Clickable Dialdehyde-Amine Polymerization (cDAP)

Abstract

Synthetic polymers are important components of modern functional materials. Developing efficient polymerization processes with “clickable” features will enhance the diversity of available structures and facilitate exploration of new properties. In this work, we developed a strategy to synthesize isoindolin-1-one-based alternating copolymers through a new mode of step-growth polycondensation of functionalized bis-ortho-phthalaldehyde and diamine monomers. The reaction was performed in DMF and catalyzed by pyridine/AcOH at room temperature, affording linear copolymers with high molecular weights. This reaction enabled the production of alternating copolymers in a modular manner, where different functional units could be simply incorporated by varying the linker units in monomer structures. This approach was further expanded to synthesize branched and cross-linked polymer networks by introducing a triamine brancher and a dithiol cross-linker into the polymerization system. Some of the isoindolin-1-one-based copolymers behaved as thermoplastic elastomers, demonstrating the potential of this polymerization in materials sciences.

Introduction

Polymers from both natural sources and chemical syntheses serve as functional materials and shape modern life. The beneficial properties of polymers like mechanical strength, biocompatibility, stimuli responsiveness, and degradability are determined by their chemical structures and molecular weights. The development of new polymerization processes will strongly improve the toolbox of polymer chemistry and make more structures achievable. As one important pathway toward new polymerization chemistry, robust carbon–carbon and carbon–heteroatom bond forming reactions like click reactions well established on small molecular substrates can be leveraged to synthesize polymer chains via iterative reaction of monomers in a step-growth manner. Click reactions like Cu­(I)-catalyzed azide–alkyne cycloaddition pioneered by Meldal and Sharpless, strain-promoted azide–alkyne cycloaddition explored by Bertozzi, SuFEx reaction developed by Finn and Sharpless, and a series of X-yne additions (X = thiol, alcohol or amine) , have demonstrated their great potentials in polymer chemistry. − Both Cu­(I)-catalyzed − and strain-promoted , azide–alkyne cycloadditions have been developed into step-growth click polymerizations forming triazole-linked linear − and branched polymers, while the SuFEx reaction has been applied to the synthesis of polysulfate, , polysulfonates, , and polysulforidoimidates. Polymerizations based on other click-type reactions like thiol–yne addition, , amino–yne addition, , hydroxyl–yne addition, , pyridinium–yne, and multicomponent reactions − have also been reported. Those contributions substantially enhance the capability to construct structurally diverse polymers and build a solid basis for functional material research and development.

Ortho-phthalaldehyde (OPA) and compounds containing OPA as structural units show unique chemical properties in the reactions with variable nucleophiles. When OPA reacts with the primary amine, the proximal aldehyde groups work in a synergistic manner via a formal disproportionation process, affording an isoindolin-1-one structure. This OPA-amine two-component reaction (2CR) was first reported by Thiele and Schneider in 1909 (Figure b), before scientists discovered its natural version in the biosynthesis of Stachybotrys microspora triprenol phenol natural products. This OPA-amine 2CR was later adopted in the synthesis of isoindolin-1-one containing small molecules. The reaction was carried out in organic solvents with either Lewis acid or Brønsted acid as the catalyst, affording products in low to moderate yields. − In 2016, our group first identified the fast kinetic property of the OPA-amine 2CR in near-neutral PBS buffer and developed it into an efficient amine-selective bioconjugation method for peptide/protein modification (Figure b). This aqueous phase OPA-amine condensation exhibited notable “clickable” features, including high chemoselectivity, rapid (∼4.3 M^–1·s^–1) and clean conversion under biocompatible catalyst-free conditions, and good functional group tolerance. Since then, the aqueous phase OPA-amine 2CR has been widely applied in the synthesis of protein conjugates with carbohydrate, DNA, and peptides. Moreover, the biocompatible conditions allowed this reaction to be used in cell labeling and proteomic studies. The OPA-amine 2CR also attracted the attention of biomaterial scientists. In 2019, Lu et al. reported the synthesis of functional polymer brushes via grafting proteins to a poly­(DMA-co-AFP)-bearing OPA structure inside the chain. , In 2021, He and Chen et al. reported the construction of hydrogels with enhanced mechanical strength via cross-linking gelatin or hydroxyethyl chitosan (HECS) by the tetrameric OPA moiety. ,− Their applications in different molecular systems demonstrate the click-like feature of OPA-amine 2CR in an aqueous buffer.

1.

Development of click polymerization and design of the clickable dialdehyde-amine polymerization (cDAP). (a) Pioneering examples of click polymerization. (b) Evolution of the OPA-amine two-component reaction. (c) Design of the clickable dialdehyde-amine polymerization, which affords isoindolin-1-one-based polymers.

