Impact of the central atom and halido ligand on the structure, antiproliferative activity and selectivity of half-sandwich Ru(ii) and Ir(iii) complexes with a 1,3,4-thiadiazole-based ligand

Impact of the central atom and halido ligand on the structure, antiproliferative activity and selectivity of half-sandwich Ru(ii) and Ir(iii) complexes with a 1,3,4-thiadiazole-based ligand

WoS Article

Half-sandwich complexes [Ru(?(6)-pcym)(L1)X]PF6 (1, 3) and [Ir(?(5)-Cp*)(L1)X]PF6 (2, 4) featuring a thiadiazole-based ligand L1 (2-(furan-2-yl)-5-(pyridin-2-yl)-1,3,4-thiadiazole) were synthesized and characterized by varied analytical methods, including single-crystal X-ray diffraction (X = Cl or I, pcym = p-cymene, Cp* = pentamethylcyclopentadienyl). The structures of the molecules were analysed and interpreted using computational methods such as Density Functional Theory (DFT) and Quantum Theory of Atoms in Molecules (QT-AIM). A H-1 NMR spectroscopy study showed that complexes 1-3 exhibited hydrolytic stability while 4 underwent partial iodido/chlorido ligand exchange in phosphate-buffered saline. Moreover, 1-4 demonstrated the ability to oxidize NADH (reduced nicotinamide adenine dinucleotide) to NAD(+) with Ir(iii) complexes 2 and 4 displaying higher catalytic activity compared to their Ru(ii) analogues. None of the complexes interacted with reduced glutathione (GSH). Additionally, 1-4 exhibited greater lipophilicity than cisplatin. In vitro biological analyses were performed in healthy cell lines (CCD-18Co colon and CCD-1072Sk foreskin fibroblasts) as well as in cisplatin-sensitive (A2780) and -resistant (A2780cis) ovarian cancer cell lines. The results indicated that Ir(iii) complexes 2 and 4 had no effect on human fibroblasts, demonstrating their selectivity. In contrast, complexes 1 and 4 exhibited moderate inhibitory effects on the metabolic and proliferation activities of the cancer cells tested (selectivity index SI > 3.4 for 4 and 2.6 for cisplatin; SI = IC50(A2780)/IC50(CCD-18Co)), including the cisplatin-resistant cancer cell line. Based on these findings, it is possible to emphasize that mainly complex 4 could represent a further step in the development of selective and highly effective anticancer agents, particularly against resistant tumour types.

Half-sandwich complexes [Ru(?(6)-pcym)(L1)X]PF6 (1, 3) and [Ir(?(5)-Cp*)(L1)X]PF6 (2, 4) featuring a thiadiazole-based ligand L1 (2-(furan-2-yl)-5-(pyridin-2-yl)-1,3,4-thiadiazole) were synthesized and characterized by varied analytical methods, including single-crystal X-ray diffraction (X = Cl or I, pcym = p-cymene, Cp* = pentamethylcyclopentadienyl). The structures of the molecules were analysed and interpreted using computational methods such as Density Functional Theory (DFT) and Quantum Theory of Atoms in Molecules (QT-AIM). A H-1 NMR spectroscopy study showed that complexes 1-3 exhibited hydrolytic stability while 4 underwent partial iodido/chlorido ligand exchange in phosphate-buffered saline. Moreover, 1-4 demonstrated the ability to oxidize NADH (reduced nicotinamide adenine dinucleotide) to NAD(+) with Ir(iii) complexes 2 and 4 displaying higher catalytic activity compared to their Ru(ii) analogues. None of the complexes interacted with reduced glutathione (GSH). Additionally, 1-4 exhibited greater lipophilicity than cisplatin. In vitro biological analyses were performed in healthy cell lines (CCD-18Co colon and CCD-1072Sk foreskin fibroblasts) as well as in cisplatin-sensitive (A2780) and -resistant (A2780cis) ovarian cancer cell lines. The results indicated that Ir(iii) complexes 2 and 4 had no effect on human fibroblasts, demonstrating their selectivity. In contrast, complexes 1 and 4 exhibited moderate inhibitory effects on the metabolic and proliferation activities of the cancer cells tested (selectivity index SI > 3.4 for 4 and 2.6 for cisplatin; SI = IC50(A2780)/IC50(CCD-18Co)), including the cisplatin-resistant cancer cell line. Based on these findings, it is possible to emphasize that mainly complex 4 could represent a further step in the development of selective and highly effective anticancer agents, particularly against resistant tumour types.

PHOTODYNAMIC THERAPY; ANTICANCER ACTIVITY; CANCER-CELLS; BASIS-SETS; RUTHENIUM; HYPERICIN; GLUTATHIONE; DESIGN; PSEUDOPOTENTIALS; CYTOTOXICITY

PHOTODYNAMIC THERAPY; ANTICANCER ACTIVITY; CANCER-CELLS; BASIS-SETS; RUTHENIUM; HYPERICIN; GLUTATHIONE; DESIGN; PSEUDOPOTENTIALS; CYTOTOXICITY

KRIKAVOVA, R.; ROMANOVOVA, M.; JENDZELOVSKA, Z.; MAJERNIK,M.; MASARYK, L.; ZOUFALÝ, P.; MILDE, M.; MONCOL, J.; HERCHEL, R.; JENDZELOVSKY, R.; NEMEC, I.

2024

19.09.2023

Royal Society of Chemistry

CAMBRIDGE

1477-9234

DALTON TRANSACTIONS

52

36

United Kingdom of Great Britain and Northern Ireland

12717

12732

16

https://pubs.rsc.org/en/content/articlelanding/2023/dt/d3dt01696j

http://hdl.handle.net/11012/245058

d3dt01696j