Skip to main content
NCBI home page
Precision Chemistry logoLink to Precision Chemistry
. 2025 Nov 28;4(3):300–307. doi: 10.1021/prechem.5c00198

Architectural Precision in Sequence-Controlled Terpolymerization from Epoxide/Aziridine/Phthalic Thioanhydride Mixture

Yang-Yang Zhao †, Guo-Xu Wang †, Ze-Hua Liu †, Jun-Heng Li ‡, Hao-Yun Liu †, Rui-Dong Cheng †, Qiu-Yu Zhang †, Jie Li †,*
PMCID: PMC13014309  PMID: 41890401

Abstract

The monomer sequence serves as a critical determinant of a polymer’s physicochemical properties. While traditional copolymerization processes are dictated by inherent monomer reactivity disparities, the emerging paradigm of catalytic precision engineering offers unprecedented opportunities to orchestrate monomer incorporation sequences beyond thermodynamic constraints. Notably, recent efforts have concentrated on developing catalytic systems with chemo- and stereoselectivity orthogonal to monomer polarities, establishing dynamic polymerization platforms that enable real-time sequence editing through manipulation of catalysts. Herein, we disclose a modular catalytic strategy enabling atom-level control over poly­(thioester amide) sequences through organoammonium-mediated ring-opening copolymerization (ROCOP) of Cbz-aziridine and phthalic thioanhydride under ambient conditions. Furthermore, we develop a dual-catalytic system that integrates salenAl­(III)Cl and PPNOAc, establishing a dynamic multinucleophilic platform that circumvents traditional monomer reactivity hierarchies. Of importance, systematic manipulation of catalysts in epoxide/aziridine/PTA terpolymerization achieves unprecedented continuum control across gradient, statistical, and inverse gradient microstructures in poly­(thioester amide-thioester)­s. This synthetic approach establishes a generalizable platform for fabricating compositionally equivalent copolymers with digital precision and significantly enhances the mechanistic understanding of polymer physics while creating principles for high-impact applications ranging from adaptive biomaterials to intelligent responsive systems.

Keywords: alternating copolymerization, poly(thioester amide)s, aziridines, phthalic thioanhydride, sequence-controlled polymerization

graphic file with name pc5c00198_0008.jpg

graphic file with name pc5c00198_0006.jpg

Introduction

Synthetic polymers with a specific sequence wherein unique monomer units are arranged in a predetermined manner, such as alternating, di- and multiblock, gradient, and statistical, as well as topological microstructures, have become pivotal in creating development of advanced materials tailored for specific applications, including data storage, anticounterfeiting technologies, microelectronics, and nanomedicine. − The precise synthesis of copolymers with well-defined sequence structures through traditional copolymerization methods that utilize mixed-monomer feedstocks has the potential to significantly enhance the development of polymer materials. − The sequence distribution in synthetic copolymerization systems is fundamentally governed by the intrinsic reactivity of the monomers. Achieving precise sequence control in polymerization with mixed-monomer feedstocks, particularly through catalyst engineering strategies, remains a persistent challenge for constructing architecturally complex macromolecules with tailored functionality. −

Aziridines have garnered substantial attention due to the inherent ring strain of their three-membered architecture, positioning them as versatile precursors for nitrogen-rich compounds and polymeric materials. − However, methodologies for precise monomer sequence regulation in aziridine-based ring-opening polymerization (ROP) and ring-opening alternating copolymerization (ROCOP) systems remain a critical challenge in the field of precision polymer synthesis. In 2018, Wurm and co-workers documented the first combination of the living anionic ring-opening polymerization of ethylene oxide (EO) and sulfonamide-activated aziridines (TAz) to produce block copolymers in a one-pot, one-step reaction, enabled by the distinct differences in reactivity of monomers (Figure a). Concurrently, Zhao and Carlotti innovatively developed a synergistic orthogonal dual catalytic system, combining phosphazene superbases with triethyl borane (TEB), which mediate aziridine-epoxide copolymerization through a modular chain-growth mechanism to afford polyether-b-polyamine block copolymers distinct from Wurm’s approach (Figure a). Regarding ROCOP involved aziridines, Hadjichristidis and colleagues reported the first controlled ring-opening copolymerization (ROCOP) of TAz with phthalic anhydride (PA) mediated by phosphazene base catalysts. Subsequently, the same research group devised an innovative one-pot/one-step terpolymerization protocol that simultaneously incorporates aziridine, cyclic anhydride, and epoxide monomers. This advanced methodology permits the synthesis of microstructurally well-defined diblock copolymers featuring dual alternating segments, showcasing exceptional control over macromolecular architecture. Very recently, Satoh and co-workers reported the novel catalyst-controlled copolymerization of epoxides, TAz and cyclic anhydrides utilizing a combination of the phosphazene base t-BuP1 and a TEB catalytic system, achieving modulation of the resulting poly­(ester–amide ester) from ABA type real block copolymers to gradient, statistical-like, reversed gradient, and reversed BAB-type block-like copolymers (Figure b). ,

1.