Though the aqueous phase OPA-amine 2CR has shown robustness in the modification of macromolecules like proteins, polysaccharides and synthetic polymers, to the best of our knowledge, it has not been involved in the assembly of polymer chains. The critical hurdle is the solvent choice: the reaction does not behave in a clickable manner, as shown historically, while the aqueous buffer is not suitable for polymerization. Nevertheless, we challenged ourselves to identify suitable conditions and explore its potential in step-growth polymerization (Figure c). Rather than incorporating both OPA and aniline units into a single molecule, we designed bis-OPA and diamine monomers by merging the polarized OPA and aniline units in a back-to-back manner. These monomers were expected to polymerize via the OPA-amine 2CR to form alternating copolymers, where high modularity could be achieved by simply changing the “linker” parts in the two monomers. The isoindolin-1-one structure formed during polymerization can serve as an amide mimic with enhanced conformational restriction. In addition to forming linear polymers, branched and cross-linked polymers can be achieved by incorporating a triamine brancher or a dithiol cross-linker into the polymerization system, respectively.

Herein, we report our success of developing the clickable dialdehyde-amine polymerization (cDAP) based on the acid–base catalyzed organic phase of the organic phase of the OPA-amine 2CR. Polymers with molecular weights up to 1,000,000 g·mol^–1 could be formed under mild conditions in a modular manner. Some of the copolymers behaved as thermoplastic elastomers, and the rheological properties were further tuned by forming the polymeric network.

Results and Discussion

Model Reaction Study

The optimal conditions for aqueous phase OPA-amine 2CR have been well established. However, most of the synthetic polymers for nonbiomedical uses are insoluble in aqueous systems, and an organic solvent system will be essential for developing new polymerization. Unfortunately, the current organic phase conditions reported before were far from ideal, as relatively low conversion and non-negligible side reactions not only affect the chemical integrity of the polymer but also hamper the growth of the molecular weight. Thus, we first need to solve this dilemma and identify new suitable reaction conditions of the 2CR with a focus on improving conversion and suppressing side reactions.

We started our condition screening using 1.05 equiv of OPA 1 and 1.0 of equiv of PEG₄-modified aniline 2 in MeCN (Figures S1, S2 and a,b). To better mimic the conditions required for polymerization, the concentration of 1 was set as 16 mM, which was much higher than that we used in bioconjugation cases (0.5–2.0 mM). When checked at 5 min, OPA-amine 2CR product 3 was formed in only negligible amount accompanied by the OPA-amine–amine 3CR product S19 (Figure S1b, upper trace), which is consistent with the previous reports. ,, To our surprise, though the conversion of OPA was low, two putative side products S20 and S21 originating from the aldol-type reaction between 3 or S19 with OPA were generated dominantly, which was not observed in the former aqueous phase conjugation studies at a low concentration. Inspired by the beneficial effect of the buffer system in the aqueous phase 2CR, we decided to introduce an acid/base pair buffer in an organic solvent. The pyridine/HOAc mixture behaves as a buffer-like ionic solvent, , in which both free molecules with hydrogen bonding interactions and ionized species coexist. This mixture plays multiple roles in the serine/threonine ligation and cysteine/penicillamine ligation, including dissolving side-chain unprotected peptides and accelerating the multistep ligation processes. When the pyridine/HOAc 1:1 mol/mol mixture (V _solvent:V _{pyridine/HOAc} = 8:1) was added to MeCN, to our delight, almost a full conversion was achieved within 5 min, and the formation of S20/21 was largely suppressed (Figure S1b, trace 2). However, the 3/S19 ratio was not improved. Increasing or decreasing the pyridine/HOAc ratio led to similar results (Figure S1b, trace 3 and 4). Both pyridine and HOAc were indispensable to the observed effect, as using either pyridine or HOAc led to inferior results similar to the reaction in MeCN only (Figure S2, trace 1 and 2). To further improve the reaction, we changed the solvent to DMF, which is widely used in polymer synthesis. Fortunately, in the presence of pyridine/HOAc 1:1 mol/mol mixture, a fast and clean conversion to the desired 2CR product 3 was observed (Figure b, trace 2), while without adding the additive gave a poor result similar to the MeCN case (Figure b, trace 1). Increasing the V _solvent:V _pyridine to 20:1 or decreasing to 4:1 led to comparable results. Other dipole solvents like DMA, NMP, and DMSO gave similar results (Figure b, traces 3, 4, and 5), while CH₂Cl₂ was less efficient (Figure S2, trace 3). Further increasing the concentration to 32 mM also gave a clean reaction. Based on the above results, pyridine/HOAc 1:1 mol/mol in DMF was chosen as the optimal conditions for our polymerization study. To rationalize the acceleration effect of the pyridine/HOAc system, we hypothesized a synergistic acid/base catalysis mechanism, where acetic acid and pyridine possibly participate in all the four substeps within the OPA-amine 2CR (Figure c). During the hemiaminal formation I and II, acetic acid activates aldehyde groups via hydrogen bonding, while pyridine activates anilinium cation via deprotonation. In the conjugate dehydration step, the role of acetic acid moves to increase the leaving capability of the OH group, while pyridine facilitates the elimination by cleaving the C–H bond. Finally, acetic acid and pyridine serve as a proton donor and an acceptor, respectively, to accelerate the O-to-C proton shift in the tautomerization step.

