Metalloglycomics of tris(2,2' -bipyridyl) cobalt and ruthenium compounds

Metal complexes studied to date under the framework of metalloglycomics belong to the M-NH3 general motif (polynuclear platinum compounds; Werner's complex), acting mainly as cationic hydrogen bonding species toward glycosaminoglycans (GAGs), an interaction termed metalloshielding. In this paper, we expand our studies to substitution-inert octahedral cobalt(III) and ruthenium(II) complexes bearing the non-hydrogen-donor ligand 2,2 '-bipyridine (bpy). We identified by NMR spectroscopy that [Co(bpy)(3)](3+) binds to the highly sulfated synthetic pentasaccharide, Fondaparinux (FPX), while no major perturbations are found in the presence of [Ru (bpy)(3)](2+). This result is of significance as both coordination compounds have analogous 3D structures. Although weakly binding to the model GAG, [Ru(bpy)3]2+ completely inhibits the enzymatic cleavage of FPX by the bacterial heparinase II (HepII) enzyme, which is not observed for the Co(III) analog. This observation suggests a direct inhibition of HepII by the Ru compound, through a mechanism that is unrelated to metalloshielding.