Efficient and Controlled Singlet Oxygen Generation from Micellar Nanoaggregates of Organic Photoswitchable Amphiphile

Abstract Aggregation enhanced singlet oxygen (¹O₂) generation is one of the most demanding noninvasive protocols for cancer treatment using photodynamic therapy (PDT) as the nanoaggregates often offer minimal damage to surrounding healthy tissues. However, the construction of metal‐free pure organic amphiphiles that can simultaneously generate ¹O₂ with enhanced efficiency and have the ability to switch the ¹O₂ generation process with precise control in aggregated form is a challenging task. Herein, two di‐cationic naphthalimide‐dithienylethene‐naphthalene diimide (NI_octyl‐DTE‐NDI_(NMe3)2)²⁺ have been developed, which assemble as micellar nanoaggregate (≈50 nm) and demonstrated enhanced ¹O₂ generation capability in the aggregated state compared to its monomeric form. The time‐resolved emission spectroscopy (TRES) analysis at 77 K revealed that the triplet state of the nanoaggregate is stabilized by 0.14 eV compared to its monomeric form, corroborating the observation of enhanced ¹O₂ generation capacity in aggregated form. Further, the result is verified by the rate of photooxidation of several organic species (1,3‐diphenylisobenzofuran, 9,10‐dimethylanthracene, and triphenyl phosphine). To the best of our knowledge, it is a rare example of metal‐free pure organic molecule that not only enhances ¹O₂ generation in aggregated form (yield Φ_Δ≈0.42) but also allows controlled (“off/on”) ¹O₂ generation through simple UV and visible light irradiation. This system has been successfully applied in fluorescence imaging and in vitro PDT in HeLa cells in aqueous media. Further, computational calculations elucidate the excited‐state manifolds of organic photoswitchable amphiphile and energy transfer (ET) pathways involved in controlled ¹O₂ generation.