Metal complexation of deferasirox derivatives: A solid state and equilibrium study. (1st November 2020)

• Record Type: Journal Article
• Authors: Nagy, Imre; Ferenczik, Gergő; Bíró, Linda; Farkas, Etelka; Cs. Bényei, Attila; Buglyó, Péter
• Is Part Of: Polyhedron. Volume 190(2020)
• Publication Date: 2020-11-01
• Subjects: Deferasirox -- Anticancer -- Speciation -- Ru, Os, Co, Ga complexes -- Single crystal structures; Chemistry, Inorganic -- Periodicals; Chimie inorganique -- Périodiques; Organometaalverbindingen; Anorganische chemie; 546.05
• DOI: 10.1016/j.poly.2020.114780
• Languages: English
• ISSNs: 0277-5387

Abstract

Graphical abstract: Interaction of an iron sequestering agent, deferasirox, and its derivatives with various metal ions was studied in solution and in the solid state. Highlights: Synthesis of various deferasirox metal (Ru, Os, Co, Ga) complexes with likely dual anticancer activity. Synthesis of novel water soluble deferasirox derivatives. Analytical characterization of the new compounds. Speciation study with Ga(III) ions. Abstract: Complexation of deferasirox (4-[3, 5-bis(2-hydroxyphenyl)-1, 2, 4-triazol-1-yl]benzoic acid, H3 LB ) and its decarboxy derivative (H2 LA ) 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 ]∙2Pr i OH. Unprecedented formation of K2 [Os VI LB (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 H3 LB, and H2 LA, (H5 LD and H4 LC, respectively, with excellent water solubility) is also presented. Interaction of Ga(III) with H4 LD − and H3 LC − 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.