Novel cyclometalated iridium (III) complexes as antibacterial agents for photodynamic inactivation

Fallon, Muireann ; Lalrempuia, Ralte ; Tabrizi, Leila ; Brandon, Michael P. ; McGarry, Ross ; Cullen, Aoibhín ; Fernández-Alvarez, Francisco J. (Universidad de Zaragoza) ; Pryce, Mary T. ; Fitzgerald-Hughes, Deirdre

Resumen: Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) frequently cause chronic skin and soft tissue infections and device-related infections. These bacteria colonize human skin and can survive for long periods within biofilms, on indwelling medical devices, high touch surfaces and equipment in the healthcare setting, which are reservoirs for further transmission to patients. Photodynamic therapy may offer an alternative to antibiotics in the management of infections or photodynamic disinfection may limit transmission of specific pathogens in the healthcare setting. Two novel cyclometalated iridium (III) complexes [Ir(ppy)2L](PF6) (ppy: phenyl pyridine, L = 6-((2,6-diisopropylphenyl)amino)-5,6-dihydro-1,10-phenanthrolin-5-ol (Ir1) and L = N-(2,6-diisopropylphenyl)-1,10-phenanthrolin-5-amine (Ir2)) were synthesized and evaluated for their antimicrobial properties when activated by light (370 nm). Iridium complexes (Ir1 and Ir2) led to potent inactivation of planktonic Staphylococcus aureus at 5 µM (almost 5 log10 reduction in colony forming units (CFU)/mL) after light exposure (p ≤ 0.01 for dark vs light). Dark toxicity was < 1 log10. Under the same conditions, Escherichia coli killing was < 1 log10. Anti-staphylococcal activity was concentration-dependant over the range 0.1 µM − 5 µM (p ≤ 0.001, Ir1, p ≤ 0.01 Ir2). Anti-biofilm activity was observed against mature (72 h) biofilms of S. aureus including methicillin-resistant S. aureus (MRSA) biofilms but higher concentrations (50 μM) were required. Treatment with Ir1 or Ir2 resulted in removal of 20 – 32 % of biofilm biomass as measured by crystal violet staining and 24 – 73 % reduction in the metabolic activity of cells within the biofilm, using resazurin reduction assays. Cytotoxicity to cultured human keratinocytes was minimal at antimicrobial concentrations but increased with higher concentrations, for Ir1 but not Ir2 (Ir1 p ≤ 0.01, 5 Vs 50 μM). The quantum yield for singlet oxygen (1O2) emission was measured as 0.16 and 0.30 for Ir1 and Ir2 respectively. Ground and excited state UV–Vis absorption, steady-state and time-resolved studies together with cyclic voltammetry are also presented. In summary, the potent and rapid antimicrobial activity of these cyclometalated iridium (III) complexes against S. aureus and MRSA, which included biofilm eradication, highlight their potential in the management or prevention of device-associated infections or healthcare transmission involving these pathogens.

Idioma: Inglés

DOI: 10.1016/j.jphotochem.2024.116218

Año: 2024

Publicado en: JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY 462 (2024), 116218 [12 pp.]
ISSN: 1010-6030

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Química Inorgánica (Dpto. Química Inorgánica)