String-Attached Oligothiophene Substituents Determine the Fate of Excited States in Ruthenium Complexes for Photodynamic Therapy
Avinash Chettri, Kilian Schneider, Houston D. Cole, John A. Roque, Colin G. Cameron, Sherri A. McFarland, Benjamin Dietzek
Abstract
We explore the photophysical properties of a family of Ru(II) complexes, Ru-ip-nT, designed as photosensitizers (PSs) for photodynamic therapy (PDT). The complexes incorporate a 1H-imidazo[4,5-f][1,10]-phenanthroline (ip) ligand appended to one or more thiophene rings. One of the complexes studied herein, Ru-ip-3T (known as TLD1433), is currently in phase II human clinical trials for treating bladder cancer by PDT. The potent photocytotoxicity of Ru-ip-3T is attributed to a long-lived intraligand charge-transfer triplet state. The accessibility of this state changes upon varying the length (n) of the oligothiophene substituent. In this paper, we highlight the impact of n on the ultrafast photoinduced dynamics in Ru-ip-nT, leading to the formation of the function-determining long-lived state. Femtosecond time-resolved transient absorption combined with resonance Raman data was used to map the excited-state relaxation processes from the Franck–Condon point of absorption to the formation of the lowest-energy triplet excited state, which is a triplet metal-to-ligand charge-transfer excited state for Ru-ip-0T-1T and an oligothienyl-localized triplet intraligand charge-transfer excited state for Ru-ip-2T-4T. We establish the structure–activity relationships with regard to changes in the excited-state dynamics as a function of thiophene chain length, which alters the photophysics of the complexes and presumably impacts the photocytotoxicity of these PSs.