1

Open in a new tab

(a and b) General scheme for monomer sequence regulation in aziridine-based ring-opening polymerization systems. (c) The concept of this research.

We herein report a modular catalytic strategy for the precision synthesis of sequence-defined poly­(thioester amide)­s via organoammonium-salt-mediated ring-opening copolymerization (ROCOP) of N-benzyloxycarbonyl (Cbz)-protected aziridine (CAz) with phthalic thioanhydride (PTA) under mild conditions. Notably, we further demonstrate the versatility of this approach by developing a salenAl­(III)­Cl/PPNOAc-catalyzed terpolymerization system involving epoxides, aziridines, and PTA. Through systematic adjustment of catalyst stoichiometry, we achieve unprecedented control over monomer sequence architectures in poly­(thioester amide-thioester)­s, enabling precise tailoring of microstructure gradientsfrom gradient and statistical-like to reversed gradient sequences (Figure c). This work establishes a robust platform for engineering sequence-specific functional polymers with programmable thermo-mechanical and degradation properties.

Results and Discussion

Well-Controlled ROCOP of CAz with PTA

N-unsubstituted aziridines are prone to facile cationic ring-opening polymerization, which typically results in poorly controlled formation of hyperbranched polymeric architectures. The introduction of strong electron-withdrawing groups effectively diminishes the nucleophilicity of aziridine’s ring nitrogen, consequently converting N-substituted aziridines into electrophilic monomers amenable to anionic polymerization. In our prior research, carbobenzyloxy (Cbz) substituents were strategically employed as electronic modulators to orchestrate the redistribution of nitrogen’s lone pair electrons through conjugation effects, successfully achieving ring-opening copolymerization (ROCOP) between N-Cbz aziridine (CAz) and cyclic anhydrides, which produced linear poly­(ester amide)­s (PEAs) with unprecedented structural precision.

In this systematic investigation, we first explored the feasibility of direct copolymerization between CAz and phthalic thioanhydride (PTA) in the absence of initiators and catalysts (Table , entry 1). Continuous monitoring by 1H NMR spectroscopy over 36 h at ambient temperature demonstrated complete absence of characteristic copolymer resonances (Figure S1), definitively precluding spontaneous zwitterionic copolymerization mechanisms in this binary system. A systematic screening protocol was then implemented in anhydrous 1,4-dioxane (molar ratio [CAz]/[PTA]/[Initiator] = 50:50:1) to assess three structurally distinct bicyclic amidine organocatalysts: 1,5,7-triazabicyclo[4.4.0]­dec-5-ene (TBD), 7-methyl-TBD (MTBD), and 1,8-diazabicyclo[5.4.0]­undec-7-ene (DBU). Intriguingly, all catalytic systems manifested profound kinetic inhibition, with time-resolved 1H NMR tracking revealing statistically insignificant monomer conversion (<10%) throughout the 72-h temporal window (Table , entries 2–4). Building upon established success in ROCOP of epoxides with cyclic anhydrides, bis­(triphenylphosphoranylidene)­ammonium (PPN) salts were methodologically examined as precision catalysts for sequence-controlled copolymer architectures. , At benchmark 2 mol % loading, organocatalysts displayed exceptional performance metrics, with PPNOAc demonstrating superior catalytic efficiency as evidenced by achieving 91% monomer conversion within 4 h (Table , entry 7). After identifying PPNOAc as the optimal catalyst, we screened the reaction solvent in common solvents such as toluene (TOL), acetonitrile (AN), dichloromethane (DCM), tetrahydrofuran (THF), dimethylformamide (DMF), and 1,4-dioxane (Table S1). While copolymerizations in AN, THF, and DMF achieved polymers with substantial molecular weights (Mn > 5.0 kDa), solvent-mediated reaction kinetics induced prohibitive polymerization durations (>50 h) (Table S1, entries 2, 4, and 5). Dioxane was ultimately selected as the copolymerization exhibited higher reaction reactivity and selectivity, and provided polymers with high molecular wight and narrow distribution. (Table S1, entry 6). The 1H NMR analysis of the resulting copolymer revealed no detectable signals corresponding to polyamide units, confirming the formation of a perfectly alternating structure (Figure a). Notably, catalytic efficiency persisted at substoichiometric 0.2 mol % PPNOAc loading, enabling synthesis of precisely engineered poly­(thioester amide)­s (PTEAs) with predictable molecular weights (M n = 23.9 kDa) and exceptionally narrow dispersity (Đ = 1.30) (Table , entry 8).

