Geminal Dimethyl Substitution Enables Controlled Polymerization of Penicillamine-Derived β-Thiolactones and Reversed Depolymerization

•Highly controlled polymerization using gem-dimethyl substituted β-thiolactones•Efficient depolymerization due to a conformationally constrained terminal thiol•Semicrystalline polythioesters with high molar mass and tunable mechanical properties•Thorpe-Ingold effect for tuning the reversibility of ring-opening polymerization Chemically recyclable polymers from renewable feedstock hold great promise for solving the imminent global plastic-waste crisis. Despite recent advances, challenges including high energy consumption, the limited choices of sustainable polymers, and side reactions that could hamper complete monomer recovery are still yet to be addressed. By introducing a gem-dimethyl substitution, we succeeded in regulating both the forward polymerization of β-thiolactones and the backward depolymerization of polythioesters in a highly controlled fashion and with low energy input. Moreover, our strategy allows facile access to semicrystalline plastics with tailorable mechanical and thermal properties from biorenewable penicillamine feedstock. We envision that our design principle can facilitate the development of a new generation of chemically recyclable polythioester-based polymers, providing a sustainable solution to the ongoing environmental and economic challenge caused by nondegradable plastics. To access infinitely recyclable plastics, one appealing approach is to design thermodynamically neutral systems based on dynamic covalent bond, the (de)polymerization of which can be easily manipulated with low energy cost. Here, we demonstrate the feasibility of this concept via the efficient synthesis of polythioesters PNR-PenTE from penicillamine-derived β-thiolactones and their convenient depolymerization under mild conditions. The gem-dimethyl group adjusts the thermodynamics of (de)polymerization to near equilibrium, confers better (de)polymerization control by reducing the activity and conformational possibilities of the chain-end thiolate groups, and stabilizes the thioester linkages in the polymer backbone. PNR-PenTE with tailored properties is conveniently accessible by altering the side chains. PNR-PenTE can be recycled to pristine enantiopure β-thiolactones at >95% conversion from minutes to a few hours at room temperature. This work highlights the power of judicious molecular design and could greatly facilitate the development of a wide range of recyclable polymers with immense application potentials. To access infinitely recyclable plastics, one appealing approach is to design thermodynamically neutral systems based on dynamic covalent bond, the (de)polymerization of which can be easily manipulated with low energy cost. Here, we demonstrate the feasibility of this concept via the efficient synthesis of polythioesters PNR-PenTE from penicillamine-derived β-thiolactones and their convenient depolymerization under mild conditions. The gem-dimethyl group adjusts the thermodynamics of (de)polymerization to near equilibrium, confers better (de)polymerization control by reducing the activity and conformational possibilities of the chain-end thiolate groups, and stabilizes the thioester linkages in the polymer backbone. PNR-PenTE with tailored properties is conveniently accessible by altering the side chains. PNR-PenTE can be recycled to pristine enantiopure β-thiolactones at >95% conversion from minutes to a few hours at room temperature. This work highlights the power of judicious molecular design and could greatly facilitate the development of a wide range of recyclable polymers with immense application potentials. 