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Cationic Ru(η 6 ‐ p ‐cymene) Complexes of 3‐Hydroxy‐4‐pyr(id)ones – Lipophilic Triphenylphosphine as Co‐Ligand Is Key to Highly Stable and Cytotoxic Anticancer Agents
Author(s) -
Parveen Shahida,
Hanif Muhammad,
Movassaghi Sanam,
Sullivan Matthew P.,
Kubanik Mario,
Shaheen Muhammad Ashraf,
Söhnel Tilo,
Jamieson Stephen M. F.,
Hartinger Christian G.
Publication year - 2017
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.201601163
Subject(s) - chemistry , triphenylphosphine , cationic polymerization , ligand (biochemistry) , aqueous solution , stereochemistry , phosphine , ruthenium , medicinal chemistry , chelation , cytotoxicity , bromide , dithiocarbamate , in vitro , organic chemistry , catalysis , biochemistry , receptor
Ru(arene)[3‐hydroxy‐4(1 H )‐pyr(id)one]Cl complexes are known to be converted intodinuclear Ru(arene) compounds with three hydroxido bridges in aqueous solution. In an attempt to obtain anticancer Ru(arene) complexes of 3‐hydroxy‐4(1 H )‐pyr(id)one ligands that are stable in aqueous solution, triphenylphosphine (PPh 3 ) and 1,3,5‐triaza‐7‐phoshatricyclo[3.3.1.1]decane (pta) were introduced as co‐ligands instead of the chlorido ligand. This led to a series of cationic complexes that were characterized by using standard methods and X‐ray diffraction analysis. The pta complexes were found to be highly stable in aqueous solution for up to 120 h. While they were unreactive in the presence of l ‐histidine (His) and l ‐methionine (Met), l ‐cysteine (Cys) induced cleavage of the 3‐hydroxy‐4(1 H )‐pyr(id)one ligands from the Ru center. In vitro cytotoxicity assays against human cancer cell lines revealed that the complexes with the more lipophilic phosphine ligand were cytotoxic in the low‐micromolar concentration range, while the analogous pta compounds did not significantly inhibit cell proliferation.