Temperature‐Driven Switching Between Block, Near‐Statistical, and Gradient Copolymers Enabled by Multinuclear Aluminum Catalysis

ABSTRACT

Precise control over microstructure in the ring‐opening copolymerization of ε‐caprolactone (CL) and lactide (LA) remains challenging because of intrinsic monomer reactivity differences and concomitant transesterification, which often obscure the origin of the final sequence distribution. Here we show that a single tetrameric multinuclear aluminum catalyst provides programmable access to block, near‐statistical, and gradient CL/LA copolymers within one catalytic platform. The complex mediates well‐controlled ring‐opening polymerization of both monomers, enabling the synthesis of diblock, triblock, and multiblock architectures by sequential monomer addition under insertion‐dominated conditions. Under simultaneous copolymerization conditions, variation of the reaction temperature modulates the balance between propagation and exchange processes and thereby governs the copolymer microstructure. At lower temperature, the copolymers display reactivity ratios close to unity, average sequence lengths near two, and thermal behavior consistent with near‐statistical incorporation. At elevated temperature, enhanced transesterification leads to pronounced growth of homologous sequences and compositional drift along the chains, characteristic of gradient architectures. Taken together, these findings establish a unified kinetic–thermodynamic framework for sequence control in CL/LA copolymerization and reveal multinuclear aluminum catalysis as an effective strategy to traverse distinct copolymer microstructures using an earth‐abundant metal system.

A single multinuclear aluminum catalyst enables temperature‐driven switching between block‐enriched, near‐statistical, and gradient CL/LA copolymer microstructures. Modulation of propagation and exchange processes within one catalytic platform provides a unified kinetic–thermodynamic framework for sequence control in biodegradable polyester copolymerization.

1. Introduction

Controlling sequence distribution in copolymers remains a central challenge in polymer chemistry, as microstructure directly governs material properties such as thermal behavior, mechanical performance, and degradation profiles. In particular, the ring‐opening copolymerization of lactide (LA) and ε‐caprolactone (CL) represents a prototypical system in which intrinsic differences in monomer reactivity and concurrent transesterification complicate predictable sequence control. While block, near‐statistical, and gradient copolymers can each be accessed under specific conditions, achieving programmable control over these distinct microstructures within a single catalytic system remains an unmet challenge.

The development of sustainable polymeric materials with controlled physicochemical properties has become a central objective in modern materials science, driven by the increasing demand for environmentally benign alternatives to conventional petroleum‐based plastics [1, 2, 3]. Among these materials, aliphatic polyesters such as poly(lactide) (PLA) and poly(ε‐caprolactone) (PCL) have attracted considerable attention owing to their biodegradability, biocompatibility, and derivation from renewable resources [4, 5, 6]. However, their practical applications remain limited by their intrinsically contrasting properties: PLA is typically brittle with relatively fast degradation, whereas PCL is flexible but degrades significantly more slowly [7, 8, 9].

Copolymerization of LA and CL represents an effective strategy to overcome these limitations by enabling fine‐tuning of thermal, mechanical, and degradation properties [10, 11, 12]. Importantly, beyond overall composition, the sequence distribution of monomer units plays a decisive role in determining material performance [13, 14, 15]. Random copolymers typically exhibit homogeneous properties and uniform degradation profiles, whereas block or gradient copolymers often lead to phase separation and heterogeneous behavior [16, 17, 18].

Despite these advantages, achieving truly random copolymerization of LA and CL remains a longstanding challenge. A limited number of catalyst systems have been reported to furnish random or near‐random copolymers, underscoring the rarity of well‐controlled statistical incorporation in this monomer pair [19, 20]. A major complication is that microstructures that appear random may not always originate from intrinsic statistical monomer insertion during propagation. In several systems, transesterification contributes substantially to sequence redistribution, thereby obscuring the true origin of the final copolymer microstructure [21, 22, 23].

This challenge originates from the inherent mismatch in monomer reactivity during ring‐opening polymerization (ROP). The different propagation preferences of LA and CL disfavor ideal statistical incorporation and instead promote deviations toward non‐random sequence distributions [24, 25, 26]. These effects are strongly influenced by catalyst structure, and even closely related metal alkoxide or coordination‐insertion systems can exhibit markedly different monomer incorporation behavior depending on ligand environment and metal coordination mode [27, 28].

