Transition metal complexes with the quinolone antibacterial agent pipemidic acid: Synthesis, characterization and biological activity Eleni K. Efthimiadou a,b , Yiannis Sanakis c , Nikos Katsaros a , Alexandra Karaliota b , George Psomas a, * a Institute of Physical Chemistry, NCSR ‘‘Demokritos’’, GR-15310 Aghia Paraskevi Attikis, Greece b Department of Inorganic Chemistry, Faculty of Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli Zographou, GR-15701 Athens, Greece c Institute of Materials Science, NCSR ‘‘Demokritos’’, GR-15310 Aghia Paraskevi Attikis, Greece Received 29 August 2006; accepted 6 October 2006 Available online 19 October 2006 Abstract Nine new mononuclear metal complexes of the quinolone antibacterial agent pipemidic acid (= HPPA) with VO 2+ , Mn 2+ , Fe 3+ , Co 2+ , Ni 2+ , Zn 2+ , MoO 2 2þ , Cd 2+ and UO 2 2þ have been prepared and characterized with physicochemical and spectroscopic techniques. In all the complexes, pipemidic acid acts as a bidentate deprotonated ligand bound to the metal through the pyridone oxygen atom and one carboxylate oxygen atom. All the complexes are six-coordinate and the geometry round the metal atom can be described as a slightly distorted octahedron. For VO(PPA) 2 (H 2 O), the axial position, trans to the vanadyl oxygen, is occupied by one pyridone oxygen atom. Molecular mechanics calculations in the gas state have been performed in order to propose a model for the structure of the Fe 3+ , VO 2+ and MoO 2 2þ complexes. The antimicrobial activity of the complexes has been tested on three different microorganisms. The investigation with diverse spectroscopic techniques of the interaction of the complexes with calf-thymus DNA has shown that the complexes can be bound to DNA resulting in a B ! A DNA transition. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: Pipemidic acid; Quinolones; Metal complexes; Spectroscopic study; Interaction with CT DNA; Antibacterial activity 1. Introduction Study of the interaction between drugs and transition metals is an important and active research area in bioinor- ganic chemistry [1–4]. It is well known that the action of many drugs is dependant on the coordination with metal ions [1] or/and the inhibition [2] on the formation of metal- loenzymes. Therefore, metal ions might play a vital role during the biological process of drug utilization in the body. Quinolones, a commonly used term for the quinolone- carboxylic acids or 4-quinolones, are a group of synthetic antibacterial agents containing a 4-oxo-1,4-dihydroquino- line skeleton (Fig. 1a) [5]. They can act as antibacterial drugs that effectively inhibit DNA replication and are commonly used as treatment for many infections. Cipro- floxacin, cinoxacin, norfloxacin and nalidixic acid are among the most common and widely used quinolones. The interaction of metal ions with diverse deprotonated quinolones as ligands has been thoroughly studied [5]. In the literature, there have been reported complexes of cipro- floxacin with V(IV)O 2+ [6], Fe(III) [7] and Cu(II) [8,9], com- plexes of cinoxacin with Co(II) [10], Ni(II) [11], Cu(II) [12,13], Zn(II) [11] and Cd(II) [14,15], of nalidixic acid with Zn(II) [16], of ofloxacin with Cu(II) [17] and two complexes of norfloxacin with Zn(II) [18]. There have also been reported mixed ligand copper(II) complexes of phenanthroline with nalidixic acid [19], cinoxacin [20] and ciprofloxacin [21] as well as ionic complexes of protonated norfloxacin with Zn(II) and Cu(II) [22], Cu(I) [23] and Mn [24]. For Mo only two cip- 0277-5387/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.poly.2006.10.017 * Corresponding author. Tel.:+30 2106503611; fax: +30 2106511766. E-mail address: gpsomas@chem.demokritos.gr (G. Psomas). www.elsevier.com/locate/poly Polyhedron 26 (2007) 1148–1158