Universidad Nacional de La Plata

In this work, we report the synthesis and characterization of three novel ruthenium(II) p-cymene complexes coordinated with acylthiourea ligands (L1-L3), of general formula [Ru(η⁶-p-cymene)(PPh₃)(L1-L3)Cl]PF₆ (1-3). Single-crystal X-ray crystallography of the free ligands and their complexes [Ru(η⁶-p-cymene)(PPh₃) (κ¹-S)-(N-benzoyl-N´-cyclopropylthiourea)Cl]PF₆ (1), Ru(η⁶-p-cymene)(PPh₃) (κ¹-S)-(N-2-furoyl-N´-cyclopropylthiourea)Cl]PF₆ (2), [Ru(η⁶-p-cymene)(PPh₃)] (κ¹-S)-(N-thiophene-2-carbonyl-N´-cyclopropyl thiourea)Cl]PF₆ (3) revealed that the acylthiourea ligands act as neutral monodentate donors, coordinating through the sulfur atom (κ¹-S). Application of the Extended Transition State-Natural Orbitals for Chemical Valence method demonstrated that the dominant interaction in complexes 1-3 originates from the overlap between the sulfur lone pair of the ligands and a Ru d-orbital, which plays a decisive role in their stability. The Interacting Quantum Atom analysis showed that both the free and coordinated acylthiourea ligands stabilize their structure through an intramolecular N-H···O=C hydrogen bond. The cytotoxicity of complexes 1-3 was evaluated against the A549 (lung) and MDA-MB-231 (breast) human cancer cell lines. To assess their selectivity, the compounds were also tested against two non-cancerous cell models: MRC-5 (lung fibroblasts) and MCF-10 A (breast epithelial cells). The study revealed high cytotoxicity against the MDA-MB-231 cell line, with IC₅₀ values of 0.62 ± 0.05 μM (1), 0.66 ± 0.12 μM (2), and 0.53 ± 0.12 μM (3). Activity against the A549 cell line was also significant, with IC₅₀ values of 1.05 ± 0.11 μM (1), 2.60 ± 0.25 μM (2), and 1.04 ± 0.21 μM (3). The combination of phosphine and acylthiourea ligands appears critical for achieving high cytotoxic activity.