Rhenium Complexes Based on an N2O Tridentate Click Scaffold: From Synthesis, Structural and Theoretical Characterization to a Radiolabelling Study

A general synthetic approach for a novel range of semi-rigid bifunctional chelating agents (BCAs) including an aromatic ring and a triazolyl moiety in the chelating unit, for the fac-[M(CO)3]+ core (M = 185/187Re or 188Re) was investigated. The strategy included the facile preparation of these N2O ligands bearing various functionalized arms (carboxylate, terminal alkyne, aromatic amine…). The reaction of commercial [Re(CO)5Cl] (or freshly prepared [Re(H2O)3(CO)3]Brprecursor) with our BCAs in methanol led to the formation of stable neutral tricarbonylrhenium complexes of general formula [Re(CO)3(L)] (LH = 5, 10, 11), in high yield. These compounds were characterized by means of IR, mass spectrometry, NMR, electrochemistry, X-ray crystallography for compounds [Re(CO)3(5)] and [Re(CO)3(11)] as well as DFT calculations. The analogous rhenium-188 complexes [188Re(CO)3(5)] and [188Re(CO)3(11)] were also prepared, from acceptable to excellent yield, by the reaction of 5 or 11 with the fac- [188Re(OH2)3(CO)3]+precursor at 80oC in methanol. The structural identity of the radioactive complexes were assessed by means of HPLC studies. The good affinity of these click ligands for the Re(I) core combined with the ease of their derivatization make this chelating system promising for the conception of target-specific radiopharmaceuticals for therapy.