Solution studies, synthesis and antibacterial activity of Ga(III) complexes with bis-kojate derivatives

Given the recognized major problem of microbial drug resistance for human health, new metal-based drugs have been currently explored for their antimicrobial properties, including gallium-based compounds as potential metallophores that could perturb Fe’s interactions with proteins. Herein we have designed and synthesized two bis-kojate ligands (named L4 and L6) and studied their Ga(III) complexes for their physico-chemical and biological properties. In particular a detailed study of their complexation properties in aqueous solution, showed equilibrium models with formation of quite stable dinuclear 2:3 metal:ligand complexes, though with different stability. Solid state complexes were also prepared and characterized and complementary DFT studies indicated that [Ga2(L4)3] complex, with higher stability, seems to adopt a three-ligand bridging conformation, while that for L6 adopt a one ligand bridging conformation. Preliminary investigation of the antibacterial activity of these gallium complexes showed antipseudomonal activity, which appeared higher for the complex with L4, a feature of potential interest for the scientific community. The solution studies, the synthesis and characterization of new Ga(III)-kojate compounds evidenced the formation of binuclear complexes with antibacterial activity against the Gram-negative bacteria P. aeruginosa though little or no activity as expected against Gram-positive S. aureus. [Display omitted] •Novel Ga(III) complexes with bis-kojate derivatives•Kojate coordination via the carbonyl oxygen and vicinal deprotonated hydroxy group•Ga(III) complexes active against Gram-negative bacteria P. aeruginosa•Similarities between Ga(III) and Fe(III) complexation•One- and three bridged conformations of Ga2L3 complexes