The phosphane Cu(I) complex [Cu(thp)4][PF6], 1 (thp=tris(hydroxymethyl)phosphane) shows notable in vitro antitumour activity against a wide range of solid tumours. Uptake experiments performed in 1-treated colon cancer cells by atomic absorption spectrometry, reveal that the antiproliferative activity is consistent with the intracellular copper content. The solution chemistry of this agent, investigated by means of X-ray Absorption Spectroscopy and spectrophotometric titrations in aqueous media, indicates that 1 is labile giving coordinative unsaturated [Cu(thp)n]+ species (n =3 and 2) at micromolar concentrations. [Cu(thp)n]+ are reactive species that yield the mixed-ligand complex [Cu(thp)2(BCS)]- (BCS: bathocuproinedisulphonate(2-)) upon interaction with N,N-diimine. Analogously, [Cu(thp)n]+ interact with the methionine-rich peptide sequence (Ac-MMMMPMTFK-NH2; Pep1), relevant in the recruiting of physiological copper, giving [Cu(thp)(Pep1)]+ and [Cu(Pep1)]+ species. The formation of these adducts was assessed by electrospray mass spectrometry in the positive ion mode and validated by density functional theory investigations. The possibility to trans-chelate Cu(I) from pure inorganic [Cu(thp)n]+ assemblies into more physiological adducts represents a pathway that complex 1 might follow during the internalization process into cancer cells.
Tisato, F., Marzano, C., Peruzzo, V., Tegoni, M., Giorgetti, M., Damjanovic, M., et al. (2016). Insights into the cytotoxic activity of the phosphane copper(I) complex [Cu(thp)4][PF6]. JOURNAL OF INORGANIC BIOCHEMISTRY, 165, 80-91 [10.1016/j.jinorgbio.2016.07.007].
Insights into the cytotoxic activity of the phosphane copper(I) complex [Cu(thp)4][PF6]
GIORGETTI, MARCO;DAMJANOVIC, MARKO;
2016
Abstract
The phosphane Cu(I) complex [Cu(thp)4][PF6], 1 (thp=tris(hydroxymethyl)phosphane) shows notable in vitro antitumour activity against a wide range of solid tumours. Uptake experiments performed in 1-treated colon cancer cells by atomic absorption spectrometry, reveal that the antiproliferative activity is consistent with the intracellular copper content. The solution chemistry of this agent, investigated by means of X-ray Absorption Spectroscopy and spectrophotometric titrations in aqueous media, indicates that 1 is labile giving coordinative unsaturated [Cu(thp)n]+ species (n =3 and 2) at micromolar concentrations. [Cu(thp)n]+ are reactive species that yield the mixed-ligand complex [Cu(thp)2(BCS)]- (BCS: bathocuproinedisulphonate(2-)) upon interaction with N,N-diimine. Analogously, [Cu(thp)n]+ interact with the methionine-rich peptide sequence (Ac-MMMMPMTFK-NH2; Pep1), relevant in the recruiting of physiological copper, giving [Cu(thp)(Pep1)]+ and [Cu(Pep1)]+ species. The formation of these adducts was assessed by electrospray mass spectrometry in the positive ion mode and validated by density functional theory investigations. The possibility to trans-chelate Cu(I) from pure inorganic [Cu(thp)n]+ assemblies into more physiological adducts represents a pathway that complex 1 might follow during the internalization process into cancer cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
