Thio-naphthalene-modified artificial bases as targeted photosensitizers for two-photon photodynamic therapy

•A set of quasi-intrinsic artificial bases are proposed as targeted photosensitizer for PDT applications.•The efficient two-photon absorption of P-base analogs fall in the therapeutic window (550-850 nm).•The reduced singlet-triplet energy gaps and large SOC constants ensure an efficient ISC process.•Photosensitivity reliability in biological environments verified by base pairing and linking to deoxyribose. In this work, a series of quasi-intrinsic photosensitizers (PSs) are designed based on 2-amino-8-(1′-β-d-2′-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one (P), which could pair with the 6-amino-5-nitro-3-(1-β-d-2′-deoxyribofuranosyl)-2(1H)-pyridone (Z) and specifically recognize breast and liver cancer cells. The spectra calculations show that the modified bases possess efficient two-photon absorption in red and near-infrared spectra region that contribute to an efficient photodynamic therapy (PDT) for deep-seated tumors. After the vertical excitation, these modified bases in the excited singlet state exhibit a predominance of intersystem crossing to the triplet state channels, which can be predicted by the energy difference and the spin-orbit coupling values between the singlet and triplet states. Additionally, the triplet state lifetimes are examined by considering the radiative and non-radiative rates, thus reflecting the interaction time of the PS with molecular oxygen. To evaluate the direct usefulness in PDT, we further investigated the effect of base pairing and linking to deoxyribose on photosensitivity. [Display omitted]