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Phosphate‐Based Self‐Immolative Linkers for Tuneable Double Cargo Release
Author(s) -
Šimon Petr,
Tichotová Markéta,
García Gallardo María,
Procházková Eliška,
Baszczyňski Ondřej
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202101805
Subject(s) - phosphate , chemistry , phenol , linker , hydrolysis , drug delivery , combinatorial chemistry , nanotechnology , materials science , organic chemistry , computer science , operating system
Phosphorus‐based self‐immolative (SI) linkers offer a wide range of applications, such as smart materials and drug‐delivery 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.