Interaction of biomacromolecules with ionic liquids

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Therapeutic potential of vanadium complexes with 1,10-phenanthroline ligands, quo vadis? Fate of complexes in cell media and cancer cells

Publication . Nunes, Patrique; Correia, Isabel; Cavaco, Isabel; Marques, Fernanda; Pinheiro, Teresa; Avecilla, Fernando; Pessoa, Joao Costa

(VO)-O-IV-complexes formulated as [(VO)-O-IV(OSO3)(phen)(2)] (1) (phen = 1,10-phenanthroline), [(VO)-O-IV(OSO3) (Me(2)phen)(2)] (2) (Me(2)phen = 4,7-dimethyl-1,10-phenanthroline) and [(VO)-O-IV(OSO3)(amphen)(2)] (3) (amphen = 5-amino-1,10-phenanthroline) were prepared and stability in cell incubation media evaluated. Their cytotoxicity was determined against the A2780 (ovarian), MCF7 (breast) and PC3 (prostate) human cancer cells at different incubation times. While at 3 and 24 h the cytotoxicity differs for complexes and corresponding free ligands, at 72 h incubation all compounds are equally active presenting low IC50 values. Upon incubation of A2780 cells with 1-3, cellular distribution of vanadium in cytosol, membranes, nucleus and cytoskeleton, indicate that the uptake of V is low, particularly for 1, and that the uptake pattern depends on the ligand. Nuclear microscopic techniques are used for imaging and elemental quantification in whole PC3 cells incubated with 1. Once complexes are added to cell culture media, they decompose, and with time most V-IV oxidizes to V-V-species. Modeling of speciation when [(VO)-O-IV(OSO3)(phen)(2)] (1) is added to cell media is presented. At lower concentrations of 1, (VO)-O-IV- and phen-containing species are mainly bound to bovine serum albumin, while at higher concentrations [(VO)-O-IV (phen)n](2+)-complexes become relevant, being predicted that the species taken up and mechanisms of action operating depend on the total concentration of complex. This study emphasizes that for these (VO)-O-IV-systems, and probably for many others involving oxidovanadium or other labile metal complexes, it is not possible to identify active species or propose mechanisms of cytotoxic action without evaluating speciation occurring in cell media.

2021-04Journal article

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Copper Complexes with 1,10-Phenanthroline Derivatives: Underlying Factors Affecting Their Cytotoxicity

Publication . Nunes, Patrique; Correia, Isabel; Marques, Fernanda; Matos, Antonio Pedro; dos Santos, Margarida M. C.; Azevedo, Cristina G.; Capelo, Jose-Luis; Santos, Hugo M.; Gama, Sofia; Pinheiro, Teresa; Cavaco, Isabel; Pessoa, Joao Costa

The interpretation of in vitro cytotoxicity data of Cu(II)-1,10-phenanthroline (phen) complexes normally does not take into account the speciation that complexes undergo in cell incubation media and its implications in cellular uptake and mechanisms of action. We synthesize and test the activity of several distinct Cu(II)-phen compounds; up to 24 h of incubation, the cytotoxic activity differs for the Cu complexes and the corresponding free ligands, but for longer incubation times (e.g., 72 h), all compounds display similar activity. Combining the use of several spectroscopic, spectrometric, and electrochemical techniques, the speciation of Cu-phen compounds in cell incubation media is evaluated, indicating that the originally added complex almost totally decomposed and that Cu(II) and phen are mainly bound to bovine serum albumin. Several methods are used to disclose relationships between structure, activity, speciation in incubation media, cellular uptake, distribution of Cu in cells, and cytotoxicity. Contrary to what is reported in most studies, we conclude that interaction with cell components and cell death involves the separate action of Cu ions and phen molecules, not [Cu(phen)(n)] species. This conclusion should similarly apply to many other Cu-ligand systems reported to date.

2020-07Journal article

Open Access