Density Functional Theory Studies on the Synthesis of Poly(α-Amino Acid)s Via the Amine-Mediated Ring Opening Polymerizations of N-Carboxyanhydrides and N-Thiocarboxyanhydrides

Bai, Tianwen; Zheng, Biao; Ling, Jun

doi:10.3389/fchem.2021.645949

Cited by 7 publications

(5 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ROP was so slow that monomer conversion only reached ∼24% after 24 h even at elevated temperature (80 °C) (Table ). The much slower polymerization of the more sterically hindered β-branched monomer [ Me N -( l )-Val-NCA] than the γ-branched monomers [ Me N -( l )-Leu-NCA and Me N -( l )-Phe-NCA] is consistent with previously reported studies. , It should also be noted that monomers with different side chains all exhibited first-order polymerization kinetics (Figure S33), further supporting the living nature of ROPs.…”

Section: Resultssupporting

confidence: 90%

Efficient Synthesis of N-Methyl Polypeptides by Organic Acid Promoted Controlled Ring-Opening Polymerization of N-Methyl-α-Amino Acids N-Carboxyanhydrides

Yu,

Wang,

Dong

et al. 2023

Macromolecules

View full text Add to dashboard Cite

N-Methyl peptides, which are widely found in nature, have emerged as an intriguing material in both polymer science and the biomedical field. The inefficient synthesis of Nmethyl peptides, however, has greatly impeded the progress toward their structure−property investigation and applications. Here, we report an efficient, moisture-tolerant, primary amine-initiated, and acetic acid-catalyzed ring-opening polymerization of enantiomerically pure N-methyl-α-amino acids N-carboxyanhydrides, yielding well-defined, stereoregular, and structurally diverse N-methyl polypeptides. The concentration of the acetic acid, polarity of solvents, and stiffness of polymer chains were found to be crucial to the rate of the polymerization. The acetic acid was proposed to activate the monomer through hydrogen bonding interaction, promote the release of CO 2 , and form an acid−base equilibrium with the secondary amine chain end. The obtained N-methyl polypeptides exhibited stable helix structures, revealing chain stiffness, consistent with the high glass transition temperatures (>250 °C) from DSC measurements. Moreover, preliminary studies indicated that N-methyl polypeptides are nontoxic both in vitro and in vivo and are enzymatically stable toward trypsin treatment. Together, this study provides a mild and efficient method for the preparation of N-methyl polypeptides, opening avenues for their further structure−property investigation and potential applications.

show abstract

Section: Resultssupporting

confidence: 90%

Efficient Synthesis of N-Methyl Polypeptides by Organic Acid Promoted Controlled Ring-Opening Polymerization of N-Methyl-α-Amino Acids N-Carboxyanhydrides

Yu,

Wang,

Dong

et al. 2023

Macromolecules

View full text Add to dashboard Cite

show abstract

“…All above monomers have similar fivemembered cyclic anhydride structures, of which the carbonyl carbon at position 5 on the monomer rings can act as an active site for nucleophilic attack during the initiation and propagation steps through either activated monomer mechanism (AMM) or normal amine mechanism (NAM). [110][111][112][113] Therefore, these monomers are expected to proceed copolymerization under appropriate conditions to prepare peptide/peptoid hybrid polymers.…”

Section: Polymerization Methodsmentioning

confidence: 99%

Advance in Hybrid Peptides Synthesis

Zou

Zhou

Xiao

et al. 2022

Macromol. Rapid Commun.

View full text Add to dashboard Cite

Hybrid peptides with heterogeneous backbone are a class of peptide mimics with adjustable proteolytic stability obtained from incorporating unnatural amino acid residues into peptide backbone. 𝜶/𝜷-peptides and peptide/peptoid hybrids are two types of hybrid peptides that are widely studied for diverse applications, and several synthetic methods have been developed. In this mini review, the advance in hybrid peptide synthesis is summarized, including solution-phase method, solid-phase method, and novel polymerization method. Conventional solution-phase method and solid-phase method generally result in oligomers with defined sequences, while polymerization methods have advantages in preparing peptide hybrid polymers with high molecular weight with simple operation and low cost. In addition, the future development of polymerization method to realize the control of the peptide hybrid polymer sequence is discussed.

show abstract

“…In NAM, carbonyl addition and decarboxylation steps are considered as two possible rate-determining steps, which is still in debates. [30] AMM was first proposed to illustrate a tertiary amine initiated L -phenylalanine NCA polymerization system by Ballard and Bamford, [32,33] who also worked in basic salt initiation systems. Compared with NAM, the initiator in AMM acts more as a base rather than a nucleophile.…”

Section: Mechanism Of Nca Polymerizationsmentioning

confidence: 99%

Section: Advances In Polymerizations Of Ncasmentioning

confidence: 99%

An Inspection into Multifarious Ways to Synthesize Poly(Amino Acid)s

Zheng

Bai

Tao

et al. 2021

Macromol. Rapid Commun.

Self Cite

View full text Add to dashboard Cite

Poly(𝜶-amino acid)s (PAAs) attract growing attention due to their essential role in the application as biomaterials. To synthesize PAAs with desired structures and properties, scientists have developed various synthetic techniques with respective advantages. Here, different approaches to preparing PAAs are inspected. Basic features and recent progresses of these methods are summarized, including polymerizations of amino acid N-carboxyanhydrides (NCAs), amino acid N-thiocarboxyanhydrides (NTAs), and N-phenoxycarbonyl amino acids (NPCs), as well as other synthetic routes. NCA is the most classical monomer to prepare PAAs with high molecular weights (MWs). NTA polymerizations are promising alternative pathways to produce PAAs, which can tolerate nucleophiles including alcohols, mercaptans, carboxyl acids, and water. By various techniques including choosing appropriate solvents or using organic acids as promoters, NTAs polymerize to produce polypeptoids and polypeptides with narrow dispersities and designed MWs up to 55.0 and 57.0 kg mol −1 , respectively. NPC polymerizations are phosgene-free ways to synthesize polypeptides and polypeptoids. For the future prospects, detail investigations into polymerization mechanisms of NTA and NPC are expected. The synthesis of PAAs with designed topologies and assembly structures is another intriguing topic. The advantages and unsettled problems in various synthetic ways are discussed for readers to choose appropriate approaches for PAAs.

show abstract

Density Functional Theory Studies on the Synthesis of Poly(α-Amino Acid)s Via the Amine-Mediated Ring Opening Polymerizations of N-Carboxyanhydrides and N-Thiocarboxyanhydrides

Cited by 7 publications

References 51 publications

Efficient Synthesis of N-Methyl Polypeptides by Organic Acid Promoted Controlled Ring-Opening Polymerization of N-Methyl-α-Amino Acids N-Carboxyanhydrides

Efficient Synthesis of N-Methyl Polypeptides by Organic Acid Promoted Controlled Ring-Opening Polymerization of N-Methyl-α-Amino Acids N-Carboxyanhydrides

Advance in Hybrid Peptides Synthesis

An Inspection into Multifarious Ways to Synthesize Poly(Amino Acid)s

Contact Info

Product

Resources

About