Leveraging Stereochemistry to Optimize the Properties of Polyhydroxyalkanoates

Abstract

The recycling of low-density polyethylene (LDPE) is challenging due to difficulties with sorting and contamination, leading to environmental harm. Polyhydroxyalkanoates (PHAs) are at the forefront of high-performance biodegradable alternatives to olefinic plastics, but few offer LDPE-like properties such as low strength and crystallinity while maintaining high ductility and thermal stability. Herein, we report a series of isoenriched trans-poly­(3-hydroxy-2-methylbutyrates) (trans-PHMBs) with tunable mechanical and thermal properties. These polymers were synthesized through ring-opening polymerization of racemic trans-3,4-dimethylpropiolactone (rac-trans-DMPL), sourced from C1 and C4 feedstocks, using a new class of “sandwich” C ₂ symmetric rac-(^ArBDI*)­ZnO ⁱ Pr catalysts (where BDI = β-diketiminate). Variation of aromatic groups (Ar) and polymerization temperature yielded mm%s between 45–79% and melting temperatures (T _m) between 141–174 °C. trans-PHMB with intermediate isotacticities of 73 and 75 mm% exhibit similar stress–strain profiles to LDPE, indicating that these polymers have the potential to serve as higher melting, degradable substitutes for LDPE.

Introduction

Low-density polyethylene (LDPE) accounts for approximately 12% of all plastic produced globally. Due to its low strength, low crystallinity, chemically inert hydrocarbon backbone, and excellent moisture barrier properties, LDPE is used as a thin coating on biodegradable materials, as landscape films, and in many other single use applications. − Since the majority of LDPE is not recycled due to challenges associated with collection, sorting, and contamination, the development of biodegradable alternatives to LDPE is imperative to mitigate environmental damage. ,,

While poly­(butylene adipate terephthalate) (PBAT) is considered a biodegradable substitute for LDPE, it exhibits minimal ocean degradability and produces degradation products with significant plant and soil toxicity. , Alternatively, polyhydroxyalkanoates (PHAs) are naturally produced and degraded by bacteria into H₂O and CO₂. − The most studied PHA, (R)-poly­(3-hydroxybutyrate) ((R)-PHB, Scheme A) is semicrystalline, with a high melting temperature (T _m = ∼175 °C) and excellent ultimate tensile strength (σ_B = 30–40 MPa). − However, (R)-PHB is brittle and exhibits low thermal stability resulting in a narrow melt processing window. ,,

1. (A) Strategies to Improve PHA Properties; (B) Previous Routes to (R,R)-trans-PHMB; (C) This Work: Isoenriched trans-PHMB with LDPE-like Mechanical Properties.

One strategy to enhance PHB properties is by incorporating stereodefects or longer alkyl substituents to decrease crystallinity thereby improving ductility and lowering T _m (Scheme A). − For example, Rieger and co-workers synthesized isoenriched PHB with an m% (percent of ester linkages with a meso configuration) of 84% and enhanced ductility (elongation at break (ε_B) = 392%). Simultaneously, the introduction of stereoerrors reduced the T _m from 175 to 140 °C, enabling a broader melt processing window. The second strategy enhances thermal stability through the substitution of the α carbon of PHAs (Scheme A). − In PHB, the arrangement of acidic α-carbonyl protons and β-acetoxy leaving groups facilitates elimination reactions which reduce molecular weight and deteriorate mechanical properties. The addition of a cis-methyl or geminal dimethyls to the α carbon of PHB suppresses chain scission, increasing the degradation temperature (T _d) from 241 °C to ∼275 °C and ∼325 °C, respectively. ,, Despite these advances, no thermally stable PHA exhibits LDPE-like mechanical properties.

A particularly promising PHA for achieving a biodegradable LDPE alternative is (R,R)-trans-poly­(3-hydroxy-2-methylbutyrate) (trans-PHMB), a thermally stable PHA (T _d = 283 °C) which can be synthesized through bacterial fermentation of tiglic acid (Scheme B). , While chloroform-cast (R,R)-trans-PHMB films exhibit mechanical properties similar to isotactic polypropylene (σ_B = 37 MPa, ε_B = 520%), a chemically synthesized sample (Scheme B) was too brittle for tensile testing after melt pressing. , We hypothesized that introducing stereoerrors into trans-PHMB would reduce crystallinity to (1) improve melt processability and (2) soften the material to mimic the mechanical properties of LDPE (Scheme C).