2.

Model study of the OPA-amine two-component reaction. (a) Model reaction of OPA with PEG₄-modified aniline. (b) UPLC traces of the model 2CR in different solvents in the presence of pyridine/HOAc 1:1 mol/mol mixture (V _solvent:V _{pyridine/HOAc} = 8:1). The reactions were monitored after 5 min. (c) Proposed synergistic acid/base catalytic effect in OPA-amine 2CR.

Polymerization Study

With the optimized conditions in hand, we investigated the amine-OPA polymerization process. As illustrated in Figure , we designed a series of bis-OPA monomer M1 to M5 by inserting representative linker structures (e.g., PEG₄, isophorone, triphenylamine, C6 carbon chain, and carbazole) with varied length, flexibility, and conjugation status between two OPA units. Meanwhile, diamine monomers M6 to M9 with spacers ranging from two to >100 atoms containing flexible and rigid moieties between the aniline units were chosen for the polymerization study. The monomers were obtained either commercially or via chemical synthesis (Supporting Information).

3.

Polymerization (cDAP) of M1 and M6 and structure of P1-6 and monomers in the current study.

In our polymerization study, equal molar amounts of bis-OPA monomers and diamine monomers were used in all cases, and the reactions were carried out under an argon atmosphere. We first studied the effect of the monomer concentration on the molecular weight. Initially, a concentration of 7 mM for M1 and M6 was utilized in the copolymerization, and the alternating copolymer product P1-6 was analyzed by gel penetration chromatography (GPC) to measure the weight-average molecular weight (M _w). As shown in Table (entry 1) and Figure S6a (red curve), the M _w of P1-6 reached 3.65 kg·mol^–1 with D̵ = 5.4 after 1 h. When the concentration of M1/M6 was increased to 21 mM, a higher M _w at 8.22 kg·mol^–1 with D̵ = 5.1 was obtained within the same polymerization time (Table , entry 2, Figure S6a, blue curve). A similar trend was observed in the copolymerization of M1 with M7 (Figures a and S6b). P1-7 with a M _w of 78.05 kg·mol^–1, D̵ = 18.1, was achieved after 1 h using an M1 concentration of 21 mM (Table , entry 4 and Figure a, dark curve), while a lower M _w at 40.27 kg·mol^–1 was obtained even after 21 h with an M1 concentration of 7 mM (Table , entry 3, and Figure S6b). It is worth noting that the significantly lower molecular weight of the polymer was yielded at low monomer concentration after achieving a similar level of functional group consumption after extending the polymerization time. This performance might be attributed to the termination of the polymer chain elongation by forming cyclic polymers under low monomer concentration.

1. Polymerization Results of Polymers.

entry	Di-OPA	di/trianiline	polymers	time (h)	M n,GPC (kg·mol–1)	M w,GPC (kg·mol–1)	D̵	yield (%)
1	M1	M6	P1-6	1	0.67	3.65	5.4	72
2	M1	M6	P1-6	1	1.61	8.22	5.1	76
3	M1	M7	P1-7	1	1.49	40.27	26.9	93
4	M1	M7	P1-7	1	4.31	78.05	18.1	95
5	M1	M7	P1-7	5	4.73	626.83	132.5	96
6	M1	M7	P1-7	15	6.44	1019.81	158.3	96
7	M2	M6	P2-6	2	6.01	16.92	2.8	80
8	M2	M9	P2-9	4	21.23	157.91	7.4	70
9	M3	M6	P3-6	2	5.94	16.12	2.7	81
10	M4	M6	P4-6	2	5.05	13.43	2.7	82
11	M5	M8	P5-8	3	31.62	109.99	3.4	92
12	M2	M9/M10	P2-9-10	4	15.02	118.67	7.9	78

^aReaction conditions: Monomer (0.052 mmol) in 2 mL of DMF and 0.5 mL of Pyridine/HOAc (molar ratio 1/1). Monomer (0.017 mmol). M _n, M _w, and D̵ determined by GPC using DMF or at 150 °C using.

^b1,2,4-Trichlorobenzene (TCB) as an eluent.

^cThe yield was obtained by weighing the isolated product which precipitated in diether ether or MeOH.

4.