Recent studies have demonstrated that transesterification can be deliberately exploited to modulate copolymer microstructure, particularly in rare‐earth systems where the balance between propagation and exchange processes can be tuned through catalyst design or reaction medium [29]. However, these approaches typically rely on specific catalyst environments and do not provide a general strategy for dynamically accessing multiple microstructural regimes within a single catalytic platform. In particular, there is no reported system that offers unified and predictable access to block, near‐statistical, and gradient copolymers from the same LA/CL monomer pair using one well‐defined catalyst framework. From a broader perspective, multinuclear catalysts are attractive candidates to address this challenge, because interactions between adjacent metal centers can, in principle, regulate both monomer insertion and transesterification [30]. In the context of aluminum‐based ring‐opening polymerization, however, reported multinuclear complexes have largely focused on enhancing activity or producing a single, fixed microstructure, without offering access to multiple, well‐defined sequence regimes within one catalyst platform [20, 21]. Notably, temperature‐triggered switching from kinetically controlled near‐statistical copolymerization to thermodynamically driven gradient structures has not been demonstrated for aluminum‐based catalysts, despite related behavior in rare‐earth systems [29].

In this context, we report a tetrameric multinuclear aluminum catalyst that enables programmable control over copolymer microstructure in the ring‐opening copolymerization of LA and CL. This single catalyst platform exhibits living behavior toward both monomers, allowing the synthesis of block‐enriched microstructures via sequential monomer addition under insertion‐dominated conditions. Under simultaneous copolymerization, variation of reaction temperature modulates the balance between propagation and exchange processes, leading to a transition from a kinetically controlled near‐statistical regime to gradient architectures under increasing transesterification. Together, these findings establish a unified kinetic–thermodynamic framework for sequence control in LA/CL copolymerization and identify multinuclear aluminum catalysis as an effective, earth‐abundant platform for accessing block, near‐statistical, and gradient microstructures.

The conceptual framework of this study is summarized in Figure 1. A single multinuclear aluminum catalyst enables access to distinct copolymer microstructures as a function of reaction conditions. Sequential monomer addition preserves insertion‐defined sequences and yields block‐enriched microstructures, whereas simultaneous copolymerization produces near‐statistical or gradient structures depending on temperature. This behavior reflects a shift in the relative contributions of propagation and exchange processes: insertion‐dominated conditions retain sequence fidelity, while increasing exchange leads to progressive sequence redistribution and the formation of gradient architectures. In this way, temperature provides a direct experimental handle to traverse multiple microstructural regimes within a single catalytic system.

FIGURE 1.

Multinuclear aluminum‐catalyzed switching between block, near‐statistical, and gradient copolymer microstructures.

2. Results and Discussion

2.1. Design and Mechanistic Hypothesis of a Multinuclear Aluminum Catalyst

To enable programmable control over copolymer microstructure, we designed a tetrameric multinuclear aluminum catalyst featuring closely positioned metal centers capable of potentially cooperative substrate activation. The catalyst was fully characterized by NMR spectroscopy and single‐crystal X‐ray diffraction (Scheme 1 and Figures S1–S5).

SCHEME 1.

Synthetic Route for Tetrameric Aluminum Complex 1.

The solid‐state structure reveals a tetranuclear aluminum framework composed of one octahedral and three tetrahedral aluminum centers bridged by oxygen donors, with short Al–Al distances (∼2.84 Å). Such a multinuclear arrangement may facilitate interactions between adjacent metal centers between adjacent metal centers, potentially enabling simultaneous activation of monomers and propagating polymer chains.

From a mechanistic perspective, we hypothesized that this system could modulate the relative rates of monomer insertion and transesterification, thereby controlling copolymer microstructure. In particular, tuning reaction temperature is expected to shift the system from insertion‐dominated behavior toward regimes in which exchange processes become comparable to or exceed propagation, providing a basis for switching between distinct sequence regimes [30].

2.2. Controlled Homopolymerization: Establishing the Kinetic Platform

The catalytic performance of complex 1 was first evaluated in the ring‐opening polymerization (ROP) of CL, l‐LA, and rac‐LA (Tables S1 and S2) using 0.5 mol% complex 1 and 1.0 mol% 9‐hydroxyfluorene in toluene. Polymerization of CL at room temperature proceeded rapidly, reaching full conversion within 35 min with narrow dispersities (M_w /M_n ≈ 1.07–1.09), while LA polymerization at 70°C afforded PLA with predictable molecular weights and narrow dispersities. Owing to the multiple possible coordination environments within the tetranuclear framework and the in situ generation of the catalyst in the presence of 9‐hydroxyfluorene, the precise distribution of aluminum alkoxide initiating sites and the exact number of active propagating chains cannot be determined unambiguously from the present data. Accordingly, no specific initiation structure or definitive number of propagating chains is assigned in this study.

