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Journal ArticleDOI

Primary ammonium/tertiary amine-mediated controlled ring opening polymerisation of amino acid N-carboxyanhydrides.

15 Oct 2015-Chemical Communications (Royal Society of Chemistry)-Vol. 51, Iss: 86, pp 15645-15648
TL;DR: Stable commercial primary ammonium chlorides were combined with tertiary amines to initiate the controlled ring opening polymerisation of amino acid N-carboxyanhydrides to yield polypeptides with defined end group structure, predetermined molar mass and narrow molarmass distribution.
About: This article is published in Chemical Communications.The article was published on 2015-10-15 and is currently open access. It has received 43 citations till now. The article focuses on the topics: Tertiary amine & Molar mass distribution.

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Summary

  • Stable commercial primary ammonium chlorides were combined with tertiary amines to initiate the controlled ring opening polymerisation of amino acid N-carboxyanhydrides to yield polypeptides with defined end group structure, predetermined molar mass and narrow molar mass distribution.
  • Achieving good control over polymerisation reactions is essential for the synthesis of well-defined polymers.
  • Typically, anionic, cationic, controlled radical and ring opening polymerisation (ROP) techniques are applied to synthesise polymers with predetermined composition, functionality, molar mass, and low dispersity.
  • These properties are essential in the fields of selfassembly and biomimicry.
  • Self-assembled and biomimetic supramolecular assemblies, such as micelles, vesicles, hydrogels and hierarchical scaffolds, are often developed for biomedical or materials science applications. [2] [3] [4] [5] [6] [7].
  • Polypeptides are very interesting polymers, not only because they can be designed to be biocompatible and biodegradable, but also because they can be synthesised in a controlled manner by ROP of amino acid N-carboxyanhydrides (NCAs).
  • 8, 9 The non-metal catalysed ROP of NCAs is known to proceed via two distinct pathways, namely the normal amine mechanism (NAM) and the activated monomer mechanism (AMM) (Scheme 1a and b).
  • 10 The NAM is favoured by the use of nucleophilic initiators such as primary amines and yields welldefined polypeptides.
  • The AMM is favoured by bases, such as tertiary amines, and yields polypeptides with high molar mass and dispersity.
  • It is challenging to completely suppress the AMM.
  • Over the past two decades, considerable advances in controlled NCA polymerisation have been realised.

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Citations
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Journal ArticleDOI
TL;DR: Computational screening with high-throughput robotic synthesis is combined to create a hybrid discovery workflow for discovering new organic cage molecules, and by extension, other supramolecular systems that form cleanly in one-pot syntheses.
Abstract: Supramolecular synthesis is a powerful strategy for assembling complex molecules, but to do this by targeted design is challenging. This is because multicomponent assembly reactions have the potential to form a wide variety of products. High-throughput screening can explore a broad synthetic space, but this is inefficient and inelegant when applied blindly. Here we fuse computation with robotic synthesis to create a hybrid discovery workflow for discovering new organic cage molecules, and by extension, other supramolecular systems. A total of 78 precursor combinations were investigated by computation and experiment, leading to 33 cages that were formed cleanly in one-pot syntheses. Comparison of calculations with experimental outcomes across this broad library shows that computation has the power to focus experiments, for example by identifying linkers that are less likely to be reliable for cage formation. Screening also led to the unplanned discovery of a new cage topology-doubly bridged, triply interlocked cage catenanes.

134 citations

Journal ArticleDOI
TL;DR: Key architectures obtained through NCA ROP or in combination with other polymerization methods are reviewed, as these play an important role in the wide range of applications towards which polypeptides have been applied.
Abstract: Polypeptides have attracted considerable attention in recent decades due to their inherent biodegradability and tunable cytocompatibility. Macromolecular design in conjunction with rational monomer composition can direct architecture, self-assembly and chemical behavior, ultimately guiding the choice of appropriate application within the biomedical field. This review focuses on the applications of polypeptides alongside the synthetic advances in the ring opening polymerization of α-amino acid N-carboxyanhydrides achieved in the past five years. Key architectures obtained through NCA ROP or in combination with other polymerization methods are reviewed, as these play an important role in the wide range of applications towards which polypeptides have been applied.

131 citations

Journal ArticleDOI
TL;DR: Lithium hexamethyldisilazide is used to initiate α-amino acid N-carboxyanhydride polymerizations that is very fast and can be conducted in an open vessel, and rapid synthesis of polypeptide libraries for high-throughput functional screening.
Abstract: Polypeptides have broad applications and can be prepared via ring-opening polymerization of α-amino acid N-carboxyanhydrides (NCAs). Conventional initiators, such as primary amines, give slow NCA polymerization, which requires multiple days to reach completion and can result in substantial side reactions, especially for very reactive NCAs. Moreover, current NCA polymerizations are very sensitive to moisture and must typically be conducted in a glove box. Here we show that lithium hexamethyldisilazide (LiHMDS) initiates an extremely rapid NCA polymerization process that is completed within minutes or hours and can be conducted in an open vessel. Polypeptides with variable chain length (DP = 20–1294) and narrow molecular weight distribution (Mw/Mn = 1.08–1.28) were readily prepared with this approach. Mechanistic studies support an anionic ring opening polymerization mechanism. This living NCA polymerization method allowed rapid synthesis of polypeptide libraries for high-throughput functional screening. Ring-opening polymerizations of α-amino acid N-carboxyanhydrides to form polypeptides are usually sensitive to moisture, slow and can undergo side reactions. Here the authors use lithium hexamethyldisilazide to initiate α-amino acid N-carboxyanhydride polymerizations that is very fast and can be conducted in an open vessel.

