Metal Complexation of Deferasirox Derivatives: A Solid State and Equilibrium Study

Complexation of deferasirox (4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic acid, H3LB) and its decarboxy derivative (H2LA) with Ru(III), Os(IV), Co(III) and Ga(III) was studied. These novel complexes with likely multitargeted capabilities are expected to show anticancer potential after biotransformation via both of the metal ion and the liberated ligand. Formation of 1:2 octahedral complexes with a (O,N,O) tridentate coordination of the ligands was found yielding K3[Ru(LB)2], K[Co(LA)2], K3[Co(LB)2] and (guanidinium)Na2[Ga(LB)2], respectively. The molecular structure obtained by single crystal X-ray diffraction also confirmed the octahedral geometry for K[Co(LA)2]∙2PriOH. Unprecedented formation of K2[OsVILB(O)2(OH)] having a tridentate (O,N,O) coordinating ligand, two oxo groups and a hydroxide ion in the coordination sphere of the metal ion with + 6 oxidation state was also found. Simple synthesis and solid state structure of the novel disulfonated derivatives of H3LB, and H2LA, (H5LD and H4LC, respectively, with excellent water solubility) is also presented. Interaction of Ga(III) with H4LD− and H3LC− resulted in the formation of 1:1 and 1:2 complexes with different protonation degree in aqueous solution among them [Ga(LD)2]7− and [Ga(LC)2]5− being the major species under physiologically relevant conditions.