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

• Acetylplatinum(II) complexes containing PTA were synthesized and characterized. • Cis – trans isomerization of [Pt(COMe)₂(PTA)₂] was confirmed by X-ray. • DFT and QTAIM analysis revealed partial covalent Pt–ligand bonding character. • GIAO NMR analysis supported experimental spectral assignments. • cis -[Pt(COMe)₂(PTA)₂] showed selective cytotoxicity toward A549 and A2780 cells. 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.