Ru(II) Phenanthroline-Based Oligothienyl Complexes as Phototherapy Agents.

Ru(II) polypyridyl complexes have gained widespread attention as photosensitizers for photodynamic therapy (PDT). Herein, we systematically investigate a series of the type [Ru(phen)(IP-T)], featuring 1,10-phenanthroline (phen) coligands and imidazo[4,5-][1,10]phenanthroline ligands tethered to 0-4 thiophene rings (IP-T). The complexes were characterized and investigated for their electrochemical, spectroscopic, and (photo)biological properties. The electrochemical oxidation of the T unit shifted by -350 mV as = 1 → 4 (+920 mV for , +570 mV for ); T reductions were observed in complexes (-2530 mV) and (-2300 mV). Singlet oxygen quantum yields ranged from 0.53 to 0.88, with and being equally efficient (∼0.88). Time-resolved absorption spectra of - were dominated by metal-to-ligand charge-transfer (MLCT) states (τ = 0.40-0.85 μs), but long-lived intraligand charge-transfer (ILCT) states were observed in - (τ = 25-148 μs). The ILCT energies of and were computed to be 1.6 and 1.4 eV, respectively. The phototherapeutic efficacy against melanoma cells (SK-MEL-28) under broad-band visible light (400-700 nm) increases as = 0 → 4: was inactive up to 300 μM, - were moderately active (EC ∼ 600 nM, PI = 200), and (EC = 57 nM, PI > 1100) and (EC = 740 pM, PI = 114,000) were the most phototoxic. The activity diminishes with longer wavelengths of light and is completely suppressed for all complexes except and in hypoxia. is the more potent and robust PS in 1% O over seven biological replicates (avg EC = 1.3 μM, avg PI = 985). exhibited hypoxic activity in five of seven replicates, underscoring the need for biological replicates in compound evaluation. Singlet oxygen sensitization is likely responsible for phototoxic effects of the compounds in normoxia, but the presence of redox-active excited states may facilitate additional photoactive pathways for complexes with three or more thienyl groups. The ILCT state with its extended lifetime (30-40× longer than the MLCT state for and ) implicates its predominant role in photocytotoxicity.