biostudies-literatureUnknown147(33)Stitch MPhotosensitized damage by the mechanism of direct 1e^- transfer from a nucleobase to the metal complex is a complementary approach to type I and type II methods of photodynamic therapy. In this ultrafast spectroscopic study we report the ability of a nitrile infrared redox probe to report on the photo-oxidation of guanine-rich DNA, comprising persistent runs of guanine, by the dppz-10-CN containing complex [Ru(TAP)₂(dppz-10-CN)]²⁺ (<b>1</b>²⁺), dppz-10-CN = 10-cyano-dipyrido[3,2-a:2',3'-c]phenazine and TAP = 1,4,5,8-tetraazaphenanthrene. Our study reveals the ability of the enantiomers of <b>1</b>²⁺ to photo-oxidize guanine in double-stranded and quadruplex DNA. Transient visible absorption reveals a high yield of the formation of the photoreduced metal complex due to photo-oxidation of guanine in the quadruplex-bound <b>1</b>²⁺ systems, and that this is greater for the Λ enantiomer. Spectro-electrochemical and computational studies indicate the role of the dppz-10-CN as the preferred site of reduction, while time-resolved electronic absorption (TrA) spectroscopy highlights the impact of the enantiomers on the yield of photo-oxidation in the DNA systems. Notably, time-resolved infrared (TRIR) spectroscopy allows comprehensive tracking of the photo-oxidation dynamics by monitoring four key components, namely: (1) the transient band of the Ru/TAP-based lowest ³MLCT excited state, (2) bleach bands associated with DNA bases in close proximity to the excited state "site effect", (3) the guanine radical cation band at ca. 1700 cm^-1 and (4) the amplification of the red-shifted nitrile stretching vibration of the transient dppz-reduced complex. Together, these results allow detailed profiling of photoinduced electron transfer in DNA-bound ruthenium(II) polypyridyl complex systems and highlight the potential of such redox probes. Overall, this study presents an important insight regarding the nature of charge transfer in a Hoogsteen-bound guanine quadruplex compared to Watson-Crick GC base pairings.Journal of the American Chemical Society29801-29814https://www.ebi.ac.uk/biostudies/studies/S-EPMC12371865biostudies-literatureEyes on the Prize: Tracking Electron Transfer in G-Rich Duplex and Quadruplex DNA Using Enantiopure Ruthenium Polypyridyl Infrared Redox Probes.PMC12371865Towrie MHartl FLehane NGreetham GMQuinn SJStitch MPizl MfalseEyes on the Prize: Tracking Electron Transfer in G-Rich Duplex and Quadruplex DNA Using Enantiopure Ruthenium Polypyridyl Infrared Redox Probes.Photosensitized damage by the mechanism of direct 1e^- transfer from a nucleobase to the metal complex is a complementary approach to type I and type II methods of photodynamic therapy. In this ultrafast spectroscopic study we report the ability of a nitrile infrared redox probe to report on the photo-oxidation of guanine-rich DNA, comprising persistent runs of guanine, by the dppz-10-CN containing complex [Ru(TAP)₂(dppz-10-CN)]²⁺ (<b>1</b>²⁺), dppz-10-CN = 10-cyano-dipyrido[3,2-a:2',3'-c]phenazine and TAP = 1,4,5,8-tetraazaphenanthrene. Our study reveals the ability of the enantiomers of <b>1</b>²⁺ to photo-oxidize guanine in double-stranded and quadruplex DNA. Transient visible absorption reveals a high yield of the formation of the photoreduced metal complex due to photo-oxidation of guanine in the quadruplex-bound <b>1</b>²⁺ systems, and that this is greater for the Λ enantiomer. Spectro-electrochemical and computational studies indicate the role of the dppz-10-CN as the preferred site of reduction, while time-resolved electronic absorption (TrA) spectroscopy highlights the impact of the enantiomers on the yield of photo-oxidation in the DNA systems. Notably, time-resolved infrared (TRIR) spectroscopy allows comprehensive tracking of the photo-oxidation dynamics by monitoring four key components, namely: (1) the transient band of the Ru/TAP-based lowest ³MLCT excited state, (2) bleach bands associated with DNA bases in close proximity to the excited state "site effect", (3) the guanine radical cation band at ca. 1700 cm^-1 and (4) the amplification of the red-shifted nitrile stretching vibration of the transient dppz-reduced complex. Together, these results allow detailed profiling of photoinduced electron transfer in DNA-bound ruthenium(II) polypyridyl complex systems and highlight the potential of such redox probes. Overall, this study presents an important insight regarding the nature of charge transfer in a Hoogsteen-bound guanine quadruplex compared to Watson-Crick GC base pairings.2025-01-01T00:00:00Z2025 Aug2026-05-08T10:50:45.778Z2026-05-03T03:05:55.342ZS-EPMC123718654078401610.1021/jacs.5c05736