Theoretical explore of bridge and donor engineering for novel naphthalimide based photosensitizers for two-photo photodynamic therapy

Naphthalimide derivatives are widely used in the development of clinical drugs and fluorescent probes because of their high light stability and low dark toxicity. Among these applications, as the photosensitizer (PS) used in the two-photon photodynamic therapy (TP-PDT) process is a new application condition of naphthalimide derivatives. Nevertheless, the development of such PSs is still hampered by their short triplet state lifetime and insufficient two-photon absorption (TPA) cross section. In order to explore the influence of different pi-linkers on the efficient naphthalimide based PSs and solve the above problems, this paper characterizes the photophysical properties related to TP-PDT process of a series of naphthalimide based molecules using density functional theory (DFT) and time-dependent DFT (TD-DFT). The results reveal that compared to molecules without linkers and with phenyl as the linker, the compounds using thiophene as the pi-linker have better planarity and optical properties, such as larger TPA cross section, lower energy gap of the singlet-triplet state, larger spin-orbit coupling value, and longer triplet state lifetime. Specifically, molecules 3s-ph, 2s-thio similar to 4s-thio have large TPA cross section value (1028-1384 GM, 8.3-11.2 times of molecule 1s) and triplet state lifetime (1337-11609 mu s, 1.6-14.2 times of molecule 1s), making them effective for TP-PDT process. Furthermore, molecule 1s-thio acts as a promising PS candidate that can effectively undergo type I process and circumvent type II process. It is hoped that our theoretical research can provide some worthy ideas for the design and synthesis of effective naphthalimide based PSs in experiments.