👤 Alexander Pöthig

The first comprehensive study of a series of seven mesoionic tetrazolylidene gold(I) chloride complexes (1-7) featuring a range of alkyl and aryl substituents (Me, t-Bu, iPr, Ph, Tol, Dipp, Mes) is reported. Three synthetic pathways enabling access to scarcely explored abnormal 1,3-disubstituted tetrazolium ligand precursors (L₁-L₇) have been established. All complexes are characterized by NMR spectroscopy, mass spectrometry, and elemental analysis, confirming their composition and purity. Single-crystal X-ray crystallography of six gold(I) complexes (1-6) reveals nearly linear coordination (176.49(11)-179.0(2)°) at the gold(I) center and a distinct geometric arrangement across the series. NMR stability studies with model nucleophiles L-cysteine (Cys) and glutathione (GSH) support the structural findings, demonstrating rapid and complete reaction of complexes 1-7 with thiols, as confirmed by ¹H NMR and ESI-MS. The antiproliferative activity of the obtained complexes (1-7) and selected precursors (L₂, L₃, L₅, L₇) has been evaluated using MTT assays against human A2780 (ovarian) and A549 (lung) cancer cell lines, alongside noncancerous VERO E6 kidney cells for comparison. Most of the complexes display high selectivity indices (SI^A2780 = 63.2-86.7) and potent antiproliferative effects in the low submicromolar range against A2780, outperforming cisplatin and matching the activity of auranofin. Overall, the results presented here demonstrate the potential of gold(I) tetrazolylidene-based complexes for medicinal applications. Show less

Two new 'hybrid' metallodrugs of Au(III) (AuTAML) and Cu(II) (CuTAML) were designed featuring a tamoxifen-derived pharmacophore to ideally synergize the anticancer activity of both the metal center and the organic ligand. The compounds have antiproliferative effects against human MCF-7 and MDA-MB 231 breast cancer cells. Molecular dynamics studies suggest that the compounds retain the binding activity to estrogen receptor (ERα). In vitro and in silico studies showed that the Au(III) derivative is an inhibitor of the seleno-enzyme thioredoxin reductase, while the Cu(II) complex may act as an oxidant of different intracellular thiols. In breast cancer cells treated with the compounds, a redox imbalance characterized by a decrease in total thiols and increased reactive oxygen species production was detected. Despite their different reactivities and cytotoxic potencies, a great capacity of the metal complexes to induce mitochondrial damage was observed as shown by their effects on mitochondrial respiration, membrane potential, and morphology. Show less