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. Four new thieno‐expanded purine analogs are computationally designed based on the isomorphic th‐ and tz‐bases. The structural, electronic, and photophysical properties are studied by means of DFT and TDDFT calculations. Micro‐environment effects of hydration, base pairing, and further hydration of base pairs on photophysical properties are examined and the results are compared with their parental bases. The predictions may be helpful for experimental design of novel nucleobase analogs. [ABSTRACT FROM AUTHOR]