X- and Q-band electron paramagnetic resonance (EPR) spectroscopy was used to characterize polycrystalline Cu(II) complexes that contained sodium 5-sulfonate salicylaldehyde thiosemicarbazones possessing a hydrogen, methyl, ethyl, or phenyl substituent at the terminal nitrogen. The ability of thiosemicarbazone proligands to generate superoxide radical anions and hydroxyl radicals upon their exposure to UVA irradiation in aerated aqueous solutions was evidenced by the EPR spin trapping technique. The UVA irradiation of proligands in neutral or alkaline solutions and dimethylsulfoxide (DMSO) caused a significant decrease in the absorption bands of aldimine and phenolic chromophores. Mixing of proligand solutions with the equimolar amount of copper(II) ions resulted in the formation of 1:1 Cu(II)-to-ligand complex, with the EPR and UV-Vis spectra fully compatible with those obtained for the dissolved Cu(II) thiosemicarbazone complexes. The formation of the complexes fully inhibited the photoinduced generation of reactive oxygen species, and only subtle changes were found in the electronic absorption spectra of the complexes in aqueous and DMSO solutions upon UVA steady-state irradiation. The dark redox activity of copper(II) complexes and proligand/Cu(II) aqueous solutions towards hydrogen peroxide which resulted in the generation of hydroxyl radicals, was confirmed by spin trapping experiments.

A series of four water-soluble salicylaldehyde thiosemicarbazones with a positively charged trimethylammonium moiety ([H₂L^R]Cl, R = H, Me, Et, Ph) and four copper(II) complexes [Cu(HL^R)Cl]Cl (1–4) were synthesised with the aim to study (i) their antiproliferative activity in cancer cells and, (ii) for the first time for thiosemicarbazones, the interaction with membrane transport proteins, specifically organic cation transporters OCT1–3. The compounds were comprehensively characterised by analytical, spectroscopic and X-ray diffraction methods. The highest cytotoxic effect was observed in the neuroblastoma cell line SH-5YSY after 24 h exposure and follows the rank order: 3 > 2 > 4 > cisplatin > 1 >> [H₂L^R]Cl. The copper(II) complexes showed marked interaction with OCT1–3, comparable to that of well-known OCT inhibitors (decynium 22, prazosin and corticosterone) in the cell-based radiotracer uptake assays. The work paves the way for the development of more potent and selective anticancer drugs and/or OCT inhibitors.

În acest articol sunt descrise metode de sinteză și analiza fizico-chimică a 5 compuși coordinativi în baza ionului de Cu(II) și 4-ciclohexil-tiosemicarbazona aldehidei 3-etoxisalicilice. În primul pas a fost efectuată sinteza ligandului prin intermediul a două metode clasice cu perfecționarea ulterioară, obținându-se astfel H2L în calitate de chelator al ionilor de cupru(II). Pentru cercetarea structuri și geometria 4-ciclohexil- tiosemicarbazonei aldehidei 3-etoxisalicilice a fost aplicată spectroscopia 1H, 13C și 15N-RMN, 13C- DEPT- 135 RMN și 15N HSQC-RMN. Substanțele sintetizate au fost analizate prin intermediul metodelor moderne de cercetare precum: spectroscopia FTIR, UV-vis și analizei elementale, difracția razelor X pe monocristal; activitatea biologică este în proces de studiu. Cuvinte-cheie: compuși coordinativi, 4-ciclohexil-tiosemicarbazone, aldehida 3-etoxisalicilică. DOI: https://doi.org/10.59295/sum1(171)2023_26

The process of formation of Cu(II) complexes with cyclohexyl-thiosemicarbazone 2-acetylpyridine in solution was studied. It was established that in the electronic absorption spectrum of the ligand in solution there is one maximum at wavelength 309 nm, and in the absorption spectrum of the complex there are two maxima - at 294 nm and 385 nm. It was also determined that with increasing pH of the solution the intensity of the absorption maximum of the complex decreases, but this decrease is not considerable. By the Ostromromisslensky-Job method and the saturation method it was determined that the composition of the coordinative compound in solution corresponds to the stoichiometric ratio M:L = 1:1. By the Komari method it was determined that the value of the stability constant of the complex is equal to 5.731∙106 L.mol-1. The Gibbs potential variation of the complex formation process in solution is equal to -37,908 kJ∙mol-1.