Contrasting Photosensitized Processes of Ru(II) Polypyridyl Structural Isomers Containing Linear and Hooked Intercalating Ligands Bound to Guanine-Rich DNA

• Published in: The journal of physical chemistry. B 2024-08, Vol.128 (32), p.7803-7812
• Main Authors: Stitch, Mark, Sanders, Rosie, Sazanovich, Igor V., Towrie, Michael, Botchway, Stanley W., Quinn, Susan J.
• Format: Article
• Language: English
• Subjects: B: Biophysical and Biochemical Systems and Processes; Coordination Complexes - chemistry; Coordination Complexes - metabolism; DNA - chemistry; DNA - metabolism; Guanine - chemistry; HeLa Cells; Humans; Intercalating Agents - chemistry; Isomerism; Ligands; Molecular Structure; Photochemical Processes; Photosensitizing Agents - chemistry; Photosensitizing Agents - metabolism; Pyridines - chemistry; Ruthenium - chemistry
• ISSN: 1520-6106; 1520-5207; 1520-5207
• DOI: 10.1021/acs.jpcb.4c04129

The DNA binding and cellular uptake of the lambda enantiomer of two bis-tetraazaphenanthrene (TAP) Ru­(II) polypyridyl complexes containing either a linear dppn (1) or a hooked bdppz (2) benzodipyridophenazine ligand are reported, and the role of different charge-transfer states of the structural isomers in the photo-oxidation of guanine is explored. Both complexes possess characteristic metal-to-ligand charge-transfer (MLCT) bands between 400 and 500 nm and emission at ca. 630 nm in an aerated aqueous solution. Transient visible absorption (TrA) spectroscopy reveals that 400 nm excitation of 1 yields a dppn-based metal-to-ligand charge-transfer (MLCT) state, which in turn populates a dppn intraligand (3IL) state. In contrast, photoexcitation of 2 results in an MLCT state on the TAP ligand and not the intercalating bdppz ligand. Both 1 and 2 bind strongly to double-stranded guanine-rich DNA with a loss of emission. Combined TrA and time-resolved infrared (TRIR) spectroscopy confirms formation of the guanine radical cation when 2 is bound to the d­(G5C5)2 duplex, which is not the case when 1 is bound to the same duplex and indicates a different mechanism of action in DNA. Utilizing the long-lived triplet excited lifetime, we show good uptake and localization of 2 in live cells as well as isolated chromosomes. The observed shortening of the excited-state lifetime of 2 when internalized in cell chromosomes is consistent with DNA binding and luminescent quenching due to guanine photo-oxidation.