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Traceless beta-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations.Chem. Sci. 2018; 9: 1940-1946Crossref PubMed Google Scholar We first synthesized five penicillamine-derived β-thiolactone monomers (NR-PenTL) with different side-chains (Scheme 1B), including NAc-PenTL and NBoc-PenTL as white crystals, as well as NC8-PenTL, Nene-PenTL, and NEG4-PenTL as colorless oils (1H and 13C NMR, high-resolution mass spectrometry, and X-ray diffraction in Figures S1–S16). Notably, the monomer synthesis is a simple and robust one-pot process and can be easily scaled up to ten-gram scale per batch in the laboratory. The ROP of each substrate was then initiated by benzyl mercaptan and catalyzed by an organobase of suitable basicity (Scheme 1B). No ROP of NAc-PenTL or NBoc-PenTL was observed (Table 1, entries 1 and 2), most likely because of their limited solubility (less than ∼90 mg/mL in tetrahydrofuran [THF]), which is lower than the equilibrium monomer concentration. We therefore focused our effort on the ROP of the three liquid monomers because they were substantially more soluble in common organic solvents or could be even executed for bulk polymerization. We measured the [M]eq of Nene-PenTL at various temperatures to draw the Van’t Hoff plot (Figure S17). According to the linear regression, the enthalpy (ΔHP°) and entropy (ΔSP°) changes of the ROP were calculated to be −9.4 kJ mol−1 and −28.1 J mol−1 K−1, respectively. This, in turn, gave a ΔGP° of −1.0 kJ mol−1 (−0.24 kcal mol−1) at 25°C and a ceiling temperature (Tc) of 61°C at an initial monomer concentration ([M]0) of 1.0 M.Table 1Ring-Opening Polymerization of NR-PenTLEntryMonomerBase[M]0/[I]0/[Base]0Time (h)Mncal (g mol−1)aMncal = calculated number-average molar mass based on the feeding M/I ratio.Mnobt (g mol−1)bMnobt = obtained number-average molar mass determined by SEC in DMF with 0.1 M LiBr.ĐcĐ = dispersity.Conv.dMonomer conversion, determined by 1H NMR spectroscopy.1NAc-PenTLTEA50/1/1248,700––02NBoc-PenTLTEA50/1/12411,600––03Nene-PenTLTEA100/1/17234,70019,4001.1061%4Nene -PenTLDBU30/1/0.1110,4006,4001.1158%5Nene -PenTLDBU50/1/0.1317,4009,9001.0960%6Nene -PenTLDBU75/1/0.14.526,00013,7001.1561%7Nene -PenTLDBU100/1/0.1634,70018,5001.1459%8NC8-PenTLDBU100/1/10.328,70020,1001.2170%9NC8-PenTLtBuP4250/1/12071,80052,4001.2669%10NC8-PenTLtBuP4350/1/124100,50070,6001.2370%11NBoc -PenTL, NC8-PenTLDBU30/70/0.5/1127,00014,1001.2442%, 56%12NEG4-PenTLDBU50/1/1618,30013,9001.3057%Polymerizations were initiated with benzyl mercaptan in a glovebox at room temperature. All entries were performed as bulk polymerizations except for entries 1 and 2, which were conducted in THF.a Mncal = calculated number-average molar mass based on the feeding M/I ratio.b Mnobt = obtained number-average molar mass determined by SEC in DMF with 0.1 M LiBr.c Đ = dispersity.d Monomer conversion, determined by 1H NMR spectroscopy. Open table in a new tab Polymerizations were initiated with benzyl mercaptan in a glovebox at room temperature. All entries were performed as bulk polymerizations except for entries 1 and 2, which were conducted in THF. To increase reaction efficiency, we conducted bulk polymerization of Nene-PenTL and NC8-PenTL at room temperature and a feeding monomer/initiator ratio (M/I) of 100/1. To our gratification, the ROP of Nene-PenTL, catalyzed by a weak organobase, triethylamine (TEA, pKaDMSO = 9.0),55Tshepelevitsh S. Kütt A. Lõkov M. Kaljurand I. Saame J. Heering A. Plieger P.G. Vianello R. Leito I. On the basicity of organic bases in different media.Eur. J. Org. Chem. 2019; 2019: 6735-6748Crossref Scopus (157) Google Scholar afforded the desired polymer product PNene-PenTE (1H NMR in Figure S18) with a considerably larger Mn and narrower dispersity (entry 3, Table 1; Mn = 19.4 kg/mol, Đ ∼ 1.10) than those of similar PTEs synthesized previously from CysTLs (Mn ∼8.8 kg/mol, Đ ∼ 2.4) at the same M/I ratio.50Suzuki M. Makimura K. Matsuoka S. Thiol-mediated controlled ring-opening polymerization of cysteine-derived beta-thiolactone and unique features of product polythioester.Biomacromolecules. 2016; 17: 1135-1141Crossref PubMed Scopus (31) Google Scholar Replacing TEA (1.0 equiv relative to initiator) with 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU, 0.1 equiv), a stronger base with a pKaDMSO of 12,55 greatly accelerated the ROP reaction (Table 1, entries 4–7; Figure 1A) while preserving the controllability, as evidenced by the unimodal peaks in size-exclusion chromatography (SEC) analysis. Increasing the M/I ratio resulted in a corresponding linear elevation in the Mn of PNene-PenTE (Figure 1A). The DBU-catalyzed ROP of Nene-PenTL also demonstrated other typical features of controlled polymerization, such as the observation that the monomer conversion displayed a linear relationship with Mn (Figure 1B). The ROP of NC8-PenTL showed very similar controllability to that of Nene-PenTL (Table 1, entries 8–10). For example, DBU-catalyzed formation of PNC8-PenTE (1H NMR in Figure S19) at a M/I ratio of 100/1 exhibited a Mn of 20.1 kg/mol and Đ of 1.21 (Table 1, entry 8). Employing tBuP4, a phosphazene superbase with a pKaDMSO of 30.3,55 further boosted the Mn to 52.4 and 70.6 kg/mol at a M/I ratio of 250/1 and 350/1, respectively, while maintaining a Đ less than 1.30 (Table 1, entries 9 and 10). Copolymerization of NC8-PenTL and NBoc-PenTL mixture gave a random copolymer with a Mn of 14.1 kg/mol and a Đ ∼1.24 (Table 1, entry 11). The ROP of NEG4-PenTL, a monomer containing an oligoethyleneglycol side chain, afforded a PEG-like polymer PNEG4-PenTE (1H NMR in Figure S20) also with satisfactory control (Table 1, entry 12). Notably, all polymerizations became viscuous immediately after the addition of base and gelized eventually as a result of the high concentration. It is also noteworthy that the polymerizations needed to be carefully quenched before subsequent processing because of the reversibility. Next, we examined the chain-end group of the resulting PNene-PenTE and its ability to undergo post-polymerization modification. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrum of benzyl mercaptan-initiated PNene-PenTE15 contained only one set of molecular ion peaks with a spacing of 347 Da between two adjacent peaks, which corresponded to the molar mass of the monomer (Figure 1C). Moreover, the end groups were unambiguously assigned to the initiating PhCH2S‒ group on the α end and free tertiary thiol on the ω terminus (Figure 1C, plus Na+ or K+). When the ROP was quenched with a small molecular capping agent, such as iodoacetamide, MALDI-TOF analysis gave exclusively PNene-PenTE bearing PhCH2S‒ and ‒CH2CONH2 as the α and ω end groups, respectively (Figure S21). Similarly, PNC8-PenTE also gave well-defined chain end groups in the MALDI-TOF analysis (Figures S22 and S23). Moreover, PNene-PenTE (ω end capped) was found to withstand typical UV-triggered thiol-ene reactions, and the side chain alkenes were converted to long alkyls (Figure S24) or anionic sulfate (Figure S25) groups almost quantitatively. Together, these results indicate that not only the chain ends but also the side chain groups are easily tunable, allowing facile introduction of a variety of functionalities. Next, we studied the thermal properties of PNC8-PenTE (Mn ∼70.6 kg/mol) via thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). PNC8-PenTE showed a 5%-weight-loss decomposition temperature (Td) of ∼192°C regardless of the capping status at the ω end (Figure S27). DSC depicted a weak glass transition at ∼50°C (Tg), and a large endotherm peaked at ∼100°C, which corresponds to crystal melting in the heating scan (Figure 2A). Upon cooling, an exothermic peak was observed at a temperature slightly lower than the melting temperature (Tm). Dilatometry testing suggested that the Tg and Tm of the same polymer were ∼45°C and ∼100°C (Figure S28), respectively, which agreed well with the DSC results. In the tensile test using dynamic mechanical analysis (DMA), PNC8-PenTE showed a Young’s modulus of 300 MPa at 30°C and a catastrophic facture before yielding with a strain of 2.8% (Figure 2B). Above Tg, the Young’s modulus reduced to 110 Mpa, and on the other hand, the breaking strain increased to 170% at 60°C (Figure 2B). PNC8-PenTE can be manufactured into a transparent film by hot compression or flexible fibers by melt drawing at 140°C with no detectable decomposition (Figures 2C and 2D). To investigate the depolymerization of the ω-end-uncapped PNC8-PenTE, we tested all reactions in diluted CDCl3 (initial polymer concentration = 5.0 mg/mL) by employing various bases and temperatures. When PNC8-PenTE was mixed with 0.05 equiv DBU (relative to the number of polymer chains) at 65°C, the gradual regeneration of NC8-PenTL was confirmed by 1H NMR spectroscopy and SEC. The conversion of depolymerization exhibited an inverse linear relationship with the remaining Mn of the polymer (Figure 3B). Moreover, only unimodal peaks were observed in the SEC analysis of the depolymerization of PNC8-PenTE, implying that no oligomerization occurred (Figure 3C). Meanwhile, as shown in Figure S29, the DBU (0.5 equiv)-mediated depolymerization of PNC8-PenTE (degree of polymerization ∼ 40) at room temperature