The platinum(II) complexes of general formula [PtCl₂(dstp)(S-donor)] were dstp 5,7-dimethyl-1,2,4-triazolo[1,5-a]-pyrimidine (dmtp), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp), 5-methyl-7-isobutyl-1,2,4-triazolo[1,5-a]pyrimidine (ibmtp) or 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp), whereas S-tetrahydrothio-phene-1-oxide (TMSO) or diphenyl sulfoxide (DPSO) were synthesized in a one-pot reaction. Here, we present experimental data (¹H, ¹³C, ¹⁵N, ¹⁹⁵Pt NMR, IR, X-ray) combined with density functional theory (DFT) computations to support and characterize structure–spectra relationships and determine the geometry of dichloride platinum(II) complexes with selected triazolopyrimidines and sulfoxides. Based on the experimental and theoretical data, factors affecting the stability of platinum(II) complexes have been determined.

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. We studied those complexes as potential anticancer prodrugs.

Four new azole-platinum(II) complexes with the general formulas cis-[PtCl₂(L1)₂] (1), cis-[PtCl₂(L2)₂] (2), trans-[PtCl₂(L1)(DMSO)] (3), and trans-[PtCl₂(L2)(DMSO)] (4), where L1 is 1-(benzofuran-2-yl)-2-(1H-1,2,4-triazol-1-yl)ethenone, L2 is (benzofuran-2-yl)-2-(1H-imidazol-1-yl)ethenone, and DMSO is dimethyl sulfoxide, were synthesized and fully characterized. The compositions of the coordination spheres were established using spectroscopic methods (¹H, ¹³C, ¹⁵N, ¹⁹⁵Pt NMR; IR; X-ray). Complexes (1) and (2) adopted cis geometries, featuring two triazole ligands L1 in (1) or two imidazole ligands L2 in (2), each coordinated through the nitrogen donor atom N4″, along with two chloride ions. In contrast, complexes (3) and (4) exhibited trans configurations and contained one azole ligand (L1 or L2), each coordinated via a nitrogen donor N4″ atom, an S-donor DMSO molecule, and two chloride ions. All complexes displayed moderate lipophilicity (logP = 0.92-1.12) and markedly reduced reactivity toward glutathione compared with cisplatin, reflecting the steric shielding provided by the azole ligands. Despite these favorable physicochemical features, only complex (1) demonstrated notable intrinsic in vitro cytotoxicity. It showed activity against a lung cancer cell line (A549) and four bladder cancer cell lines (T24, HT1376, 5637, and HB-CLS-1), with IC₅₀ values ranging from 5.00 to 8.50 µM. Comparable toxicity was observed toward normal SV-HUC-1 urothelial cells (IC₅₀ = 8.54 µM). Notably, complex (1) induced only minor alterations in the cell-cycle profile, suggesting a mechanism of action distinct from those of classical DNA-targeting platinum drugs. To improve its therapeutic performance, complex (1) was encapsulated in polymeric micelles formed by PEO-PPO-PEO triblock copolymers. This nanoformulation resulted in a striking increase in anticancer activity, yielding submicromolar IC₅₀ values (0.13-0.94 µM). The corresponding toxicity toward normal SV-HUC-1 cells ranged from IC₅₀ = 0.17 to 0.75 µM. The substantial increase in potency suggests that micellar delivery enhances intracellular accumulation while protecting the complex from premature deactivation. These results suggest that triazole-based platinum(II) complexes, particularly when combined with polymeric nanocarriers, may represent a promising system for further investigation in the development of platinum-based chemotherapeutic drugs.