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Base‐Catalyzed Hydrolysis of a Ru II –Chloro–dmso Complex and Its Reactivity towards L ‐Methionine
Author(s) -
Brindell Małgorzata,
Dyduch Karol,
Adamowicz Agnieszka,
Urbanowicz Elżbieta,
Oszajca Maria,
Michalak Artur,
Stochel Grażyna,
van Eldik Rudi
Publication year - 2014
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201301154
Subject(s) - chemistry , ruthenium , thioether , moiety , hydrolysis , dissociation (chemistry) , reactivity (psychology) , medicinal chemistry , ligand (biochemistry) , catalysis , stereochemistry , organic chemistry , medicine , biochemistry , alternative medicine , receptor , pathology
The ruthenium(II) complex cis ‐[RuCl 2 (dmso) 4 ] is known for its antiproliferative properties. This has stimulated the discovery of a wide group of new ruthenium complexes considered as potential anticancer drugs. The stability of these ruthenium complexes under physiological conditions and their interaction with protein amino acid residues are particularly important because of their intravenous administration. The studies presented here are devoted to the stability of cis ‐[RuCl 2 (dmso) 4 ] under physiological pH conditions and its reactivity towards L ‐methionine. Immediate dissociation of one dmso ligand from the parent complex after dilution in water leads to the formation of fac ‐[RuCl 2 (H 2 O)(dmso) 3 ], which under basic conditions undergoes stepwise dissociation of chloride ions without further dmso release. The hydrolysis of fac ‐[RuCl 2 (H 2 O)(dmso) 3 ] at pH 7.4 and also base‐catalyzed hydrolysis were investigated in detail by application of kinetic and spectroscopic (UV/Vis, NMR) measurements. The combined experimental and theoretical study revealed that L ‐methionine coordinates to fac ‐[RuCl(OH)(H 2 O)(dmso) 3 ] by substituting a water ligand with simultaneous dmso release. Detailed NMR characterization of the product indicated that methionine coordinates through the NH 2 group rather than the thioether moiety. This conclusion was further supported by theoretical calculations with the application of ETS–NOCV analysis.