String-Attached Oligothiophene Substituents Determine the Fate of Excited States in Ruthenium Complexes for Photodynamic Therapy

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Molecules, spectroscopy, kinetics, environment, & general theory, 2021-08, Vol.125 (32), p.6985-6994
• Main Authors: Chettri, Avinash, Schneider, Kilian R. A, Cole, Houston D, Roque, John A, Cameron, Colin G, McFarland, Sherri A, Dietzek, Benjamin
• Format: Article
• Language: English
• Subjects: A: Structure, Spectroscopy, and Reactivity of Molecules and Clusters
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/acs.jpca.1c04900

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.