Dirhenium core-based cyclic and acyclic helicates as anticancer agents for breast cancer and skin cancer cells

The design and synthesis of dirhenium(I)-based heteroleptic helicates, <i>fac</i>-[Re(CO)₃(μ-L^<i>n</i>)(μ-L5)Re(CO)₃] (1-2), where (L^<i>n</i>; <i>n</i> = 1, 3) L1 = 2,2'-(1,1'-((methylazanediyl)bis(4,1-phenylene))bis(benzoimidazole-2,1-diyl))diphenol, L3 = 2,2'-(1,1'-(oxybis(4,1-phenylene))bis(benzoimidazole-2,1-diyl))diphenol and L5 = bis(3-((1<i>H</i>-naphtho[2,3]imidazol-1-yl)methyl)-2,4,6-trimethylphenyl)methane, are reported along with two dinuclear acyclic helicates, <i>fac</i>-[Re(CO)₃(μ-L^<i>n</i>)₂Re(CO)₃] (3-4), where (L^<i>n</i>; <i>n</i> = 2, 4) L2 = 2-(1-(4-((4-bromophenyl)(methyl)amino)phenyl)-benzoimidazolyl)phenol and L4 = 2-(1-(4-(4-bromophenoxy)phenyl)-benzoimidazolyl)phenol. Solid state structures were confirmed by single crystal X-ray diffraction analysis, while ¹H-NMR data of 1-4 revealed the retention of the structures in the solution state as well. Cytotoxicity of these complexes was evaluated in triple-negative breast cancer cells (4T1) and skin cancer cells (B16). 1-4 showed greater cytotoxicity than the widely used medication cisplatin, and one of the helicates, 2, was investigated further to assess the complex's antimetastatic properties and capacity to induce apoptosis by disrupting the membrane potential. Complex 2 was found to be lipophilic and displayed substantial stability in biological media.