Utilization of Guanidine-Based Ancillary Ligands in Arene–Ruthenium Complexes for Selective Cytotoxicity

A family of three
water-soluble half-sandwich arene–ruthenium
complexes, depicted as C1–C3, having the general formula [Ru­(p-cymene)­(L)­Cl]Cl has been synthesized, where L represents
(1H-benzo­[d]­imidazol-2-yl)­guanidine
(L1) or (benzo­[d]­oxazol-2-yl)­guanidine (L2)
or (benzo­[d]­thiazol-2-yl)­guanidine (L3). The crystal structure of complex C3 has been determined. The complexes
show several absorption bands in the visible and ultraviolet regions,
and they also show prominent emission in the visible region while
excited near 400 nm. Studies on the interaction of ligands L1–L3 and complexes C1–C3 with calf thymus DNA reveal that
the complexes are better DNA binders than the ligands, which is attributable
to the imposed planarity of the ruthenium-bound guanidine-based ligand,
enabling it to serve as a better intercalator. Molecular docking studies
show that the complexes effectively bind with DNA through electrostatic
and H-bonding interactions and partial intercalation of the guanidine-based
ligands. Cytotoxicity studies carried out on two carcinoma cell lines
(PC3 and A549) and on two non-cancer cell lines (BPH1 and WI-38) show
a marked improvement in antitumor activity owing to complex formation,
which is attributed to improvement in cellular uptake on complex formation.
The C1 complex is found to exhibit
the most prominent activity against the PC3 cell line. Inclusion of
the guanidine-based ligands in the half-sandwich ruthenium–arene
complexes is found to be effective for displaying selective cytotoxicity
to cancer cells and also for convenient tracing of the complexes in
cells due to their prominent emissive nature.