Neutral iridium(iii) complexes bearing BODIPY-substituted N-heterocyclic carbene (NHC) ligands: synthesis, photophysics, in vitro theranostic photodynamic therapy, and antimicrobial activity. Issue 10 (21st August 2019) - Liu, Bingqing
Abstract : Neutral Ir(iii ) complexes bearing BODIPY-substituted N-heterocyclic carbene ligands exhibited moderate to strong photodynamic therapeutic effects toward SKMEL28 cells and antimicrobial activity upon broadband visible light activation. Abstract : The synthesis, photophysics, and photobiological activities of a series of novel neutral heteroleptic cyclometalated iridium(iii ) complexes incorporating boron dipyrromethene (BODIPY) substituted N-heterocyclic carbene (NHC) ligands (Ir1–Ir5 ) are reported. The effect of the substitution position of BODIPY on the NHC ligands, either on C4 of the phenyl ring (Ir1–Ir3 ) or C5 of the benzimidazole unit (Ir4 and Ir5 ), and its linker type (single or triple bond) on the photophysical properties was studied. Ir1–Ir5 exhibited BODIPY-localized intense 1 IL (intraligand transition)/ 1 MLCT (metal-to-ligand charge transfer) absorption at 530–543 nm and 1, 3 IL/ 1, 3 CT (charge transfer) emission at 582–610 nm. The nanosecond transient absorption results revealed that the lowest triplet excited states of these complexes were the BODIPY-localized 3 π, π* states. Complexes Ir4 and Ir5 exhibited blue-shifted 1 IL absorption and 1, 3 IL/ 1, 3 CT emission bands compared to the corresponding absorption and emission bands in complexes Ir1 and Ir3 . However, replacing the methyl substituents on N3 of benzimidazole in complexes Ir1 and Ir4 with oligoether substituents in Ir3 and Ir5, respectively, did not impact the energies of the low-energy absorption and emission bands in the corresponding complexes. Water-soluble complexes Ir3 and Ir5 have been explored as photosensitizers for in vitro photodynamic therapy (PDT) effects toward human SKMEL28 melanoma cells. Ir3 showed no dark cytotoxicity (EC50 > 300 μM) but good photocytotoxic activity (9.66 ± 0.28 μM), whereas Ir5 exhibited a higher dark cytotoxicity (20.2 ± 1.26 μM) and excellent photocytotoxicity (0.15 ± 0.01 μM). The phototherapeutic indices with visible light (400–700 nm) activation were >31 for Ir3 and 135 for Ir5 . Ir3 and Ir5 displayed 1 O2 quantum yields of 38% and 22% in CH3 CN, respectively, upon 450 nm excitation. Ir5 was more effective at generating reactive oxygen species (ROS) in vitro . Ir5 was also active against Staphylococcus aureus upon visible light activation, with a phototherapeutic index of >15 and EC50 value of 6.67 μM. These photobiological activities demonstrated that these neutral Ir(iii ) complexes are promising in vitro PDT reagents, and substitution at C5 on the benzimidazole group of the NHC ligand was superior to C4 substitution on the phenyl ring.