期刊
INORGANIC CHEMISTRY
卷 60, 期 15, 页码 11297-11319出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.inorgchem.1c01275
关键词
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资金
- Austrian Science Fund [I4729]
- Russian Foundation for Basic Research [20-53-14002]
- Lendulet program of the Hungarian Academy of Sciences [LP2019-6/2019]
- National Research, Development and Innovation Office-NKFIA [FK 124240, GINOP-2.3.2-15-2016-00038]
- Ministry of Human Capacities, Hungary [TKP-2020]
- Scholarship Foundation of the Republic of Austria [ICM-2019-14969]
- Slovak Research and Development Agency [APVV-15-0053, APVV-19-0024, DS-FR-19-0035]
- Slovak Scientific Grant Agency VEGA [1/0504/20]
- COST Action [CA18202]
- NECTAR-Network for Equilibria and Chemical Thermodynamics Advanced Research
- Austrian Science Fund (FWF) [I4729] Funding Source: Austrian Science Fund (FWF)
Three new thiosemicarbazones with redox-active phenolic moiety were synthesized and formed copper(II) complexes with good stability and redox activity in various conditions. Electrochemical studies confirmed metal-centered reduction and ligand-centered oxidation processes, showing potential as antiproliferative agents against cancer cells.
Three new thiosemicarbazones (TSCs) HL1-HL3 as triapine analogues bearing a redox-active phenolic moiety at the terminal nitrogen atom were prepared. Reactions of HL1-HL3 with CuCl2 center dot 2H(2)O in anoxic methanol afforded three copper(II) complexes, namely, Cu(HL1)Cl-2 (1), [Cu(L-2)Cl] (2'), and Cu(HL3)Cl-2 (3), in good yields. Solution speciation studies revealed that the metal-free ligands are stable as HL1-HL3 at pH 7.4, while being air-sensitive in the basic pH range. In dimethyl sulfoxide they exist as a mixture of E and Z isomers. A mechanism of the E/Z isomerization with an inversion at the nitrogen atom of the Schiff base imine bond is proposed. The monocationic complexes [Cu(L1-3)](+) are the most abundant species in aqueous solutions at pH 7.4. Electrochemical and spectroelectrochemical studies of 1, 2', and 3 confirmed their redox activity in both the cathodic and the anodic region of potentials. The one-electron reduction was identified as metal-centered by electron paramagnetic resonance spectroelectrochemistry. An electrochemical oxidation pointed out the ligand-centered oxidation, while chemical oxidations of HL1 and HL2 as well as 1 and 2' afforded several two-electron and four-electron oxidation products, which were isolated and comprehensively characterized. Complexes 1 and 2' showed an antiproliferative activity in Colo205 and Colo320 cancer cell lines with half-maximal inhibitory concentration values in the low micromolar concentration range, while 3 with the most closely related ligand to triapine displayed the best selectivity for cancer cells versus normal fibroblast cells (MRC-5). HL1 and 1 in the presence of 1,4-dithiothreitol are as potent inhibitors of mR2 ribonucleotide reductase as triapine.
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