The performance of DESC is showcased in Fig. , which lists the PSS compositions (blue font) for all the nine model azoarenes shown in Fig. (encapsulated within C in water with 0.05 eq of the selected sensitizer; ps2 for 1-7 and ps1 for 8 and 9). The reactions were performed on the NMR scale (i.e., milligram quantities of 1-9) and can readily be upscaled to obtain the Z isomers on the preparative scale. As control experiments (red font), we irradiated 1-9 under the same conditions and in the presence of the PS but without cage C (hence, in an organic solvent). In the absence of C, the E isomers could not be co-confined with the PS, which resulted in negligible amounts of the Z isomer via direct photoexcitation (only azobenzene 6, known for its visible-light-responsiveness , afforded a sizeable (14%) amount of Z). We note that the positively charged azobenzene 53 5 (often recognized as a prototypical photopharmacophore ) showed a particularly impressive contrast in behavior between the presence and absence of the cage, giving rise to 98% of Z. Notably, such a Z-rich PSS cannot be achieved by direct photoisomerization (of neither (E-5)2⊂C or free 5) with any wavelength of light (the same is true for compounds 1, 3, and 6) because of the partial overlap of the absorption bands of the two isomers . In contrast, the PSS composition in our system is dictated by the tendency of the two isomers to form the ternary (azo⋅PS)⊂C complex, and this tendency is much higher for the E isomer. Having demonstrated that the positively charged E-5 can be successfully transformed into Z-5 despite its low affinity to the like-charged C, we speculated that other water-soluble azobenzenes may also be efficiently disequilibrated using a substoichiometric amount of not only the PS but also the cage. Figure shows the result of an experiment in which an aqueous solution of the negatively charged 3 was exposed to red light in the presence of 0.005 eq of (ps4)2⊂C. The absorption spectrum of this solution is dominated by E-3's intense absorption peak in the near-UV region; the minute amount of the sensitizer appears as a weak band at ~600 nm (Fig. ). Remarkably, exciting this band with low-intensity 635 nm light resulted in a near-complete disappearance of the much more prominent peak originating from another species (E-3). We found that the PSS contained 88% of Z-3 (vs. ~0% in the absence of either C or ps4; Supplementary Fig. ), indicating that each cage hosted at least 180 E→Z isomerization events on average. To further showcase the potential of DESC, we explored the cavity size and charge (+12) of cage C to discriminate between photoreactive compounds whose absorption bands overlap, and which otherwise cannot be converted selectively. To this end, we mixed E-3 and E-5 in a 1:3 ratio and added (ps2)2⊂C (0.5 eq with respect to 3; Fig. ). At low (micromolar) concentrations, only the negatively charged 3 exhibits a strong affinity to C; 5 is not encapsulated owing to the Coulombic repulsion. Indeed, yellow light (561 nm) illumination of this mixture led to a highly selective switching of E-3 (despite the threefold excess of E-5 (Fig. and Supplementary Fig. ). In contrast, exposure to UV light induced nonselective switching of both azobenzenes via direct excitation. In the second example, we worked with a mixture of E-4 and 9-bromoanthracene, both in the form of encapsulated homodimers with C. Upon exposure to UV light, the encapsulated anthracene rapidly dimerizes to afford the corresponding dianthracene under the same irradiation conditions that trigger the direct E→Z photoisomerization of 4 (Fig. , right). However, exposing the same mixture to yellow light in the presence of (ps2)2⊂C induced highly selective photoisomerization of azobenzene, leaving the anthracene intact (Fig. , dotted line). These experiments demonstrate that DESC can be combined with substrate selectivity found in enzymatic systems , bringing us closer to realizing the potential of synthetic supramolecular catalysts as "artificial enzymes" .