Half-sandwich ruthenium(II)-arene complexes: synthesis,spectroscopic studies,biological properties,and molecular modeling |
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Authors: | Stefan Nikolić Sanja Grgurić-Šipka Ivana S. Djordjević Rahma Dahmani Dragana Dekanski Sašenka Vidičević |
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Affiliation: | 1. Innovative Centre of the Faculty of Chemistry, University of Belgrade, Belgrade, Serbia;2. Faculty of Chemistry, University of Belgrade, Belgrade, Serbia;3. Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Belgrade, Serbia;4. Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208 CNRS, Université Paris-Est, Marne-La-Vallée, France;5. Unité de Recherche Physico-Chimie des Matériaux à l’Etat Condensé, Faculté des Sciences de Tunis, Université Tunis El Manar, Tunis, Tunisie;6. Laboratoire de Spectroscopie Atomique, Moléculaire et Applications (LSAMA), Université de Tunis El Manar, Tunis, Tunisia;7. Biomedical Research, R and D Institute, Galenika a.d, Belgrade, Serbia;8. Institute of Medical and Clinical Biochemistry, School of Medicine, University of Belgrade, Belgrade, Serbia |
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Abstract: | In search for antitumor metal-based drugs that would mitigate the severe side-effects of cisplatin, Ru(II) complexes are gaining increasing recent interest. In this work, we report on the synthesis, characterization (1H- and 13C-NMR, FT-IR), and cytotoxicity studies of two new half-sandwich organometallic Ru(II) complexes of the general formula [Ru(η6-arene)(XY)Cl](PF6) where arene?=?benzene or toluene and XY?=?bidentates: dipyrido[3,2-a:2′,3′-c]phenazine (dppz) or 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip), which are bound to Ru(II) via two phenanthroline-N atoms in a characteristic “piano-stool” configuration of Ru(II)-arene complexes—as confirmed by vibrational and NMR spectra. In addition, cytotoxic studies were performed for similar half-sandwich organometallic [Ru(η6-p-cymene)(Me2dppz)Cl]PF6 complex (Me2dppz = 11,12-dimethyl-dipyrido[3,2-a:2′,3′-c]phenazine). This study is complemented with elaborate modeling with density functional theory (DFT) calculations, which provided insight into reactive sites of Ru(II) structures, further detailed by molecular docking on the B-DNA dodecamer, which identified binding sites and affinities: most pronounced for the [Ru(η6-benzene)(aip)Cl](PF6) in both A-T and G-C regions of the DNA minor groove. Cytotoxic activity was probed versus tumor cell lines B16, C6, and U251 (B16 mouse melanoma, C6 rat glioma, U251 human glioblastoma) and non-tumor cell line HACAT (HACAT normal human keratinocytes). |
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Keywords: | Ruthenium complexes DNA docking cytotoxicity studies DFT calculations intercalation |
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