Impact of Metal Center on Photophysics and <i>In Vitro</i> Photodynamic Therapeutic Activities of Ru(II)/Os(II)/Ir(III) Bis-terpyridine Complexes Bearing Oligothienyl Substituents

Six bis-terpyridine Ru(II) and Os(II) complexes ( n T-Ru/Os, n = 2–4) incorporating oligothienyl-substituted terpyridines were synthesized and compared with analogous Ir(III) complexes to evaluate how metal centers and thienyl substitution affect photophysics and photodynamic therapeutic (PDT) activity against SKMEL28 melanoma and MDA-MB-231 breast cancer cells under normoxia and hypoxia. Increasing thienyl groups induced bathochromic shifts in absorption, with n T-Ru/Os displaying more intense, narrower, and red-shifted bands than n T-Ir; n T-Os also showed a broad 600–750 nm band. All complexes emitted near-IR phosphorescence with triplet lifetimes of 0.12–47.5 μs and produced singlet oxygen (Φ Δ = 0.13–0.84). Generally, n T-Ir/Ru gave higher Φ Δ than n T-Os, though 4T-Os matched 4T-Ir under green light irradiation. In vitro, all complexes exhibited minimal dark cytotoxicity but strong photocytotoxicity under broadband visible, blue, green, or red-light activation, except 2T-Ir, which was red-inactive. Importantly, 3T-Ir, 4T-Ir, and 4T-Ru maintained phototoxicity toward SKMEL28 cells under hypoxia, and 2T-Ru – 4T-Ru toward MDA-MB-231 cells. Notably, 4T-Ru retained strong red-light activity under hypoxia against both cell lines. Mechanistic studies suggest that singlet oxygen, superoxide, and peroxynitrite contribute to activity. These findings highlight n T-Ru/Os/Ir complexes as promising PDT agents with distinct photophysical tunability and hypoxia resilience.