(a) The polymerization system of M1 and M7 monitored by in situ GPC at 1, 5 and 15 h. Reaction conditions: M1 (30 mg, 0.052 mmol) and M7 (18 mg, 0.052 mmol) in 2 mL of DMF and 0.5 mL of pyridine/HOAc (molar ratio 1/1). (b) The extent of the reaction (p) versus time for the polymerization of M1 and M7 (blue line) and M6 (red line), respectively (data from Table S1, Supporting Information). (c,d) ¹H NMR and HSQC spectra (in CDCl₃) of P1-6. (e) ¹H NMR spectrum (in CDCl₃) of P5-8. M _n, M _w, and D̵ determined by GPC in DMF, PMMA as the calibration standard. Asterisk (*) is DMF or H₂O.

When monitoring the polymerization of M1 with M7 by in situ GPC, the polymer P1-7 with M _w = 626.83 kg·mol^–1 was generated under high monomer concentration after 5 h, and an exceptionally high molecular weight polymer with M _w = 1019.81 kg·mol^–1 was achieved by extending the reaction time to 15 h, as depicted by the blue curve in Figure a and Table , entries 5 and 6, showcasing the efficiency of the 2CR reaction for polymer synthesis. On the other hand, it was observed that product precipitation occurred during the polymerization process after a long reaction time (e.g., 15 h). Some of the products remained partially soluble in the reaction mixture but became insoluble after precipitation in ether or methanol. Additionally, it is worth mentioning that the polydispersity of P1-7 exhibited an extremely high value compared to that of P1-5. To understand the reason, we attempted to polymerize M1 and M7 over a shorter reaction time, aiming to obtain lower molecular weight P1-7 for further analysis. Surprisingly, we found that P1-7 was soluble in the reaction mixture solution but insoluble after precipitation, even with a polymerization time of only 5 min. Furthermore, we tried to use an access amount of M1 to react with M7 (molar ratio, M1/M7 = 3/2) for 5 min. Similar to the previous case, the resulting product was insoluble in the solvents we tested (e.g., DMF, NMP, THF, CH₂Cl₂, and toluene). The extremely poor solubility of P1-7 after precipitation hindered further analysis. However, as displayed in Figure a, GPC curves showed that the broad and multimodal distribution areas at later elution times decreased and shifted toward earlier elution times with prolonged reaction time. This is possibly attributed to lower molecular weight products gradually transformed into higher molecular weight products over time. Based on the trend observed in GPC curves, we speculated that cyclic polymers may have been formed, or the dialdehyde-amine-amine 3CR , may occur to yield the iminoisoindoline containing branched polymer. This could result in the broad polydispersity observed in P1-7.

To understand the kinetics of the OPA-amine polymerization, we measured the extent of the reaction (p) in the polymerization systems of M1/M7 (Figure b, blue line) and M1/M6 (Figure b, red line) by in situ ¹H NMR spectrometry. The disappearance of the formyl group (δ = 10.57, 10.61 ppm) was monitored, using the methylene proton signal of 1,3-dioxane (δ = 4.81 ppm) as an internal standard. Monitoring the –NH₂ group of terminal aniline is hampered by the overlap of its proton signal with PEG. The results are depicted in Figure b and Table S2. Both polymerization systems display a leveling off of kinetics with reaction time, which is characteristic of step-growth polymerization. A similar value of p obtained in both systems, except at the 10 min mark, implies that the activity of the monomer is not significantly influenced by electron-donating (e.g., M6) or electron-withdrawing (e.g., M7) groups in the diamine monomers. The other four linear copolymers P2-6, P2-9, P3-6, and P4-6 were synthesized under the same conditions as P1-6 and P1-7 (Table , entries 7–10 and Supporting Information). To demonstrate the applicability of the current approach to rigid polymer synthesis, we designed and synthesized an M5 containing conjugated carbazole moiety as an example. We tested the copolymerization of M5 and M8 (containing a fluorene unit) under the same conditions used for the linear polymers described above. The results showed that the M _w of P5-8 was 109.99 kg·mol^–1, as determined by GPC at 150 °C using 1,2,4-trichlorobenzene as the eluent (Table , entry 11, and Figure S52).