1. Initiator Screen for CAz/PTA Copolymerization .

graphic file with name pc5c00198_0005.jpg

entry initiator (I) aziridine/PTA/initiator time [h] conv. [%] M n,SEC [kDa] Đ
1 / 50:50:1 36      
2 DBU 50:50:1 72 <10    
3 TBD 50:50:1 72 <10    
4 MTBD 50:50:1 72 <10    
5 PPNCl 50:50:1 24 71 4.1 1.29
6 PPNNO3 50:50:1 27 62 3.8 1.35
7 PPNOAc 50:50:1 4 91 6.1 1.20
8 PPNOAc 500:500:1 26 81 23.9 1.30
Open in a new tab
a

Reactions were performed with the CAz/PTA/Initiator = 50:50:1 at room temperature, [anhydride]0 = 1.0 mol L–1 in dioxane in a 10 mL vial unless noted otherwise.

b

Conversion of aziridine was calculated using 1H NMR spectroscopy.

c

Number-average molecular weights (Mn ) and dispersity values were determined by size exclusion chromatography (SEC) in THF, calibrated with polystyrene.

d

Reaction was conducted with Aziridine/PTA/Initiator = 500:500:1, [anhydride]0 = 1.0 mol L–1 in dioxane.

2.

2

Open in a new tab

(a) 1H NMR spectrum (400 MHz, DMSO-d 6) of copolymers; (b) M n,SEC (kDa) and Đ versus conversion of poly­(CAz-alt-PTA) and SEC traces of copolymers with increasing monomer conversion, calibrated relative to monodisperse polystyrene standards.

The architectural precision of the alternating copolymer was methodically elucidated through triple-modality spectroscopic interrogation (1H/13C NMR and MALDI-TOF MS). 1H NMR analysis revealed a diagnostic deshielding effect, where the methylene protons (δ 2.23 ppm) in the CAz monomer underwent a 2.07–3.87 ppm downfield shift upon thioester–amide bond formation (Figure a). This significant chemical displacement directly corroborated the nucleophilic ring-opening mechanism during chain propagation. Notably, the complete absence of resonances in the δ 1.8–2.5 ppm regime (characteristic of amide homopolymers) provided unequivocal evidence for sequence-controlled alternating architecture. Complementary 13C NMR data exhibited discrete carbonyl signatures at δ 190.8 (thioester) and 171.2 ppm (amide), confirming chemically differentiated repeating units (Figure S3). The controlled polymerization dynamics were further substantiated by linear evolution of molecular weights with conversion, accompanied by exceptionally narrow dispersities (Đ = 1.16–1.20) across all growth stages (Figure b). This dual verification systemcombining structural fingerprinting with polymerization kineticsestablished unprecedented control in alternating copolymer synthesis. The structural regularity was further confirmed by MALDI-TOF MS, which exhibited a periodic peak pattern with a uniform mass interval of 341.1 Da. Each repeating unit was identified as containing an acetate group and the structure derived from ring-opened CAz at the chain end. Crucially, the mass spectrum showed no detectable signals corresponding to branched or cyclic byproducts from intermolecular/intramolecular nucleophilic side reactions, confirming the absence of competitive side pathways (Figures S4 and S5). Furthermore, these observations were consistent with a living chain-growth mechanism, wherein each acetate anion initiator (derived from PPNOAc) selectively reacted with CAz to generate a single active polymer chain.

Terpolymerization of PGE/CAz/PTA with SalenAl­(III)­Cl/PPNOAc Binary Catalyst System for Monomer Sequence-Controlled Polymerization

The precise synthesis of sequence-controlled polymersmacromolecular architectures with programmed monomer arrangementhas emerged as a transformative frontier in polymer science, driven by their unique structure–property relationships. − Through rational modulation of comonomer reactivity ratios, researchers can engineer advanced polymeric systems with precisely tailored microarchitectures (e.g., gradient, block, or alternating sequences), enabling predictive optimization of bulk material properties for specific functional demands. In this work, we demonstrate a well-controlled terpolymerization of epoxide/aziridine/phthalic thioanhydride, establishing a versatile platform for architectural precision in resulting terpolymers.

Based on the pronounced activation capability of epoxide groups in ring-opening (co)­polymerization systems, − we strategically employed the salenAl­(III)Cl complex in conjunction with nucleophilic PPNOAc to establish a highly efficient catalytic platform. This synergistic dual-catalyst system enables strict sequence control during the room-temperature copolymerization of sulfur-containing monomers, demonstrating remarkable stereochemical precision in monomer incorporation.

