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Control of Reversible Activation Dynamics of [Ru{η 6 :κ 1 ‐C 6 H 5 (C 6 H 4 )NH 2 }(XY)] n + and the Effect of Chelating‐Ligand Variation
Author(s) -
MartínezPeña Francisco,
Pizarro Ana M.
Publication year - 2017
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.201701681
Subject(s) - chemistry , ruthenium , protonation , steric effects , reactivity (psychology) , ligand (biochemistry) , stereochemistry , nucleobase , reaction dynamics , phosphine , medicinal chemistry , chelation , crystallography , catalysis , inorganic chemistry , molecule , ion , medicine , biochemistry , alternative medicine , receptor , organic chemistry , pathology , dna
The potential use of organoruthenium complexes as anticancer drugs is well known. Herein, a family of activatable tethered ruthenium(II) arene complexes of general formula [Ru{η 6 :κ 1 ‐C 6 H 5 (C 6 H 4 )NH 2 }(XY)] n + (closed tether ring) bearing different chelating XY ligands (XY=aliphatic diamine, phenylenediamine, oxalato, bis(phosphino)ethane) is reported. The activation of these complexes (closed‐ to open‐tether conversion) occurs in methanol and DMSO at different rates and to different reaction extents at equilibrium. Most importantly, Ru II ‐complex activation (cleavage of the Ru−N tether bond) occurs in aqueous solution at high proton concentration (upon N tether protonation). The activation dynamics can be modulated by rational variation of the XY chelating ligand. The electron‐donating capability and steric hindrance of XY have a direct impact on the reactivity of the Ru−N bond, and XY= N , N′ ‐dimethyl‐, N , N′ ‐diethyl‐, and N , N , N′ , N′ ‐tetramethylethylenediamine afford complexes that are more prone to activation. Such activation in acidic media is fully reversible, and proton concentration also governs the deactivation rate, that is, tether‐ring closure slows down with decreasing pH. Interaction of a closed‐tether complex and its open‐tether counterpart with 5′‐guanosine monophosphate revealed selectivity of the active (open) complex towards interaction with nucleobases. This work presents ruthenium tether complexes as exceptional pH‐dependent switches with potential applications in cancer research.