The ¹H and HSQC NMR spectra (in CDCl₃) of P1-6 are shown in Figure c,d. A prominent proton signal at δ = 4.70 ppm was observed, which can be assigned to the –CH₂– group of the isoindoline moiety within the five-membered ring. This signal is consistent with the proton signal of the isoindoline –CH₂– group (δ = 4.79 ppm) observed in the 2-component product 3 (Figures S61 and S62), indicating the generation of the isoindolin-1-one group in the polymer backbone. The signal at 5.13 ppm can be assigned to benzyloxy protons, while peaks at 3.36 to 4.09 ppm were assigned to PEG segments. The terminal dialdehyde group was also observed at 10.44 and 10.47 ppm. Moreover, the integration ratio of –CH₂– (from benzyloxy protons, labeled c in Figure c) to –CH₂– (from isoindolin-1-one, labeled a) is 8.81/5.63 = 1.56. The deviation from the ideal ratio (close to 1) is attributed to the low molecular weight of P1-6 that we used for NMR analysis and that was soluble in deuterium solvent (prepared by shortening the polymerization time). The aromatic proton signals in the 6.90 to 7.90 ppm region showed complicated patterns, which was observed in all synthesized polymers. Similar phenomena were also found in all ¹³C NMR spectra, where multiple sets of peaks always coexisted. These phenomena can be attributed to the low regioselectivity of the dialdehyde-amine 2CR, where regioisomers of the isoindolin-1-one unit are randomly formed and coexist in the polymer backbones. The formation of isomeric 2CR products can be identified in the model reaction between substituted OPA and aniline 2 (Figure S3). The ¹H NMR spectrum of P5-8 is displayed in Figure e. Similarly, the signal at 5.07 ppm can be assigned to –CH₂– of the isoindolin-1-one moiety, which was supported by HSQC and COSY spectra as provided in Figures S19 and S20. The ¹H-, ¹³C NMR and COSY spectra of other linear polymers (except for P3-6 insoluble in deuterated solvent) are presented in the Supporting Information (Figures S21–S24, S29–31, and S34–38).

Meanwhile, we tried to synthesize two types of polymer networks by introducing a branched structure and a bifunctional cross-linker. The branched polymer network P2-9-10 was prepared by introducing the triamine brancher M10 (20% molar ratio to M2, see the Supporting Information) into the copolymerization of M2 and M9 (Figure a). To our delight, P2-9-10 showed comparably good solubility as the linear polymer P2-9 in DMF and gave M _w = 118.67 kg·mol^–1 in GPC analysis (Figure b and Table , entry 12). Compared to the ¹H NMR spectrum of P2-9, a new broad peak at 7.00–7.19 ppm was observed in P2-9-10 (Figure S27), which can be assigned to the proton signals of triphenylamine. This indicates that the branch linker M10 was successfully incorporated into the polymer backbone. On the other hand, we synthesized the cross-linked network P2-9-D by adding the dithiol cross-linker 3,6-dioxa-1,8-octanedithiol (DODT) 4 (20% molar ratio to M2, see the Supporting Information), where the thiol group participated in the OPA-amine-thiol three-component reaction (3CR) − to give rise to a 1-alkylthioisoindole structure. This 1-alkylthioisoindole formation in DMF under pyridine/HOAc catalysis was validated in our model study (Figures S4 and S5). Furthermore, the cross-linked P2-9-D was analyzed by Raman spectroscopy. As depicted in Figure c, both the signals from the C–S–C linkage (670 cm^–1) and the C-SS linkage (640 cm^–1) were observed, indicating the coexistence of 1-alkylthioisoindole and disulfide structures. Based on this, two types of cross-linking structures were proposed via the 2-fold three-component reaction on both ends of DODT and disulfide formation between rest free thiol groups on 1-alkylthioisoindole (Figure d).

5.

Synthesis of 2D polymeric networks via brancher incorporation and cross-linking. (a) Synthetic scheme of P2-9-10 and P2-9-D. (b) GPC result of P2-9-10. (c) Raman spectrum of P2-9-D. (d) Illustration of the two possible cross-linking structures in P2-9-D.

Moreover, compared to the carbon NMR spectra of P2-9 and P2-9-10, two new peaks at 121.8 and 122.6 ppm appeared in P2-9-D (Figure S28), which can be assigned to the two carbons of the thioisoindole moiety in a five-membered ring, further confirming the formation of cross-linked units in the polymer backbone. COSY, ¹H-, and ¹³C-NMR spectra of the branched P2-9-10 and cross-linked P2-9-D are provided in the Supporting Information (Figures S25–26, S32–33, and S39–40).

The synthetic linear polymers (i.e., P1-6, P2-6 and P2-9) as well as the branched P2-9-10 and cross-linked P2-9-D were processed to form polymer films (see the Supporting Information for detailed protocol). Though a dark brown color was observed, these polymer films were slightly transparent, and the transparency data of these polymers are provided in Table S3.

UV–vis absorption spectra of linear copolymers P1-6, P1-7, P2-6, P3-6, P4-6, and P5-8 were recorded in DMF solution, and the results are shown in Figure a. These products exhibited similar broad absorption bands, extending to 530 nm, well aligned with the absorption of the isoindolin-1-one structure originating from the π–π* transition (Figure S9). Compared to the other four products, P3-6 and P5-8 exhibited a broad intensive absorption in the range of 300–480 nm and 300–400 nm, respectively, relating to the triphenylamine (TPA) and carbazole group in the main chain, which is consistent with the absorption of M3 and M5 (Figure S10).

