NIR-Absorbing Ru^II Complexes Containing α-Oligothiophenes for Applications in Photodynamic Therapy

The design of near-infrared (NIR)-active photosensitizers (PSs) for light-based cancer treatments such as photodynamic therapy (PDT) has been a challenge. While several NIR-Ru^II scaffolds have been reported, this approach has not been proven in cells. This is the first report of NIR-Ru^II PSs that are phototoxic to cancer cells, including highly pigmented B16F10 melanoma cells. The PS family incorporated a bis(1,8-naphthyridine)-based ligand (tpbn), a bidentate thiophene-based ligand (nT; n=0-4), and a monodentate 4-picoline ligand (4-pic). All compounds absorbed light >800 nm with maxima near 730 nm. Transient absorption (TA) measurements indicated that n=4 thiophene rings (4T) positioned the PDT-active triplet intraligand charge transfer (³ ILCT) excited state in energetic proximity to the lowest-lying triplet metal-to-ligand charge transfer (³ MLCT). 4T had low-micromolar phototoxicity with PI_vis and PI_733nm values as large as 90 and 12, respectively. Spectroscopic studies suggested that the longer-lived (τ_TA =3-6 μs) ³ ILCT state was accessible from the ³ MLCT state, but energetically uphill in the overall photophysics. The study highlights that phototoxic effects can be achieved with NIR-absorbing Ru^II PSs as long as the reactive ³ ILCT states are energetically accessible from the low-energy ³ MLCT states. It also demonstrates that tissue-penetrating NIR light can be used to activate the PSs in highly pigmented cells where melanin attenuates shorter wavelengths of light.