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Simultaneous “O−Alkyl” and “O−Acyl” Lactone Cleavages from Hydroxy−Carboxylic Acid Initiators: Direct Access to Multiblock Architectures Bryan Raeskinet,† Sébastien Moins,† Luke Harvey,∥ Julien De Winter,‡ Céline Henoumont,§ Sophie Laurent,§,⊥ and Olivier Coulembier*,†

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†

Laboratory of Polymeric and Composite Materials (LPCM), Center of Innovation and Research in Materials and Polymers (CIRMAP), ‡Organic Synthesis and Mass Spectrometry Laboratory (S2MOS), Materials Institute, and §General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Place du Parc 20, 7000 Mons, Belgium ∥ ENSICAEN, UNICAEN, Normandy University, 14000 Caen, France ⊥ Center for Microscopy and Molecular Imaging (CMMI), Rue Adrienne Bolland 8, 6041 Gosselies, Belgium S Supporting Information *

ABSTRACT: Multiblock copolymers represent fascinating architectures that are generally prepared from heterofunctional initiators through independent polymerization processes. So far, most of those processes exploited the nature of different monomers to simultaneously associate different kind of compatible mechanisms including ATRP, NMP, RAFT, and ROP. Herein, we demonstrate the possibility to prepare multiblock polyester-based copolymers in a “one-pot, one-step” approach from independent and simultaneous ROPs of 4- and 6-membered lactones. The independent behavior of those polymerizations appears to be possible due to the ability of 4- and 6-membered lactones to polymerize selectively by “O−alkyl” and “O−acyl” cleavages, respectively. Those two types of lactone bond ruptures have been initiated from various heterofunctional moieties bearing hydroxyl and 1,8diazabicyclo[5.4.0]undec-7-ene (DBU)-based carboxylic salt functions. While DBU-based salts allow β-lactones to be polymerized by an anionic process, they also act as catalyst by activating the hydroxyl dandling functions, thus polymerizing 6membered lactones, such as L-lactide, by a H-bonding mechanism. In that work, dimethylated benzyl β-malolactonate was used as β-lactone representative. Depending on the initiator used, structures such as diblock, Y-shaped, and 4-arm stars have been prepared in a controlled manner in solution and at room temperature.

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INTRODUCTION The desire to control polymer properties by playing with the macromolecular engineering is an intense and continuous theme throughout the polymer community. Usually, multiblock copolymer structures are obtained by the coupling of preformed end-functionalized polymer blocks or by independent polymerizations of various monomers from a heterofunctional initiator. In the former case, sequential polymerizations are generally performed (called the “one-pot, two-step” process) since parallel polymerizations, in which the heterofunctional moieties initiate selectively and simultaneously independent polymerizations (called the “one-pot, onestep” process), are usually constraining. To date, only a handful of studies have focused on the simultaneous polymerizations of comonomers.1−9 By use of heterodifunctional initiators, most of those studies have reported on the possibility to take advantage of the different natures of the comonomers employed (lactone, (meth)acrylate, epoxide, etc.) to associate different controlled polymerization processes such as cationic and nitroxidemediated polymerizations or atom transfer radical polymerization and (enzymatic) ring-opening polymerization.1−5,7 Very interestingly, the preparation of diblock copolymers has © XXXX American Chemical Society

also been rendered possible from a single polymerization mechanism and in a “one-pot, one-step” process by taking advantage of the comonomer reactivity ratios.8,9 Lactone monomers have been polymerized by various polymerization processes according to the nature of the initiator/catalyst duo.10 Among those processes, the anionic ring-opening polymerization (AROP) offers many possibilities of control and is known to induce different types of mechanisms depending on the lactone ring size. In contrast to the anionic polymerization of higher 6- or 7-membered lactones (also including lactide), initiating the AROP of 4membered lactones, i.e., β-lactones, from an alkoxide initiator proceeds ambidently, namely with acyl−oxygen (“O−acyl”) and alkyl−oxygen (“O−alkyl”) bond scissions (Scheme 1a).11 Although it is recognized that factors such as temperature, steric hindrance (of both the initiator and the β-lactone), and solvent polarity have an effect on the “O−acyl” to “O−alkyl” proportion, it is admitted that alkoxide initiating species allow a mixture of alkoxide and carboxylate active species to be Received: June 21, 2019 Revised: August 6, 2019

A

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Scheme 1. (a) “O−Acyl” and “O−Alkyl” Cleavages of β-Lactones from Alkoxide Initiator (Cation Omitted for Clarity); (b) Selective “O−Alkyl” Cleavage of β-Lactones from Activated 12-Hydroxydodecanoate Dual Initiator (Potassium and 18-Crown6 Ether Omitted for Clarity); (c) Catalytic Bifunctional Mechanism Involved in the Lactide ROP from Exogenous Alcohol and in the Presence of an Equimolar Mixture of Benzoic Acid and DBU17

carboxylic acid salts activated by organic superbases,18−20 hydroxy−carboxylic acid dual initiators activated by either amidine or guanidine superbases, i.e., DBU and 1,5,7triazabicyclo[4.4.0]dec-5-ene (TBD), were studied (Scheme 2). Moreover, to get rid of inescapable proton β-eliminations