112 citations

Journal ArticleDOI
TL;DR: This dual-functional polymer brush coating can be immobilized on the surface of multiple categories of materials through the mussel-inspired pDA coating, and thus should be widely applicable for combating infection in many classes of bio-medical materials.

85 citations

Journal ArticleDOI
TL;DR: This review aims to summarize the recent advances in PLL-based nanomaterials in these biomedical fields over the last decade by describing the synthesis of PLL and its derivatives and the main text of their recent biomedical applications and translational studies.

84 citations


Cites background from "Primary ammonium/tertiary amine-med..."

  • ...Diverse initiators such as hexamethyldisilazane, used by Cheng [19], lithium hexamethyldisilazide, used by Liu [20]; trimethylsilyl and trimethylstannyl sulfide, used by Lu [21,22]; ammonium salts, used by Schlaad [23,24]; frustrated Lewis pairs, used by Yang [25]; catalysts such as cobalt and nickel organometallic catalysts, used by Deming [26]; organophosphates catalysts used by Yang [27]; and 1,1,3, 3-tetramethylguanidine used by Cabral [28] have been reported for the controlled synthesis of PLL and other polypeptides....

    [...]

References
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Journal ArticleDOI
TL;DR: This work reviews recent advances and challenges in the developments towards applications of stimuli-responsive polymeric materials that are self-assembled from nanostructured building blocks and provides a critical outline of emerging developments.
Abstract: Responsive polymer materials can adapt to surrounding environments, regulate transport of ions and molecules, change wettability and adhesion of different species on external stimuli, or convert chemical and biochemical signals into optical, electrical, thermal and mechanical signals, and vice versa. These materials are playing an increasingly important part in a diverse range of applications, such as drug delivery, diagnostics, tissue engineering and 'smart' optical systems, as well as biosensors, microelectromechanical systems, coatings and textiles. We review recent advances and challenges in the developments towards applications of stimuli-responsive polymeric materials that are self-assembled from nanostructured building blocks. We also provide a critical outline of emerging developments.

4,908 citations

Journal ArticleDOI
17 Nov 2006-Science
TL;DR: A challenge for future studies is to create hierarchically structured composites in which each sublayer contributes a distinct function to yield a mechanically integrated, multifunctional material.
Abstract: The mixing of polymers and nanoparticles is opening pathways for engineering flexible composites that exhibit advantageous electrical, optical, or mechanical properties. Recent advances reveal routes to exploit both enthalpic and entropic interactions so as to direct the spatial distribution of nanoparticles and thereby control the macroscopic performance of the material. For example, by tailoring the particle coating and size, researchers have created self-healing materials for improved sustainability and self-corralling rods for photovoltaic applications. A challenge for future studies is to create hierarchically structured composites in which each sublayer contributes a distinct function to yield a mechanically integrated, multifunctional material.

2,396 citations

Journal ArticleDOI
27 Nov 1997-Nature
TL;DR: A polymerization strategy that overcomes difficulties by using organonickel initiators which suppress chain-transfer and termination side reactions is described, which allows the facile synthesis of block copolypeptides with well-defined sequences, which might provide new peptide-based biomaterials with potential applications in tissue engineering, drug delivery and biomimetic composite formation.
Abstract: Many natural polymeric materials (particularly structural proteins) display a hierarchy of structure over several length scales. Block copolymers are able to self-assemble into ordered nanostructures1,2, but the random-coiled nature of their polymer chains usually suppresses any further levels of organization. The use of components with regular structures, such as rigid-rod polymers, can increase the extent of spatial organization in self-assembling materials3. But the synthesis of such polymeric components typically involves complicated reaction steps that are not suitable for large-scale production. Proteins form hierarchically organized structures in which the fundamental motifs are generally α-helical coils and β-sheets4. Attempts to synthesize polypeptides with well-defined amino-acid sequences, which might adopt similar organized structures, have been plagued by unwanted side reactions5 that give rise to products with a wide range of molecular weights6,7,8,9,10, hampering the formation of well-defined peptide block copolymers11,12,13,14,15,16,17. Here I describe a polymerization strategy that overcomes these difficulties by using organonickel initiators which suppress chain-transfer and termination side reactions. This approach allows the facile synthesis of block copolypeptides with well-defined sequences, which might provide new peptide-based biomaterials with potential applications in tissue engineering, drug delivery and biomimetic composite formation.

598 citations

Journal ArticleDOI
TL;DR: This review summarizes the literature after 1985 and reports on new aspects of the polymerization processes, such as the formation of cyclic polypeptides or novel organometal catalysts and the role of NCAs in molecular evolution on the prebiotic Earth is discussed.
Abstract: Syntheses and polymerizations of alpha-amino acid N-carboxyanhydrides (NCAs) were reported for the first time by Hermann Leuchs in 1906. Since that time, these cyclic and highly reactive amino acid derivatives were used for stepwise peptide syntheses but mainly for the formation of polypeptides by ring-opening polymerizations. This review summarizes the literature after 1985 and reports on new aspects of the polymerization processes, such as the formation of cyclic polypeptides or novel organometal catalysts. Polypeptides with various architectures, such as diblock, triblock, and multiblock sequences, and star-shaped or dendritic structures are also mentioned. Furthermore, lyotropic and thermotropic liquid-crystalline polypeptides will be discussed and the role of polypeptides as drugs or drug carriers are reviewed. Finally, the hypothetical role of NCAs in molecular evolution on the prebiotic Earth is discussed.

503 citations

Journal ArticleDOI
TL;DR: This article summarizes recent developments in the synthesis of copolypeptides from polymerization of α-amino acid-N-carboxyanhydrides (NCAs), focusing on their development for potential use in biomedical applications.

463 citations