Homoleptic oligothienyl-substituted bis(terpyridine) Ir(III) and Ru(II) complexes: synthesis, photophysics, and anticancer and antimicrobial photodynamic therapeutic effects.
Abstract
Four homoleptic bis(terpyridine) Ir(III) and Ru(II) complexes bearing oligothienyl substituents on both tpy ligands (M(nT-tpy)2, M = Ir, Ru; n = 3, 4) were synthesized and characterized to evaluate their photophysical properties, including UV-Vis absorption, emission, and transient absorption, and photodynamic therapeutic (PDT) effects toward melanoma cells and Gram-positive Staphylococcus aureus and Gram-negative P. aeruginosa bacteria. The UV-Vis absorption studies revealed that the low-energy absorption bands at >350 nm red-shifted as the number of thienyl rings increased. Additionally, the Ru(II) complexes displayed further red-shifts alongside increased molar extinction coefficients. All complexes exhibited phosphorescence in the NIR region with lifetimes spanning from 1.4 μs to 7.4 μs in DMSO. These long-lived triplet excited states resulted in efficient singlet oxygen generation (ΦΔ = 0.30-0.69), with Ru complexes being more effective singlet oxygen generators than their Ir analogues. Oligothienyl chain extension primarily tuned the ligand-centered redox behavior of both the Ir(III) and Ru(II) complexes, shifting oligothienyl oxidation cathodically and oligothienyl reduction anodically. It had little effect on the Ru2+/Ru3+ oxidation or the terpyridine-centered reduction potentials, while no Ir3+/Ir4+ oxidation was observed within the potential window examined. In vitro PDT studies demonstrated strong photocytotoxicity under normoxia and hypoxia towards SKMEL28 melanoma cells, with Ir(4T-tpy)2 emerging as the most promising PDT agent among these four complexes. These complexes also exhibited potent light-activated antibacterial activity against Staphylococcus aureus at nanomolar concentrations, with Ru(3T-tpy)2 showing the strongest aPDT effect, surpassing that of the most commonly used antimicrobial photosensitizers. Ir(3T-tpy)2 also induced complete inactivation of Gram-negative Pseudomonas aeruginosa bacteria at 10 μM with 5 J cm-2 light dosage. These results highlight the potential of M(nT-tpy)2 as photosensitizers for both cancer and antimicrobial photodynamic therapy.