6.

Optical, thermal, and mechanical properties of polymers. (a) UV–vis spectra of P1-6, P1-7, P2-6, P3-6, P4-6 and P5-8 measured in DMF with concentration at 1.5 × 10^–2 mg·mL^–1. (b) TGA results of P1-6, P1-7, P2-6 and P3-6, tested under a N₂ atmosphere. (c) DSC results of P1-6, P1-7 and P2-6. (d) XRD results of P1-6, P1-7 and P2-6. (e) Stress–strain curve of P1-6. (f) Breaking-strain and -stress of P1-6 and P2-6, data extracted from stress–strain curves. (g) Rheological time sweeps of P1-6. (h,i) FT-IR spectra of P1-6 and P2-6 in the CO stretching vibration region.

Thermal stabilities of P1-6, P1-7, P2-6, P3-6, P4-6, and P5-8 were evaluated by thermal gravimetric analysis (TGA), and samples were measured under a nitrogen atmosphere (Figures b and S11). Generally, the major decompositions of these products all took place in the range of 300–500 °C, with varied onset temperatures for weight loss and decomposition temperature (T _d, 5% weight loss) related to thermostability. For polymers P1-6, P2-6, P1-7 and P4-6, three-stage weight loss patterns consistent with urethane-based polymers were observed. The first stage weight loss (280–350 °C) is attributed to the decomposition of the urethane linkage, while the degradation of the soft segments (e.g., PEG) and isophorone segments happened in the second stage (350–460 °C). The isoindolin-1-one decomposed in the third stage (above 460 °C) and finally led to ca. 20% remnant mass above 750 °C. For polymer P3-6 lacking the urethane moiety, a two-stage weight loss pattern was observed. Due to the incorporation of triphenylamine moieties into the polymer chain, P3-6 showed enhanced thermostability in the TGA test and gave significantly higher T _d (413 °C vs 229–319 °C) and remnant mass (ca. 40% at 800 °C) than the above four polymers. A similar TGA result was observed for P5-8. In the differential scanning calorimetry (DCS) analysis, the glass transition temperature (T _g) value of polymers increased when introducing hard domains such as isophorone or phenyl benzoate instead of soft PEG segments in the polymer chain (Figure c). In the X-ray diffraction (XRD) results of P1-6, P1-7, and P2-6 presented in Figure d, a similar broad peak was detected in the X-ray diffraction curves of these polymers, which is a typical pattern of materials with a low degree of crystallinity. The amorphous properties of these urethane containing polymers show similarity with polyurethane.

The mechanical properties of P1-6 and P2-6 were evaluated through tensile tests conducted at a stretching speed of 20 mm/min. As shown in Figure e,f, P1-6 displayed a tensile strength of 16.45 MPa and an elongation at break of 273%. In contrast, P2-6 exhibited a higher tensile strength of 35.22 MPa but a remarkably lower elongation at a break of 5% (Figure S12). These values indicate longer flexible chains facilitate stress relaxation in the polymer networks. To further evaluate the recovery behavior of P1-6, a rheological time sweep was conducted. As shown in Figure g, after the shear strain reached 100% in the second stage, the modulus in the third stage recovered 91% to the value of the first stage after the strain recovered to 1%, indicating the existence of some irreversible conformational transformations in the largely reversible process under external force. Fourier-transform infrared (FT-IR) spectroscopy was utilized to analyze the hydrogen bonding interactions in P1-6, P2-6, P3-6, and P1-7. The CO stretching region was resolved into four subpeaks (Figures h–i and S14), which were assigned to the free and hydrogen-bonded CO groups in the urethane and amide groups. The fractions of H-bonded CO in P1-6, P1-7 and P2-6 were 54%, 45% and 58%, respectively. On the contrary, P3-6 lacking a urethane structure exhibited only a 7% fraction of H-bonded CO, indicating that the H-bonded CO interactions in the polymer chain are mainly contributed by urethane.

Comparative Study of the Mechanical Properties of the Polymer with Different Topologies

To elucidate the properties of topological polymers for better comparison, the linear polymer P2-9, branched 2D polymeric network P2-9-10 and cross-linked polymer P2-9-D were selected for investigation. The branched P2-9-10 and the cross-linked P2-9-D were prepared as described in the former section. First, TGA experiments were conducted to evaluate the thermal stability of these products. As depicted in Figure a, major decomposition of all products took place in the range of ca. 300–450 °C. The branched P2-9-10 exhibited a slightly higher T _d at ca. 330 °C than that linear P2-9 at ca. 302 °C, while a lower T _d of cross-linked P2-9-D was observed at ca. 282 °C. The higher thermal stability of P2-9-10 is attributed to the hard segments of the triphenylmethane group in the polymer chain which increased the content of aromatic carbon. Though the remnant mass was ca. 5% above 750 °C for all these polymers, a higher residual of P2-9-D than the other two was observed in the temperature region of 450–800 °C, indicating the energy required for bond breaking was increased in the cross-linked bulk polymeric matrix.

