Antiproliferative activity of (η⁶-arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines

Three [(η⁶-arene)RuC₂B₉H₁₁] complexes (arene = p-cymene (2), biphenyl (3) and 1-Me-4-COOEt-C₆H₄ (4)) were synthesised according to modified literature procedures and fully characterised. 2-4 were found to be moderately active against two types of tumour cell lines (HCT116 and MCF7), with IC₅₀ values in the low micromolar range. However, viability of normal, healthy cells (MRC-5 cell line, MLEC and mouse macrophages) was not affected by treatment with 2-4, indicating high selectivity of the metallacarborane complexes towards tumour cell lines, compared to the unselective antitumour agent cisplatin and other potential Ru^II drugs. Moreover, flow cytometric analysis suggested that 4 induces cell death via a caspase-dependent apoptotic mechanism. DFT calculations of the frontier molecular orbitals showed that the HOMO-LUMO gap in 2-4 is smaller than in the corresponding cyclopentadienyl complexes 2-Cp-4-Cp (e.g. 5.47 (2) vs. 6.31 eV (2-Cp)). In order to assess the stability of 2-4, particularly the ruthenium-dicarbollide bond, energy decomposition analysis (EDA) of 2-4, together with the respective cyclopentadienyl analogues 2-Cp-4-Cp, was performed. EDA suggests that the ruthenium(ii)-dicarbollide bond in the three complexes is mostly ionic and far stronger than the ruthenium(ii)-arene bond.