Superfast and Water‐Insensitive Polymerization on α‐Amino Acid <i>N</i>‐Carboxyanhydrides to Prepare Polypeptides Using Tetraalkylammonium Carboxylate as the Initiator

Wu, Yueming; Chen, Kang; Wu, Xinsheng; Liu, Longqiang; Zhang, Weiwei; Ding, Yun; Liu, Shiqi; Zhou, Min; Shao, Ning; Ji, Zhemin; Chen, Jiacheng; Zhu, Minghui; Liu, Runhui

doi:10.1002/ange.202103540

Cited by 7 publications

(5 citation statements)

References 72 publications

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“…Inspired by the recent pioneering report by Liu on a rapid, water-insensitive strategy for NCA ring-opening polymerization using tetraalkylammonium carboxylate as the initiator, we explored the method for synthesis of polysaccharide-peptide block copolymers by generating polysaccharide macroinitiators. In this investigation, we selected dextran, a well-studied polysaccharide for polymer-drug conjugates in combination with drugs, proteins, hormones, and enzymes .…”

Section: Introductionmentioning

confidence: 99%

Dextran Macroinitiator for Synthesis of Polysaccharide-b-Polypeptide Block Copolymers via NCA Ring-Opening Polymerization

Wang,

Tang,

Kou

et al. 2024

Biomacromolecules

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Synthesis of polysaccharide-b-polypeptide block copolymers represents an attractive goal because of their promising potential in delivery applications. Inspired by recent breakthroughs in N-carboxyanhydride (NCA) ring-opening polymerization (ROP), we present an efficient approach for preparation of a dextran-based macroinitiator and the subsequent synthesis of dextran-b-polypeptides via NCA ROP. This is an original approach to creating and employing a native polysaccharide macroinitiator for block copolymer synthesis. In this strategy, regioselective (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) oxidation of the sole primary alcohol located at the C-6 position of the monosaccharide at the nonreducing end of linear dextran results in a carboxylic acid. This motif is then transformed into a tetraalkylammonium carboxylate, thereby generating the dextran macroinitiator. This macroinitiator initiates a wide range of NCA monomers and produces dextran-b-polypeptides with a degree of polymerization (DP) of the polypeptide up to 70 in a controlled manner (Đ < 1.3). This strategy offers several distinct advantages, including preservation of the original dextran backbone structure, relatively rapid polymerization, and moisture tolerance. The dextran-b-polypeptides exhibit interesting self-assembly behavior. Their nanostructures have been investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and adjustment of the structure of block copolymers allows self-assembly of spherical micelles and worm-like micelles with varied diameters and aspect ratios, revealing a range of diameters from 60 to 160 nm. Moreover, these nanostructures exhibit diverse morphologies, including spherical micelles and worm-like micelles, enabling delivery applications.

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Section: Introductionmentioning

confidence: 99%

Dextran Macroinitiator for Synthesis of Polysaccharide-b-Polypeptide Block Copolymers via NCA Ring-Opening Polymerization

Wang,

Tang,

Kou

et al. 2024

Biomacromolecules

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“…In addition, the recent development of accelerated polymerization strategies not only shortened the polymerization time, but also outpaced various side reactions during NCA polymerization. [20][21][22][23][24][25][26][27][28] Polypeptides were prepared in a controlled manner even in the presence of aqueous phase, [29][30][31] which was impossible in conventional polymerization considering the water-induced NCA degradation.…”

Section: Introductionmentioning

confidence: 99%

Accelerated and controlled polymerization of N-carboxyanhydrides catalyzed by acids

Liu,

Huang,

Wang

et al. 2023

Preprint

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It has been widely accepted that acidic species, such as HCl, inhibit the polymerization process of N-carboxyanhydrides (NCAs), which have to be removed to guarantee the successful synthesis of polypeptides. Herein, we showed that the im-pact of organic acids on NCA polymerization was dependent on their pKa values in dichloromethane. While stronger acids like trifluoroacetic acids completely blocked the chain propagation as expected, weaker acids such as acetic acids accel-erated the polymerization rate instead. The addition of acids not only protonated the propagating amino groups but also activated NCA monomers, whose balance determined the catalytic or inhibitory effect. Additionally, the acid-catalyzed polymerization exhibited one-stage kinetics that differed from conventional cooperative covalent polymerizations, result-ing in excellent control over molecular weights even with an accelerated rate. The pKa-dependence inspired us to turn the inhibitory acids into catalysts on demand, promoting the controlled polymerization from non-purified NCA monomers. This work highlights the possibility to change the conventional understanding of a catalyst/inhibitor by altering reaction conditions, which not only sheds light on the design of new catalysts, but also offers a practical strategy to prepare poly-peptide materials in an efficient and controlled manner.

