Benzyl amine and similar structures are well-known to form supramolecular complexes with CB with a high binding affinity of about 10 5 to 10 7 M -1 . We initially designed a self-immolative linker SIE1 (Figure ) incorporating a benzylamine group at the nitrogen atom distal from the cargo loading site. SIE1 was readily synthesized in two simple steps from commercially available starting materials (See SI for details). Its protonated form, SIE1-TFA, is a gummy solid that is stable in the refrigerator for over a year. SIE1-TFA also exhibited good stability in water, while it quickly released the coumarin cargo through a well-understood cyclization-elimination reaction once the pH of aqueous solution was raised by adding buffering salts. The half-life (t1/2) of cargo release was estimated to be 0.45 h in pH 6.5 phosphate buffer according to NMR measurements (Figures and).