Transformation of Thioester‐Initiated Star Polymers into Linear Arms via Native Chemical Ligation

Abstract

The synthesis of a new class of Cu‐mediated polymerization initiators with thioester functionality is demonstrated and their polymerization kinetics via single‐electron transfer living radical polymerization is reported. From periodic sampling, it is found that thioester‐ or ester‐based initiators can be employed interchangeably, resulting in very similar polymerization rates. Furthermore, a multifunctional thioester initiator is employed for the preparation of a well‐defined four‐arm star‐shaped polymer. It is further shown that the full dissociation of the star polymer into linear arms via native chemical ligation can easily be followed via size exclusion chromatography, as a result of the change in hydrodynamic volume. Finally, the obtained linear polymers are characterized via matrix‐assisted laser desorption/ionization–time of flight mass spectrometry and found to be in good agreement with the expected molecular weight distribution that confirms the successful transformation.

Native Chemical Ligation: Ultrafast Synthesis of Block Copolymers

“…To confirm the block copolymer nature of PC1, a series of NMR analyses was performed (see the Supporting Information). 1 H and 13 C NMR analysis confirmed the presence of characteristic signals from both homopolymers. Moreover, a DOSY NMR analysis showed one diffusion coefficient for the chemical signatures of both polymer blocks, confirming the excellent conjugation efficiency between the two homopolymers (Figure S1).…”

“…Beside monodispersed natural peptides synthesis, NCL has also been exploited for block copolypeptide and copolypeptoid synthesis. , Although NCL is often used for the synthesis of highly functional biomacromolecules such as peptides, the use of such ligation techniques for non-natural functional polymer synthesis is limited. Nonetheless, the NCL technique has also been used for non-natural block copolymer, hydrogel, star, and degradable star copolymer syntheses. − However, a detailed analysis of the NCL coupling efficiency with diverse coupling partners is scarce. We, therefore, believe that the NCL technique has the potential for a more widespread use in polymer and materials chemistry.…”

Degradable thioester core-crosslinked star-shaped polymers

“…20,23,30,31 While amidation, hydrolysis, transthioesterification and oxidative hydrolysis have previously been reported for the complete and selective degradation of polymers containing thioesters in the backbone, they remain unexplored for the design of degradable core-crosslinked star-shaped polymers. 18,[21][22][23][30][31][32] Herein, we introduce thioester linkages into the crosslinked core of star-shaped polymers in order to exploit their more pronounced reactivity and degradability compared to ester derivatives. Core-crosslinked polymers were prepared from defined poly(methyl methacrylate) arms, obtained through RAFT polymerisation, upon the addition of a synthesised bi-functional thiomethacrylate crosslinker.…”

“…20,23,30,31 While amidation, hydrolysis, transthioesterification and oxidative hydrolysis have previously been reported for the complete and selective degradation of polymers containing thioesters in the backbone, they remain unexplored for the design of degradable core-crosslinked star-shaped polymers. 18,21–23,30–32…”

Thiol‐Bromo Click Reaction for One‐Pot Synthesis of Star‐Shaped Polymers

“…[15][16][17] By employing a multifunctional thioester-containing initiator for Cu-RDRP derived polymers also enabled the synthesis of star polymers. [18] Furthermore, the high bromine end-group fidelity of Cu-RDRP was harnessed for the high-yielding reaction with thiol compounds to form dendrimers in an iterative reaction sequence. [19] Besides the rapid reaction between thiols and alkyl bromides, thiol-ene/yne, p-fluoro-thiol and thiol-Michael reactions are extensively used in polymer chemistry to synthesize sophisticated polymer architectures.…”