Chemical and biological characterization of technetium(I) and Rhenium(I) tricarbonyl complexes with dithioether ligands serving as linkers for coupling the Tc(CO)(3) and Re(CO)(3) moieties to biologically active molecules.

摘要: The organometallic precursor (NEt(4))(2)[ReBr(3)(CO)(3)] was reacted with bidendate dithioethers (L) of the general formula H(3)C-S-CH(2)CH(2)-S-R (R = -CH(2)CH(2)COOH, CH(2)-CtCH) and R'-S-CH(2)CH(2)-S-R' (R' CH(3)CH(2)-, CH(3)CH(2)-OH, CH(2)COOH) in methanol to form stable rhenium(I) tricarbonyl complexes composition [ReBr(CO)(3)L]. Under these conditions, functional groups do not participate coordination. As a prototypic representative this type Re compounds, propargylic group bearing complex [ReBr(CO(3))(H(3)C-S-CH(2)CH(2)-S-CH(2)CtCH)] Re2 studied by X-ray diffraction analysis. Its molecular structure exhibits slightly distorted octahedron facial coordination carbonyl ligands. potentially tetradentate ligand HO-CH(2)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(2)-OH trinitrato [Re(NO(3))(3)(CO)(3)](2-) yield cationic [Re(CO)(3)(HO-CH(2)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(2)-OH)]NO(3) Re8 which shows one hydroxy group. has been characterized correct elemental analysis, infrared spectroscopy, capillary electrophoresis, Ligand exchange reaction carboxylic ligands H(3)C-S-CH(2)CH(2)-S-CH(2)CH(2)-COOH HOOC-CH(2)-S-CH(2)CH(2)-S-CH(2)-COOH water equimolar amounts NaOH led bromide is replaced analysis [Re(CO)(3)(OOC-CH(2)-S-CH(2)CH(2)-S-CH(2)-COOH)] Re6 second noncoordinated offering an ideal site for functionalization or coupling biomolecule. no-carrier-added preparation analogous (99m)Tc(I) thioether could be performed using fac-[(99m)Tc(H(2)O)(3)(CO)(3)](+), yields up 90%. behavior chlorine containing (99m)Tc [(99m)TcCl(CO)(3)(CH(3)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(3))] Tc1 aqueous solution at physiological pH value investigated. In saline, chromatographically separated compound least 120 min. However, chloride-free solution, water-coordinated species Tc1a proposed [(99m)Tc(H(2)O)(CO)(3)(CH(3)CH(2)-S-CH(2)CH(2)-S-CH(2)CH(3))](+) occurred. charge conversion product confirmed electrophoresis. By introduction into as third donor group, suppressed thus neutrality preserved. Biodistribution studies rat demonstrated neutral [(99m)TcCl(CO)(3)(CH(2)-S-CH(2)CH(2)-S-CH(2)-CtCH)] Tc2 significant initial brain uptake (1.03 +/- 0.25% 0.78 0.08% ID/organ 5 p.i.). Challenge experiments glutathione clearly indicated that no transchelation occurs vivo.