title: Insights into the cytotoxic activity of the phosphane copper(I) complex [Cu(thp)4][PF6].
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.
authors.affiliation: CNR-ICMATE, Corso Stati Uniti 4, 35127 Padova, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tisato
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, 35131 Padova, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Marzano
authors.affiliation: CNR-ICMATE, Corso Stati Uniti 4, 35127 Padova, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Peruzzo
authors.affiliation: Department of Chemistry, University of Parma, Parco Area delle Scienze 17A, 43124 Parma, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Tegoni
authors.affiliation: Department of Industrial Chemistry, University of Bologna, Viale del Risorgimento 4, 40136 Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Giorgetti
authors.affiliation: Department of Industrial Chemistry, University of Bologna, Viale del Risorgimento 4, 40136 Bologna, Italy.
authors.forename: Marko
authors.initials: M
authors.lastname: Damjanovic
authors.affiliation: CNR-IOM-OGG c/o ESRF, Rue Jules Horowitz 6, 38043 Grenoble, France.
authors.forename: Angela
authors.initials: A
authors.lastname: Trapananti
authors.affiliation: Department of Chemistry, University of Padova, via Marzolo 1, 35131 Padova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bagno
authors.affiliation: School of Science and Technology - Chemistry Division, University of Camerino, via S. Agostino 1, 62032 Camerino (MC), Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Santini
authors.affiliation: School of Science and Technology - Chemistry Division, University of Camerino, via S. Agostino 1, 62032 Camerino (MC), Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Pellei
authors.affiliation: CNR-ICMATE, Corso Stati Uniti 4, 35127 Padova, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Porchia
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via Marzolo 5, 35131 Padova, Italy. Electronic address: valentina.gandin@unipd.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandin
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017553:Phosphorus Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D003603:Cytotoxins; D017553:Phosphorus Compounds; D003300:Copper
keywords: Antitumour activity; Complex lability; Phosphane copper(I) complexes