DNA Noncovalent Interactions of Dinuclear η 6 ‐Arene Ru(II) Complexes: Influence of Complex Charge and Bridging Ligand Length on DNA Binding Mode and Cytotoxic Activity
Year: 2025
Type: article
Abstract: A series of dinuclear η⁶‐arene Ru(II) complexes with the general formulae {[(η⁶‐p‐cym)Ru(L1)] 2 (μ‐BL‐i)} 2+ ( 1 )–( 3 ) and {[(η⁶‐p‐cym) 2 Ru 2 (L1)(L2)](μ‐BL‐i)} 3+ ( 4 )–( 6 ), [L1 = benzo[h]quinoline ( bq ), L2 = 1,10‐phenanthroline ( phe ) and BL‐i the bridging ligands with i = 1 ‐3, 4,4′‐bipyridine (BL‐1), 1,2‐bis(4‐pyridyl)ethane (BL‐2) and 1,3‐bis(4‐pyridyl)propane (BL‐3)] were synthesized and fully characterized by high‐resolution mass spectrometry and NMR spectroscopy. The crystal structures of the complexes ( 1 )–( 3 ) were determined by single‐crystal X‐ray diffraction. DNA binding interactions of the water‐soluble chloride salts of the complexes ( 4 )–( 6 ) were investigated by NMR spectroscopy using the B‐type DNA model oligonucleotide duplex d(5′‐CGCGAATTCGCG‐3′) 2 . 1 H NMR chemical shift changes revealed that the chelating ligands ( phe or bq ) partially intercalate and/or bind in the helix minor groove. Among these, complex {[(η⁶‐p‐cym) 2 Ru 2 (phe)(bq)](μ‐BL‐1)} 3+ , ( 4 ), induced the most pronounced perturbations, including partial helix unwinding. Fluorescence quenching experiments yielded the Stern–Volmer constants ( K sv ) and the binding constants ( K b ) in the moderate‐to‐high affinity range, consistent with the NMR observations. Preliminary cytotoxicity studies showed that the chloride salts of the complexes ( 1 )–( 6 ) exhibit low‐micromolar IC 50 values against MCF‐7, A2780, and cisplatin‐resistant A2780cis‐resistant cell lines, while showing moderate selectivity for cancer cells over normal fibroblasts.
Source: Chemistry - A European Journal
Authors: Dimitrios Thomos, Theodoros Tsolis, John C. Plakatouras, Ioannis‐Michail Chronakis, Angeliki Magklara, Achilleas Garoufis
Institution: University of Ioannina
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,640
OpenAlex ID: W4416100319