largely present in the human body do not interfere with the copper(II) chelates. All complexes are very slow to form, and [CuL2] and [CuL1] are extremely inert to demetallate, especially [CuL2]. The acid-assisted dissociation of [CuL1] led to a half-life of 4.28 h in 5 M HCl at 363.2 K, while [CuL2] needed harsher conditions of 12 M HCl at 363.2 K with a half-life of 30.8 days. To the best of our knowledge, [CuL2] exhibits the highest half-life value for a copper(II) complex of a polyazamacrocycle derivative reported in the literature until now. Single crystal X-ray diffraction determined for [Cu(H2L1)](ClO4)2 showed the copper center in a distorted octahedral environment bound to the N4O donors of the macrobicycle and one oxygen atom from a carboxylic arm, while for [CuL2] it showed the copper center in a trigonal bipyramid geometry only bound to the donors of the macrobicycle and leaving the carboxylate arms away from the coordination sphere. UV-vis-NIR and X-band EPR spectra showed that in [CuL1] the copper center adopts a distorted compressed octahedral environment, which is the only structure found in solution for this complex, while in [CuL2] a similar environment was found in the first stages of its slow formation but reached a square-pyramidal geometry upon stabilization. The acetate arms play therefore an important role during the formation of the complex, as revealed by the comparison of its complexation behavior with the corresponding parent compounds.
authors.affiliation: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal.
authors.forename: Catarina V
authors.initials: CV
authors.lastname: Esteves
authors.forename: Pedro
authors.initials: P
authors.lastname: Lamosa
authors.forename: Rita
authors.initials: R
authors.lastname: Delgado
authors.forename: Judite
authors.initials: J
authors.lastname: Costa
authors.forename: Pauline
authors.initials: P
authors.lastname: Désogère
authors.forename: Yoann
authors.initials: Y
authors.lastname: Rousselin
authors.forename: Christine
authors.initials: C
authors.lastname: Goze
authors.forename: Franck
authors.initials: F
authors.lastname: Denat
mesh_terms: D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000737:chemistry; D013057:Spectrum Analysis; D013816:Thermodynamics
chemical_list: D000085:Acetates; D001572:Benzofurans; D002614:Chelating Agents; D056831:Coordination Complexes; D000080027:Cyclams; D006571:Heterocyclic Compounds; D047028:Macrocyclic Compounds; D010647:Phenyl Ethers; C031538:phenyl ether; D003300:Copper; C023614:dibenzofuran; C038072:cyclen