Quasi-intrinsic fluorescent probes for detecting the DNA adduct (ABPdG) based on an excited-state intermolecular charge transfer mechanism.

Abstract

N'-(2'-Deoxyguanosin-8-yl)-4-aminobiphenyl (ABPdG) is one of the most representative carcinogenic DNA adducts formed by human exposure to 4-aminobiphenyl (4-ABP) during dye production, rubber-manufacturing processes and cigarette smoke. Accordingly, the ultrasensitive detection of ABP-derived adducts in DNA with minimal interference to the native structures becomes key for elucidating carcinogenesis mechanisms and mitigating the risk of cancer. In view of the lack of efficient optical emission in ABPG, we report a theoretical study on the photophysical properties of a set of quasi-intrinsic fluorescent C-analogues, which can form stable W-C base pairs with ABPG. It is found that fluorophore replacement and ring-expansion can bring a red-shifted absorption and bright photoluminescence due to additional π-conjugation. In particular, because the tricyclic cytosine analogue 1,3-diaza-2-oxophenoxazine (tCO) possesses distinct optical properties, it is proposed as a biosensor to identify ABPG. The TDDFT-calculated absorption maximum of tCO is red-shifted by 97 nm in comparison with that of the native C base, which contributes to selective excitation after incorporating into the nucleic acids. Although the fluorescence is insensitive to base pairing with natural guanine, the excited state intermolecular charge transfer (ESICT)-governed "OFF-ON" signal can be observed in the presence and absence of ABPG. Moreover, to evaluate the direct availability of the bright C-analogues with high selectivity for the deoxyguanosine adduct ABPG in DNA, we further investigated thoroughly the effects of its linking to deoxyribose on its absorption and emission, which shows little difference from that of experiment.