Computational investigations of the excited state dynamics and quenching mechanisms of polycyclic aromatic hydrocarbon DNA adducts in solution

Synthetically modified fluorescent nucleotides (SFNs) are highly popular in a variety of experiments to explore biochemistry in molecular imaging, but the connection between their photodynamics and quenching mechanisms to their molecular structure remain relatively unstudied computationally. We combine various levels of theory, including classical force field dynamics and excited state quantum mechanic/molecular mechanic Born–Oppenheimer dynamics to characterize a set of polycyclic aromatic hydrocarbon based substituents bound to cytidine (dC) and guanine (dG) nucleobases. We specifically focus on perylene (P) bound to C5 and C6 of dC, and the naturally occurring benzo[a]pyrene diol epoxide (B[a]PDE) on dG. We find that specific angles of the connection points between them modulate mechanisms of intramolecular charge transfer, where an electron moves from P to dC and dG to B[a]PDE once an optimal angle is reached. Functionalization location and flexibility of the substituent affect access to these angles and, therefore, the amount of rapid charge transfer quenching of the fluorescence that we observe. This work demonstrates that the choice of functionalization location for SFNs changes the accessibility of charge transfer mechanisms via steric hindrance, and suggest that this feature can be applied for future tuning of fluorescence properties.