Premium
Synthesis, Characterization and Cytotoxicity of (η 6 ‐ p ‐cymene)ruthenium(II) Complexes of α‐Amino Acids
Author(s) -
Egbewande Folake A.,
Paul Lydia E. H.,
Therrien Bruno,
Furrer Julien
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.201301297
Subject(s) - chemistry , ruthenium , denticity , amino acid , chelation , stereochemistry , electrospray ionization , medicinal chemistry , ligand (biochemistry) , aqueous solution , trifluoromethanesulfonate , cytotoxicity , nuclear magnetic resonance spectroscopy , metal , organic chemistry , catalysis , in vitro , receptor , biochemistry , ion
Arene ruthenium complexes of α‐amino acids, obtained by mixing aqueous solutions of [(η 6 ‐ p ‐cymene)RuCl 2 ] 2 in the presence of AgCF 3 SO 3 with various amino acids, have been studied at 37 °C using NMR spectroscopy and electrospray ionization mass spectrometry (ESI‐MS). Small hydrophobic α‐amino acid anions were found to form bidentate N , O ‐chelate complexes, whereas α‐amino acids with coordinating side chains (e.g. serine, aspartic acid, histidine) acted as tridentate ligands. For many amino acids, more than two chelate complexes were formed. Presumably, complexes with the general formula [(η 6 ‐ p ‐cymene)Ru(AA) 2 ] n + and bridged complexes with the general formula [{(η 6 ‐ p ‐cymene)Ru} 2 (μ‐AA) 2 (μ‐OH)] + were observed together with the expected bi‐ and tridentate chelate complexes. All complexes, isolated as triflate salts, were evaluated for their in vitro anticancer activity against the human ovarian cancer cell line A2780 and its cisplatin‐resistant mutant A2780cisR. All complexes were found to be highly cytotoxic, with IC 50 values ranging from 0.16–19.8 μ M . Interestingly, all complexes were selectivity active against A2780 cells relative to the A2780cisR variants, indicating a distinct mechanism of action that differs from that of many previously reported cytotoxic ruthenium complexes. No direct correlation between the kinetics of complex formation and cytotoxicity was apparent, suggesting that other physicochemical parameters such as complex stability and ligand exchange kinetics may play important roles in the biological activity.