Computational design and characterization of new thieno-expanded tricyclic purine analogs

Unnatural nucleobases are under intense research due to their widespread applications in nucleic acids research. In this work, four new thieno-expanded purine analogs comprising ^ttzA, ^tthA, ^ttzG, and ^tthG were computationally designed based on the isomorphic tz- and th-bases. These base analogs can also be seen as modified derivatives of the previously reported tricyclic purine analogs (^ttA and ^ttG). The structural, electronic, and photophysical properties are studied by means of DFT and TDDFT calculations. We find out that these new bases can form stable Watson-Crick base pairs with natural counterparts, thus potentially mimicking natural nucleobases in DNA/RNA duplexes. Calculations reveal that these bases have smaller AIPs and HOMO-LUMO gaps than natural ones, suggesting that they are candidates for applications in nanowire technology. Particularly, the photophysical properties were explored, and the results are compared with those for tz-, th-, and tt-bases. The nature of the low-lying excited states is discussed, and analyses reveal that the thiophene-homologation would not change excitation maxima of ^thA and ^tzA, while it will result in large red-shifts of those of ^thG and ^tzG. Meanwhile, thiophene insertion has relatively larger influences on the emissions ^thA and ^tzG, for which the fluorescence was 37 nm blue-shifted and 19 nm red-shifted, respectively. Taking these new bases as derivatives of ^ttA and ^ttG, it was found that the modifications would result in large red-shifts of both the excitation maxima and the fluorescence. The effects of water solution and base paring on the phtotophysical properties were also considered.