Self-Immolative Spacers: Kinetic Aspects, Structure-Property Relationships, and Applications

• Published in: Angewandte Chemie International Edition Vol. 54; no. 26; pp. 7492 - 7509
• Main Authors: Alouane, Ahmed, Labruère, Raphaël, Le Saux, Thomas, Schmidt, Frédéric, Jullien, Ludovic
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 22.06.2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Edition: International ed. in English
• Subjects: Activation; Chemical bonds; Chemical Sciences; Demand; Disassembly; Dismantling; Drug Delivery Systems - methods; Kinetics; Life Sciences; Molecular Structure; Protective; self-immolation; self-immolative spacers; Spacers; Stimulation; self-immolation; kinetics; self-immolative spacers; disassembly
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201500088

Self‐immolative spacers are covalent assemblies tailored to correlate the cleavage of two chemical bonds after activation of a protective part in a precursor: Upon stimulation, the protective moiety is removed, which generates a cascade of disassembling reactions leading to the temporally sequential release of smaller molecules. Originally introduced to overcome limitations for drug delivery, self‐immolative spacers have gained wide interest in medicinal chemistry, analytical chemistry, and material science. For most applications, the kinetics of the disassembly of the activated self‐immolative spacer governs functional properties. This Review addresses kinetic aspects of self‐immolation. It provides information for selecting a particular self‐immolative motif for a specific demand. Moreover, it should help researchers design kinetic experiments and fully exploit the rich perspectives of self‐immolative spacers. Time to cleave: Self‐immolative spacers are covalent assemblies tailored to ensure the temporally tailored cleavage of two chemical bonds on activation. Upon stimulation, a protective moiety is removed from one side of the spacer, which then triggers the release of a desired molecule. This Review deals with the kinetics of disassembly in self‐immolative spacers and provides information for selecting a particular self‐immolative motif for a specific demand.