New Study of TLD1433 & TLD1633 by Dr. McFarland et al. McFarland Labs and the Leibniz Insitute of Photonic Technology in Germany collaborated on this study to determine the mechanism behind the photoinduced cytotoxicity of TLD1433 and its derivative TLD1633. Only the abstract is available for free. The full text of this one costs US $40.
Interaction with a Biomolecule Facilitates the Formation of the Function-Determining Long-Lived Triplet State in a Ruthenium Complex for Photodynamic Therapy Avinash Chettri, Houston D. Cole, John A. Roque III, Kilian R. A. Schneider, Tingxiang Yang, Colin G. Cameron, Sherri A. McFarland, and Benjamin Dietzek-Ivani Publication Date: February 18, 2022 Abstract
TLD1433 is the first ruthenium (Ru)-based photodynamic therapy (PDT) agent to advance to clinical trials and is currently in a phase II study for treating nonmuscle bladder cancer with PDT. Herein, we present a photophysical study of TLD1433 and its derivative TLD1633 using complex, biologically relevant solvents to elucidate the excited-state properties that are key for biological activity. The complexes incorporate an imidazo [4,5-f][1,10]phenanthroline (IP) ligand appended to α-ter- or quaterthiophene, respectively, where TLD1433 = [Ru(4,4′-dmb)2(IP-3T)]Cl2 and TLD1633 = [Ru(4,4′-dmb)2(IP-4T)]Cl2 (4,4′-dmb = 4,4′-dimethyl-2,2′-bipyridine; 3T = α-terthiophene; 4T = α-quaterthiophene). Time-resolved transient absorption experiments demonstrate that the excited-state dynamics of the complexes change upon interaction with biological macromolecules (e.g., DNA). In this case, the accessibility of the lowest-energy triplet intraligand charge-transfer (3ILCT) state (T1) is increased at the expense of a higher-lying 3ILCT state. We attribute this behavior to the increased rigidity of the ligand framework upon binding to DNA, which prolongs the lifetime of the T1 state. This lowest-lying state is primarily responsible for O2 sensitization and hence photoinduced cytotoxicity. Therefore, to gain a realistic picture of the excited-state kinetics that underlie the photoinduced function of the complexes, it is necessary to interrogate their photophysical dynamics in the presence of biological targets once they are known.