Structurally Diverse Metal Coordination Compounds, Bearing Imidodiphosphinate and Diphosphinoamine Ligands, as Potential Inhibitors of the Platelet Activating Factor

Metal complexes bearing dichalcogenated imidodiphosphinate [R(2)P(E)NP(E)R(2)′](−) ligands (E = O, S, Se, Te), which act as (E,E) chelates, exhibit a remarkable variety of three-dimensional structures. A series of such complexes, namely, square-planar [Cu{(OPPh(2))(OPPh(2))N-O, O}(2)], tetrahedral [Zn{(EPPh(2))(EPPh(2))N-E,E}(2)], E = O, S, and octahedral [Ga{(OPPh(2))(OPPh(2))N-O,O}(3)], were tested as potential inhibitors of either the platelet activating factor (PAF)- or thrombin-induced aggregation in both washed rabbit platelets and rabbit platelet rich plasma. For comparison, square-planar [Ni{(Ph(2)P)(2)N-S-CHMePh-P, P}X(2)], X = Cl, Br, the corresponding metal salts of all complexes and the (OPPh(2))(OPPh(2))NH ligand were also investigated. Ga(O,O)(3) showed the highest anti-PAF activity but did not inhibit the thrombin-related pathway, whereas Zn(S,S)(2), with also a significant PAF inhibitory effect, exhibited the highest thrombin-related inhibition. Zn(O,O)(2) and Cu(O,O)(2) inhibited moderately both PAF and thrombin, being more effective towards PAF. This work shows that the PAF-inhibitory action depends on the structure of the complexes studied, with the bulkier Ga(O,O)(3) being the most efficient and selective inhibitor.