<i>N</i>-Heterocyclic Carbene-Mediated Zwitterionic Polymerization of N-Substituted <i>N</i>-Carboxyanhydrides toward Poly(α-peptoid)s: Kinetic, Mechanism, and Architectural Control

Guo, Li; Lahasky, Samuel H.; Ghale, Kushal; Zhang, Donghui

doi:10.1021/ja210842b

Cited by 148 publications

(190 citation statements)

References 52 publications

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“…Similar spirocyclic intermediates were previously observed from lactones and saturated NHC 12 and proposed as intermediates in the ZROP of N-carboxyanhydrides. 9 Figure 2c and d). Figure 2c shows that, as the first δ-valerolactone ring opens, a partial positive charge of +0.72e needs to develop on the carbonyl carbon atom bound to the imidazolium heterocycle.…”

Section: ■ Results and Discussionmentioning

confidence: 94%

Experimental and Computational Studies on the Mechanism of Zwitterionic Ring-Opening Polymerization of δ-Valerolactone with N-Heterocyclic Carbenes

et al. 2014

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Experimental and computational investigations of the zwitterionic ring-opening polymerization (ZROP) of δ-valerolactone (VL) catalyzed by the N-heterocyclic carbenes (NHC) 1,3-diisopropyl-4,5-dimethyl-imidazol-2-ylidene (1) and 1,3,4,5-tetramethyl-imidazol-2-ylidene (2) were carried out. The ZROP of δ-valerolactone generates cyclic poly(valerolactone)s whose molecular weights are higher than predicted from [VL]0/[NHC]0. Kinetic studies reveal the rate of polymerization is first order in [VL] and first order in [NHC]. Density functional theory (DFT) calculations were carried out to elucidate the key steps involved in the ring-opening of δ-valerolactone and its subsequent oligomerization. These studies have established that the initial steps of the mechanism involve nucleophilic attack of the NHC on δ-valerolactone to form a zwitterionic tetrahedral intermediate. DFT calculations indicate that the highest activation barrier of the entire mechanism is associated with the ring-opening of the tetrahedral intermediate formed from the NHC and δ-valerolactone, a result consistent with inefficient initiation to generate reactive zwitterions. The large barrier in this step is due to the fact that ring-opening requires a partial positive charge to develop next to the directly attached NHC moiety which already bears a delocalized positive charge.

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Section: ■ Results and Discussionmentioning

confidence: 94%

Experimental and Computational Studies on the Mechanism of Zwitterionic Ring-Opening Polymerization of δ-Valerolactone with N-Heterocyclic Carbenes

et al. 2014

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“…[62] Reprinted with permission from American Chemical Society with narrow dispersity and tunable ring sizes (Scheme 7). [37,66] The polymer molecular weight and the ring size can be adjusted by controlling the initial monomer to NHC feed ratio. The polymerization proceeded through a zwitterionic propagating intermediate where the two oppositely charged chain ends are held in proximity through electrostatic interaction (Scheme 7).…”

Section: Synthesis Of Linear Polypeptoidsmentioning

confidence: 99%

“…The reactions proceed in a controlled manner in SCHEME 5 ROPs of R-NTAs using rare earth metal borohydrides or primary amine initiators to produce polypeptoids or their copolymers SCHEME 6 Aminoalcohol-initiated ROP of R-NTAs (R@Me, Et) to produce telechelic polypeptoids [5,6] and cyclic random and block copolypeptoids. [15,37,67,68] Bu-NCA similar to NHCs (Scheme 8). [69] The reaction occurs in a controlled manner in low dielectric solvents (eg, THF and toluene), allowing access of polypeptoids having low to medium molecular weights (DP < 300) and narrow PDI (1.02-1.12), similar to what has been reported for NHCs.…”

Section: Synthesis Of Linear Polypeptoidsmentioning

confidence: 99%

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Polypeptoid polymers: Synthesis, characterization, and properties

