Inhibitory activity of the novel Zn[(OPPh 2 )(SePPh 2 )N] 2 complex towards the Platelet Activating Factor (PAF) and thrombin: Comparison with its isomorphous Co(II) and Ni(II) analogues Eleftherios Ferentinos a , Alexandros B. Tsoupras b , Maria Roulia a , Spyros D. Chatziefthimiou c , Constantinos A. Demopoulos b , Panayotis Kyritsis a,⇑ a Inorganic Chemistry Laboratory, Faculty of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, Greece b Biochemistry Laboratory, Faculty of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece c EMBL Hamburg, Notkestrasse 85, D-22603 Hamburg, Germany article info Article history: Received 14 March 2011 Received in revised form 23 June 2011 Accepted 12 August 2011 Available online 30 August 2011 Keywords: Zinc Imidodiphosphinato Isomorphous X-ray crystallography PAF Thrombin abstract The Zn[(OPPh 2 )(SePPh 2 )N] 2 complex was prepared by a metathetical reaction between a Zn(II) salt and the deprotonated form of the dichalcogenoimidodiphosphinato ligand [(OPPh 2 )(SePPh 2 )N]  . X-ray crys- tallography revealed a pseudo-tetrahedral MO 2 Se 2 coordination sphere, owed to the asymmetric (O,Se) nature of the chelating ligand. A comparison between the structural features of the M[(OPPh 2 )(SeP- Ph 2 )N] 2 complexes, M = Co, Ni, Zn, shows that the three complexes are isomorphous. The IR and 31 P NMR properties of Zn[(OPPh 2 )(SePPh 2 )N] 2 are analyzed in the framework of its crystallographic structure, and are compared with data on similar systems. The above three complexes, along with the (OPPh 2 )(SeP- Ph 2 )NH ligand and SeO 2 , are investigated as inhibitors of the Platelet Activating Factor (PAF) and throm- bin activities. The paramagnetic M[(OPPh 2 )(SePPh 2 )N] 2 complexes, M = Co, Ni, exhibit an approximately 65-fold increased activity, compared to diamagnetic Zn[(OPPh 2 )(SePPh 2 )N] 2 , in both the PAF- and the thrombin-induced aggregation of washed rabbit platelets (WRP). The above three complexes show a comparable significant inhibitory activity in the PAF-induced aggregation of rabbit platelet rich plasma (RPR). Remarkably, SeO 2 , a form of Se present in blood, exhibits a very strong and selective inhibitory activity towards the PAF-induced aggregation of WPR. Our studies extend the dataset of metal complexes investigated as inhibitors of PAF and thrombin. Ó 2011 Elsevier B.V. All rights reserved. 1. Introduction Dichalcogenoimidodiphosphinic acids of type (XPR 2 )(YPR 0 2 )NH, (LH), have been extensively employed for the synthesis of a host of coordination compounds, involving both main group and transi- tion metal centers [1–4]. The deprotonated form of these ligands, [(XPR 2 )(YPR 0 2 )N]  , denoted in the following as (X,Y), X or Y = O, S, Se, Te, usually affords metal complexes in which the metal center is coordinated by both X and Y chalcogen atoms, leading to six- membered M–X–P–N–P–Y chelate rings. The ligands of this type are either symmetric or asymmetric, based on the nature of either the peripheral R, R organic groups, or the X and Y chalcogen atoms bonded to the P atoms. With respect to the latter, reports on metal complexes involving symmetric ligands have been expanding over the last four decades [1–4]. On the other hand, studies on the synthesis and properties of complexes bearing the mixed chalcogen, asymmetric, (O,S) ligands, have started to emerge only during the last few years. For instance, the synthesis of the four-coordinate M[(OPPh 2 )(SPPh 2 )N] 2 series of complexes, M = Mn [5,6], Co [7], Ni [8], Cu [9], has been accom- plished during the last decade. The Zn[(OPPh 2 )(SPPh 2 )N] 2 complex is currently being studied in our laboratory [10], whereas the anal- ogous Zn[(SPPh 2 ){OP(OEt) 2 }N] 2 complex has already been reported in the literature [11]. In addition, complexes bearing (O,S) ligands have been synthesized for the following metal ions: Mo(V) [12], Pd(II) [13–15], Pt(II) [16], Sn(IV) [17–20], Sb(III) [21], Sb(V) [22], Bi(III) [23], Ga(III) [24,25], In(III) [26,27], Hg(II) [28], Pb(II) [29] and Cd(II) [30]. Compared to the above systems, only occasional reports on the coordination properties of the corresponding (O,Se) ligands have been presented to date. For instance, a series of square planar Pd(II) complexes involving the (O,Se) and different types of ligands were studied a few years ago [31]. At the same time, Pd(II) was also shown to afford the square planar cis-Pd[(OPPh 2 )(SePPh 2 )N] 2 com- plex [16]. On the other hand, the synthesis of the tetrahedral M[(OPPh 2 )(SePPh 2 )N] 2 complexes, M = Co, Ni, was reported very recently [32]. This work opened up the possibility to extend the 0020-1693/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.ica.2011.08.029 ⇑ Corresponding author. Tel.: +30 210 7274268; fax: +30 210 7274782. E-mail address: kyritsis@chem.uoa.gr (P. Kyritsis). Inorganica Chimica Acta 378 (2011) 102–108 Contents lists available at SciVerse ScienceDirect Inorganica Chimica Acta journal homepage: www.elsevier.com/locate/ica