title: Aqueous synthesis of derivatized cyclopentadienyl complexes of technetium and rhenium directed toward radiopharmaceutical application.
abstract: Half-sandwich complexes of the type [(RCOCp)M(CO)(3)] with M = Re and (99(m))Tc were synthesized from [M(OH(2))(3)(CO)(3)](+) in water. The R group can be an organic residue or a receptor binding biomolecule with a spacer to cyclopentadienyl (Cp). This provides a general route to Cp complexes of technetium without the need for starting from [TcBr(CO)(5)]. The X-ray structure of [(C(6)H(5)CH(2)COC(5)H(4))Tc(CO)(3)] has been elucidated. The compound crystallizes in the monoclinic space group P2(1)/c with a = 16.1454(9), b = 7.6300(6), and c = 12.3922(7) A and beta = 107.792(6) degrees. We have chosen a serotonergic receptor ligand (WAY) as an example for the derivatization of Cp with a bioactive molecule. WAY is linked to Cp by an aliphatic chain of variable length. The half-sandwich complexes were prepared from water and organic solvents. The structure of [(WAY4-Cp)Re(CO)(3)] could be elucidated. The compound crystallizes in the monoclinic space group P2(1)/c with a = 15.7112(6), b = 6.8775(3), and c = 25.5217(12) A and beta = 103.778(5) degrees. Quantification of inhibition constants gave a clear structure-activity relationship. A single methylene group between the receptor binding site and the half-sandwich complex gave an IC(50) of 217 nM for HT(1A), whereas a butylene linker resulted in retention of the inhibition constant with an IC(50) of 6 nM with respect to underivatized WAY. For use as radiopharmaceuticals, the compounds have also been prepared with (99m)Tc in quantitative yield.
authors.affiliation: Institute of Inorganic Chemistry, University of Zürich, CH-8057 Zürich, Switzerland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bernard
authors.forename: Kirstin
authors.initials: K
authors.lastname: Ortner
authors.forename: Bernhard
authors.initials: B
authors.lastname: Spingler
authors.forename: H-J
authors.initials: HJ
authors.lastname: Pietzsch
authors.forename: Roger
authors.initials: R
authors.lastname: Alberto
mesh_terms: D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D012211:Rhenium / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012211:Rhenium