Enhanced Rigidity Changes Ultraviolet Absorption: Effect of a Merocyanine Binder on G-Quadruplex Photophysics

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.

Sampling effects in quantum mechanical/molecular mechanics trajectory surface hopping non-adiabatic dynamics

“…At the same time, we are aware these sampling methods are not the only possibly way to generate initial condition for semi-classical non-adiabatic dynamics. Mixed classical-quantum methods have been highly promising to describe the shape of the UV absorption of dyes [ 40 , 41 ] or more complicated systems as transition metal complexes [ 39 ] or biological structures [ 42 ] in explicit solvent environments. It would be interesting to compare their applicability along non-adiabatic dynamics simulations.…”

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

“…A quantitative description, encompassing electronic relaxation and conformational motions in the entire G4, could be achieved by integrating molecular dynamics simulations. Such an approach, already applied for the determination of FC states in small G4, 29 should become affordable in the near future for the study of dynamical processes in larger systems.…”

Identification of Thioflavin T Binding Modes to DNA: A Structure-Specific Molecular Probe for Lasing Applications

“…19 Among the specific DNA cavities there are a few of high biological significance, including i-motifs and G-quadruplexes (G4). 20,21 Both DNA structures are formed by stacking of Hoogsteen base pairs of cytosines or guanines, respectively. Their genetic relevance found in the expression of tumor cells, gene regulation, or cell division 22−24 stimulated an interest in finding selective biomarkers for these motifs.…”

“…Recently, interactions of ThT with DNA have been reported. − It was found that ThT exhibits a moderate emission enhancement in the presence of single- and double-stranded DNA, whereas a strong fluorescence could be detected upon ThT insertion into DNA cavities such as internal gaps or mismatch sites . Among the specific DNA cavities there are a few of high biological significance, including i-motifs and G-quadruplexes (G4). , Both DNA structures are formed by stacking of Hoogsteen base pairs of cytosines or guanines, respectively. Their genetic relevance found in the expression of tumor cells, gene regulation, or cell division − stimulated an interest in finding selective biomarkers for these motifs.…”