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Osmium(II) and Ruthenium(II) Arene Maltolato Complexes: Rapid Hydrolysis and Nucleobase Binding
Author(s) -
Peacock Anna F. A.,
Melchart Michael,
Deeth Robert J.,
Habtemariam Abraha,
Parsons Simon,
Sadler Peter J.
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200601152
Subject(s) - chemistry , aquation , adduct , osmium , chelation , ruthenium , ligand (biochemistry) , medicinal chemistry , dimer , stereochemistry , nuclear magnetic resonance spectroscopy , nucleobase , inorganic chemistry , kinetics , dna , reaction rate constant , catalysis , organic chemistry , receptor , quantum mechanics , biochemistry , physics
Density functional calculations show that aquation of [Os(η 6 ‐arene)(XY)Cl] n + complexes is more facile for complexes in which XY=an anionic O,O‐chelated ligand compared to a neutral N,N‐chelated ligand, and the mechanism more dissociative in character. The O,O‐chelated XY=maltolato (mal) [M(η 6 ‐ p ‐cym)(mal)Cl] complexes, in which p ‐cym= p ‐cymene, M=Os II ( 1 ) and Ru II ( 2 ), were synthesised and the X‐ray crystal structures of 1 and 2⋅ 2 H 2 O determined. Their hydrolysis rates were rapid (too fast to follow by NMR spectroscopy). The aqua adduct of the Os II complex 1 was 1.6 p K a units more acidic than that of the Ru II complex 2 . Dynamic NMR studies suggested that O,O‐chelate ring opening occurs on a millisecond timescale in coordinating proton‐donor solvents, and loss of chelated mal in aqueous solution led to the formation of the hydroxo‐bridged dimers [(η 6 ‐ p ‐cym)M(μ‐OH) 3 M(η 6 ‐ p ‐cym)] + . The proportion of this dimer in solutions of the Os II complex 1 increased with dilution and it predominated at micromolar concentrations, even in the presence of 0.1 M NaCl (conditions close to those used for cytotoxicity testing). Although 9‐ethylguanine (9‐EtG) binds rapidly to Os II in 1 and more strongly (log K =4.4) than to Ru II in 2 (log K =3.9), the Os II adduct [Os(η 6 ‐ p ‐cym)(mal)(9EtG)] + was unstable with respect to formation of the hydroxo‐bridged dimer at micromolar concentrations. Such insights into the aqueous solution chemistry of metal–arene complexes under biologically relevant conditions will aid the rational design of organometallic anticancer agents.