Thiomaltol-Based Organometallic Complexes with 1-Methylimidazole as Leaving Group: Synthesis, Stability, and Biological Behavior.

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 IrIII complexes 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 by 1 H 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.