Initially, CAz, PGE, and PTA were used as model monomers to assess the influence of salenAl­(III)Cl on the copolymerization of epoxides with cyclic thioanhydrides and aziridines with cyclic thioanhydrides. The initial concentration of PTA was 1.5 mol L–1, with fixed monomer to PPNOAc ratios (PGE/PTA and CAz/PTA) at 50:50:1, and varying amounts of salenAl­(III)­Cl. When PPNOAc was the only catalyst in the copolymerization of PGE and PTA, the polymerization rate was low, with only 11.6% PGE conversion observed after 2 h (Table S2, entry 1). The addition of salenAl­(III)­Cl significantly increased the polymerization rate. With 0.25, 0.50, and 1.0 equiv of salenAl­(III)­Cl, PGE consumption reached 49.3%, 53.9%, and 81.6%, respectively, after 2 h (Table S2, entries 2–5). Increasing the amount of salenAl­(III)Cl to 2.0 and 5.0 equiv. only slightly improved the polymerization rate (Figure a and Table S2, entries 6–7). The utilization of PPNOAc in the ROCOP of CAz and PTA demonstrated high efficiency, yielding a 73.3% conversion of CAz within 2 h (Table S2, entry 8). While the presence of salenAl­(III)Cl exhibited a mild inhibitory impact on the polymerization process, increasing amounts of salenAl­(III)Cl led to a reduction in the polymerization rate of CAz and PTA to levels lower than that of PGE and PTA under similar conditions (Figure a and table S2, entries 9–14). These findings suggested that salenAl­(III)Cl functioned as an “activator” in the ROCOP of PGE and PTA, while acting as a mild “depressor” in the ROCOP of CAz and PTA. This outcome suggested that by integrating these two ROCOP pathways and adjusting the addition of salenAl­(III)­Cl, a controllable polymerization system can be established to precisely regulate the ternary polymerization process under ambient conditions.

3.

3

Open in a new tab

(a) Plots of PGE/PTA and CAz/PTA ring-opening alternating copolymerization turnover frequency values (TOF) with different salenAl­(III)Cl addition amounts; (b) 1H NMR spectra (400 MHz, CDCl3) of PGE, CAz, and PTA terpolymerization at different reaction times; (c) 1H NMR spectrum of poly­(CAz-alt-PTA)-co-poly­(PGE-alt-PTA).

Subsequently, the terpolymerization of PGE/CAz/PTA was conducted at a molar ratio of [PPNOAc]0/[PGE]0/[CAz]0/[PTA]0 set at 1.0:50:50:100 and an initial PTA concentration of 3 M in dioxane (Table S4, entry 2). The reactivity ratios (r CAz, r PGE) were calculated using the nonterminal Beckingham–Sanoja–Lynd (BSL) copolymerization model. As the nucleophilic attack of carboxylate anion (A*) on epoxide (E) or CAz (C) was considered as an independent step regarding the second monomer unit from the propagating chain end. Ultimately, the calculated reactivity ratios were r CAz = 4.72 and r PGE = 0.212 (Figure a), indicating that the resulting terpolymer exhibited a gradient structure.

4.

4

Open in a new tab

Copolymerization of CAz, PGE, and PTA with different PPNOAc/salenAl­(III)­Cl ratios. (a) PPNOAc/salenAl­(III)Cl = 1.0:0.0; (b) PPNOAc/salenAl­(III)­Cl = 1.0:0.5; (c) PPNOAc/salenAl­(III)Cl = 1.0:1.0; (d) PPNOAc/salenAl­(III)­Cl = 1.0:5.0; (e) reactivity ratio of epoxide and CAz under epoxide/CAz/PTA ROCOP with different conditions.

Comprehensive NMR characterization revealed that during the first hour of the reaction, the ROCOP of CAz/PTA proceeded first, and before CAz was fully consumed, the ROCOP of PGE/PTA had already commenced, ultimately yielding the terpolymer with gradient nature (Figure b,c). DOSY spectrum showed a single diffusion coefficient, distinct from those of the individually prepared PGE/PTA and CAz/PTA polymers (Figures S22–S24), confirming that the CAz/PTA and PGE/PTA segments were connected by chemical bonds rather than through simple physical blending.

