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

Abstract

Metal complexes bearing dichalcogenated imidodiphosphinate[R2P(E)NP(E)R2′]-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{(OPPh2)(OPPh2)N-O,O}2], tetrahedral[Zn{(EPPh2)(EPPh2)N-E,E}2], E = O, S, and octahedral[Ga{(OPPh2)(OPPh2)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{(Ph2P)2N-S-CHMePh-P,P}X2], X = Cl, Br, the corresponding metal salts of all complexes and the(OPPh2)(OPPh2)NHligand were also investigated.Ga(O,O)3showed the highest anti-PAF activity but did not inhibit the thrombin-related pathway, whereasZn(S,S)2, with also a significant PAF inhibitory effect, exhibited the highest thrombin-related inhibition.Zn(O,O)2andCu(O,O)2inhibited 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 bulkierGa(O,O)3being the most efficient and selective inhibitor.