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Stimuli-responsive disassembly of the mechanical bond: Synthesis and properties of ring-opening 2,2'-bipyridine macrocycles

Stimuli-responsive disassembly of the mechanical bond: Synthesis and properties of ring-opening 2,2'-bipyridine macrocycles
Stimuli-responsive disassembly of the mechanical bond: Synthesis and properties of ring-opening 2,2'-bipyridine macrocycles
The development of template-directed methodologies have facilitated the synthesis of structurally-diverse mechanically interlocked molecules (MIMs) and prompted investigations into their unique chemical properties. In doing so, MIMs have been transformed from mere synthetic curiosities to functional materials with applications in a range of fields, such as molecular machines, materials, and catalysis. Although often overlooked among the plethora of application-based MIM literature, the use of MIMs in biological applications is a flourishing field. The introductory chapter provides a scoping review of current literature on synthetic interlocked molecules used for biological applications. By analysing the MIMs with respect to the properties of the mechanical bond, the chemical behaviour underpinning their biological function is elucidated. Chapter 2 details the synthesis of a ring-opening 2,2'-bipyridine macrocycle, which mediated AT-CuAAC rotaxination with high efficiency. Upon exposure to UVB light, the photolabile diethylaminobenzyl (DEABn) within the macrocycle backbone was cleaved, resulting in the ring-opening and release of the corresponding axle. In lieu of the expected photocleavage pathway, a surprising intramolecular photo-induced rearrangement was instead found to dominate. The photocleavable macrocycle was successfully incorporated into a dinucleotide rotaxane and later into a model oligonucleotide rotaxane structure. In Chapter 3, the development of a modular platform approach for the generation of ring-opening 2,2'-bipyridine macrocycles is described. A series of macrocycles designed to cleave in response to several different stimuli (pH, chemical, UV, light) were rapidly and conveniently synthesised, and shown to mediate AT-CuAAC rotaxination with high efficiency. Cleavage of the trigger unit in response to the appropriate stimulus generated an intermediate rotaxane species which underwent ring-opening to liberate the axle from the interlocked structure with varying degrees of success. Tailoring the electronic properties of the self-immolative spacer within the macrocycle backbone through judicious structural modification was later shown to significantly improve the ring-opening capability of the macrocycle.
University of Southampton Library
Fitzpatrick, Matthew Peter
5721699f-b516-42ab-aa75-cfa857f6b472
Fitzpatrick, Matthew Peter
5721699f-b516-42ab-aa75-cfa857f6b472
Goldup, Stephen
0a93eedd-98bb-42c1-a963-e2815665e937
Tavassoli, Ali
d561cf8f-2669-46b5-b6e1-2016c85d63b2

Fitzpatrick, Matthew Peter (2023) Stimuli-responsive disassembly of the mechanical bond: Synthesis and properties of ring-opening 2,2'-bipyridine macrocycles. University of Southampton, Doctoral Thesis, 465pp.

Record type: Thesis (Doctoral)

Abstract

The development of template-directed methodologies have facilitated the synthesis of structurally-diverse mechanically interlocked molecules (MIMs) and prompted investigations into their unique chemical properties. In doing so, MIMs have been transformed from mere synthetic curiosities to functional materials with applications in a range of fields, such as molecular machines, materials, and catalysis. Although often overlooked among the plethora of application-based MIM literature, the use of MIMs in biological applications is a flourishing field. The introductory chapter provides a scoping review of current literature on synthetic interlocked molecules used for biological applications. By analysing the MIMs with respect to the properties of the mechanical bond, the chemical behaviour underpinning their biological function is elucidated. Chapter 2 details the synthesis of a ring-opening 2,2'-bipyridine macrocycle, which mediated AT-CuAAC rotaxination with high efficiency. Upon exposure to UVB light, the photolabile diethylaminobenzyl (DEABn) within the macrocycle backbone was cleaved, resulting in the ring-opening and release of the corresponding axle. In lieu of the expected photocleavage pathway, a surprising intramolecular photo-induced rearrangement was instead found to dominate. The photocleavable macrocycle was successfully incorporated into a dinucleotide rotaxane and later into a model oligonucleotide rotaxane structure. In Chapter 3, the development of a modular platform approach for the generation of ring-opening 2,2'-bipyridine macrocycles is described. A series of macrocycles designed to cleave in response to several different stimuli (pH, chemical, UV, light) were rapidly and conveniently synthesised, and shown to mediate AT-CuAAC rotaxination with high efficiency. Cleavage of the trigger unit in response to the appropriate stimulus generated an intermediate rotaxane species which underwent ring-opening to liberate the axle from the interlocked structure with varying degrees of success. Tailoring the electronic properties of the self-immolative spacer within the macrocycle backbone through judicious structural modification was later shown to significantly improve the ring-opening capability of the macrocycle.

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Submitted date: July 2022
Published date: January 2023

Identifiers

Local EPrints ID: 473202
URI: http://eprints.soton.ac.uk/id/eprint/473202
PURE UUID: 0df120cd-d294-4f89-a333-76e899e379b5
ORCID for Stephen Goldup: ORCID iD orcid.org/0000-0003-3781-0464
ORCID for Ali Tavassoli: ORCID iD orcid.org/0000-0002-7420-5063

Catalogue record

Date deposited: 12 Jan 2023 17:39
Last modified: 17 Mar 2024 03:07

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Contributors

Author: Matthew Peter Fitzpatrick
Thesis advisor: Stephen Goldup ORCID iD
Thesis advisor: Ali Tavassoli ORCID iD

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