Terpolymerization of PGE/CAz/PTA was conducted by adding varying equiv of salenAl­(III)Cl while maintaining all other conditions constant at room temperature. With 0.5 equiv. salenAl­(III)Cl (Table S4, entry 3), the activation of PGE mediated by Lewis acid partially synchronized comonomer consumption (r CAz ≈ 1.75, r PGE ≈ 0.57; Figure b, S16 and S17), ultimately yielding statistical distributed sequences. Notably, at 1.0 equiv. cocatalyst loading (Table S4, entry 4), we observed counterintuitive reactivity inversion (r CAz = 0.68 vs r PGE = 1.46, Figure c, S18 and S19), where the electronic effects from Al­(III)-epoxide complexation likely induced transition-state configurations favoring PGE incorporation, resulting in reversed statistical terpolymers. The introduction of 5.0 equiv. salenAl­(III)Cl (Table S4, entry 5) triggered a dramatic reactivity inversion, with ratios shifting to r Caz = 0.313 and r PGE = 3.19 (Figure d, S20 and S21). This inversion established a reverse-gradient architecture, wherein PGE/PTA units dominated the early polymerization phase before CAz/PTA incorporation ensues.

To elucidate the specific feature of this system, we systematically investigated the terpolymerization of TAz/PTA/PGE using both single- and dual-catalytic systems. When employing PPNOAc as the sole initiator (0 mol % salenAl­(III)­Cl), in situ 1H NMR analysis revealed sequential polymerization stages: complete conversion of TAz and PTA occurred within 30 min, followed by delayed initiation of PGE/PTA copolymerization to afford well-defined block architectures (r TAz = 33.91 vs r PGE = 0.0295, table S3 entry 2 and, Figures S7–S9). Remarkably, introducing 1.0 equiv salenAl­(III)Cl induced dynamic catalyst activation, as demonstrated by real-time NMR monitoring, the reaction ratios shifted to r TAz = 8.75 and r PGE = 0.114, indicating a gradient sequence terpolymers were obtained (Table S3 entry 3 and Figures S10–S12). Therefore, kinetic modulation of terpolymerization of TAz/PTA/PGE through catalyst ratio adjustments only enables architectural transitionsfrom block to gradient structures.

These results not only demonstrated proportional catalyst-dependent reactivity reversal but also validated the system’s capacity for architectural programming through binary catalytic modulation.

Monomer Scope

After establishing precision control over PGE/CAz/PTA sequences through binary catalytic modulation, we systematically expanded this methodology to diverse epoxide counterparts (Figure e). Using CAz (aziridine) and PTA (thioanhydride) with five distinct epoxides, we observed reactivity-dependent architectural evolution. For low-reactivity epoxides (PO, BO) under PPNOAc-only conditions, kinetically locked block-type polymers formed (r CAz > 20; r epoxide < 0.05) (Table S5, entries 1 and 4, Figures S27–S29 and S36–S38). Remarkably, introducing incremental salenAl­(III)­Cl (0.5–1.0 equiv) progressively erased this kinetic preference, transitioning architectures through gradient intermediates to ultimately statistical distributions (Table S5, entries 2–3 and 5–6 and Figures S30–35 and S39–S44).

As dual-substituent scaffold in CHO/VCHO imposed regiodefinitive steric congestion, catalytic evaluation under PPNOAc-dominant conditions revealed complete polymerization arrest for both monomers, with <5% incorporation efficiency observed (Table S5, entries 7 and 11, Figures S45 and S54). When the equiv of salenAl­(III)­Cl was adjusted to 0.25, coordinated activation strategies overcame steric barriers of CHO/VCHO and initiated sequence-programmable chain growth to yield terpolymers with block distribution. Escalating salenAl­(III)­Cl to 1.0 equiv. triggered chain-growth mode switching, inducing macroscopic sequence redistribution that generated gradient architectures (Table S4, entries 8–9,12–13 and Figures S46–S51 and S55–S60).However, even when the amount of salenAl­(III)Cl was further increased to 5.0 equiv., the macroscopic sequence of the CHO polymer still exhibited a gradient profile (Table S5, entry 10 and Figures S52 and S53). Given that VCHO demonstrates similar reactivity to CHO, further polymerization attempts with VCHO were not pursued. To investigate the impact of monomer-sequence on the thermal properties of terpolymers, differential scanning calorimetry (DSC) measurements were performed with varying monomer sequences (Figures S61–S65). Taking poly­(CAz-alt-PTA)-co-poly­(PGE-alt-PTA) as the example, the terpolymers exhibited only a single glass transition temperature (T g) between 40.0–50.0 °C, indicating the lack of phase separation due to sharing the same moiety from monomers and the relatively low molecular weight character.

