title: Synthesis and characterization of the copper(II) complexes of new N2S2-donor macrocyclic ligands: synthesis and in vivo evaluation of the (64)Cu complexes.
abstract: The aim of this work was to prepare a novel class of (64)Cu(II) labeled complexes with the new macrocyclic ligands 1,10-dithia-4,7-diazacyclododecane-3,8-dicarboxylic acid (NEC-SE, 1), 1,10-dithia-4,7-diazacyclotridecane-3,8-dicarboxylic acid (NEC-SP, 2) and 1,10-dithia-4,7-diazacyclotetradecane-3,8-dicarboxylic acid, (NEC-SB, 3 ) to evaluate the usefulness of these macrocycles for potential utility as (64)Cu(II) chelators. The corresponding non-radioactive complexes [Cu(NEC-SE)] x 3H(2)O (4), [Cu(NEC-SP)] x 3H(2)O (5) and [Cu(NEC-SB)] (6) were prepared and their (64)Cu-analogs, [(64)Cu(NEC-SE)] (7) and [(64)Cu(NEC-SP)] (8) and [(64)Cu(NEC-SB)] (9) were produced in >98% radiochemical purity. Rats were injected with complex 7, 8 or 9 and were euthanized at 1, 4 and 24 h. All three complexes are cleared from the blood over the first hour following injection but there is poor clearance of this activity over 24 h. A similar pattern of retention was noted in the liver where the levels of activity in this tissue at 1 h are not statistically different from those at 24 h. Molecular mechanics and DFT studies were performed on the complexes in order to gain insight into the lower stability.
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Camerino, via S. Agostino 1, 62032, Camerino, MC, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Papini
authors.forename: Simone
authors.initials: S
authors.lastname: Alidori
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lewis
authors.forename: David E
authors.initials: DE
authors.lastname: Reichert
authors.forename: Maura
authors.initials: M
authors.lastname: Pellei
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Gioia Lobbia
authors.forename: Gráinne B
authors.initials: GB
authors.lastname: Biddlecombe
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
authors.forename: Carlo
authors.initials: C
authors.lastname: Santini
mesh_terms: D000818:Animals; D003300:Copper / Q000737:chemistry*; D008024:Ligands; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D051381:Rats; D011917:Rats, Inbred Lew; D013440:Sulfides / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D008024:Ligands; D047028:Macrocyclic Compounds; D013440:Sulfides; D003300:Copper