Substituted pyridine-quinoline ligands as building blocks for neutral rhodium(III) complexes. Synthesis, structural characterization studies and anti-platelet activity towards the Platelet-Activating Factor (PAF)

Two octahedral rhodium(III) complexes incorporating new substituted pyridine-quinoline ligands were synthesized and structurally characterized. Biological studies demonstrate that the new complexes are potent anti-platelet agents in the micro-molar scale, owing to their potency to inhibit the action of PAF (Platelet-Activating Factor). This is an approach of continuous interest for the development of metal complexes with possible anti-inflammatory activity. [Display omitted] •Synthesis and characterization of the substituted 2-(2΄-Pyridyl)quinoline ligands 1, 2.•Structural characterization of mer-[RhCl3(1)(CH3OH)] (3) and mer-[RhCl3(2)(CH3OH)] (4).•Complexes 3 and 4 are potent inhibitors of PAF in the micromolar scale.•3 and 4 are possible anti-inflammatory agents. The Friedländer condensation reaction was employed to synthesize the new bidentate ligands namely 6-bromo-4-phenyl-2-pyridin-2-yl-quinoline (1) and 4-(4-phenyl-2-(pyridin-2-yl)quinolin-6-yl)phenol (2). These compounds were fully characterized including the X-ray structures of 1 and the protonated form of 2, i.e. 2·HCl·H2O. We also report the synthesis and spectroscopic characterization of two rhodium(III) complexes of the general formula [Rh(1)Cl3(CH3OH)] (3) and [Rh(2)Cl3(CH3OH)] (4). The molecular structures of 3·2CH3OH and 4 were determined by single-crystal X-ray diffraction studies, revealing that these complexes adopt the mer-configuration. The solution stability of 3, 4 was studied by a combination of UV–Vis and 1H NMR spectroscopic techniques. All compounds were biologically evaluated for their anti- platelet activity using their potency to inhibit the action of PAF (Platelet-Activating Factor), which is an approach of continuous interest in the field. Complexes 3 and 4 were found to be potent PAF inhibitors with IC50 values in the micromolar range (1.0 μM and 3.9 μM respectively). Since PAF is the most potent inflammatory lipid mediator, the PAF-inhibitors and consequently the title compounds may be considered as potent examples in the search for novel anti-inflammatory drugs.