More and more independent researchers seem to be recognizing the power of TLD1433 PDT.
https://onlinelibrary.wiley.com/doi/10.1002/anie.202423335?af=R Advances in the Design of Photoactivatable Metallodrugs: Excited State Metallomics
Dr. Huayun Shi, Dr. Rafael C. Marchi, Prof. Peter J. Sadler
Department of Chemistry, University of Warwick, Coventry, CV4 7AL UK
First published: 13 January 2025
"...Fasten your seat belt! Choose lightning-speed, photoactivated journeys for complexes by selecting the metal, its oxidation state, ligands and geometry. Track complexes through excited singlet (S) states, intersystem crossing (ISC) to triplet (T) states, energy/charge-transfer, luminescence, ligand substitutions and redox reactions. Pathways to novel drugs with new mechanisms of action. Unravelling excited metallomics on the way is challenging...."
"...Besides red-shifting the absorption band, another strategy to increase the effectiveness of metal-based photocatalysts is the formation of low-lying 3IL* and/or 3ILCT* states. Generally, low-lying excited states are favorable due to spin-orbit coupling between a ligand and a heavy atom, and their long lifetimes lengthen the time of interaction with substrates to form radicals.27 The remarkable photocytotoxicity of TLD1433 is based on this strategy, which facilitates the formation of ROS via Type I and II mechanisms.6 The Os(II) complex bearing four thiophenes rings derived from TLD1433, Os-1 (Figure4), exhibits a long-lived, low-lying 3ILCT state (τo=3–4μs) for the photoinduced production of O2⋅− and 1O2. Its phototoxicity indices (PI) are > 106 and > 70 under normoxia and hypoxia, respectively, despite the activation wavelengths (white visible light, 523nm and 633nm).28 The elevated phototoxicity under hypoxia can be attributed to a change in the character of the low-lying triplet excited state from 3MLCT* to 3ILCT* with increase in the number of thiophene rings..."
"...OPE (One-photon Excitation) is also frequently applied to complexes designed to combat antimicrobial resistance (AMR), a global issue. Photoactivatable metallodrugs for antimicrobial PDT (aPDT) can introduce damage to multiple bacterial targets by ROS generation.75 The Ru(II) drug TLD1433 for example shows activity against Staphylococcus aureus and resistant Staphylococcus aureus under green light through ROS generated by Type I and Type II mechanisms.76..."
"...The excited state dynamics of TLD1433 (Figure1) in MCF7 breast cancer cells using a modified transient absorption (TA) system in a vertical position that orients the laser pulses perpendicular to the plane of the optical table, has been studied.132 TLD1433 (40μM) in fixed MCF7 cells showed bi-exponential kinetics related with vibrational conversion from 3MLCT to 3ILCT (τ = 1.5ps) and vibration relaxation within 3ILCT (13ps). In cellulo measurements showed no decay of the long-lived 3ILCT in a 1.9ns window, while a decay (35 %) was observed in aqueous solution. The same kinetic profile was observed for highly concentrated TLD1433 in water (500μM) or when TLD1433 interacts with calf thymus DNA (ct-DNA) in solution. Moreover, TA microscopy showed the heterogeneity in excited-state dynamics across different cellular regions where the photosensitizer was densely concentrated, reflecting local environmental influences (Figure11b). This is a good example of how the cellular medium may alter the lifetime of the excited states, making them different from those tracked in solution. This work opens the possibility to explore in depth excited-state dynamics of photosensitizers in their relevant biological environment...."