In Vitro Biological Activity of α-Diimine Rhenium Dicarbonyl Complexes and Their Reactivity with Different Functional Groups

Cancer remains one of the leading causes of death worldwide. The interest in organometallic complexes as anticancer drug candidates continues to be pivotal for many researchers. Initially underestimated for their therapeutic potentials, rhenium complexes are now slowly gaining momentum. While tricarbonyl complexes of rhenium are widely investigated, dicarbonyl derivatives of the cis-[Re(CO)₂]⁺ core remain largely unexplored. In this study, we tested in vitro a variety of rhenium dicarbonyl complexes for their activity towards three cancer cell lines (A549, MCF-7 and HCT116) and one healthy cell line (HEK293). The most lipophilic compounds showed, like the tricarbonyl species, good activity against specific cancer lines (IC₅₀ = 1.5–2.5 µM); however, the same were also toxic towards healthy cells. In order to understand these differences, we performed a reactivity study of cis-[Re(CO)₂(NN)]⁺ species (where NN = diimine) with biologically relevant functional groups (-COOH, -NH₂, -SH and aromatic nitrogen-based ligands) and compared the chemistry to what is known for the fac-[Re(CO)₃]⁺ core. Overall, we found that the rhenium dicarbonyl complexes only show good reactivity with aromatic nitrogen-based ligands. The reaction of cis-[Re(CO)₂(NN)]⁺ species with common bio-functional groups leads, rather, to the formation of bis-diimine dicarbonyl complexes (cis-[Re(CO)₂(NN)₂]⁺) as the major by-product.