The ring-opening polymerization (ROP) of rac-trans-3,4-dimethylpropiolactone (rac-trans-DMPL) is an atom-economical route to trans-PHMB polymers with tunable isotacticities. Rac-trans-DMPL is synthesized through sequential epoxidation and catalytic carbonylation of cis-2-butene, two processes amenable to scaleup. , The cis-2-butene can be selectively synthesized through Z-selective dimerization of ethylene or hydrogenation of 2-butyne. − For the polymerization, we aimed to design a racemic catalyst that can quantitatively convert rac-trans-DMPL into semicrystalline isoenriched trans-PHMB, as this would be the most practical and cost-efficient strategy in an industrial setting. To achieve these requirements, we investigated earth abundant metal and highly active zinc β-diketiminate alkoxide (BDIZnOR) catalyst frameworks. This strategy enabled access to high molecular weights (>100 kDa) necessary for the investigation of mechanical properties. − Furthermore, the tunability of BDIZnOR frameworks was leveraged to produce trans-PHMB polymers with varying degrees of isoenrichment and their resulting thermal and mechanical properties were systemically studied.

Results and Discussion

First, an efficient but nonstereoselective catalyst for β-butyrolactone ROP, [( ^iPrBDI)­ZnO ⁱ Pr]₂ (Scheme ), was tested for the polymerization of trans-DMPL. Atactic trans-PHMB (mm% = 20%, Table S6; where mm% is the percent of triads with a meso configuration across both ester linkages) was obtained, indicating that C _2v symmetry does not invoke stereoselectivity. To improve stereocontrol, we modified the BDI framework by (1) introducing steric bulk in the axial positions and (2) imparting chirality via C ₂ symmetry about the metal center, a strategy motivated by group IV metallocene catalysts for isotactic polypropylene synthesis. Inspired by the “sandwich” diimine ligands reported by Brookhart and Daugulis, we synthesized a series of C ₂ symmetric BDI*H ligands using 8-aryl-1-aminonaphthalenes. , Six rac-(^ArBDI*)­ZnO ⁱ Pr complexes (Scheme ) with varying 8-aryl groups (Ar) were synthesized in a one-pot procedure by complexation of the ligand with Zn­(N­(SiMe₃)₂)₂ at 150 °C, followed by addition of ⁱ PrOH. After recrystallization at −25 °C, the desired rac-(^ArBDI*)­ZnO ⁱ Pr complexes were isolated in good yield (59–84% yield).

2. Isoselective Polymerization Design Strategy .

^a TPP = meso-tetraphenylporphyrinato.

The catalyst with Ar = 4-Me-Ph (rac-(^4‑MeBDI*)­ZnO ⁱ Pr) was examined, and it yielded isoenriched trans-PHMB with a mm% of 73 at 25 °C (Table , entry 2). Evaluation of the stereoerrors in the ¹³C­{¹H} NMR spectra of this polymer suggest a primarily chain-end stereocontrol mechanism that would result in stereoblock trans-PHMB (See SI, section 3.2). Additionally, rac-(^4‑MeBDI*)­ZnO ⁱ Pr is ∼20 times faster than [( ^iPrBDI)­ZnO ⁱ Pr]₂, reaching 96% and 13% conversion of 2000 equiv trans-DMPL in 18 h, respectively (Table S5). The catalyst rac-(^4‑MeBDI*)­ZnO ⁱ Pr can also access trans-PHMB with varying isotacticities through temperature modulation, as mm%s vary between 77 and 66% when T _rxn = 0–50 °C (Table , entries 1–4). At these higher temperatures, the dispersities remain narrow, suggesting that minimal transesterification and elimination side reactions occur. Moreover, introduction of chain-transfer agent (CTA) enables rac-(^4‑MeBDI*)­ZnO ⁱ Pr to perform immortal and stereoselective ROP at catalyst loadings as low as 0.02 mol %. Indeed, using a [trans-DMPL]₀:[catalyst]₀:[ ⁱ PrOH]₀ ratio of 5000:1:4 yielded isoenriched trans-PHMB (mm% = 73%; M _n = 93.9 kDa, Đ = 1.10; Table S10). Overall, rac-(^4‑MeBDI*)­ZnO ⁱ Pr can access high molecular weights needed for good mechanical properties at low loadings while maintaining stereoselectivity.