The living nature of the system was further confirmed by monitoring the evolution of molecular weight with monomer conversion. As shown in Figure 2, the number‐average molecular weight (M_n ) increases linearly with conversion for all three monomers, while the dispersity values remain low throughout the polymerization. For CL, l‐LA, and rac‐LA, the M_w /M_n values remain within a narrow range (≈ 1.07–1.09), indicating minimal chain transfer or termination. The consistent linear growth of M_n with conversion across all monomers demonstrates that propagation proceeds in a controlled manner, consistent with living polymerization behavior reported for well‐defined aluminum catalysts [21, 22, 23].

FIGURE 2.

Evolution of number‐average molecular weight (M_n , determined by NMR) and dispersity (M_w /M_n ) with monomer conversion in the polymerization of (a) CL, (b) l‐LA, and (c) rac‐LA, demonstrating controlled/living polymerization behavior.

These results establish a well‐defined kinetic baseline for the system and confirm that complex 1 mediates controlled polymerization of both lactones and lactides, providing a reliable platform for subsequent sequence‐controlled copolymerization studies. In addition, the experimentally obtained M_n (NMR) and M_n (GPC) values are in reasonably good agreement with the calculated molecular weights based on monomer conversion and the initial monomer‐to‐initiator ratio (Tables S1 and S2).

2.3. Sequential Polymerization: Block Benchmark

The controlled/living nature of the system enables precise sequence control via sequential monomer addition. As shown in Table 1, stepwise addition of LA and CL (LA→CL→LA→CL) affords copolymers with block‐enriched microstructures.

TABLE 1.

Synthesis of block copolymers via sequential monomer addition using complex 1. ^{a .}

Entry	CL/LA in copolymer b	T g (°C) c	T m(CL) (°C) c	T m(LA) (°C) c	Mn (GPC) d	Mw/Mn d
1	51:49	−54.04	51.16	149.73	14400	1.17
2 e	51:49	−57.15	48.30	150.07	14300	1.31
3 f	30:70	—	53.54	146.99	35000	1.24
4 g	45:55	—	52.99	150.36	51000	1.59

^a Solution polymerization condition: [Al] = 40 µmol, [9‐hydroxyfluorene] = 80 µmol, [l‐LA] = [ε‐CL] = 4 mmol, [l‐LA]/[ε‐CL]/[Al]/[9‐hydroxyfluorene] = 100/100/1/2, toluene = 8 mL.

^b CL/LA mole ratio in the copolymer obtained by ¹H NMR spectroscopy.

^c Obtained by DSC analysis.

^d Obtained by GPC analysis and calibrated using a polystyrene standard.

^e When ε‐CL is initially inserted, followed by l‐LA.

^f Triblock copolymer.

^g Terblock copolymer. All copolymerization reactions proceeded to conversions higher than 99% under the employed conditions, as determined by ¹H NMR spectroscopy.

Importantly, unlike many aluminum‐based systems in which transesterification becomes significant at elevated temperatures, complex 1 maintains negligible sequence scrambling even at 130°C. This feature is critical for preserving insertion‐defined sequences and establishing a block‐enriched reference microstructure, which serves as a reference for distinguishing subsequent temperature‐dependent microstructural evolution [21, 22, 23].

GPC analysis shows clear molecular weight growth after each addition step without the appearance of low‐molecular‐weight shoulders, indicating preservation of active chain ends. Representative GPC traces for selected diblock (Table 1, entry 1) and triblock (Table 1, entry 3) copolymer samples are provided in Figures S47 and S48. Spectroscopic analysis further confirms the block architecture, with dominant LA–LA and CL–CL sequences and minimal heterosequences.

The absence of CL–LA–CL signals in the ¹³C NMR spectra (see Figures S21–S24) indicates that transesterification is effectively suppressed under these conditions. These observations define an insertion‐dominated regime in which propagation proceeds faster than exchange processes on the experimental timescale, favoring the formation of block‐enriched microstructures [21, 22].

2.4. Simultaneous Copolymerization at Low Temperature: Near‐Statistical Regime

Building on the spectroscopic distinctions established in Figure 3, copolymerization behavior under simultaneous conditions was further investigated as a function of temperature. At lower temperatures (50–70°C), the resulting copolymers exhibit characteristics consistent with near‐statistical microstructures (Table 2, entries 1–2).

FIGURE 3.

