title: Thiomaltol-Based Organometallic Complexes with 1-Methylimidazole as Leaving Group: Synthesis, Stability, and Biological Behavior.
abstract: Thiomaltol, a potential S,O-coordinating molecule, has been utilized for the complexation of four different organometallic fragments, yielding the desired RuII, OsII, RhIII, and IrIIIcomplexes having a "piano-stool" configuration. In addition to the synthesis of these compounds with a chlorido leaving group, the analogous 1-methylimidazole derivatives have been prepared, giving rise to thiomaltol-based organometallics with enhanced stability under physiological conditions. The organometallic compounds have been characterized by NMR spectroscopy, elemental analysis, and X-ray diffraction analysis. Their behavior in aqueous solution and their interactions with certain amino acids have been studied by ESI mass spectrometry. Their pH-dependent stability has been investigated by1H NMR in aqueous solution, and their cytotoxicity against three different cancer cell lines has been investigated. Furthermore, their capacity as topoisomerase IIα inhibitors as well as their effect on the cell cycle distribution and reactive oxygen species (ROS) generation have been elucidated.
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Hackl
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Legina
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria.
authors.forename: Verena
authors.initials: V
authors.lastname: Pichler
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schmidlehner
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Roller
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary.|MTA-SZTE Bioinorganic Chemistry Research Group, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Dömötör
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, 6720, Szeged, Hungary.
authors.forename: Eva A
authors.initials: EA
authors.lastname: Enyedy
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria.|Research Platform "Translational Cancer Therapy Research", University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jakupec
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria.|Research Platform "Translational Cancer Therapy Research", University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria.
authors.forename: Wolfgang
authors.identifier: http://orcid.org/0000-0002-5630-712X
authors.initials: W
authors.lastname: Kandioller
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria.|Research Platform "Translational Cancer Therapy Research", University of Vienna, Waehringer Str. 42, 1090, Vienna, Austria.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
mesh_terms: D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009942:Organometallic Compounds / Q000737:chemistry*; D011714:Pyrans / Q000737:chemistry*; D013871:Thiones / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: C583493:3-hydroxy-2-methyl-4H-pyran-4-thione; D007093:Imidazoles; D009942:Organometallic Compounds; D011714:Pyrans; D013871:Thiones; C018100:1-methylimidazole
keywords: antitumor agents; leaving group variation; medicinal chemistry; organometallics; thiomaltol