Cu K-edge EXAFS on copper(I) complexes containing dihydridobis(3-nitro-1,2,4-triazol-1-yl)borate and bis(1,2,4-triazol-1-yl)acetate ligand: Evidence for the Cu–O interaction Marco Giorgetti a, * , Lorella Guadagnini a , Steven G. Fiddy b , Carlo Santini c , Maura Pellei c a Department of Physical and Inorganic Chemistry, University of Bologna and Unità di Ricerca INSTM di Bologna, Viale del Risorgimento 4, 40136 Bologna, Italy b Daresbury Laboratory, Daresbury Science and Innovation Campus, Warrington WA4 4AD, UK c Dipartimento di Scienze Chimiche, Università degli Studi di Camerino, Via S. Agostino 1, 62032 Camerino, MC, Italy article info Article history: Received 14 April 2009 Accepted 16 July 2009 Available online 24 July 2009 Keywords: EXAFS Multiple scattering Cu(I) Scorpionates abstract X-ray absorption spectroscopy (XAS) has been used to probe the local structure of copper(I) complexes containing the dihydridobis(3-nitro-1,2,4-triazol-1-yl)borate and the bis(1,2,4-triazol-1-yl)acetate ligands. The material is polycrystalline and no crystal structure is available in the literature. The EXAFS analysis has permitted the identification of the local environment of the copper site. Copper is found to be 4-fold coordinated with two sets of Cu–N and Cu–P interactions describing a quasi planar figure. An additional coordination is revealed for the copper(I) complex of bis(1,2,4-triazol-1-yl)acetate due to the interaction of the copper with the acetate of the scorpionate ligand. XANES spectra of the studied samples show a resolved pre-edge peak at about 8983 eV which is assigned to the 1s ? 4p transition, whose intensities can be explained considering the copper in a 4-fold coordination. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction The well known biochemistry of copper underlines the crucial role played by this metal in different enzymes that catalyze oxida- tion/reduction phenomena correlated with the antioxidant sys- tems of living organisms. It has been established that the properties of copper-coordinated compounds are largely deter- mined by the nature of ligands and donor atoms bound to the me- tal ion [1]. Phosphine complexes of group 11 metals, especially those including the gold(I) and copper(I) ions, have been proposed as alternative anticancer drugs to the cisplatin reference drug [2–6]. Recently, mechanistic information were provided by the design of two water soluble complexes featuring the ‘CuP 4 ’ coordination sphere, namely [Cu(thp) 4 ][PF 6 ] (thp = tris(hydroxymethyl)phos- phine) and [Cu(bhpe) 2 ][PF 6 ] (bhpe = bis[bis(hydroxymethyl)phos- phino]ethane) [7]. Physico-chemical characterization indicated that they possessed a tetrahedral geometry both in the solid [8] and in the solution state [7]. ESI-MS data supported the view of an extremely stable substitution-inert entity in the case of [Cu(bh- pe) 2 ][PF 6 ] showing the molecular ion peak without detectable frag- mentation, whereas [Cu(thp) 4 ][PF 6 ] exhibited some lability showing the ‘CuP 4 ’ molecular ion along with the ‘CuP 3 ’ and ‘CuP 2 ’ molecular fragments at higher concentrations. This remarkable dif- ferent behavior in the ion trap had a major impact on the cytotoxic profile of these two species. [Cu(thp) 4 ][PF 6 ] complex has been shown to be about 1 order of magnitude more cytotoxic than cis- platin, while [Cu(bhpe) 2 ][PF 6 ] complex showed negligible in vitro antitumor activity suggesting that a marked kinetic inertness of the copper species is not a primary requirement. On the contrary, it appeared that, as already shown by other cytotoxic copper com- plexes, labile sites at copper are necessary for the pro-drug to dis- play its antiproliferative action. Many efforts have been focused to the design of hydrophilic copper(I) derivatives as in the case of the partial substitution of the ‘CuP 4 ’ arylphosphine coordination sphere with heterocyclic thiones [9], acetonitrile [10] and N-heterocycles, producing ‘mixed-ligand’ type compounds [10]. Following a similar ‘mixed-li- gand’ approach, several N 2 -scorpionate ligands have been attached to a coordination vacant lipophilic ‘CuP 2 ’ moiety (P 2 = bidentate dppe or two monodentate arylphosphines). The use of scorpionate co-ligands such as the dihydridobis(3-nitro-1,2,4-triazol-1-yl)bo- rate [11], ½H 2 Bðtz NO 2 Þ 2   , the bis(1,2,4-triazol-1-yl)acetate [12], ½HCðCO 2 ÞðtzÞ 2   , and the bis(3,5-dimethyl-pyrazol-1-yl)acetate [12], ½HCðCO 2 Þðpz Me 2 Þ 2   , had the double aim at increasing the water solubility and the kinetic inertness of the resulting mixed- complex. Some less hydrophobic copper(I) compounds, f½H 2 Bðtz NO 2 Þ 2 Cu½ðPR 3 Þ 2 g, where R= m-tolyl or p-fluorophenyl, were proved to be easier to handle during the in vitro tests, and they retained high cytotoxic activity against a panel of human tumor cell lines [11]. The substitution of arylphosphines with 0277-5387/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.poly.2009.07.032 * Corresponding author. Tel.: +39 051 209 3666; fax: +39 051 209 3690. E-mail address: marco.giorgetti@unibo.it (M. Giorgetti). Polyhedron 28 (2009) 3600–3606 Contents lists available at ScienceDirect Polyhedron journal homepage: www.elsevier.com/locate/poly