Conclusion

We report a novel platform for synthesizing sequence-defined linear poly­(thioester amide)­s through ring-opening alternating copolymerization (ROCOP) of N-carbobenzyloxy aziridine (CAz) and cyclic thioanhydride (PTA), mediated by a sterically hindered nitrogen salt (PPNOAc) under ambient conditions. The ortho-conjugation effects of the Cbz-group induce charge redistribution at the aziridine nitrogen center, enabling regioselective monomer activation to produce strictly alternating CAz-PTA sequences with controlled molecular weights (Đ < 1.5). Expanding this platform, we develop a binary catalytic system integrating PPNOAc with a salenAl­(III)Cl complex, achieving spatiotemporal control over monomer sequences in terpolymerizations involving epoxides, CAz, and PTA via this synergistic catalysis. Kinetic modulation of competing propagation pathways through catalyst ratio adjustments enables programmable architectural transitionsfrom gradient to statistical, reversed statistical, and reversed gradient structures. The polymerization system demonstrates versatility across various epoxides, although the polymerization behavior varies depending on monomer reactivity. This strategy offers a novel approach for controlling monomer sequences in highly reactive polymerizations, enabling the synthesis of polymers with precise and customizable sequences at accelerated rates. Furthermore, this synthetic method provides a straightforward route to produce sulfur-containing copolymers with similar chemical compositions but distinct monomer sequences, which is of significant value for exploring the relationship between monomer sequences and properties in sulfur-containing polymers.

Supplementary Material

pc5c00198_si_001.pdf (5.9MB, pdf)

Acknowledgments

This work was supported by the National Natural Science Foundation of China (NSFC, Grant 22275148, 52203144 and 22301243) and the Fundamental Research Funds for the Central Universities (D5000230135).

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/prechem.5c00198.

  • Synthetic procedures of experimental procedures, characterizations, synthetic details, equipment specifications, NMR, and statistical analysis (PDF)

The authors declare no competing financial interest.

