Functionalized Rhenium(V) Organoimido Complexes as Potential Radiopharmaceuticals. 2. Synthesis, Structural Characterization, and Reactivity of <i>N</i>-Succinimidyl Ester Derivatives with Amines

Abstract

Organoimidorhenium(V) complexes were synthesized as potential labeling agents for biologically relevant organic amines using the preconjugate approach. The bistriphenylphosphine organoimidorhenium N -succinimidyl ester complex Cl 3 (PPh 3 ) 2 Re N-C 6 H 4 CO 2 N(COCH 2 ) 2 ( 2 ) was synthesized and characterized by single-crystal X-ray analysis. Complex 2 was coupled in aqueous dimethylformamide solvent with a series of primary and secondary amines, amino acids, and a biotin−ethylenediamine derivative to give the corresponding amide complexes in good yields. These results demonstrate that the organoimido linkage is resistant toward hydrolysis and stable in the presence of more basic alkylamines. An unusual oxygen atom transfer reaction was observed between the byproduct N -hydroxysuccinimide and triphenylphosphine ligands when dichloromethane was used as solvent. The dithiocarbamate complexes Cl[Et 2 NCS 2 ] 2 Re N-C 6 H 4 CO 2 N(COCH 2 ) 2 ( 3 ) and O[(Et 2 NCS 2 ) 2 Re N-C 6 H 4 CO 2 N(COCH 2 ) 2 ] 2 ( 4 ) were also synthesized from 2 . These complexes were unaffected by N -hydroxysuccinimide, but were not suitable for labeling due to hydrolysis of the organoimido groups under the reaction conditions.