Precision Synthesis of Polypeptides via Living Anionic Ring-Opening Polymerization of <i>N</i>-Carboxyanhydrides by Tri-thiourea Catalysts

Lv, Wenxiu; Wang, Yanchao; Li, Maosheng; Wang, Xianhong; Tao, Youhua

doi:10.1021/jacs.2c10950

Cited by 35 publications

(22 citation statements)

References 63 publications

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“…Overall, these results showed promise that the repertoire of anion-binding catalysis could be expanded to otherwise cationic polymerization systems, by rational design of catalysts and judicious selection of proper cationogens. More importantly, we envision that these combined with our prior studies, [5,6,10] will serve as a starting point for further explorations of anion-binding catalytic polymerization towards more intricate systems, and will encourage others to explore non-covalent catalysis further and develop it into an universal polymerization toolbox capable of achieving reactivity and selectivity comparable to or even superior to metal-based catalysis while addressing existing challenges in classical polymerization methodology.…”

Section: Methodsmentioning

confidence: 93%

Mechanistic Insight into Anion‐Binding Catalytic Living Cationic Polymerization

Zhang

et al. 2023

Angew Chem Int Ed

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Exploiting non-covalent interactions to catalyze challenging ionic polymerizations is an ambitious goal but is in its infancy. We recently demonstrated noncovalent anion-binding catalysis as an effective methodology to enable living cationic polymerization (LCP) of vinyl ethers in an environmentally benign manner. Here, we further elucidate the structure-reactivity relationships of the elaborately designed seleno-cyclodiphosph-(V)azanes catalysts and the roles of anion-binding interactions by a combined theoretical DFT study and experimental study. The investigation suggests that the distinct cis-cyclodiphosph(V)azane framework combined with "selenium effect" and electron-withdrawing 3,5-(CF 3 ) 2 -Phenyl substitution pattern in catalyst enables a critical contribution to accessing excellent stability, anion affinity and solubility under polymerization conditions. Thus, the catalyst could leverage anion-binding interactions to precisely control reversible and transient dormant-active species equilibrium, allowing it to dynamically bind, recognize and pre-organize propagating ionic species and monomer, thereby facilitating efficient chain propagation and minimizing irreversible chain transfer events under mild conditions. The more indepth understanding of the mechanism for anion-binding catalytic LCP reported herein should help to guide future catalyst design and to extend this concept to broader polymerization systems where ionic species serve as crucial intermediates.

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Section: Methodsmentioning

confidence: 93%

Mechanistic Insight into Anion‐Binding Catalytic Living Cationic Polymerization

Zhang

et al. 2023

Angew Chem Int Ed

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Section: Introductionmentioning

confidence: 99%

“…This leads to polymerization proceeding in a highly controllable mode. Very recently, Tao reported an anion-binding catalytic system combining tripodal trithiourea with sodium thiophenolate that enabled the fast and selective anionic ring-opening polymerization of NCAs . This method led to the precise construction of various polypeptides with living polymerization behavior and was evidenced by narrow molecular weight distributions, chain extension experiments, and a minimal “activated monomer” pathway, which were attributed to the intramolecular hydrogen bond within the trithiourea structure.…”

Section: Introductionmentioning

confidence: 99%

“…Compared with organometallic catalysis, organic catalysts exhibited equal or even superior competitiveness in terms of polymerization rates and selectivity. In recent years, a number of organic catalysts, 35−57 including fluorinated organic catalysts, 35 hexamethyldisilazane and trimethylsilyl agents, 36−38 thiourea, 39,40 and crown ether and ammonium salts, 41−45 have been widely investigated in the ROP of NCA, with an aim to avoiding the doping of metal elements in the produced polypeptides. Inspired by natural enzyme catalysis, the vast concerted efforts revealed that the bifunctional catalysts (the nucleophilic site and the electrophilic center covalently bonded in one molecule) usually displayed superior activity and selectivity over their binary counterparts under the same conditions.…”

Section: ■ Introductionmentioning

confidence: 99%

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Thiourea-Based Bifunctional Catalysts for Epoxide-Involved Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydrides

Wang

2023

Macromolecules

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Thiourea-quaternary ammonium salt bifunctional catalysts with both electrophilic and nucleophilic centers were designed in this paper to initiate the ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCAs) for the efficient synthesis of polypeptides. We disclosed this kind of bifunctional catalyst for the efficient synthesis of polypeptides in the presence of propylene oxide (PO), which was judiciously added as an in situ activator for the efficient ROP of NCA. By MALDI-TOF MS and 1H NMR analysis, we identified the end groups of the polymer and clarified the ROP process in the presence of the bifunctional catalyst. We showed that the PO was initially ring-opened by the nucleophilic attack of a halogen ion; then, the newly formed alkoxide ions attacked the electrophilic carbonyl of NCA, providing the carbamate anion. After undergoing a decarboxylation of the carbamate anion, the nucleophilic attack of N to the carbonyl on an NCA ring occurred synergistically to complete the chain growth. The involved three steps formed the whole catalytic cycle. We also disclosed that the structural factors, including the electronic effect on electrophilic/nucleophilic centers, steric factors, and the coupling thermodynamics, have a strong relationship with catalyst performance. We believe the insightful structure–performance relationship will shed light on further metal-free catalyst design for artificial polypeptide synthesis.

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“…The anion-binding approach complements the conventional use of H-bond donors by interacting with the negatively charged nucleophilic species in the polymerization. Wang and Tao used thioureas to stabilize the carboxylate chain end to access controlled anionic ROP of O -carboxyanhydrides and N -carboxyanhydrides . Fors extended the use of an anion-binding catalyst, thiophosphoramide, to arrest the reactive countercation and furnish an air-tolerant cationic polymerization of vinyl ethers .…”

Section: Introductionmentioning

confidence: 99%

Controlled and Regioselective Ring-Opening Polymerization for Poly(disulfide)s by Anion-Binding Catalysis

Du,

Shen,

Dai

et al. 2023

J. Am. Chem. Soc.

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Precision Synthesis of Polypeptides via Living Anionic Ring-Opening Polymerization of N-Carboxyanhydrides by Tri-thiourea Catalysts

Cited by 35 publications

References 63 publications

Mechanistic Insight into Anion‐Binding Catalytic Living Cationic Polymerization

Mechanistic Insight into Anion‐Binding Catalytic Living Cationic Polymerization

Thiourea-Based Bifunctional Catalysts for Epoxide-Involved Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydrides

Controlled and Regioselective Ring-Opening Polymerization for Poly(disulfide)s by Anion-Binding Catalysis

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