Phosphorus-based self-immolative (SI) linkers offer a wide range of applications, such as smart materials and drugdelivery systems. Phosphorus SI linkers are ideal candidates for double-cargo delivery platforms because they have a higher valency than carbon. A series of substituted phosphate linkers was designed for releasing two phenolic cargos through SI followed by chemical hydrolysis. Suitable modifications of the lactate spacer increased the cargo release rate significantly, from 1 day to 2 hours or 5 minutes, as shown for linkers containing p-fluoro phenol. In turn, double cargo linkers bearing p-methyl phenol released their cargo more slowly (4 days, 4 hours, and 15 minutes) than their p-fluoro analogues. The α-hydroxyisobutyrate linker released both cargos in 25 minutes. Our study expands the current portfolio of SI constructs by providing a double cargo delivery option, which is crucial to develop universal SI platforms.

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Phosphorus‐based self‐immolative linkers activated by light sequentially release two phenolic cargos. Structurally modifying the lactate spacer responsible for self‐immolation allows adjustable cargo release, ranging from minutes to days. The cargo release rate can be additionally tuned by varying the cargos. NMR spectroscopy coupled to UV light illumination enabled us to track and characterize products released during the self‐immolation process. More information can be found in the Full Paper by E. Procházková, O. Baszczyňski, et al. (DOI: 10.1002/chem.202101805).

The most significant result is the development of an ew class of phosphate-based linkers, which can release two structurally different phenolic cargos in several adjustable modes. This option may be useful in designing drug delivery strategies or developing new innovative materials.