Eyes 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+ (12+), dppz-10-CN = 10-cyano-dipyrido3,2-a:2',3'-cphenazine and TAP = 1,4,5,8-tetraazaphenanthrene. Our study reveals the ability of the enantiomers of 12+ 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 12+ 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.