References

  1. Lutz J.-F., Ouchi M., Liu D. R., Sawamoto M.. Sequence-controlled polymers. Science. 2013;341:1238149. doi: 10.1126/science.1238149. [DOI] [PubMed] [Google Scholar]
  2. Matyjaszewski K.. Architecturally Complex Polymers with Controlled Heterogeneity. Science. 2011;333:1104–1105. doi: 10.1126/science.1209660. [DOI] [PubMed] [Google Scholar]
  3. Badi N., Lutz J.-F.. Sequence control in polymer synthesis. Chem. Soc. Rev. 2009;38:3383–3390. doi: 10.1039/b806413j. [DOI] [PubMed] [Google Scholar]
  4. Mutlu H., Lutz J. F.. Reading Polymers: Sequencing of natural and synthetic macromolecules. Angew. Chem., Int. Ed. 2014;53:13010–13019. doi: 10.1002/anie.201406766. [DOI] [PubMed] [Google Scholar]
  5. Bates F. S., Hillmyer M. A., Lodge T. P., Bates C. M., Delaney K. T., Fredrickson G. H.. Multiblock Polymers: Panacea or Pandora’s Box? Science. 2012;336:434–440. doi: 10.1126/science.1215368. [DOI] [PubMed] [Google Scholar]
  6. Meier M. A. R., Barner-Kowollik C.. A New Class of Materials: Sequence-Defined Macromolecules and Their Emerging Applications. Adv. Mater. 2019;31:1806027. doi: 10.1002/adma.201806027. [DOI] [PubMed] [Google Scholar]
  7. Kim M. S., Khang G., Lee H. B.. Gradient polymer surfaces for biomedical applications. Prog. Polym. Sci. 2008;33:138–164. doi: 10.1016/j.progpolymsci.2007.06.001. [DOI] [Google Scholar]
  8. Miura Y., Shibata T., Satoh K., Kamigaito M., Okamoto Y.. Stereogradient polymers by ruthenium-catalyzed stereospecific living radical copolymerization of two monomers with different stereospecificities and reactivities. J. Am. Chem. Soc. 2006;128:16026–16027. doi: 10.1021/ja067587n. [DOI] [PubMed] [Google Scholar]
  9. Yang C., Wu K. B., Deng Y., Yuan J., Niu J.. Geared Toward Applications: A Perspective on Functional Sequence-Controlled Polymers. ACS Macro Lett. 2021;10:243–257. doi: 10.1021/acsmacrolett.0c00855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lutz J.-F.. Sequence-controlled polymerizations: the next Holy Grail in polymer science? Polym. Chem. 2010;1:55–62. doi: 10.1039/b9py00329k. [DOI] [Google Scholar]
  11. Tang X., Westlie A. H., Watson E. M., E Chen Y. X.. Stereosequenced crystalline polyhydroxyalkanoates from diastereomeric monomer mixtures. Science. 2019;366:754–758. doi: 10.1126/science.aax8466. [DOI] [PubMed] [Google Scholar]
  12. Butler F., Fiorentini F., Eisenhardt K. H. S., Williams C. K.. Structure-Activity Relationships for s-Block Metal/Co­(III) Heterodinuclear Catalysts in Cyclohexene Oxide Ring-Opening Copolymerizations. Angew. Chem., Int. Ed. 2025;64:e202422497. doi: 10.1002/anie.202422497. [DOI] [PubMed] [Google Scholar]
  13. Gregory G. L., Sulley G. S., Kimpel J., Łagodzińska M., Häfele L., Peña Carrodeguas L., Williams C. K.. Block Poly­(carbonate-ester) Ionomers as High-Performance and Recyclable Thermoplastic Elastomers. Angew. Chem., Int. Ed. 2022;61:e202210748. doi: 10.1002/anie.202210748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Romain C., Zhu Y., Dingwall P., Pail S., Rzepa H. S., Buchard A., Williams C. K.. Chemoselective Polymerizations from Mixtures of Epoxide, Lactone, Anhydride, and Carbon Dioxide. J. Am. Chem. Soc. 2016;138:4120–4131. doi: 10.1021/jacs.5b13070. [DOI] [PubMed] [Google Scholar]
  15. Lin F., Wang M.-Y., Pan Y.-P., Tang T., Cui D.-M., Liu B.. Sequence and regularity controlled coordination copolymerization of butadiene and styrene: strategy and mechanism. Macromolecules. 2017;50:849–856. doi: 10.1021/acs.macromol.6b02413. [DOI] [Google Scholar]
  16. Li J., Liu Y., Ren W.-M., Lu X.-B.. Enantioselective terpolymerization of racemic and meso-epoxides with anhydrides for preparation of chiral polyesters. Proc. Natl. Acad. Sci. U.S.A. 2020;117:15429–15436. doi: 10.1073/pnas.2005519117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dequina H. J., Jones C. L., Schomaker J. M.. Recent updates and future perspectives in aziridine synthesis and reactivity. Chem. 2023;9:1658–1701. doi: 10.1016/j.chempr.2023.04.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sweeney J. B.. Aziridines: epoxides’ ugly cousins? Chem. Soc. Rev. 2002;31:247–258. doi: 10.1039/B006015L. [DOI] [PubMed] [Google Scholar]
  19. Huang H., Zheng S., Luo J., Gao L., Fang Y., Zhang Z., Dong J., Hadjichristidis N.. Step-growth polymerization of aziridines with elemental sulfur: easy access to linear polysulfides and their use as recyclable adhesives. Angew. Chem., Int. Ed. 2024;63:e202318919. doi: 10.1002/anie.202318919. [DOI] [PubMed] [Google Scholar]
  20. Fan J., Ju C., Fan S., Li X., Zhang Z., Hadjichristidis N.. Inverse vulcanization of aziridines: enhancing polysulfides for superior mechanical strength and adhesive performance. Angew. Chem., Int. Ed. 2025;64:e202418764. doi: 10.1002/anie.202418764. [DOI] [PubMed] [Google Scholar]
