As eries of 16 dinuclear thiopyridone-basedo rganometallics with excellent water solubility,i ncreased stability and remarkablec ytotoxicity were synthesized and characterized. Thecomplexes of this work formed dimericspecies featuring ad ouble positive charge in polar protic solvents, accounting for their outstanding solubility in aqueous solution. Most of them displayedh igher antiproliferativea ctivity than their parental thiomaltol complex, with unexpected cytotoxicity trends depending on the employed metal center, ligand modification, and cell line. Insights into their behavior in biological systemsw ere gatheredb ym eans of amino-acid interactions tudies,c ytotoxicity tests in 3D spheroid models, laser ablation,c ellular accumulationm easurements, as well as cell cycle experiments. Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.org/10.Scheme1.Overview of synthesized thiopyridone-based piano-stool complexes. (i)methylamine, water and reflux overnight (1a), or aniline, benzylamine, or 1-naphthylamine,0.38 m HCl and microwave irradiation (t = 30 min, T = 165 8C) (1b-d); (ii)Lawesson's reagent, abs. toluene, Schlenk technique, reflux 4-16 h; (iii)[(p-cym)/(Cp*)MCl 2 ] 2 ,N aOMe, MeOHa bs.,4 08C, 1-3.5h. images of HCT-116 tumor spheroid sections incubated with organometallic ruthenium (3a,c), rhodium (5a,c), or iridium (6a,c)c omplexes at the respectiveIC 50 concentrationf or 96 h; scaleb ar 100 mm.
