A π-extended double-cavity cyclophane with enhanced host-guest charge transfer for NIR-II photothermal therapy

Small-molecule near-infrared-II (NIR-II, 1000–1350 nm) photothermal agents (PTAs) are highly desirable for deep-tissue therapy but are often constrained by complex covalent syntheses that limit structural precision and accessibility. Herein, we report a rationally designed, water-soluble double-cavity cyclophane, GBox-5⁴⁺ (“Gemini Box”), featuring an electron-deficient naphthalene diimide core and π-extended biquinolinium sidewalls. Through host-guest charge transfer and face-to-face π–π stacking interactions, GBox-5⁴⁺ can bind different electron-rich planar guests with a 1:2 host/guest stoichiometry. Compared to its previously reported analogue, GBox-5⁴⁺ exhibits significantly enhanced absorption intensity and photothermal conversion effect upon host-guest complexation, attributed to its expanded π-conjugated sidewalls. Complexation with an oligo (ethylene glycol)-substituted diaminofluorene guest yields a stable water-soluble host–guest assembly that demonstrates efficient photothermal conversion under 1064 nm irradiation and effectively eradicates both Gram-negative and Gram-positive bacteria in vitro. This work highlights the critical role of rational molecular design in the development of advanced functional materials and provides a structurally defined supramolecular platform for future biomedical applications.