New dicarbonyl and first monocarbonyl Re and 99mTc complexes with quinaldic acid and cyclohexyl isocyanide

Abstract

Complexes of rhenium and technetium-99 m that accommodate both bidentate and monodentate ligands provide versatile chemical platforms with potential in radiopharmaceutical design. By combining quinaldic acid (quinH) with cyclohexyl isocyanide (cisc), we explored the reactivity of the fac-[M(CO)₃]⁺ synthon (M = Re, ^99mTc) beyond the classical [2 + 1] system. This approach led to the isolation of three distinct species: the expected tricarbonyl trans-[M(CO)₃(quin)(cisc)], the dicarbonyl trans-cis-[M(CO)₂(quin)(cisc)₂], and, notably, the monocarbonyl mer-[M(CO)(quin)(cisc)₃], reported here for the first time. The rhenium analogues were fully characterized by elemental analysis, IR, NMR, and single-crystal X-ray diffraction, while the technetium congeners were prepared under analogous conditions and identified by comparative HPLC. All technetium complexes displayed excellent in vitro stability in the presence of histidine and cysteine (>95 % RCP at 6 h). Lipophilicity values (logD_7.4 = 2.8–4.0) indicated that these compounds are highly hydrophobic. Biodistribution studies in mice confirmed that hepatobiliary clearance is the dominant excretion route, with negligible uptake in the stomach and spleen. Among them, the monocarbonyl complex exhibited remarkably rapid clearance, with >65 % of the injected dose recovered in the intestines at 2 h post-injection. These findings expand the chemistry of isocyanide-containing ^99mTc/Re carbonyl complexes and provide new opportunities for constructing multifunctional radiopharmaceutical scaffolds where the pharmacophore can be attached either to the bidentate or to the isocyanide ligands.