Real-time Monitoring Excitation Dynamics of Human Telomeric Guanine Quadruplexes: Effect of Folding Topology, Metal Cation, and Confinement by Nanocavity Water Pool

Abstract

Guanine(G)-rich human telomeric (HT) DNA repeats, crucial to maintenance of genome stability, readily form G-quadruplexes (GQs) with various folding topologies. Research on excitation dynamics of HT-GQs is, however, scarce. Herein, we report a femtosecond time-resolved fluorescence coupled with transient absorption investigation on HT-GQ with the baskettype structure in Na + solution. The result unveils an unusual multichannel nonradiative mechanism dominated by states with varying character of charge transfer lasting ten and hundreds of picoseconds, accounting altogether for an overwhelming ∼85% of the overall deactivation involving proton transfer. Our comparative study shows that encapsulating the GQ in nanocavity water pool or changing it into hydrid-type topologies with the presence of K + ions alter differently energies and lifetimes of these states, yet without affecting the nature of the electronic excitation involved. The finding of this work underscores a leading role of structural rigidity in regulating the interplay with the microenvironment of photoexcited monomolecularly folded HT-GQs.

Guanine Radicals Generated in Telomeric G-Quadruplexes by Direct Absorption of Low-Energy UV Photons: Effect of Potassium Ions

“…In the frame of this scenario, K + ions, which are larger and less mobile than Na + , should hinder the stabilization of CT states, favoring charge separation instead. This is corroborated by a recent time-resolved study focusing on the excited states, which shows that the transient absorption of CT states is more important for TEL21/Na + compared to TEL21/K + [22].…”

“…The mechanism proposed to explain the φ 1 enhancement is related to a non-vertical electron photo-detachment and is described in reference [11]. Briefly, charge transfer (CT) states are formed during the excited state relaxation [20][21][22]. A small fraction of the CT states may undergo charge migration, followed by charge separation.…”

Guanine Radicals Induced in DNA by Low-Energy Photoionization

“…Population of excited CT states both in duplexes [42][43][44] and G4 41,45,46 is well documented. The occurrence of charge separation along DNA strands has also been reported.…”

“…39 In the frame of such a scenario, Na + cations, smaller and more mobile than K + , 40 allow the geometrical arrangement accompanying stabilization of CT states 41 and, hence, reducing the probability of charge separation. Population of excited CT states both in duplexes 42−44 and G4 41,45,46 is well documented. The occurrence of charge separation along DNA strands has also been reported.…”

The Structural Duality of Nucleobases in Guanine Quadruplexes Controls Their Low-Energy Photoionization

“…Femtosecond studies detected the population of CT states in telomeric G4. − It was also shown that the excited state relaxation pattern remains the same in reversed micelles, mimicking the crowding conditions in cells . QM calculations performed for such G4 showed that CT states may be formed between a T in the loop and a G in the core, but experiments have not disentangled this type of mixed CT states from those involving two guanines .…”