et al. 2017

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Polypeptoids, a class of peptidomimetic polymers, have emerged at the forefront of macromolecular and supramolecular science and engineering as the technological relevance of these polymers continues to be demonstrated. The chemical and structural diversity of polypeptoids have enabled access to and adjustment of a variety of physicochemical and biological properties (eg, solubility, charge characteristics, chain conformation, HLB, thermal processability, degradability, cytotoxicity and immunogenicity). These attributes have made this synthetic polymer platform a potential candidate for various biomedical and biotechnological applications. This review will provide an overview of recent development in synthetic methods to access polypeptoid polymers with well-defined structures and highlight some of the fundamental physicochemical and biological properties of polypeptoids that are pertinent to the future development of functional materials based on polypeptoids. | I N TR ODU C TI ONPolypeptoids composed of N-substituted polyglycine backbones are structural mimics of polypeptides ( Figure 1). Because of N-substitution, polypeptoids lack stereogenic centers and hydrogen bonding interactions along the main chains, in sharp contrast to polypeptides.As a result, the global conformations of polypeptoids are strongly dependent on the N-substituent structures, giving rise to random coils or well-defined secondary structures [eg, polyproline I (PPI) helix [1][2][3][4][5][6] and R-sheets] [7][8][9][10][11][12] that are reminiscent of those of polypeptides. The polypeptoid backbone containing tertiary amide linkages is highly polar and hydrophilic. The physicochemical properties of polypeptoids can be tailored by the N-substituent structures, enabling control over the hydrophilicity and lipophilicity balance (HLB), charge characteristics, [13,14] backbone conformation, [1][2][3][4][5][6][7][8][9][10][11][12] solubility, [15][16][17][18][19][20] thermal and crystallization properties of the polypeptoids. [21][22][23][24] Without extensive hydrogen bonding, polypeptoids are thermally processable similar to conventional thermoplastics, [20][21][22][23][24] whereas polypeptides undergo thermal degradation before they can be melt-processed due to the extensive hydrogen bonding interactions. While polypeptoids exhibited enhanced proteolytic stability relative to peptides, [25,26] they can be oxidatively degraded under conditions that mimic tissue inflammation, [27] suggesting their potential in vivo uses as biodegradable materials.Recent advances in the controlled polymerization methods have enabled access to a suite of structurally well-defined polypeptoids with various N-substituent structures and molecular architectures, setting the stage for the future development of polypeptoid materials for various targeted applications. Several review articles on the synthesis, properties, and application of polypeptoids for biomedical or nonbiomedical uses have been published in recent years. [28][29][30][31][32] As a result, this...

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“…7b) [26]. The control over the polymer molecular weight strongly depends on the solvents and the NHC structure, since only low molecular weight polymers were obtained regardless of the initial monomer/initiator ratio when N,N-dimethylformamide was used.…”

Section: Polymerization Mechanismsmentioning

confidence: 99%

Ring-Opening Polymerization of N-Carboxyanhydrides for Preparation of Polypeptides and Polypeptide-Based Hybrid Materials with Various Molecular Architectures

Pahovnik

Hadjichristidis

2015

Anionic Polymerization

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Different synthetic approaches utilizing ring-opening polymerization of N-carboxyanhydrides for preparation of polypeptide and polypeptide-based hybrid materials with various molecular architectures are described. An overview of polymerization mechanisms using conventional (various amines) as well as some recently developed initiators (hexamethyldisilazane, N-heterocyclic persistent carbenes, etc.) is presented, and their benefits and drawbacks for preparation of polypeptides with well-defined chain lengths and chain-end functionality are discussed. Recent examples from literature are used to illustrate different possibilities for synthesis of pure polypeptide materials with different molecular architectures bearing various functional groups, which are introduced either by modification of amino acids, before they are transformed into corresponding Ncarboxyanhydrides, or by post-polymerization modifications using protective groups and/or orthogonal functional groups. Different approaches for preparation of polypeptide-based hybrid materials are discussed as well using examples from recent literature. Syntheses of simple block copolymers or copolymers with more complex molecular architectures (graft and star copolymers) as well as modifications of nanoparticles and other surfaces with polypeptides are described.

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N-Heterocyclic Carbene-Mediated Zwitterionic Polymerization of N-Substituted N-Carboxyanhydrides toward Poly(α-peptoid)s: Kinetic, Mechanism, and Architectural Control

Cited by 148 publications

References 52 publications

Experimental and Computational Studies on the Mechanism of Zwitterionic Ring-Opening Polymerization of δ-Valerolactone with N-Heterocyclic Carbenes

Experimental and Computational Studies on the Mechanism of Zwitterionic Ring-Opening Polymerization of δ-Valerolactone with N-Heterocyclic Carbenes

Polypeptoid polymers: Synthesis, characterization, and properties

Ring-Opening Polymerization of N-Carboxyanhydrides for Preparation of Polypeptides and Polypeptide-Based Hybrid Materials with Various Molecular Architectures

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