NDLI: Factors that influence the antiproliferative activity of half sandwich $Ru^{II}–[9]aneS3$ coordination compounds: activation kinetics and interaction with guanine derivatives

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zangrando, Ennio Rilak, Ana Kljun, Jakob Bugarcic, Zivadin D. Alessio, Enzo Bratsos, Ioannis Turel, Iztok
Description	Author Affiliation: Rilak A ( Faculty of Science, University of Kragujevac, R. Domanovica 12, P. O. Box 60, 34000 Kragujevac, Serbia.)
Abstract	Half sandwich Ru(II)–[9]aneS3 complexes ([9]aneS3 = 1,4,7-trithiacyclononane ) are being studied for their antiproliferative activity. We investigated here the activation kinetics of three such complexes, namely $[Ru([9]aneS3)(en)Cl](PF_{6})$ (1), $[Ru([9]aneS3)(bpy)Cl](PF_{6})$ (2) and [Ru([9]aneS3)(pic)Cl] (3) (en = 1,2-diaminoethane , pic = picolinate), and their interaction with DNA model bases. The aim of the study was to assess how they are affected by the nature and charge of the chelating ligand . The model reactions of 1–3 with the guanine derivatives 9-methylguanine (9MeG), guanosine (Guo), and guanosine 5′-monophosphate (5′-GMP) were studied by NMR spectroscopy . All reactions lead, although with different rates and to different extents, to the formation of monofunctional adducts with the guanine derivatives N7-bonded to the Ru center. Two products, the complexes $[Ru([9]aneS3)(en)(9MeG-N7)](PF_{6})_{2}$ (4) and $[Ru([9]aneS3)(pic)(9MeG-N7)](PF_{6})$ (10), were structurally characterized also by X-ray crystallography . The structure of 4 is stabilized by strong intramolecular H-bonding between an NH of en and the carbonyl O6 of 9MeG. The kinetics of aquation and anation of complexes 2 and 3, as well as the kinetics and the mechanism of the reaction of complexes 1–3 with the biologically more relevant 5′-GMP ligand were studied by UV-Vis spectroscopy . The rate of the reaction of 1–3 with 5′-GMP depends on the nature of the chelating ligand rather than on the charge of the complex, decreasing in the order 3 ≈ 2 > 1. The measured enthalpies and entropies of activation $(ΔH^{≠}$ > 0, $ΔS^{≠}$ < 0) support an associative mechanism for the substitution process.
ISSN	14779226
Issue Number	38
Volume Number	41
e-ISSN	13645447
Journal	Dalton Trans.
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2012-10-14
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Antineoplastic Agents Chemistry Coordination Complexes Guanine Analogs & Derivatives Ruthenium Toxicity Cell Line, Tumor Cell Survival Drug Effects Chelating Agents Crystallography, X-Ray DNA Metabolism Guanosine Guanosine Monophosphate Humans Hydrogen Bonding Kinetics Ligands Molecular Conformation Journal Article Research Support, Non-U.S. Gov't
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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