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

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.

Figure 1.

(a) Chemical structures of the complexes investigated. (b) Steady state UV-vis absorption and emission spectra of Ru-ip-0T-4T in water (emission spectra are normalized to the MLCT emission maximum at 640 nm). The UV-vis absorption and emission spectra were reported previously. The ratio of the Resonance Raman band intensity at 1450 cm⁻¹ (due to bpy) relative to that at 1320 cm⁻¹ (due to the thienyl rings) are indicated by the red circles and show the increased contribution of the thienyl vibration with increasing n for Ru-ip-0T-4T with 476 nm excitation. (c) Resonance Raman spectra (normalized to the bpy band at 1320 cm⁻¹) of Ru-ip-0T-4T in water with 476 nm excitation. Resonance Raman bands associated with phen are marked by the vertical black dashed lines; thiophene-associated bands are marked by the grey dashed lines.

Figure 2.

Femtosecond transient absorption spectra of Ru-ip-0T (a) and Ru-ip-1T (b) in water upon excitation at 480 nm at various delay times. The shaded spectra represent transient absorption spectra recorded at a delay time of 500 ns. The strong negative differential absorption band at probe wavelengths longer than 570 nm is due to emission from the excited complex. The insets show transient absorption kinetics at selected probe wavelengths. The ns transient absorption data has been reported previously and is reproduced here to give a comprehensive summary of the overall excited-state decay.

Figure 3.

(a) Femtosecond TA spectra of Ru-ip-2T in water with 480 nm excitation at different delay times and a spectrum at 1 μs from nanosecond TA. The negative signal beyond 600 nm in the ns TA spectrum is due to phosphorescence from the complex. The inset shows kinetics at the respective wavelengths on the ps to μs time scale. (b) DAS with the inverted absorption spectrum. The spectrum at 1 μs was determined by ns transient absorption spectroscopy, which has been reported previously. The spectrum is included here to give a full account of excited state lifetimes.

Figure 4.

(a), (c) Femtosecond TA spectra of Ru-ip-3T and Ru-ip-4T, respectively, in water with 480 nm excitation at different delay times. The insets show the kinetics at the respective wavelengths on the ps and μs timescales for Ru-ip-3T and Ru-ip-4T, respectively. The previously published μs kinetic data is included to give a full account of the excited state lifetimes. (b), (d) The DAS of Ru-ip-3T and Ru-ip-4T, respectively. The black curve (Inf.) refers to the infinite spectrum on the ultrafast timescale.

Figure 5.

(a) Jablonski diagram for Ru-ip-0T and Ru-ip-1T where relaxation occurs via the emissive ³MLCT state. (b) In Ru-ip-2T addition of a second thiophene ring to the chain leads to population of an ³ILCT state which is nearly isoenergetic with the emissive ³MLCT state. (c) In Ru-ip-3T and Ru-ip-4T the ³ILCT state is highly stabilized and acts as a major relaxation pathway with only a minor fraction of molecules relaxing via the ³MLCT state.

Figure 6

(a) Femtosecond TA spectra of Ru-ip-3T in water with 400-nm excitation at different delay times. The inset shows the kinetics at the respective wavelengths on the ps time scale. (b) DAS of Ru-ip-3T. The black curve (Inf.) refers to the infinite spectrum on the ultrafast timescale.