Conjugation-driven modulation of excited-state dynamics and photobiological activity in Ru(II) bis-terpyridyl oligothienyl complexes.

To elucidate how ligand conjugation modulates photophysical behavior and photobiological activity, a new family of bis-terpyridyl Ru(II) complexes bearing oligothienyl-substituted ligands, [Ru(tpy)(tpy-nT)]2+ (n = 0-4; Ru-nT), were synthesized and comprehensively characterized. Progressive thiophene extension produced predictable bathochromic shifts and enhanced intensity of intraligand (ILCT) and metal-to-ligand charge-transfer (MLCT) absorption bands, accompanied by red-shifted phosphorescence (673-818 nm), microsecond excited-state lifetimes, and singlet‑oxygen generation (ΦΔ = 0.46-0.86). The transition from Ru-1T to Ru-2T marked a sharp increase in triplet-state lifetime and ΦΔ, signifying a shift from predominantly MLCT to mixed MLCT/ILCT character. Photocytotoxicity toward SK-MEL-28 melanoma cells revealed wavelength- and oxygen-dependent structure-activity relationships: Ru-2T exhibited exceptional potency under normoxia (EC50 ≈ 0.5 nM, PI >103), whereas Ru-4T retained sub-micromolar activity and high phototoxic indices under hypoxia and red-light irradiation. Increasing thiophene length also enhanced lipophilicity (log Do/w ≈ -1.8 → +0.2), correlating with diminished photocytotoxicity but sustained activity under oxygen limitation. Extension of these studies to microbial models revealed parallel trends - Ru-2T was most effective against Gram-positive E. faecalis V587 (EC50 = 0.17 μM, PI = 216), while Ru-4T showed selective photoactivity toward Gram-negative E. coli W3110 (EC50 = 6.5 μM, PI ≈ 21). Collectively, these results demonstrate that systematic control of conjugation and polarity in Ru(II) bis-terpyridyl frameworks enables tuning of excited-state character, wavelength responsiveness, and biological activity, establishing design principles for oxygen-adaptive photoactive metallodrugs.