Abstract
The urge to discover selective fluorescent binders to G-quadruplexes (G4s) for rapid diagnosis must be linked to understand the effect that those have on the DNA photophysics. Herein, we report on the electronic excited states of a bound merocyanine dye to c-Myc G4 using extensive multiscale quantum mechanics/molecular mechanics calculations. We find that the absorption spectra of c-Myc G4, both without and with the intercalated dye, are mainly composed of exciton states and mixed local/charge-transfer states. The presence of merocyanine hardly affects the energy range of the guanine absorption or the number of guanines excited. However, it triggers a substantial amount (16%) of detrimental pure charge-transfer states involving oxidized guanines. We identify the rigidity introduced by the probe in G4, reducing the overlap among guanines, as the one responsible for the changes in the exciton and charge-transfer states, ultimately leading to a redshift of the absorption maximum.
Highlights
The urge to discover selective fluorescent binders to G-quadruplexes (G4s) for rapid diagnosis must be linked to understand the effect that those have on the DNA photophysics
Only if the nature of the perturbation induced by the probe is clearly identified is it possible to understand the native properties developed in G4 after light excitation
Molecular dynamics studies have been carried out with G4 binders[26−28] with the aim to monitor the spatiotemporal status of G4s by means of fluorescent probes and shed light into the biological role of these DNA structures
Summary
The location of H and E reveals that these pure charge-transfer states correspond to guanineoxidized states, as the H is fully localized on the guanines (G+.) and E on the probe (P−.) These states are dark ( fosc < 0.006) and lie between the QMCH and G4 absorption bands (3.1−3.9 eV, Table 1), and they exist due to oxidative nature of the positively charged merocyanine.[30,39] these states cannot be directly populated by absorption of light, if they are accessed non-radiatively after excitation, they would lead to an oxidative damage of the genetic code.[40] We see that the H can be differently delocalized on nucleobases according to the electronic nature of the ligand, as shown for different merocyanine derivatives intercalated in duplex A/T.39.
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