Acetylplatinum(II) complexes containing PTA-derived ligands : synthesis, quantum-chemical characterization, and in vitro cytotoxicity

Acetylplatinum(II) complexes containing the water-soluble phosphine ligands based on PTA (1,3,5-triaza-7-phosphaadamantane) were synthesized and structurally characterized: cis-[Pt(COMe)₂(PTA)₂] (3) and trans-[Pt(COMe)Cl(PTA)₂] (4). The trans-[Pt(COMe)₂(PTA)₂] (3a) was obtained from the methanol solution of 3 and structurally characterized. The compounds were investigated by elemental analysis, IR, multinuclear NMR spectroscopy, and mass spectrometry. X-ray crystallography confirmed the square-planar geometry of complexes 3 and 3a, and their supramolecular architectures were examined using Hirshfeld surface analysis. DFT calculations at the B3LYP/LanL2DZ level provided good agreement with experimental bond lengths and angles. NMR spectra were further supported by GIAO-calculated chemical shifts. Intermolecular and intramolecular interactions were elucidated through QTAIM analysis, revealing partial covalent character of metal-ligand bonds and weak non-covalent stabilizing interactions. Complexes 3 and 4 were tested for their in vitro cytotoxicity against five human cancer cell lines (8505C thyroid cancer, A253 head and neck tumor, A549 lung carcinoma, A2780 ovarian cancer, and DLD-1 colon carcinoma). Complex 3 showed selective activity against lung A549 and ovarian A2780 cell lines, comparable to cisplatin, whereas complex 4 exhibited broader but less selective cytotoxicity. These results suggest that the PTA-based acetylplatinum(II) complexes represent promising candidates for further development of water-soluble antitumor agents.