Homoleptic oligothienyl-substituted bis(terpyridine) Ir(III) and Ru(II) complexes: synthesis, photophysics, and anticancer and antimicrobial photodynamic therapeutic effects.
TL;DR
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, surpassing that of the most commonly used antimicrobial photosensitizers.
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.