title: Kinetically Inert Bispidol-Based Cu(II) Chelate for Potential Application to (64/67)Cu Nuclear Medicine and Diagnosis.
abstract: A family of 2,4-pyridyl-disubstituted bispidol derivatives bearing methylene carboxylic acid ethyl esters (L1-L3), methylene carboxylic acids (L4 and L5), or methylenethiophene (L6) groups were synthesized. In water, all ligands form rigid 1:1 complexes in the presence of Zn(II) in which the bicycle adopts a chair-chair conformation (cis isomer), as observed by (1)H NMR and, in the case of ligand L1, by an X-ray diffraction crystal structure. Interestingly, addition of Zn(II) ions on ligand L1 induces a metal-mediated selective hydrolysis of the ethyl esters. This selective hydrolysis was not observed upon addition of other cations such as Na(+), Mg(+), and Ca(2+). Reduction of the central ketone was achieved to prevent ring opening via retro Diels-Alder reactions and to afford highly stable and water-soluble ligands (L4, L5, L6). The complexation properties of L4 and L6 were studied in solution, with a particular interest for ligand L4. Fast complexation occurs in strongly acidic media (pH = 1), with a high affinity toward Cu(II) (log KCuL4 = 19.2(3), pCu = 17.0 at pH 7.4, pCu = -log[Cufree], [Cu] = 1 × 10(-6) M, [L] = 1 × 10(-5) M) and high selectivity versus Co(II), Ni(II), and Zn(II), as shown by the values of the binding constants obtained from potentiometric and spectrophotometric titrations. Reversible redox potential with E1/2 = -430 mV (vs normal hydrogen electrode) was measured. The complex was found to be fairly inert from acid-assisted dissociation experiments in 5 M HClO4 (t1/2 = 110 d at 25 °C).
authors: †Laboratoire d'Ingénierie Moléculaire Appliquée à l'Analyse and ‡Laboratoire de Reconnaissance et Procédés de Séparation Moléculaire, IPHC, UMR 7178 CNRS/UdS, IPHC, UMR 7178 CNRS/UdS, ECPM, Bât R1N0, 25 rue Becquerel, 67087 Strasbourg Cedex 02, France.
authors: Amandine
authors: A
authors: Roux
authors: †Laboratoire d'Ingénierie Moléculaire Appliquée à l'Analyse and ‡Laboratoire de Reconnaissance et Procédés de Séparation Moléculaire, IPHC, UMR 7178 CNRS/UdS, IPHC, UMR 7178 CNRS/UdS, ECPM, Bât R1N0, 25 rue Becquerel, 67087 Strasbourg Cedex 02, France.
authors: Aline M
authors: AM
authors: Nonat
authors: †Laboratoire d'Ingénierie Moléculaire Appliquée à l'Analyse and ‡Laboratoire de Reconnaissance et Procédés de Séparation Moléculaire, IPHC, UMR 7178 CNRS/UdS, IPHC, UMR 7178 CNRS/UdS, ECPM, Bât R1N0, 25 rue Becquerel, 67087 Strasbourg Cedex 02, France.
authors: Jérémy
authors: J
authors: Brandel
authors: †Laboratoire d'Ingénierie Moléculaire Appliquée à l'Analyse and ‡Laboratoire de Reconnaissance et Procédés de Séparation Moléculaire, IPHC, UMR 7178 CNRS/UdS, IPHC, UMR 7178 CNRS/UdS, ECPM, Bât R1N0, 25 rue Becquerel, 67087 Strasbourg Cedex 02, France.
authors: Véronique
authors: V
authors: Hubscher-Bruder
authors: †Laboratoire d'Ingénierie Moléculaire Appliquée à l'Analyse and ‡Laboratoire de Reconnaissance et Procédés de Séparation Moléculaire, IPHC, UMR 7178 CNRS/UdS, IPHC, UMR 7178 CNRS/UdS, ECPM, Bât R1N0, 25 rue Becquerel, 67087 Strasbourg Cedex 02, France.
authors: Loïc J
authors: LJ
authors: Charbonnière
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis*; D003300:Copper / Q000737:chemistry*; D003301:Copper Radioisotopes; D018360:Crystallography, X-Ray; D061565:Cycloaddition Reaction; D006801:Humans; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009683:Nuclear Medicine / Q000295:instrumentation / Q000379:methods; D011199:Potentiometry; D019275:Radiopharmaceuticals; D013876:Thiophenes / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry
chemical_list: D002264:Carboxylic Acids; D056831:Coordination Complexes; D003301:Copper Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D013876:Thiophenes; D003300:Copper; D015032:Zinc