Ruthenium-Thymine Acetate binding modes

Nucleobases coordinated to Ruthenium centres have shown several promising properties for cancer treatments, demonstrating to have efficiency comparable to that of cis-Pt compounds, limiting toxic effects to intact cells and overcoming the drugs resistance after longer treatments. Thymine acetate (THAc) is proposed as a biomimetic model ligand to design potential Ruthenium-based antitumor drugs. Herein we report the reaction between Ru(H)2(CO)(PPh3)3, 1 and THAcH. The X-ray structure of the mono-,dihapto-thymine acetate species [(k1-O)(k2-O,O)Ru(THAc)2(CO)(PPh3)2] 2, unexpectedly exhibits cis-location for acetate ligands, likely ascribed to the prevalence of H-bonds and -stacking interactions. Conversely, DFT-calculations and NMR spectra suggest lower energy for the trans form where there are no contacts between the bulky phosphines. The DFT-calculated energies suggest the nature for NMR-intercepted plausible k1- or k2-intermediates. The carboxy-metal coordination is able to stabilize enol-tautomers through supramolecular H-interactions. The rotations of k1- and k2-acetate side arm of the THAc have also been exploited by correlating NMR signal patterns with the DFT energies. Figure 1: Torsional barrier of k1-(O) 3 and k2-(O,O) 4