title: Neutral and charged phosphine/scorpionate copper(I) complexes: effects of ligand assembly on their antiproliferative activity.
abstract: Ligand-exchange reactions of copper(I) precursors ([Cu(CH(3)CN)(4)]BF(4), CuCl) with a panel of bis(azolyl)borates or poly(pyrazolyl)methanes and a tertiary monodentate phosphine (PTA = 1,3,5-triaza-7-phosphaadamantane, PCN = tris(cyanoethyl)phosphine) produced two series of heteroleptic, either '2 + 1 + 1'- or '3 + 1'-type complexes, which have been characterized by elemental analysis, FT-IR, ESI-MS and multinuclear (31)P and (1)H NMR. '2 + 1 + 1'-type complexes include a N,N-bidentate chelate and two monodentate phosphines (1-8) and '3 + 1'-type complexes comprise a N,N,O- or N,N,N-tridentate chelate and one monodentate phosphine (9-12). All these complexes adopt a four-coordinate, tetrahedral geometry. '3 + 1' complexes show better red-ox stability and a greater tendency to retain the native '3 + 1' mixed-ligand structure. Conversely, '2 + 1 + 1' complexes exhibit increased propensity to dissociation as shown by ESI-MS measurements and X-ray structure determination at low temperature (150 K) of the polymeric complex {[H(2)B(tz(NO2))(2)]Cu[PCN]}(n)6b. In this complex, either the bis(triazolyl)borate and the PCN ligands act as bidentate, with PCN being also the μ(2)-bridiging linker between adjacent monomers. Compound 6b is the first reported example of a polymeric PCN compound with a tetra-coordinate metal centre. Cytotoxic activity of all compounds has been evaluated by MTT test against a panel of several human tumor cell lines including examples of breast (MCF-7), colon (HCT-15 and LoVo), lung (A549), cervix (A431) and ovarian (2008 and its cisplatin resistant variant, C13*) carcinoma, melanoma (A375) and promyelocytic leukemia (HL60). Copper complexes generally show in vitro antitumour activity comparable to that of cisplatin. In particular, neutral '3 + 1'-type complexes 9 and 10, show IC(50) values appreciably lower than those exhibited by the reference metallodrug.
authors.affiliation: I.C.I.S.-C.N.R., Corso Stati Uniti 4, 35127 Padova, Italy. porchia@icis.cnr.it
authors.forename: Marina
authors.initials: M
authors.lastname: Porchia
authors.forename: Alessandro
authors.initials: A
authors.lastname: Dolmella
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandin
authors.forename: Cristina
authors.initials: C
authors.lastname: Marzano
authors.forename: Maura
authors.initials: M
authors.lastname: Pellei
authors.forename: Valentina
authors.initials: V
authors.lastname: Peruzzo
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Refosco
authors.forename: Carlo
authors.initials: C
authors.lastname: Santini
authors.forename: Francesco
authors.initials: F
authors.lastname: Tisato
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D010720:Phosphines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D010720:Phosphines; D003300:Copper