Synthesis and cytotoxicity of new Pt(IV) complexes of 2,2 0 -biimidazole and derivatives Jose ´ S. Casas, Alfonso Castin ˜ eiras, Yolanda Parajo ´, Agustı ´n Sa ´nchez, A ´ ngeles Sa ´nchez-Gonza ´lez, Jose ´ Sordo * Departamento de Quı ´mica Inorga ´ nica, Universidad de Santiago de Compostela, Facultad de Farmacia, Campus Univ., E-15782 Santiago de Compostela, Spain Received 14 February 2005; accepted 5 April 2005 Available online 23 May 2005 Abstract Compounds of type [PtCl 4 (LL)] [LL = 2,2 0 -biimidazole (H 2 bim); N-methyl-2,2 0 -biimidazole (MeHbim); N-hydroxyethyl-2,2 0 - biimidazole (HOEtHbim); or N,N 0 -dimethyl-2,2 0 -biimidazole (Me 2 bim)] were prepared and characterized. The structure of [PtCl 4 (Me 2 bim)] was determined by X-ray diffractometry. The crystal consists of discrete [PtCl 4 (Me 2 bim)] units in which the Pt atom is coordinated to the four Cl atoms and to the unmethylated N atoms in a distorted octahedral environment. Spectroscopic data suggest that all the other complexes have similar structures. The complexes of H 2 bim, MeHbim and Me 2 bim showed cytotoxic activ- ity against both human ovarian carcinoma A2780 and the corresponding cisplatin-resistant line, A2780cis. Ó 2005 Elsevier Ltd. All rights reserved. Keywords: Pt(IV) complexes; 2,2 0 -Biimidazole; Substituted 2,2 0 -biimidazoles; Crystal structure; Cytotoxic activity 1. Introduction The anti-cancer drug cisplatin, though very success- ful, has side effects that include nephrotoxicity, cytotox- icity, myelo-suppression, neurotoxicity, nausea and vomiting [1]. Among the numerous other platinum [2] or non-platinum metal compounds [3] that have been prepared with a view to avoiding these effects (and with the additional aims of allowing oral administration and achieving activity against cisplatin-resistant tumour lines), several Pt(IV) derivatives have high activity in vi- tro [4] and are currently being tested clinically; cases in point are the orally administrable di(acetato)amminedi- chloro(cyclohexylamine)platinum(IV) (JM216) and derivatives and analogues, some of which circumvent certain mechanisms of cisplatin resistance [2]. The re- sults of recent in vitro studies suggest that in most Pt(IV) drugs the platinum is reduced to Pt(II) at some point, and that it is the resulting Pt(II) species that is the effec- tive anti-cancer agent [5,6]. In a previous study in which we synthesized a num- ber of dihaloplatinum and dihalopalladium complexes of 2,2 0 -biimidazole (H 2 bim) and N,N 0 -dimethyl-2,2 0 - biimidazole (Me 2 bim) we found that the dichloroplat- inum derivatives of these ligands were capable of significant interaction with DNA [7]. Here we report the synthesis and spectroscopic characterization of tet- rachloro-platinum complexes of H 2 bim, MeHbim, HOEtHbim and Me 2 bim (Scheme 1), the crystal struc- ture of [PtCl 4 (Me 2 bim)], and the in vitro cytotoxicity of the new compounds against cells of the human ovarian cancer line A2780 and its cisplatin-resistant mutant A2780cis. 0277-5387/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.poly.2005.04.008 * Corresponding author. Tel.: +34 981 528 074; fax: +34 981 547 102. E-mail address: qijsordo@usc.es (J. Sordo). www.elsevier.com/locate/poly Polyhedron 24 (2005) 1196–1202