Enhancing photothermal energy transduction through inter- and intramolecular interactions of multiple two-photon dyes appended onto Calix[4]arene

Organic dyes-based photothermal agents (OPTAs) has received increasing attention as alternative to inorganic materials due to their higher biocompatibility and extensive diversification. Maximizing non-radiative deexcitation channels is crucial to improve the photothermal conversion efficiency (PCE) of OPTAs. This is typically achieved through individual molecular design or collective enhancement using supramolecular strategies. Furthermore, photothermal therapy (PTT) generally relies on linear one-photon absorption of the light source by the OPTA, with less consideration given to non-linear two-photon absorption (2PA) strategies, despite their potential benefits. Here, a synergistic strategy, which combines intramolecular and intermolecular quenching, is employed to maximize the photothermal efficiency of diphenylamino substituted distyryl dicyanobenzene (DSB), an outstanding two-photon absorbing chromophore. One to three DSB units have been introduced on the conic p-tert-butyl-calix[4]arene (CX), serving as a preorganizing platform to allow aggregates formation and promote intramolecular quenching within the multichromophoric systems. Importantly, the multichromophoric molecules had very high two photon absorption capabilities with cross sections (2PA) reaching maximal values of 3290 GM at 810 nm. Experimental data accompanied by large scale Molecular Dynamics (MD) simulations and Time-Dependent Density Functional Theory (TD-DFT) calculations shed light onto the interaction mechanism in those multiple DSB-appended CX compound to rationalize their optical properties. Then, the formulation with Pluronic F127 amphiphile yields water-dispersible nanoprecipitates (Nps) in which the PCE is further maximized and the photobleaching reduced due to the combination of intra and intermolecular quenching. The high two-photon absorption in the near-infrared (NIR) window associated to high PCE of these nanosized OPTAs could serve as basis to future in vivo 2P-PTT applications.