2‐Thiophenyl–Isoquinoline Ir(III) Complex: A Promising Tool in Antipseudomonal Photodynamic Therapy under Red Irradiation

Abstract

Innovative therapeutic strategies are more than ever needed to counter the rise of antibiotic‐resistant bacterial pathogens worldwide. The use of light, and especially photodynamic therapy (PDT) appears as a promising alternative or complement to antibiotic treatments, fostered by the development of new photosensitizers. In this study, eight luminescent Ir(III) complexes were synthesized and evaluated for their photoactivation properties and capacity to generate radical species under blue (452 nm), green (525 nm), and red (631 nm) LED light, respectively. Their antibacterial properties were assessed on Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus with most of these complexes exhibiting potentially useful activities upon light irradiation, at concentrations below 10 mg/L. A complex of Ir(III) cyclometallated to thiophenyl‐isoquinoline (tiq) and bearing 2,2’‐bipyridine (bipy) as ancillary ligand was further investigated. This latter showed a concentration‐ and light intensity‐dependent bactericidal activity on P. aeruginosa when irradiated under blue to red lights, proving that such complexes would be suitable candidates for PDT. Importantly, this lead complex remained active against antibiotic resistant clinical strains and was unaffected by active efflux systems. These data open interesting perspectives for the development of new treatments to tackle antibiotic resistant Gram‐negative bacteria.