Theoretical study on fluorescent T-analogues for selective recognition of 2-aminoadenine (Z) in aqueous solution via base-pair induced ESICT mechanism

The unusual 2-aminoadenine (Z), a fairly exceptional base that is different from four types of normal nucleobases (ATCG), has also been detected in carbon-rich meteorites and revealed from the cyanophage S-2L. Rare in nature, the Z-base still pairs with thymine (T) but with three hydrogen bonds. To better understand the origin and formation of Z-DNA, we proposed a set of optical indicators to recognize the Z-base in aqueous solution theoretically. Herein, the fluorescent probes are constructed based on the natural thymine, which could pair with Z-base without perturbing the native duplex. Compared with the canonical thymine base, the T-analogues can yield red-shifted absorption and efficient fluorescence emission owing to the extended pi-conjugation. In particular, the T-R1 possesses large Stokes shifts (>82 nm) that could avoid self-absorption and the highest fluorescence intensity, which makes it a promising optical biosensor to identify the Z-base at molecular level. The TDDFT-calculated fluorescent wavelengths of T-R1 locate around 420 nm outside the emission band of the natural nucleobases (similar to 320 nm). More importantly, the base-pair induced selective fluorescence quenching is observed in T-R1:Z following the excited state intermolecular charge transfer (ESICT), while the efficient photoluminescence of T-R1 is insensitive to base pairing with adenine (A). To ensure the direct utilization of the quasi-intrinsic T-analogues in biological environment, we examined the effects of linking deoxyribose on corresponding optical spectra, which shows little differences with the experimental observation.