  21. Xu J., Hadjichristidis N.. Well-defined poly­(ester amide)-based homo- and block copolymers by one-pot organocatalytic anionic ring-opening copolymerization of n-sulfonyl aziridines and cyclic anhydrides. Angew. Chem., Int. Ed. 2021;60:6949–6954. doi: 10.1002/anie.202015339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gleede T., Reisman L., Rieger E., Mbarushimana P. C., Rupar P. A., Wurm F. R.. Aziridines and Azetidines: Building Blocks for Polyamines by Anionic and Cationic Ring-Opening Polymerization. Polym. Chem. 2019;10:3257–3283. doi: 10.1039/C9PY00278B. [DOI] [Google Scholar]
  23. Gleede T., Rieger E., Blankenburg J., Klein K., Wurm F. R.. Fast Access to Amphiphilic Multiblock Architectures by the Anionic Copolymerization of Aziridines and Ethylene Oxide. J. Am. Chem. Soc. 2018;140:13407–13412. doi: 10.1021/jacs.8b08054. [DOI] [PubMed] [Google Scholar]
  24. Song Q., Qiu H., Liu L., Zhang G., Peruch F., Carlotti S., Zhao J.. Janus Effect of Lewis Acid Enables One-Step Block Copolymerization of Ethylene Oxide and N-Sulfonyl Aziridine. Angew. Chem., Int. Ed. 2023;62:e202300187. doi: 10.1002/anie.202300187. [DOI] [PubMed] [Google Scholar]
  25. Xu J., Wang X., Hadjichristidis N.. Diblock dialternating terpolymers by one-step/one-pot highly selective organocatalytic multimonomer polymerization. Nat. Commun. 2021;12:7124. doi: 10.1038/s41467-021-27377-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Gao T., Xia X., Watanabe T., Ke C.-Y., Suzuki R., Yamamoto T., Li F., Isono T., Satoh T.. Toward Fully Controllable Monomers Sequence: Binary Organocatalyzed Polymerization from Epoxide/Aziridine/Cyclic Anhydride Monomer Mixture. J. Am. Chem. Soc. 2024;146:25067–25077. doi: 10.1021/jacs.4c08009. [DOI] [PubMed] [Google Scholar]
  27. Gao T., Li F., Suzuki R., Li H., Yamamoto T., Xia X., Isono T., Satoh T.. One-Step Synthesis of Poly­(amide ester)-Based Block Copolymers with Defined Phase Separation Behavior. Macromolecules. 2023;56:8333–8343. doi: 10.1021/acs.macromol.3c01305. [DOI] [Google Scholar]
  28. Gleede T., Reisman L., Rieger E., Mbarushimana P. C., Rupar P. A., Wurm F. R.. Aziridines and azetidines: building blocks for polyamines by anionic and cationic ring-opening polymerization. Polym. Chem. 2019;10:3257–3283. doi: 10.1039/C9PY00278B. [DOI] [Google Scholar]
  29. Wang G.-X., Zhao Y.-Y., Yue T.-J., Cheng R.-D., Zhang Q.-Y., Li J.. Organocatalytic Precision Synthesis of Poly­(ester amide)­s with Enhanced Thermal Performance and Programmable Microarchitectures. Macromolecules. 2025;58:10705–10713. doi: 10.1021/acs.macromol.5c02125. [DOI] [Google Scholar]
  30. Yue T. J., Zhang M. C., Gu G. G., Wang L. Y., Ren W. M., Lu X. B.. Precise synthesis of poly­(thioester)­s with diverse structures by copolymerization of cyclic thioanhydrides and episulfides mediated by organic ammonium salts. Angew. Chem., Int. Ed. 2019;58:618–623. doi: 10.1002/anie.201812135. [DOI] [PubMed] [Google Scholar]
  31. Han B., Zhang Li., Liu B.-Y., Dong X.-F., Kim I., Duan Z.-Y., Theato P.. Controllable Synthesis of Stereoregular Polyesters by Organocatalytic Alternating Copolymerizations of Cyclohexene Oxide and Norbornene Anhydrides. Macromolecules. 2015;48:3431–3437. doi: 10.1021/acs.macromol.5b00555. [DOI] [Google Scholar]
  32. Abel B. A., Lidston C. A. L., Coates G. W.. Mechanism-Inspired Design of Bifunctional Catalysts for the Alternating Ring-Opening Copolymerization of Epoxides and Cyclic Anhydrides. J. Am. Chem. Soc. 2019;141:12760–12769. doi: 10.1021/jacs.9b05570. [DOI] [PubMed] [Google Scholar]
  33. Lidston C. A. L., Abel B. A., Coates G. W.. Bifunctional Catalysis Prevents Inhibition in Reversible-Deactivation Ring-Opening Copolymerizations of Epoxides and Cyclic Anhydrides. J. Am. Chem. Soc. 2020;142:20161–20169. doi: 10.1021/jacs.0c10014. [DOI] [PubMed] [Google Scholar]
  34. Li J., Ren B. H., Wan Z. Q., Chen S. Y., Liu Y., Ren W. M., Lu X. B.. Enantioselective resolution copolymerization of racemic epoxides and anhydrides: efficient approach for stereoregular polyesters and chiral epoxides. J. Am. Chem. Soc. 2019;141:8937–8942. doi: 10.1021/jacs.9b02722. [DOI] [PubMed] [Google Scholar]
  35. Li J., Liu Y., Ren W. M., Lu X. B.. Asymmetric alternating copolymerization of meso-epoxides and cyclic anhydrides: efficient access to enantiopure polyesters. J. Am. Chem. Soc. 2016;138:11493–11496. doi: 10.1021/jacs.6b07520. [DOI] [PubMed] [Google Scholar]
  36. Beckingham B. S., Sanoja G. E., Lynd N.. Simple and Accurate Determination of Reactivity Ratios Using a Nonterminal Model of Chain Copolymerization. Macromolecules. 2015;48:6922–6930. doi: 10.1021/acs.macromol.5b01631. [DOI] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

pc5c00198_si_001.pdf (5.9MB, pdf)

Articles from Precision Chemistry are provided here courtesy of American Chemical Society

RESOURCES