Radical based molecular design of discrete and stereoregulated oligomers via photomediated RAFT single unit monomer insertion (photo-RAFT SUMI)

Natural biopolymers, such as DNA, RNA, and proteins, are discrete macromolecules possessing inherent biological functions attributed to their highly organized chemical structures. Their precision structures, in nature, are determined by the unique microstructures (or primary structures), including two major factors throughout the polymer chain: monomer sequence and stereoregularity. For a long time, polymer chemists have dedicated themselves to achieve such dual control during the synthesis of synthetic polymers in order to emulate such structurally perfect biopolymers. Despite the success of directly utilizing natural monomers (nucleotides and amino acids) to create such macromolecules, researchers are now ambitious to employ other non-natural monomers since their broad chemical diversity would excavate even more possibilities to sophisticate functions and applications in both biological and nonbiological niches. Unfortunately, limited methods have achieved the dual control including a newly disclosed method of iterative exponential growth, leaving a gap in terms of any radical addition methods utilizing the most diverse olefins as monomers. This thesis aims to address this gap, by synthesizing discrete and stereoregulated peptide mimics through successive and iterative radical addition of olefin monomers. With significant improvements to the previously disclosed photoinduced-RAFT single unit monomer insertion (Photo-RAFT SUMI) technique, the initial study has achieved perfect monomer sequence control by sequential and alternating insertions of two families of monomers, namely indene and maleimide. In which, two pentamers were successfully synthesized as examples by five iterative insertion reactions. Subsequent chain extension has demonstrated the “livingness” of the pentamers, illustrating the feasibility of further SUMI reactions to form longer discrete polymers. Subsequently, this promising synthetic method was successfully transformed to a flow reaction system. Facilitated by automated column chromatography, gram scale of discrete oligomers with diverse monomer sequences were produced with exceptional isolated yields, short reaction time, and easy purification. Notably, subsequent investigation revealed that the utilization of these cyclic monomers has spontaneously resulted in a trans- stereospecificity within the 5-member ring during each step of insertion. This exciting finding has ultimately led to the final success of controlling both monomer sequence and stereochemistry by Photo-RAFT SUMI with further improvements. A library of enantiopure trimers with the same monomer sequence but different stereochemistry was thus obtained. These enantiopure trimers were comprehensively characterized by NMR, ESI-MS, XRD and 2D NOESY to confirm their unique stereo-structures which were then correlated to their properties including thermal transition, crystallization, and optical activity.

Grantor dc:publisher

UNSW, Sydney

Year dc:date

2021

Author dc:creator

• Huang, Zixuan

• RAFT
• Precision Polymer Science
• SUMI
• Stereochemical Control
• Photoredox Catalysis
• Living Polymerization

Statement dc:rights

• open access
• CC BY-NC-ND 3.0
• free_to_read

Licence

• https://purl.org/coar/access_right/c_abf2
• https://creativecommons.org/licenses/by-nc-nd/3.0/au/

Language dc:language

EN

Identifier

https://doi.org/10.26190/unsworks/2386

OAI identifier oai:identifier

oai:unsworks.library.unsw.edu.au:1959.4/71203