1. Polymerization of rac-trans-DMPL by rac-(^ArBDI*)­ZnO ⁱ Pr Complexes.

entry	Ar	T rxn (°C)	conv. (%)	M n,theo (kDa)	M n,SEC (kDa)	Đ	mm%	T m (°C)
1	4-Me-Ph	0	97	19.4	27.3	1.14	77	170/150
2	4-Me-Ph	25	>99	20.0	27.4	1.06	73	155/135
3	4-Me-Ph	40	>99	20.0	24.3	1.05	69	147/132
4	4-Me-Ph	50	>99	20.0	21.7	1.09	66	143
5	3,5-CF3-Ph	0	12	2.4	5.0	1.04	n.d.	n.d.
6	3,5-CF3-Ph	25	90	18.0	33.0	1.08	45	–
7	3,5-F-Ph	0	21	4.2	6.6	1.04	61	150/131
8	3,5-F-Ph	25	>99	20.0	26.6	1.05	55	–
9	3,5-Cl-Ph	0	33	6.6	9.1	1.04	n.d	141/123
10	3,5-Cl-Ph	25	>99	20.0	35.4	1.05	54	–
11	3,5-Me-Ph	0	83	16.6	19.9	1.08	75	161/138
12	3,5-Me-Ph	25	>99	20.0	23.2	1.04	65	142
13	2-naphthyl	0	88	17.6	21.6	1.19	79	174/156
14	2-naphthyl	25	98	19.6	24.3	1.04	73	156/132

^a[rac-trans-DMPL]₀:[(^ArBDI*)­ZnO ⁱ Pr)]₀ = 200:1, [trans-DMPL]₀ = 4 M in PhMe, t _rxn = 18 h.

^bDetermined by ¹H NMR spectroscopic analysis comparing the relative integration of polymer and residual monomer.

^cDetermined by SEC in THF at 30 °C, calibrated relative to monodisperse polystyrene standards.

^dDetermined by ¹³C­{¹H} NMR spectroscopic analysis.

^eDetermined by DSC, polymorph 1/polymorph 2.

^fDue to the low molecular weight of this sample, the DSC data was omitted from subsequent thermal properties analysis. n.d. = not determined

We hypothesized that introducing different steric and electronic environments around zinc, by changing Ar, would enable access to a broader scope of isoenrichments. Intriguingly, when Ar = 3,5-CF₃-Ph, a drop in isoselectivity (45 mm% at 25 °C) and a reduction in activity (Table , entries 5 and 6) was observed. We theorize that the electron-withdrawing substituents increase the Lewis acidity of the Zn center, strengthening Zn-alkoxide coordination. The reactivity of the propagating alkoxide is therefore reduced and results in a slower monomer insertion step. Such an effect may also contribute to the reduced stereoselectivity observed for the more electron-deficient systems. Supporting this hypothesis, as the strength of the electron withdrawing groups in the meta positions was decreased from F to Cl to Me, the mm% content increased to 55, 54, and 65 mm%, respectively (Table , entries 8, 10, and 12). A corresponding enhancement in activity was also noted at 0 °C across the series (Table , entries 7, 9, 11, and 13). Notably, the catalyst with Ar = 3,5-Me-Ph exhibited a 10 mm% increase in isoselectivity upon lowering the temperature to 0 °C compared to a 4 mm% increase when Ar = 4-Me-Ph (Table , entries 1, 2, 11, and 12). We suspect this observation is due to a higher barrier for 3,5-Me-Ph rotation which is enhanced at lower temperatures, thus rigidifying the catalyst increasing stereoselectivity.

Based on these results, we targeted trans-PHMB with mm%s greater than 77 by designing a catalyst with a steric environment intermediate between 4-Me-Ph and 3,5-Me-Ph. At 0 °C, these two catalysts exhibit the highest mm% and the greatest enhancement of isoselectivity (compared to 25 °C), respectively. We envisioned that an intermediate steric environment could be furnished by installing an asymmetric 2-naphthyl group, which could improve isoselectivity. At 25 °C, the 2-naphthyl substituted catalyst exhibited identical isoselectivity to the 4-Me-Ph catalyst (mm% = 73%; Table , entries 2 and 14). Gratifyingly, at 0 °C, rac-(^2‑naphthylBDI*)­ZnO ⁱ Pr yielded the highest isotacticity (79 mm%) (Table , entry 13). This polymer has a moderately broadened dispersity, which we attribute to slightly different rates of polymerization of the three rotational isomers (Figures S80 and S81).

By modifying reaction temperature and ligand stereoelectronics, we successfully synthesized trans-PHMB polymer samples spanning a broad range of isotacticities (45–79 mm%), enabling a systematic evaluation of the influence of tacticity on thermal and mechanical properties. Analysis by DSC revealed a transition from amorphous to semicrystalline between 55 and 65 mm% as demonstrated by the appearance of an endothermic melting transition (Table , entries 8 and 12). For all tested samples (between 65 and 79 mm%), a linear increase in T _m and mm% was observed (Figure ). Additionally, comparison of rac-trans-PHMB prepared from racemic monomer and racemic catalyst to enantioenriched trans-PHMB, revealed minimal differences in T _ms (Figure S34). This observation suggests that the racemic samples do not undergo significant stereocomplexation arising from their stereoblock microstructure, despite the previous reports of stereocomplexation in perfectly isotactic trans-PHMB.

