Photophysical property of fluorescent guanine analogs for selectively recognizing acetylated cytosine: A theoretical study

Abstract The photophysical properties of fluorescent nucleobase analogs play a crucial role in nucleic acids detection and the investigation of their structural and functional characteristics. In this study, we computationally designed a series of quasi-intrinsic fluorescent probes according to natural guanine (G) for selectively identifying covalent N 4 -acetylcytosine (4acC), a base that is highly correlated with active transcription and gene expression. This work aims to gain insight into the role of 4acC in biological regulation with minimal perturbation to the native DNA structure. The results indicate that these G-analogs possess extended π -conjugation in comparison with the natural guanine, which could yield efficient fluorescence emission and red-shifted absorption. Especially, the 8-thienyl-2′-deoxyguanosine (ThG) exhibits the highest fluorescence intensity and avoids self-absorption on account of the large Stokes shifts (> 67 nm). What is more, the fluorescence of ThG is unaffected to base pairing with natural cytosine, while the obvious fluorescence quenching is observed by virtue of the excited state intermolecular charge transfer after pairing with 4acC, so it is supposed as a promising biosensor for monitoring the fluorescence changes in the absence or presence of the 4acC. Additionally, the impact of binding deoxyribose on photophysical properties is explored to guarantee the biological applicability of the bright G-analogs in real environment.