Self-assembled ruthenium (II) metallacycles and metallacages with imidazole-based ligands and their in vitro anticancer activity

Six tetranuclear rectangular metallacycles were synthesized via the [2+2] coordination-driven self-assembly of imidazole-based ditopic donor 1,4-bis(imidazole-1-yl)benzene and 1,3-bis(imidazol-1-yl)benzene, with dinuclear half-sandwich p-cymene ruthenium (II) acceptors [Ru₂(μ-η⁴-oxalato)(η⁶-p-cymene)₂](SO₃CF₃)₂, [Ru₂(μ-η⁴-2,5-dioxido-1,4-benzoquinonato)(η⁶-p-cymene)₂](SO₃CF₃)₂ and [Ru₂(μ-η⁴-5,8-dioxido-1,4-naphtoquinonato)(η⁶-p-cymene)₂](SO₃CF₃)₂, respectively. Likewise, three hexanuclear trigonal prismatic metallacages were prepared via the [2+3] self-assembly of tritopic donor of 1,3,5-tri(1H-imidazol-1-yl)benzene with these ruthenium(II) acceptors respectively. Self-selection of the single symmetrical and stable metallacycle and cage was observed although there is the possibility of forming different conformational isomeric products due to different binding modes of these imidazole-based donors. The self-assembled macrocycles and cage containing the 5,8-dioxido-1,4-naphtoquinonato (donq) spacer exhibited good anticancer activity on all tested cancer cell lines (HCT-116, MDA-MB-231, MCF-7, HeLa, A549, and HepG-2), and showed decreased cytotoxicities in HBE and THLE-2 normal cells. The effect of Ru and imidazole moiety of these assemblies on the anticancer activity was discussed. The study of binding ability of these donq-based Ru assemblies with ctDNA indicated that the complex 9 with 180° linear 1 ligand has the highest bonding constant K b to ctDNA.