7.

(a) TGA results of P2-9, P2-9-10 and P2-9-D; samples were tested under a N₂ atmosphere. (b) DMA results of P2-9, P2-9-10 and P2-9-D. (c–f) FT-IR spectra of P2-9, P2-9-10 and P2-9-D in the CO stretching vibration region. (g) Digital photographs of P2-9, P2-9-10 and P2-9-D films in gauge length after being stretched to 905%, 587% and 615%, respectively, measured at a speed of 20 mm·min^–1.

To evaluate the molecular mobility capabilities and viscoelastic behaviors, the three copolymer samples were analyzed by dynamic mechanical analysis (DMA) at temperature from −80 to 40 °C. As shown in Figure b, a comparable plateau was observed in the storage modulus (E′) curves below −50 °C, with the exception of P2-9-10 displaying a plateau extending to slightly higher temperatures at −40 °C. This observation suggests that the polymers are in a glassy state, indicating the presence of frozen polymer chains at these temperatures. It can be seen that the E′ values significantly decreased with a further increase of temperature, indicating that the polymers undergo a transition from a glassy to a rubbery state and continued temperature elevation will lead them to a rubbery state. The tan δ values in the DMA curves indicate that the T _g values of P2-9, P2-9-10 and P2-9-D are at ca. −50 °C, −30 °C and −40 °C, respectively. P2-9-10 exhibited the highest T _g due to the incorporation of the rigid TPA moiety into the polymer backbone, while a slightly lower T _g of P2-9-D is due to the DODT linker, which is a soft segment that can increase the flexibility of the polymer chain. The FT-IR spectra of the three samples and analysis of their corresponding CO stretching regions of the three products are displayed in Figure c–f. The fraction of H-bonded CO in these products is similar, ca. 31% for P2-9, 40% for P2-9-10 and 25% for P2-9-D, respectively. A slightly higher fraction of H-bonded CO interactions was observed in P2-9-10 than linear P2-9, which was attributed to the shortened interchain H-bond length in the branched network. On the contrary, the decreasing fraction of H-bonded interactions in the cross-linked polymer P2-9-D is possibly caused by the formation of the 1-thio-2H-isoindole structure in the cross-linked network which lacks the CO group.

The mechanical properties of P2-9, P2-9-10 and P2-9-D were characterized by uniaxial tensile tests. Their stretched digital photographs are shown in Figure g, while the stress–strain curves along with the breaking strain (ε_b) and stress (σ_m) are depicted in Figure a,b. Unexpectedly, among the three samples, linear polymer P2-9 exhibited a remarkable elongation capability, being able to stretch to 905% and withstand a high tensile stress of 6.25 MPa during the tensile test without experiencing any fractures (Figure g). For the branched P2-9-10 and cross-linked P2-9-D, the maximum tensile stresses were 3.40 and 4.29 MPa with elongations at break of 587% and 615%, respectively (Figure a&b). Comparing the elongation at break of 580% for the three polymers, the tensile stresses of the cross-linked P-2-9-D (ca. 4.07 MPa) and the branched P2-9-10 (ca. 3.38 MPa) are slightly higher than that of the linear P2-9 (ca. 3.14 MPa). These results indicate that introducing interchain covalent linkages of branch and cross-link linkages sacrifice the flexibility of the polymer and enhance the stress. Recently, Cai et al. reported that the tensile breaking strain of linear polymers could be remarkably enhanced by creating a single network within the polymer chain. However, in our case, the linear polymer exhibits excellent stretchability without the need for cross-linking. The improved modulus and toughness may be attributed to the formation of an isolindolin-1-one structure in the polymer backbone, which resembles the N-phenyl phthalimide with restricted bond rotation and the mechanical strength-enhancing effect. Additionally, in a recently published example, an elastomer comprising both isophorone and PEA2000 was synthesized via oligomerization of isophorone diisocyanate (IPDI) and PEA2000 followed by reaction with adipic dihydrazide (AD) and radical cross-linking. This elastomer showed ∼2.5 MPa tensile stress and ∼1050% elongation at break. In our case, the non-cross-linked linear polymer P2-9 exhibited a higher tensile stress of approximately 6.26 MPa and 905% elongation without generating fractures. We believe this observation can be attributed to the incorporation of the rigid N-aryl isoindolin-1-one structure into the polymer chain.

8.

