Membrane-active La(III) and Ce(III) complexes as potent antibacterial agents: synthesis, characterization, in vitro, in silico, and in vivo studies

The La(III) and Ce(III) complexes with mixed ligands of salicylic acid (Hsal) and 1,10-phenanthroline (phen), namely [La(sal)(3)(Phen)(2)] and [Ce(sal)(3)(phen)(2)], were synthesized and characterized by elemental analysis, thermal analysis, infrared, UV-visible and fluorescence spectroscopy, and single-crystal X-ray diffraction. The crystal structure analyses reveal that the Ce(III) complex is isostructural with the La(III) complex, where the Ce(III) center is chelated by two phen and three sal ligands. The comprehensive investigation on antibacterial activities and underlying mechanisms of the La(III) and Ce(III) complexes were done in vitro, in silico, and in vivo. In vitro experiments show that the coordination of the metal ions increased the antibacterial activity of the ligands. The scanning electron microscopy (SEM) images show that the Ce(III) complex may destroy the cell envelope. The molecular dynamics simulations provide complementary results that the Ce(III) complex is membrane-active against bacteria. In vivo assessments conducted using the infection wound model in mice, together with the preliminary safety evaluation, suggest that the La(III) and Ce(III) complexes may be developed as effective antimicrobial candidates. The research may contribute to the development of novel antimicrobial agents by providing new ideas. (C) 2021 Elsevier B.V. All rights reserved.