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“…The chain-growth polymerization of NCAs is most commonly achieved using primary amine initiators in highly polar solvents like dimethylformamide. , This method typically produces polypeptides with good control over molecular weight, but they often require multiple days to reach completion under ambient conditions. There has been extensive progress to increase efficiency for amine-initiated reactions, which includes removing CO 2 , − using polyamine initiators, − using halogenated solvents, using biphasic systems with poly(ethylene)glycol amine initiators, , using carboxylate initiators, and using N-heterocyclic carbenes as catalysts. , Transition metal-based catalysts derived from low-valent metals, early transition metals, and nickel with diverse ligand frameworks are also known and have been used to efficiently produce various polypeptides . Despite the number of initiators and catalysts known to polymerize NCAs, copolymers that incorporate NCA monomers with other monomers (e.g., lactones, cyclic carbonates, epoxides, etc.)…”

Section: Introductionmentioning

confidence: 99%

“…5,6 This method typically produces polypeptides with good control over molecular weight, but they often require multiple days to reach completion under ambient conditions. There has been extensive progress to increase efficiency for amine-initiated reactions, which includes removing CO 2 , 7−9 using polyamine initiators, 10−12 using halogenated solvents, 13 using biphasic systems with poly(ethylene)glycol amine initiators, 14,15 using carboxylate initiators, 16 and using Nheterocyclic carbenes as catalysts. 17,18 Transition metal-based catalysts derived from low-valent metals, 19 early transition metals, 20 and nickel 21 with diverse ligand frameworks are also known and have been used to efficiently produce various polypeptides.…”

Section: ■ Introductionmentioning

confidence: 99%

Adding Polypeptides to the Toolbox for Redox-Switchable Polymerization and Copolymerization Catalysis

et al. 2023

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Bis(imino)pyridine (BIP) iron alkoxide complexes act as catalysts to efficiently polymerize N-carboxyanhydrides (NCAs), including γ-benzyl-Lglutamate NCA (BLG-NCA) and sarcosine NCA (Sar-NCA), at room temperature. Reaction rates were greatly enhanced with the addition of mild Lewis acids, such as [CoCp 2 ][BAr F24 ], which work cooperatively with the ironbased catalysts to facilitate NCA polymerization. The reactivity of ( 2,6Me BIP)-FeOCH 2 C(CH 3 ) 3 with Sar-NCA was combined with its known reactivity for εcaprolactone polymerization to form diblock and triblock copoly(ester-bpeptides) through sequential addition of lactone and NCA monomers. Redoxswitchable polymerization reactions were developed by iteratively exposing the catalyst to redox reagents and Sar-NCA or cyclohexene oxide. The orthogonal reactivity demonstrated by the catalyst in its oxidized and reduced states led to the synthesis of diblock and triblock copoly(ether-b-peptides). Polyether segments were synthesized with the catalyst in its oxidized state, while the polyamide segments were synthesized with the catalyst in its reduced state. Both copolymerization reactions developed here are rare examples where NCA polymerization reactions can be combined with other ring-opening polymerization reactions to make copolymers containing polypeptides and other functional monomers.

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Superfast and Water‐Insensitive Polymerization on α‐Amino Acid N‐Carboxyanhydrides to Prepare Polypeptides Using Tetraalkylammonium Carboxylate as the Initiator

Cited by 7 publications

References 72 publications

Dextran Macroinitiator for Synthesis of Polysaccharide-b-Polypeptide Block Copolymers via NCA Ring-Opening Polymerization

Dextran Macroinitiator for Synthesis of Polysaccharide-b-Polypeptide Block Copolymers via NCA Ring-Opening Polymerization

Accelerated and controlled polymerization of N-carboxyanhydrides catalyzed by acids

Adding Polypeptides to the Toolbox for Redox-Switchable Polymerization and Copolymerization Catalysis

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