Expanding the Cyclopentadienyl Framework: 99mTc/Re Complexes with Orthogonal Functions for Bioconjugation.

A series of bifunctional cyclopentadienes of the type 1,3-EtOCO-HCp-linker-NH2 were synthesized. In this series, the linker length (distance between the amine functionalities and the cyclopentadiene) has been systematically varied (CH2)n (n = 1-3). The corresponding Re complexes [(η5-C5H3RR')Re(CO)3] (R = -COOEt, R' = -linker-NH2) were synthesized and structurally characterized. They exhibit extraordinary stability toward water and air. All bifunctional cyclopentadienes have been labeled with the [99mTc(CO)3]+ moiety. Whereas the reactions with ethylene and propylene linked cyclopentadiene under mild reaction conditions led to the products in high radiochemical purity (>96%) without applying further purification protocols, harsher reaction conditions were required for the synthesis of the methylene-linked cyclopentadiene compound. Masking the amine in the methylene-linked cyclopentadiene by an amide bond bypasses this problem. The very hydrophilic characters of these complexes were assessed by KOW analysis. The reported cyclopentadienes and their complexes offer a robust and versatile platform for (radio)metal incorporation into biologically active lead structures.