Five thieno[3,4-b]pyrazine-based model compounds were studied to explore the effects of the substituent groups (alkyl or aryl) on the structure, atomic charge, optical properties, ionization potential (IP), electron affinity (EA), and reorganization energy. Theoretical calculations were carried out by density functional theory (DFT) using the B3LYP hybrid function combined and CAM-B3LYP with the 6-31G(d) basis set. The lowest-lying absorption and emission spectra of 9,9′-diethylhexylfluorene-alt-5,7-dithien-2-yl-thieno[3,4-b] pyrazine (FDDTTP) with alkyl groups showed a blue-shift, while those of FDDTTP with aryl groups exhibited a red-shift. The results agree well with analytical data from reorganization energies. IPs are brought down by both alkyl and aryl groups. However, EAs are raised only by aryl units. The results indicate that aryl groups are more helpful in forming excitions for FDDTTP molecules. Consequently, FDDTTP with aryl groups are more efficient acceptor segments for designing donor–acceptor copolymers than those with alkyl groups.