Open AccessTridentate 3-Substituted Naphthoquinone Ruthenium Arene Complexes: Synthesis, Characterization, Aqueous Behavior, and Theoretical and Biological Studies
Author(s) -
Heiko Geisler,
Julia Westermayr,
Klaudia Cseh,
Dominik Wenisch,
Valentin Fuchs,
Sophia Harringer,
Sarah Plutzar,
Natalie Gajic,
Michaela Hejl,
Michael A. Jakupec,
Philipp Marquetand,
Wolfgang Kandioller
Publication year - 2021
Publication title -
inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.348
H-Index - 233
eISSN - 1520-510X
pISSN - 0020-1669
DOI - 10.1021/acs.inorgchem.1c01083
Subject(s) - chemistry , ruthenium , aqueous solution , hydrolysis , cytotoxicity , halogen , stereochemistry , combinatorial chemistry , density functional theory , medicinal chemistry , in vitro , organic chemistry , computational chemistry , catalysis , biochemistry , alkyl
A series of nine Ru II arene complexes bearing tridentate naphthoquinone-based N , O , O -ligands was synthesized and characterized. Aqueous stability and their hydrolysis mechanism were investigated via UV/vis photometry, HPLC-MS, and density functional theory calculations. Substituents with a positive inductive effect improved their stability at physiological pH (7.4) intensely, whereas substituents such as halogens accelerated hydrolysis and formation of dimeric pyrazolate and hydroxido bridged dimers. The observed cytotoxic profile is unusual, as complexes exhibited much higher cytotoxicity in SW480 colon cancer cells than in the broadly chemo- (incl. platinum-) sensitive CH1/PA-1 teratocarcinoma cells. This activity pattern as well as reduced or slightly enhanced ROS generation and the lack of DNA interactions indicate a mode of action different from established or previously investigated classes of metallodrugs.