Molecular regioisomerism: an advantageous strategy for optimizing two-photon absorption performance of organic chromophores

Two-photon absorbing fluorophores have emerged as powerful imaging agents, offering advantages such as high spatial resolution, deep light penetration, minimal photobleaching, minor photodamage, and low autofluorescence. However, existing two-photon absorbing fluorophores still face the limitation of a small two-photon absorption cross-section. The conventional approaches toward fluorophores with a large two-photon absorption cross-section involve enhancing intramolecular charge transfer, extending the π-conjugation length, increasing the number of π-conjugation paths, improving coplanarity, etc. These approaches are promising but hindered by synthesis complexities, large molecular weight (low membrane permeability), poor solubility, low photostability and aggregation-caused quenching. Herein, we summarize an emerging strategy, namely molecular regioisomerism, which could improve the two-photon absorption performance through adjusting molecular symmetries, molecular π-conjugations, molecular orbital distributions, molecular dipoles, and/or intermolecular interactions. This review can guide the design and synthesis of regioisomers of organic chromophores with good two-photon absorption performance, as well as deepen the research on the structure–property relationship of the regioisomers.