Synthesis of Iron(II)-N-Heterocyclic Carbene Complexes: Paving the Way for a New Class of Antibiotics

• Autor(a) principal: Vinagreiro, Carolina dos Santos
• Data de Publicação: 2020
• Outros Autores: Lopes, Rita, Royo, Beatriz, Silva, Gabriela Jorge da, Pereira, Mariette M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/106486; https://doi.org/10.3390/molecules25122917
• topic: N-heterocyclic carbene; iron(II)-NHC complexes; antibacterial activity; Anti-Bacterial Agents; Electron Spin Resonance Spectroscopy; Escherichia coli; Heterocyclic Compounds; Hydroxyl Radical; Imidazoles; Iron; Methane; Microbial Sensitivity Tests; Spectrophotometry, Ultraviolet; Staphylococcus aureus; Structure-Activity Relationship

The synthesis and structural modulation of five pro-ligand salts was achieved using alternative sustainable synthetic strategies, the use of microwaves being the method of choice, with an 81% yield and an E factor of 43 for 3d. After complexation with Fe3(CO)12 by direct reaction with the appropriate pro-ligands at 130 °C, a set of iron(II) N-heterocyclic carbene (NHC) complexes were isolated and fully characterized (via 1H and 13C NMR and IR spectroscopy and elemental analysis). The antibacterial activities of the iron(II)-NHC complexes were tested against standard World Health Organization priority bacterial strains: Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922. The results showed a significant effect of the Fe(II)-NHC side-chain on the antibacterial activity against both Gram-negative and Gram-positive bacteria. Among all compounds, the most lipophilic iron complex, 3b, was found to be the most active one, with a minimum inhibitory concentration of 8 µg/mL. Pioneering mechanistic studies suggested an alternative mechanism of action (OH· formation), which opens the way for the development of a new class of antibiotics.