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)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.

Synthetic and structural studies of phosphorus carbonyl rhenacycles containing the tetraphenyldithioimidodiphosphinato ligand

“…IR spectra were obtained in solution (4000e580 cm À1 ) and in KBr disk (4000e200 cm À1 ) using a Bruker Tensor 27 FT-IR spectrometer. 1 H(300 MHz), 13 C(75.57 MHz), and 31 P(121.67 MHz) NMR spectra were recorded in chloroform-d solutions at room temperature using Jeol GX300 and Bruker Advance 300 instruments. The chemical shifts are reported in ppm relative to TMS (for 1 H and 13 C), H 3 PO 4 (85% aqueous solution for 31 P).…”

“…The melting points were determined on a Fisher-Johns apparatus and are uncorrected. (1), PMePh 2 (2), PMe 2 Ph (3), and PMe 3 (4). 0.46 g (0.62 mmol) of [Re(CO) 4 {Ph 2 (S)NP(S)Ph 2 -k 2 S}] (a) were added to a 100 mL round bottom flask with stirring containing 30 mL of dry toluene.…”

“…n max (CH 2 Cl 2 )/cm À1 2021 vs, 1930 vs, 1897 vs (CO). 1 yield; 233e235 C n max (KBr)/cm À1 2019 vs, 1925 vs, 1887 vs (CO); 1223s n as (P 2 N); 572m n as (PS); 512m n s (PS). n max (CH 2 Cl 2 )/cm À1 2020 vs, 1928 vs, 1894 vs (CO).…”

“…bioinorganic chemistry [1], homogeneous catalysis [2], material sciences [3] to mention but a few); others, their capability of ligating metal centers in wide-ranging capacities and, at the same time, adopting several ring conformations in inorganic metallacycles. The fact is that the coordination chemistry of [N(EPPh 2 ) 2 ] anions has been extensively studied over the last years [4].…”

Progress in the Development of Platelet‐Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases

“…Copper(II), zinc(II), cobalt(II), nickel(II), and gallium(II) complexes containing chalcogenated imidodiphosphinato ligands are PAFr antagonists (Figure ) . These complexes feature a range of fundamental metal coordination geometries, with the bulkiest gallium complex 24 a identified as the most active of these molecules.…”