title: Bispidine dioxotetraaza macrocycles: a new class of bispidines for (64)Cu PET imaging.
abstract: The three new dioxo-tetraazamacrocyclic ligands with a fused, very rigid bispidine (3,7-diazabicyclo[3.3.1]nonane) group connecting the two tertiary amine donors, and ethyl, propyl, or benzene groups connecting the two amide donors are highly preorganized and lead to very stable, uncharged Cu(II) complexes. Solution spectroscopy and solid state structures indicate that these are square pyramidal with a solvent molecule occupying the apical position. Cyclic voltammetry defines a reversible Cu(III/II) couple and a strongly negative irreversible Cu(II/I) couple (ca. -2 V vs Fc/Fc(+)), indicating that the Cu(II) complexes are very stable in solution. This is supported by superoxide dismutase (SOD) and human serum challenge experiments as well as the biodistribution, which all show that the benzene-based ligand has the highest in vitro and in vivo stability and that this was expected on the basis of the macrocycle ring size and shape and the highest degree of preorganization. This ligand is easy to functionalize for a possible coupling to biological vector molecules and/or fluorescence markers for PET (positron emission tomography) and multimodal imaging (i.e., PET and optical imaging).
authors.affiliation: Anorganisch-Chemisches Institut, Universität Heidelberg , INF 270, D-69120 Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Comba
authors.forename: Manja
authors.initials: M
authors.lastname: Kubeil
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
authors.forename: Henning
authors.initials: H
authors.lastname: Rudolf
authors.forename: Holger
authors.initials: H
authors.lastname: Stephan
authors.forename: Kristof
authors.initials: K
authors.lastname: Zarschler
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000737:chemistry*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D003301:Copper Radioisotopes; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003301:Copper Radioisotopes; D008055:Lipids; D019275:Radiopharmaceuticals; C495809:bispidine; D013482:Superoxide Dismutase