NIR‐Absorbing Ru<sup>II</sup> Complexes Containing α‐Oligothiophenes for Applications in Photodynamic Therapy
Liubov M. Lifshits, John A. Roque, Houston D. Cole, Randolph P. Thummel, Colin G. Cameron, Sherri A. McFarland
Abstract
Abstract 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 ( n T; 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.