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

• Published in: Inorganica Chimica Acta 2011-11, Vol.378 (1), p.102-108
• Main Authors: Ferentinos, Eleftherios, Tsoupras, Alexandros B., Roulia, Maria, Chatziefthimiou, Spyros D., Demopoulos, Constantinos A., Kyritsis, Panayotis
• Format: Article
• Language: English
• Subjects: Imidodiphosphinato; Isomorphous; PAF; Thrombin; X-ray crystallography; Zinc
• ISSN: 0020-1693; 1873-3255
• DOI: 10.1016/j.ica.2011.08.029

The Zn[(OPPh 2)(SePPh 2)N] 2 complex was synthesized and characterized by X-ray crystallography and spectroscopic methods. Its inhibitory activity towards PAF and thrombin was evaluated and compared to that of the isomorphous M[(OPPh 2)(SePPh 2)N] 2 complexes, M = Co, Ni. The stereochemical and electronic characteristics of these compounds determine the extent of their inhibitory action. [Display omitted] ► The novel Zn[(OPPh 2)(SePPh 2)N] 2 complex was prepared and characterized by X-ray crystallography and spectroscopic methods. ► The Zn(II) compound was shown to be isomorphous to the recently reported analogous complexes of M(II), M = Co, Ni. ► The inhibitory activity of these complexes towards PAF and thrombin is affected by their stereochemical and electronic characteristics. 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 crystallography revealed a pseudo-tetrahedral MO 2Se 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)(SePPh 2)N] 2 complexes, M = Co, Ni, Zn, shows that the three complexes are isomorphous. The IR and 31P 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)(SePPh 2)NH ligand and SeO 2, are investigated as inhibitors of the Platelet Activating Factor (PAF) and thrombin 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.