Exploring the effect of Ru(<scp>ii</scp>) arene complexes on cytotoxicity upon co-ligand variation and loading on amine-functionalized silica nanoparticles

To overcome the undesirable side effects and acquired resistance associated with platinum-based chemotherapeutics, scientists are searching for alternative strategies involving novel metal-based compounds with improved pharmacological properties. Ruthenium complexes have emerged as prospective candidates to combat side effects and improve the selectivity of anticancer agents. In this work, a benzimidazole-based chelating ligand, <b>HL</b> (4-(1<i>H</i>-naphth[2,3-<i>d</i>]imidazol-2-yl)-1,3-benzenediol) with O and N donor atoms, was synthesized and used for complexation with ruthenium to obtain three Ru(II) arene complexes represented by [Ru(η⁶-<i>p</i>-cym)(L)Cl], [Ru(η⁶-<i>p</i>-cym)(L)(PPh₃)]⁺ and [Ru(η⁶-<i>p</i>-cym)(L)(PTA)]⁺ (where <i>p</i>-cym = <i>p</i>-cymene, PPh₃ = triphenylphosphine and PTA = 1,3,5-triaza-7-phosphaadamantane). The synthesized complexes were characterized using spectroscopic techniques. UV-Vis absorption spectroscopy and LC-MS were used to study the stability of the complexes in biological medium. Their lipophilicity was studied by calculating the partition coefficient in <i>n</i>-octanol and water. The complexes showed significant binding with biomolecules like albumin proteins and nucleic acids. All the complexes were found to be cytotoxic, with complex [Ru(η⁶-<i>p</i>-cym)(L)PPh₃]PF₆ exhibiting the highest anticancer activity. The mechanism of anticancer activity was attributed to the ability of the complexes to induce apoptosis and generate reactive oxygen species (ROS). The complexes also exhibited antimetastatic properties. Furthermore, complex [Ru(η⁶-<i>p</i>-cym)(L)PPh₃]PF₆ was loaded onto amine-functionalized mesoporous silica nanoparticles which led to an increase in its cytotoxic activity.