The [(Cp)M(CO)₃] (M=Re, ^99mTc) Building Block for Imaging Agents and Bioinorganic Probes: Perspectives and Limitations

Abstract

Starting from asymmetric Thiele's acid derivatives, two different imaging probes [(99m)Tc(CO)(3)(CpR)] (R=potential targeting vector) are generated simultaneously in one-pot and from one substrate. This extends the previously introduced labeling strategy of metal-mediated retro-Diels-Alder reaction with HCp-R dimers. We demonstrate that chemically active functionalities such as hydroxamic acids are not following this labeling strategy. Adopting the principle of replacing phenyl rings by [Re(CO)(3)(Cp)] entities, potent histone deacetylase (HDAC)-inhibiting Re analogs of suberoylanlilide hydroxamic acid (SAHA; N-hydroxy-N'-phenyloctanediamide) were synthesized and characterized. Cytotoxic evaluation on different tumor cell lines revealed low IC(50) values [μM] for these compounds, comparable to their purely organic congeners.