over geometry or function is needed at the molecular level. For instance, DAEs have been used to switch fluorescence on and off repeatedly in bioimaging. [5][6][7][8][9][10][11][12][13][14] Unlike irreversibly switchable fluorescence probes, [15][16][17] reversible fluorescence photoswitches can enhance the spatial resolution and accuracy of signals-even for images manifesting autofluorescence signals-via their rigorously controlled photo-responsive switching between ONand OFF-states. [18][19][20][21] This can be fulfilled, in terms of molecular design, either by placing a fluorophore and a DAE moiety (or multiple copies of each) nearby in the same molecule (e.g., a dyad) [5,8,9,11,14,21,22] so that fluorescence quenching is feasible through fluorescence resonance energy transfer (FRET) [23] or by using a DAE derivative alone that can fluoresce in its closed form (Scheme S1, Supporting Information). [10,[24][25][26] Recently, the latter type of fluorescence photoswitches, in particular, based on turn-on mode sulfone derivatives of DAE, [5,[24][25][26][27][28][29][30][31][32][33][34] has been intensively investigated for super-resolution imaging [5,27,29,30,[32][33][34][35][36] in aqueous solutions. [5,27,32,33] While some nanoparticulate fluorophores such as conjugated polymers [7,9] or quantum dots [20,37] of superior brightness have been reported, the dyad-type reversible fluorescence photoswitch typically employs a conventional and potentially safer small-molecule fluorescent dye as the FRET donor with relatively high molar absorptivity (e.g., cyanine [38] ). Thus, for a given DAE derivative (FRET acceptor), the performance of fluorescence photoswitching at the intended emission wavelength, as assessed by the on-off contrast, brightness, and fatigue resistance, can be improved by pairing with a fluorophore of, conceivably, better matching optical properties-e.g., absorption and emission maxima, Stokes shift, spectral bandwidth, molar absorptivity, and quantum yield.Fluorescence imaging [16,39] has been one of the most versatile and frequently used techniques in laboratories conducting experiments related to biology and medicine. Furthermore, in the clinical setting, the usage of fluorescence probes in the operation room can provide visual guidance for tissue inspection without the need for bulky and expensive instrumentation, potentially leading to substantially improved surgical outcomes. [40][41][42][43] Despite the benefits of simplicity, low cost, and Fluorescence imaging is an indispensable tool in modern biological research, allowing simple and inexpensive color-coded visualizations of real-time events in living cells and animals, as well as of fixed states of ex vivo specimens. The accuracy of fluorescence imaging in living systems is, however, impeded by autofluorescence, light scattering, and limited penetration depth of light. Nevertheless, the clinical use of fluorescence imaging is expected to grow along with advances in imaging equipment, and will increasingly demand high-accuracy probes to avoid ...