Issue 44, 2016

Hydrolytic behaviour of mono- and dithiolato-bridged dinuclear arene ruthenium complexes and their interactions with biological ligands

Abstract

The hydrolysis and the reactivity of two dinuclear p-cymene ruthenium monothiolato complexes, [(η6-p-MeC6H4Pri)2Ru2Cl2(μ-Cl)(μ-S-m-9-B10C2H11)] (1) and [(η6-p-MeC6H4Pri)2Ru2Cl2(μ-Cl)(μ-SCH2-p-C6H4–NO2)] (2), and of two dinuclear p-cymene ruthenium dithiolato complexes, [(η6-p-MeC6H4Pri)2Ru2(μ-SCH2CH2Ph)2Cl2] (3) and [(η6-p-MeC6H4Pri)2Ru2(SCH2C6H4-p-OMe)2Cl2] (4) towards amino acids, nucleotides, and a single-stranded DNA dodecamer were studied using NMR and mass spectrometry. In aqueous solutions at 37 °C, the monothiolato complexes 1 and 2 undergo rapid hydrolysis, irrespective of the pH value, the predominant species in D2O/acetone-d6 solution at equilibrium being the neutral hydroxo complexes [(η6-p-MeC6H4Pri)2Ru2(OD)2(μ-OD)(μ-SR)]. The dithiolato complexes 3 and 4 are stable in water under acidic conditions, but undergo slow hydrolysis under neutral and basic conditions. In both cases, the cationic hydroxo complexes [(η6-p-MeC6H4Pri)2Ru2(OD)(CD3CN)(μ-SR)2]+ are the only species observed in D2O/CD3CN at equilibrium. Surprisingly, no adducts are observed upon addition of an excess of L-methionine or L-histidine to the aqueous solutions of the complexes. Upon addition of an excess of L-cysteine, on the other hand, 1 and 2 form the unusual cationic trithiolato complexes [(η6-p-MeC6H4Pri)2Ru2{μ-SCH2CH(NH2)COOH}2(μ-SR)]+ containing two bridging cysteinato ligands, while 3 and 4 yield cationic trithiolato complexes [(η6-p-MeC6H4Pri)2Ru2[μ-SCH2CH(NH2)COOH](μ-SR)2]+ containing one bridging cysteinato ligand. A representative of cationic trithiolato complexes containing a cysteinato bridge of this type, [(η6-p-MeC6H4Pri)2Ru2[μ-SCH2CH(NH2)COOH](μ-SCH2-p-C6H4-But)2]+ (6) could be synthesised from the dithiolato complex [(η6-p-MeC6H4Pri)2Ru2(SCH2C6H4-p-But)2Cl2] (5), isolated as the tetrafluoroborate salt and fully characterised. Moreover, the mono- and dithiolato complexes 1–4 are inert toward nucleotides and DNA, suggesting that DNA is not a target of cytotoxic thiolato-bridged arene ruthenium complexes. In contrast to the trithiolato complexes, monothiolato and dithiolato complexes hydrolyse and react with L-cysteine. These results may have important implications for the mode of action of thiolato-bridged dinuclear arene ruthenium drug candidates, and suggest that their modes of action are different to those of other arene ruthenium complexes.

Graphical abstract: Hydrolytic behaviour of mono- and dithiolato-bridged dinuclear arene ruthenium complexes and their interactions with biological ligands

Supplementary files

Article information

Article type
Paper
Submitted
24 Mar 2016
Accepted
10 Apr 2016
First published
12 Apr 2016
This article is Open Access
Creative Commons BY license

RSC Adv., 2016,6, 38332-38341

Hydrolytic behaviour of mono- and dithiolato-bridged dinuclear arene ruthenium complexes and their interactions with biological ligands

D. Stíbal, L. Geiser, G. Süss-Fink and J. Furrer, RSC Adv., 2016, 6, 38332 DOI: 10.1039/C6RA07701C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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