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.

Insights into the cytotoxic activity of the phosphane copper(I) complex [Cu(thp)4][PF6] / Tisato, Francesco; Marzano, Cristina; Peruzzo, Valentina; Tegoni, Matteo; Giorgetti, Marco; Damjanovic, Marko; Trapananti, Angela; Bagno, Alessandro; Santini, Carlo; Pellei, Maura; Porchia, Marina; Gandin, Valentina. - In: JOURNAL OF INORGANIC BIOCHEMISTRY. - ISSN 0162-0134. - 165:(2016), pp. 80-91. [10.1016/j.jinorgbio.2016.07.007]

Insights into the cytotoxic activity of the phosphane copper(I) complex [Cu(thp)4][PF6]

TEGONI, Matteo;
2016-01-01

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.
Insights into the cytotoxic activity of the phosphane copper(I) complex [Cu(thp)4][PF6] / Tisato, Francesco; Marzano, Cristina; Peruzzo, Valentina; Tegoni, Matteo; Giorgetti, Marco; Damjanovic, Marko; Trapananti, Angela; Bagno, Alessandro; Santini, Carlo; Pellei, Maura; Porchia, Marina; Gandin, Valentina. - In: JOURNAL OF INORGANIC BIOCHEMISTRY. - ISSN 0162-0134. - 165:(2016), pp. 80-91. [10.1016/j.jinorgbio.2016.07.007]
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