Anti-Amyloid Aggregation and Anti-Hyperglycemic Activities of Novel Ruthenium Uracil Schiff Base Compounds

The formation and characterization of new diamagnetic ruthenium uracil mono-imine compounds: [(η⁶-p-cymene)Ru^II(L)Cl][BF₄] (L=H₂urpda=5-((pyridin-2-yl)methyleneamino)-6-aminouracil) for 1, urdpy=6-amino-1,3-dimethyl-5-((pyridin-2-ylmethylene)amino)uracil) for 2 or urqda=5-((quinolin-2-yl)methyleneamino)-6-aminouracil) for 3); cis-[Ru(bipy)₂(urpy)](BF₄)₂ (4) (urpy=5-((pyridin-2-yl)methyleneamino)uracil) and cis-[Ru(bipy)₂(dapd)] (5) (H₂dadp=5,6-diaminouracil) are described. A ruthenium(IV) uracil Schiff base compound, trans-[Ru(urpda)(PPh₃)Cl₂] (6) was also formed. Various physicochemical techniques were utilized to characterize the novel ruthenium compounds. Similarly, the stabilities of 1-3 and 6 monitored in chloro-containing and the non-coordinating solvent, dichloromethane show that they are kinetically inert, whereas, in a high nucleophilic environment, the chloride co-ligands of these ruthenium complexes were rapidly substituted by DMSO. In contrast, the substitution of the labile co-ligands for these ruthenium complexes by DMSO molecules in a high chloride content was suppressed. Solution chemical reactivities of the different ruthenium complexes were rationalized by density functional theory computations. Furthermore, the binding affinities and strengths between BSA and the respective ruthenium complexes were monitored using fluorescence spectroscopy. In addition, the in vitro anti-diabetic activities of the novel metal complexes were assessed in selected skeletal muscle and liver cell lines.