1.

Relationship between T _m and mm% for isoenriched trans-PHMB samples in Table . T _m of 100 mm% sample is obtained from literature. ,

We then assessed the thermal stability of isoenriched trans-PHMB by isothermally heating a sample at 170 °C under a N₂ atmosphere. While the M _n of PHB drops by ca. 50% in 30 min of heating, isoenriched trans-PHMB exhibited minimal change in M _n (105.4 kDa to 99.1 kDa; Figure S35) with negligible change in Đ. , This high thermal stability allows melt-pressing of trans-PHMB without significant molecular weight decrease, allowing systematic evaluation of the relationship between isotacticity and mechanical properties.

Next, we systematically studied the influence of isotacticity on the mechanical properties of trans-PHMB. High molecular weight samples (M _n ≈ 100 kDa) with varying isoenrichments (68, 73, 75, and 78 mm%) were melt pressed into dog bone shaped specimens and subjected to uniaxial tensile testing (Figure and Tables S8 and S9). The least isotactic sample (68 mm%) exhibited the lowest stiffness (Young’s modulus, E = 58 ± 4 MPa) and no distinct yield point, consistent with its reduced crystallinity. The material showed remarkable ductility (ε_B = 1030 ± 60%) and pronounced strain hardening. Increasing isotacticity to 73 and 75 mm% resulted in the appearance of a clear yield point (yield stress, σ_Y = 8.1 ± 0.4 MPa, 8.9 ± 0.4 MPa, respectively) and approximately doubled the modulus (E = 120 ± 10 MPa in both cases). Although elongation at break decreased (ε_B = 680 ± 130% and 750 ± 40%), both materials retained appreciable ductility and exhibited strain hardening (σ_B = 9.9 ± 1.2 and 13.00 ± 0.03 MPa). These intermediate compositions display tensile profiles closely resembling LDPE, balancing deformability with moderate mechanical resistance and yield behavior. Further increasing isotacticity to 78 mm% produced the stiffest material (E = 130 ± 10 MPa, σ_Y = 10.0 ± 0.5 MPa), and reduced elongation at break (540 ± 70%), indicating increased crystallinity.

2.

Stress–strain curves from uniaxial tensile testing of isoenriched trans-PHMB samples.

Collectively, these results demonstrate that modest variations in tacticity produce pronounced changes in mechanical behavior. Lower isotacticity yields softer, highly extendible materials, whereas higher isotactic enrichment increases stiffness and yield strength at the expense of ductility. Importantly, intermediate isotactic compositions (73–75 mm%) achieve an optimal balance of properties, closely mimicking the tensile response of LDPE. These findings underscore stereochemical control as a powerful design parameter for modulation of mechanical properties.

Conclusions

In summary, we demonstrated that the thermal and mechanical properties of trans-PHMB can be tuned with slight variations to the stereoregularity. High molecular weight polymers with a broad range of isoenrichments (mm% = 45–79%) were synthesized by ROP of trans-DMPL catalyzed by a new class of C ₂ symmetric “sandwich” Zn BDI complexes (rac-(^ArBDI*)­ZnO ⁱ Pr). Isoenriched trans-PHMB exhibits excellent thermal stability under melt conditions, and mechanical testing revealed the samples with 73 and 75 mm% display tensile properties similar to LDPE while exhibiting substantially higher melting temperatures than LDPE. This work will inform the design of future stereoselective lactone polymerization catalysts and provides a platform to tune mechanical properties through tacticity manipulation. Future work will focus on investigating the mechanism of stereocontrol for these rac-(^ArBDI*)­ZnO ⁱ Pr catalysts.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.6c08149.

• Experimental procedures; material characterization; spectral data (PDF)

∥.

M.S.Y. and Y.R. contributed equally to this work.

This work was supported by the U.S. Department of Energy (No. DE-FG02–05ER15687). This work was supported by the NSF Graduate Research Fellowship to M.S.Y. (DGE-2139899). This work made use of the Cornell University NMR (RRID:SCR_028078) and Chemistry MS (RRID:SCR_028079) Facilities. We thank Ethan B. Flanagan for assistance with the Gaussian distribution graphic and Pengfei Zhang for preparation of cis-DMPL.

The authors declare the following competing financial interest(s): A.M.L. and G.W.C. are inventors on US patent application US20240309149 covering PHMBs.