In vitro assessment of cytotoxicity, anti-inflammatory, antifungal properties and crystal structures of metallacyclic palladium(II) complexes Farkhanda Shaheen a, * , Amin Badshah a , Marcel Gielen b, * , Gianluca Croce c , Ulrich Florke d , Dick de Vos e , Saqib Ali a a Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan b Vrije Universiteit Brussel, Faculty of Engineering, HNMR Unit, B-1050 Brussels, Belgium c DISTA, Universita del Piemonte Orientale, Alessandria I- 15100, Italy d Department Chemie, Universität Paderborn, Warburgerstasse 100, D-33098 Paderborn, Germany e Pharmachemie BV, P.O. Box 552, 2003 RN Haarlem, The Netherlands article info Article history: Received 12 August 2009 Received in revised form 29 October 2009 Accepted 30 October 2009 Available online 18 November 2009 Keywords: Palladium(II) Dithiocarbamate Organophosphine Anti-inflammatory abstract Metallacyclic palladium(II) complexes [Pd(L)(R 3 P)Cl], L = TIQDTC (1,2,3,4-tetrahydroisoquinolinedithio- carbamate), 4MpipDTC (4-methylpipradinedithiocarbamate), MPizDTC (N-methylpiperazinedithio- carbamate), R 3 P = Ph 3 P, (o-tolyl) 3 P, Ph 2 ClP, were synthesized in a 1:1 molar metal–ligand ratio. These complexes were characterized by elemental analyses, FT-IR, multinuclear ( 1 H, 13 C and 31 P) NMR. The X-ray crystal structures of [Pd(TIQDTC)(Ph 3 P)Cl] and [Pd(TIQDTC)((o-tolyl) 3 P)Cl] show a slightly distorted square planar environment around the Pd(II) ion with S–Pd–S and P–Pd–Cl average bond angles of 74.51 and 92.41, respectively. These complexes were screened for cytotoxic, antifungal, anti-inflammatory and antibacterial activity. Some complexes exhibit a significant activity against fungi. Ó 2009 Elsevier B.V. All rights reserved. 1. Introduction Metal-containing compounds offer certain advantages over purely organic compounds in drug therapy and broad applications in the field of material sciences. Metal-based sulfur-containing molecules like dithiocarbamates are currently under study as adsorbents for the preparation of gold nanoparticles, stimulated by the numerous nanotechnological possibilities for the develop- ments of nanoscale optoelectronic devices, sensors and biosensors, corrosion resistant materials and new catalysts. The interest in the synthesis of functionalised monolayer protected metal nanoparti- cles is expanding with an exponential rate [1–3], also used as chemoprotectants in platinum-based chemotherapy [4]. Cisplatin is one of the most effective drugs used not only in the treatment of head and neck cancer, lung carcinoma, stomach carcinoma, tes- ticular, ovarian, bladder, oesophageal, small and non-small cell lung [5], breast, cervical and prostate cancers but also to treat Hodgkin’s and non-Hodgkin’s lymphomas, neuroblastomas, sarco- mas, multiple myelomas, melanomas and mesotheliomas [6,7]. However, the clinical usefulness of cisplatin has been frequently limited by its severe side effects such as nephrotoxicity (kidney damage), neurotoxicity (nervous system damage), ototoxicity (hearing loss) and myelotoxicity (bone marrow suppression) [8,9], and by the development of acquired resistance against breast and colon cancer [10]. Continuous efforts are still being made to re- duce the toxicity of platinum anticancer complexes towards nor- mal cells, circumventing acquired resistance to cisplatin and decreasing its side effects. The interest in the chemical and bio- chemical properties of platinum and palladium complexes with thiocarbonyl and thiol donors has been increased because sulfur- containing ligands are used as detoxicant agents against metal- containing drugs [11]. Dithiocarbamates have been used for their efficacy as inhibitors of cisplatin-induced side effects [12]. In par- ticular, dithiocarbamates selectively remove platinum from the en- zyme–thiol complexes by nucleophilic attack of the chelating sulfur atoms to the platinum moiety [13]. Moreover the selectivity protects normal tissues without inhibiting the antitumour effect [14]. Their biological as well as catalytic activities are enhanced by complexation with Pd(II) [15]. The dithiocarbamate moiety can bind (chelate) palladium by a (–S:S 0 –) coordination mode [11]. Several Pd dithiocarbamates complexes [Pd(ESTD)(2-pic)CL], [Pd(MSDTM)Br] n and [Pd(ESTD)CL] n are known to exhibit cytotoxic activities against HeLa, HL60, lung, ovarian melanoma, colon, renal, prostate and breast cancer cell lines [17–21,50]. During the last few years, we have been studying palladium(II) complexes with dithiocarbamates [20] and some mixed ligands 0022-328X/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jorganchem.2009.10.048 * Corresponding authors. Tel.: +32 (2) 629 32 79; fax: +32 (2) 629 32 81 (M. Gielen). E-mail addresses: fshaheenpk@yahoo.com (F. Shaheen), mgielen@vub.ac.be (M. Gielen). Journal of Organometallic Chemistry 695 (2010) 315–322 Contents lists available at ScienceDirect Journal of Organometallic Chemistry journal homepage: www.elsevier.com/locate/jorganchem