(a) Stress–strain curves of P2-9, P2-9-10 and P2-9-D, measured at a speed of 20 mm·min^–1. (b) Breaking-strain and breaking-stress of P2-9, P2-9-10 and P2-9-D, data extracted from stress–strain curves. (c) Energy dissipation for each circle of the cyclic tensile test curves of P2-9, P2-9-10 and P2-9-D. (d–f) Cyclic loading–unloading strain–stress curves of the P2-9, P2-9-10 and P2-9-D films at 100, 200, 300, and 400% train, respectively, and P2-9 up to 500%. (g–i) Rheological time sweeps of P2-9, P2-9-10 and P2-9-D.

Subsequently, cyclic tensile tests were conducted to explore the additional mechanical features of P2-9, P2-9-10 and P2-9-D. As depicted in Figure d–f, the three polymers exhibited significant hysteresis loops across a range of applied strains, indicating remarkable energy dissipation. Energy dissipation refers to the capacity of materials to convert mechanical energy into heat, which can be quantified by integrating the area of cyclic tensile curves. , The hysteresis areas of each loop summarized in Figure c illustrate an increase in energy dissipation with strain. To assess the deformation recovery characteristics of the three polymers, cyclic rheological time sweeps were performed, as illustrated in Figures g–i. It can be observed that after the shear strain of P2-9 reached 300% in the second step, the dynamic storage modulus (G′) almost fully recovered to the values of the first step (97% for G′) after the strain recovered to 1% (Figure g). Similarly, the storage modulus of P2-9-10 and P2-9-D almost fully recovered to the level of the first stage when the third stage began, with a recovery rate of 95% and 94%, respectively, slightly lower than that of P2-9. These results imply that some degree of interchain linkages may possibly be broken under external force, leading to an irreversible conformational transformation and deformation. On the other hand, linear polymer exhibits better flexibility and quickly returns to the original structure after the external force is released. The results of the frequency sweeps for the three polymers at different temperatures (60, 80, and 100 °C) are depicted in Figure S15. The dynamic storage modulus (G′) and loss modulus (G″) for all of these polymers increased during the ramp-up process from 0.1 to 100 rad/s, with their G′ being larger than their G″. These results indicate that the three polymers exhibit elastic behavior (G′ > G″) across the entire range of angular frequency. At the high-frequency region, the values of G′ and G″ for all polymers decreased with the temperature increased.

Conclusion

In this work, we developed a new mode of step-growth alternating copolymerization based on the click-like organic phase OPA-amine two-component reaction. This clickable dialdehyde-amine polymerization (cDAP) affords isoindolin-1-one-based copolymers through the polycondensation of functionalized bis-OPA and bis-aniline monomers. The polymerization was performed in DMF solution in the presence of pyridine/AcOH as a catalyst at room temperature and gave rise to AB-type alternating linear copolymers in high molecular weight, where pyridine/HOAc efficiently accelerated the OPA-amine condensation and suppressed side reactions via synergistic acid/base catalysis. In addition to linear polymers, branched and cross-linked polymer networks were also synthesized by introducing the triamine brancher and dithiol cross-linker into the polymerization system, respectively. The modular nature of this polymerization allows us to easily incorporate functional structural units into the copolymers, which illustrates the potential of cDAP in the construction of functional materials. Moreover, the transition-metal-free conditions will benefit the purification process and avoid metal contamination that is harmful to polymer functions like electroconductivity and light-emitting properties. Finally, we studied the mechanical properties of our synthetic linear, branched, and cross-linked copolymers. Some copolymers showed intriguing thermoplastic elastomer features.

Though cDAP is imperfectly clickable due to the requirement of a relatively high amount of catalyst and possibility of generating the iminoisoindoline side product via the dialdehyde–amine–amine three-component reaction, the fast polymerization kinetics under mild conditions and compatibility to variable monomer structures make it a useful tool for synthesizing functional alternating copolymers. We believe our current study can provide an appealing approach for the modular synthesis of isoindolin-1-one-based polymers and related polymeric network, which will pave the way for future exploration of their functional space in materials science.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacsau.5c01015.

• Supporting Information contains Tables S1–3, Figures S1–S86, characterization data, measurements, and experimental procedures for monomer, polymer, and polymer film preparation (PDF)

⊥.

X.L. and H.L. conceived and supervised the study. X.L., H.L. and L.H. designed experiments. L.H. and Y.Z. performed the experiments. X.L., H.L., L.H., and Y.Z. analyzed the data. X.L. and H.L. wrote the manuscript. L.H. and Y.Z. contributed equally to this work. CRediT: Liting He conceptualization, data curation, formal analysis, investigation, methodology, writing - original draft; Yan Zhao data curation, formal analysis, investigation, methodology; Han Liu conceptualization, project administration, writing - original draft; Xuechen Li conceptualization, funding acquisition, project administration, resources, supervision, writing - review & editing.

The authors declare no competing financial interest.