Dynamic pH responsivity of triazole-based self-immolative linkers

Stevens, Molly M.; Roberts, Derrick A.; Pilgrim, Ben S.; Dell, Tristan N.

Abstract

Gating the release of chemical payloads in response to transient signals is an important feature of ‘smart’ delivery systems. Herein, we report a triazole-based self-immolative linker that can be reversibly paused or slowed and restarted throughout its elimination cascade in response to pH changes in both organic and organic-aqueous solvents. The linker is conveniently prepared using the alkyne–azide cycloaddition reaction, which introduces a 1,4-triazole ring that expresses a pH-sensitive intermediate during its elimination sequence. Using a series of model compounds, we demonstrate that this intermediate can be switched between active and dormant states depending on the presence of acid or base, cleanly gating the release of payload in response to a fluctuating external stimulus.

• Journal Article Type: Article
• Acceptance Date: Feb 28, 2020
• Online Publication Date: Mar 3, 2020
• Publication Date: 2020
• Deposit Date: Apr 17, 2020
• Publicly Available Date: Apr 20, 2020
• Journal: Chemical Science
• Print ISSN: 2041-6520
• Electronic ISSN: 2041-6539
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 14
• Pages: 3713-3718
• DOI: https://doi.org/10.1039/d0sc00532k
• Keywords: General Chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/4300521
• Publisher URL: https://pubs.rsc.org/en/content/articlelanding/2020/SC/D0SC00532K
• Additional Information: : This document is Similarity Check deposited; : Supplementary Information; : Derrick A. Roberts (ORCID); : Derrick A. Roberts (ResearcherID); : Ben S. Pilgrim (ORCID); : Ben S. Pilgrim (ResearcherID); : Tristan N. Dell (ORCID); : Molly M. Stevens (ORCID); : Single-blind; : Received 29 January 2020; Accepted 28 February 2020; Accepted Manuscript published 3 March 2020; Advance Article published 19 March 2020; Version of Record published 8 April 2020