Comparison of the (a) ¹H NMR methine and methylene regions and (b) ^{1 3}C NMR carbonyl region for block (bottom), near‐statistical (top), and gradient (middle) copolymers.

TABLE 2.

Temperature‐dependent copolymerization of CL and LA using complex 1. ^{a .}

Entry	Temp (°C)	Time (h)	CL/LA in copolymer b	L CL/L LA c	rCL d	rLA d	r CL×r LA	T g (°C) e	Mn (GPC) f	Mw/Mn f
1	50	24	39:61	2.3/2.6	0.92	1.08	1.00	−12.97	14 400	1.17
2	70	6	41:59	2.1/2.6	0.94	1.11	1.04	−13.54	14 500	1.24
3	90	2	38:62	2.1/2.4	0.97	1.15	1.11	−15.97	14 200	1.25
4	110	1	47:53	2.4/2.4	1.14	1.20	1.37	−17.02	14 200	1.24
5	130	0.5	47:53	2.3/2.4	1.17	1.22	1.43	−17.34	14 300	1.26
6 g		3	53:47	2.3/2.7	1.35	1.30	1.75	−18.32	25 000	1.24
7 h		8	57:43	2.8/2.5	1.56	1.40	2.19	−17.82	51 000	1.28
8 i		18	54:46	3.0/2.7	1.73	1.58	2.73	−17.09	104 000	1.30
9 j		24	58:42	3.0/2.6	1.85	1.62	3.00	−16.65	130 000	1.33

^a Conditions for solution polymerization: [Al] = 40 µmol, [9‐hydroxyfluorene] = 80 µmol, [l‐LA] = [ε‐CL] = 4 mmol, [l‐LA]/[ε‐CL]/[Al]/[9‐hydroxyfluorene] = 100/100/1/2, toluene = 8 mL.

^b CL/LA mole ratio in the copolymer obtained by ¹H NMR spectroscopy

^c CL/LA mole ratio in the copolymer as determined by ¹³C NMR.

^d Calculated based on ¹H NMR data.

^e Obtained by DSC analysis.

^f Obtained by GPC analysis and calibrated using a polystyrene standard.

^g [l‐LA]: [ε‐CL]: [Cat.]: [9‐hydroxyfluorene] = 200: 200: 1: 2.

^h [l‐LA]: [ε‐CL]: [Cat.]: [9‐hydroxyfluorene] = 400: 400: 1: 2.

ⁱ [l‐LA]: [ε‐CL]: [Cat.]: [9‐hydroxyfluorene] = 800: 800: 1: 2.

^j [l‐LA]: [ε‐CL]: [Cat.]: [9‐hydroxyfluorene] = 1000: 1000: 1: 2. All copolymerization reactions proceeded to conversions higher than 99% under the employed conditions, as determined by ¹H NMR spectroscopy.

The experimentally determined reactivity ratios are close to unity (r _CL ≈0.92–0.97, r _LA ≈1.08–1.15), and the average sequence lengths (L _CL ≈ 2.1–2.3, L _LA ≈ 2.4–2.6) approach those expected for statistical incorporation. These observations indicate that monomer incorporation occurs without strong preference under these conditions.

Although a full randomness parameter analysis is beyond the scope of this work, the combined agreement of reactivity ratios, sequence lengths, and NMR triad distributions (see Figures S11, S12, S25, and S26) provides evidence consistent with near‐statistical copolymerization [23, 24, 25]. Representative GPC traces for the near‐statistical copolymer sample corresponding to Table 2, entry 1 are provided in the Supporting Information (Figure S49). Accordingly, the reported reactivity ratios are interpreted here as semi‐quantitative indicators of sequence tendency and compositional evolution rather than rigorous low‐conversion kinetic parameters.

2.5. High Temperature Copolymerization: Gradient Formation

Increasing the reaction temperature (≥110°C) results in a pronounced deviation from near‐statistical microstructures. The product r _CL × r _LA increases systematically, and homologous sequences (CL–CL–CL and LA–LA–LA) become dominant, indicating the formation of gradient copolymers.

The average sequence lengths increase correspondingly, reflecting the development of compositionally biased segments along the chain. These trends are characteristic of gradient copolymer formation, consistent with increasing contribution from transesterification processes.

Mechanistically, these observations indicate that exchange processes become increasingly competitive with propagation at elevated temperatures, enabling progressive sequence redistribution during polymerization.

These temperature‐dependent changes suggest the emergence of distinct microstructures across the polymerization regimes. To directly compare these structures, spectroscopic analysis of representative block, near‐statistical, and gradient copolymers was performed.

