Photoisomerization and ultrasensitive fluorescence detection of toxic deoxyguanosine adduct ANdG: a theoretical study

Abstract

Abstract The toxic deoxyguanosine adduct (ANdG) is one of the most representative carcinogenic DNA adducts, resulting from human exposure to aromatic amine (AA). Accordingly, the ultrasensitive detection of AA-derived adduct in DNA with minimal disturbance to the native structures is key to elucidating carcinogenesis mechanisms and mitigating cancer risk. Considering the lack of adequate intrinsic optical emission in two obtained rotamers (ANG1 and ANG2), a set of quasi-intrinsic fluorescent probes based on the complementary cytosine are proposed to identify covalent G-adduct. It is found that the expanded C-analogues in solution could bring red-shifted absorption maxima and enhanced photoluminescence due to the additional π-conjugation. In particular, because PhpC possesses large Stokes shift (98 nm) and the highest fluorescence intensity (f flu. = 0.546) in emission, it is proposed as the biosensor to monitor the optical changes in the presence and absence of the considered ANG. Compared with native C base, the absorption maximum of PhpC is red-shifted by 145 nm, which contributes to the selective excitation after incorporating into the nucleic acids. More importantly, the fluorescence is insensitive to base pairing with natural guanine, while the efficient fluorescence quenching is observed after pairing with ANG1/ANG2 as a result of the obvious excited state intermolecular charge transfer. To evaluate the direct application of the bright C-analogues with a high selectivity for deoxyguanosine adduct ANdG in DNA, we further examined the effect of linking deoxyribose on absorption and fluorescence emission, which are consistent with the experimental data.