Unveiling the promising in vitro anticancer activity of lipophilic platinum(ii) complexes containing (1S,4R,5R)-4-(4-phenyl-1H-1,2,3-triazol-1-yl)-2-((S)-1-phenylethyl)-2-azabicyclo[3.2.1]octane: a spectroscopic characterization and DFT calculation†

Abstract

The main goal of our research was to examine (1S,4R,5R)-4-(4-phenyl-1H-1,2,3-triazol-1-yl)-2-((S)-1-phenylethyl)-2-azabicyclo[3.2.1]octane (L) and its complex-forming abilities with platinum(II) ions. Herein, we present three new square planar platinum(II) complexes of the general formulas trans-[PtCl₂L₂] (1), cis-[PtCl₂(DMSO)(L)] (2) and [Pt(DMSO)(L)(mal)] (3), where DMSO: dimethyl sulfoxide; mal: malonate. Based on the experimental spectroscopic results (¹H, ¹³C, ¹⁵N, ¹⁹⁵Pt NMR, IR, X-ray analyses) and density functional theoretical calculation (DFT), a square planar geometry was proposed with one or two monodentate bound N3′ heterocyclic ligands (L). Surrounding the central atom, there are monodentate chloride (1) and (2) or chelated O,O-donor malonate ligands (3). The coordination spheres in (2) and (3) were completed by the S-donor monodentate dimethyl sulfoxide molecule. Theoretical investigations into the heterocyclic ligand coordination site and geometry around the central ion were performed by DFT calculation, and the results were consistent with the experimental data. The DFT calculations elucidate the thermodynamic preferences for cis versus trans arrangements of the ligands in the isolated platinum(II) complexes (1) and (2), suggesting that the trans arrangement of chloride anions observed in the crystals of (2a) probably results from the crystal packing. The obtained platinum(II) complexes were examined with regard to their therapeutic anticancer potential. In comparison to cisplatin, lipophilic complexes (1) and (3) exhibit lower affinity toward glutathione. According to observations, (1) presents the most satisfactory in vitro activity with the mechanism of its cytotoxic effect on cancer cells different from that of cisplatin.