Figure 3 compares the ¹H and ^{1 3}C NMR spectra of block, near‐statistical, and gradient copolymers, providing spectroscopic signatures consistent with these distinct microstructures.

The block copolymer exhibits dominant homologous sequences (LA–LA–LA and CL–CL–CL), consistent with minimal sequence mixing and preservation of insertion‐defined architecture. In contrast, the near‐statistical copolymer shows increased heterosequence signals (LA–CL–LA and CL–LA–CL), indicating statistical incorporation of monomer units. The gradient copolymer displays an intermediate pattern with enrichment of homologous sequences, reflecting progressive sequence redistribution along the chain.

Taken together, these spectral differences are consistent with insertion‐defined, kinetically controlled, and exchange‐influenced microstructures within a single catalytic system.

Figure 4 provides complementary thermal evidence for the microstructural evolution observed spectroscopically. Copolymers prepared at lower temperatures exhibit T_g values consistent with near‐statistical microstructures, whereas those obtained at higher temperatures show modest but systematic decreases in T_g values, reflecting increased compositional heterogeneity along the chain. The experimental T_g values were also compared with those estimated using the Fox equation. For low‐temperature copolymers, the measured T_g values are reasonably close to the calculated values, whereas increasing deviations are observed at elevated temperatures, consistent with increasing compositional heterogeneity and sequence redistribution.

FIGURE 4.

DSC curves of CL/LA copolymers prepared at different polymerization temperatures, showing temperature‐dependent changes in thermal behavior.

This trend directly parallels the increase in r _CL × r _LA and sequence length, indicating that exchange processes become increasingly significant at elevated temperatures. The agreement between spectroscopic (Figure 3) and thermal analyses provides consistent evidence for the transition from a kinetically controlled near‐statistical regime to gradient microstructures.

In this context, “exchange” refers primarily to transesterification between polymer chains rather than chain transfer to alcohol.

Representative GPC traces for the gradient copolymer sample corresponding to Table 2, entry 6 are provided in the Supporting Information (Figure S50).

2.6. Unified Mechanistic Picture

Taken together, these results establish a unified mechanistic framework for copolymer microstructure control, which is schematically summarized in Figure 5. The system traverses distinct regimes defined by the relative contributions of propagation and exchange processes: insertion‐dominated conditions favor block‐enriched microstructures, low‐temperature simultaneous copolymerization produces near‐statistical structures, and elevated temperatures lead to gradient microstructures as exchange becomes increasingly significant.

FIGURE 5.

Mechanistic landscape illustrating temperature‐controlled switching between block, near‐statistical, and gradient copolymer microstructures enabled by a multinuclear aluminum catalyst.

This temperature‐dependent evolution defines a kinetic–thermodynamic landscape that can be accessed within a single multinuclear aluminum catalytic platform.

3. Conclusions

In summary, we have shown that a single tetrameric multinuclear aluminum catalyst enables programmable control over microstructure in the ring‐opening copolymerization of lactide and ε‐caprolactone. The complex mediates well‐controlled polymerization of both monomers and allows the synthesis of diblock, triblock, and multiblock architectures by sequential monomer addition under conditions where insertion dominates over exchange, providing a block‐enriched reference microstructure. Under simultaneous copolymerization, variation of the reaction temperature modulates the relative contributions of propagation and transesterification, giving rise to a continuum of microstructures that spans near‐statistical copolymers at lower temperature and gradient architectures at elevated temperature.

Spectroscopic and thermal analyses reveal that low‐temperature copolymers display reactivity ratios close to unity, average sequence lengths near two, and glass transition temperatures consistent with near‐statistical incorporation, whereas high‐temperature copolymers show enrichment of homologous sequences together with modest shifts in thermal transitions characteristic of gradient structures.

These findings define a unified kinetic–thermodynamic framework for sequence control in LA/CL copolymerization and identify multinuclear aluminum catalysis as an effective, earth‐abundant strategy to traverse block, near‐statistical, and gradient microstructural regimes without changing catalyst identity. More broadly, they highlight the potential of multinuclear architectures to regulate both monomer insertion and exchange processes, suggesting new opportunities for the design of sequence‐controlled biodegradable polymers and for extending temperature‐triggered microstructure switching to other monomer pairs and catalytic manifolds.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Supporting File: marc70346‐sup‐0001‐SuppMat.docx.

Data Availability Statement

The data that support the findings of this study are available in the Supporting Information, including experimental procedures, characterization data (¹H and ^{1 3}C NMR spectra), DSC data, and representative GPC traces. Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre (CCDC 2542677).