produced in the early stage of the AROP, leading eventually to carboxylate being the only active species responsible for propagation.12,13 Such propension to be selectively opened by carboxylate active species allowed some of us to prepare diblock copolymers from the 12-hydroxydodecanoic acid dual initiator in a multistep process (Scheme 1b). In the presence of an equimolar mixture of potassium and 18-crown-6 ether, the as-obtained crowned potassium 12-hydroxydodecanoate selectively initiated the AROP of the 4-membered ring benzyl βmalolactonate (MLABn) from the activated carboxylate function allowing the synthesis of α-hydroxy−ω-carboxylic acid poly(benzyl β-malolactonate) to be fully controlled.14,15 The free hydroxy end-groups were then used to selectively polymerize larger lactones, such as ε-caprolactone or L-lactide, to produce the expected diblock copolymers. During his investigation on the catalytic effect of alkali metal carboxylates on the polymerization of cyclic esters, Satoh et al. demonstrated that the ROP of β-butyrolactone with sodium acetate proceeds exclusively in an “O−alkyl” cleavage manner even in the presence of free alcohols while those alkali metal carboxylates were discovered highly efficient to catalyze lactide (LA) ROP from exogenous alcohols.16 The same observation was addressed by Hedrick et al. in 2011 when demonstrating that benzoic acid/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) salt was an efficient bifunctional catalyst for the ROP of LA from an alcohol (Scheme 1c).17 Because “O−alkyl” bond scissions of β-lactones proceed from activated carboxylate moieties in the presence of free alcohol and because activated carboxylates (organic or organometallic) activate hydroxyl initiating/propagating endgroups to selectively polymerize LA by “O−acyl” bond cleavages, we aimed to study the simultaneous copolymerization of both β-lactone and LA from an activated hydroxy− carboxylic acid dual initiator. Because some of us already demonstrated the possibility to polymerize β-lactones with

Scheme 2. Intramolecular Activation of LA Hydroxyl Initiating ROP Site by an Activated Carboxylic Acid βLactone Initiating ROP Functiona

a

For clarity, the activation of the carboxylic acid has been represented by using DBU only. Intermolecular activations are also permitted.

of unprotected β-lactone monomers during anionic polymerizations,13 dimethylated benzyl β-malolactonate (dMMLABn) was used as a β-lactone representative. To the best of our knowledge, never have any research groups tried to simultaneously and selectively polymerize two types of lactones, i.e., LA and dMMLABn, by using the catalytic ability of one propagating site to activate another one (either intra- or intermolecularly) (Scheme 3). B

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Scheme 3. Hypothetical Scheme of Independent and Simultaneous “O−Acyl” and “O−Alkyl” Cleavages of LA and dMMLABn from a DBU Activated Hydroxy−Carboxylic Acid Salt (R′ = −CO2−C7H7)

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RESULTS AND DISCUSSION During our first investigations, the 12-hydroxydodecanoic acid (HDA) was selected to prepare two heterodifunctional salts with DBU and TBD ([HDA]0/[DBU or TBD]0 = 1). To confirm the formation of both organo-salts, the resulting mixtures were analyzed by 1H NMR in CDCl3 while their thermal behaviors were investigated by TGA. The strength of the hydrogen-bonding interactions was investigated by using 1 H NMR spectroscopy (Figure S1). When HDA is in the presence of 1 mol equiv of TBD, the methylene carboxy protons were most affected, as indicated by a change in chemical shift of the −CH2CO2H resonance (Δδ = 0.12 ppm). This shift suggests that the formation of the HDA/TBD salt takes place. The formation of the TBD.H+-based carboxylate end-group causes a downfield shift of the methylene hydroxy protons (Δδ = 0.026 ppm), implying that the carboxylate efficiently activates the hydroxyl group of the HDA.16 Similar results were observed when DBU was used to prepare the HDA/DBU salt (Δδ −CH2CO2H = 0.123 ppm; Δδ −CH2OH = 0.03 ppm). The TGA analyses of both salts revealed that the thermal stability was 277 °C for the HDA/TBD salt and 246 °C for the HDA/DBU salt, which are higher than those of the respective components. Prior to any copolymerization reactions, homopolymerizations of both LA and dMMLABn were investigated from both HDA-based salts. The polymerization of LA was first evaluated by conducting the ROP in DCM at 21 °C for a [LA]0/[HDA salt]0 of 40 and a [LA]0 = 2 M. The initial results immediately revealed the impact of the amidine or guanidine HDA salt type. While HDA/TBD yielded to a highly transesterified PLA (MnSEC = 11000 g/ mol; Mw/Mn = ĐM = 2; Figure 1), HDA/DBU generated controlled PLA with 83% conversion in 10 min (MnSEC = 7800 g/mol; ĐM = 1.1). When the reaction time was extended to 20 min, near-quantitative yields were achieved (∼97%; MnSEC = 9300 g/mol; ĐM = 1.1), thus rendering HDA/DBU more than 30 times more active than an equimolar combination of DBU and benzoic acid.17 Further prolonging of the reaction time for 30 min revealed little discernible change in the molecular weight or dispersity value (MnSEC = 10100 g/mol; ĐM = 1.2), thus suggesting that the polylactides prepared under these conditions are resistant to further transesterification reactions. Polymerization of dMMLABn was then conducted in DCM at 21 °C for an initial monomer-to-initiator ratio of 25 and a [dMMLABn]0 of 1.33 M. The evolution of the process was followed by FT-IR spectroscopy18 while the time-dependence

Figure 1. Time dependence of SEC molecular masses (MnSEC, circles) and dispersity values (ĐM, squares) of PLA samples obtained in DCM from HDA/TBD (dashed lines) and HDA/DBU (solid lines) initiating salts ([LA]0 = 2 M; [LA]0/[HDA salt]0 = 40).

evolution of experimental molecular weights was realized by SEC analyses. As clearly expressed in Figure 2, the HDA/DBU initiating system proved to be more efficient than HDA/TBD involving a more controlled process. The broader dispersity values of the

Figure 2. Time dependence of SEC molecular masses (MnSEC, circles) and dispersity values (ĐM, squares) of PdMMLABn samples obtained in DCM from HDA/TBD (dashed lines) and HDA/DBU (solid lines) initiating salts ([dMMLABn]0 = 1.33 M; [dMMLABn]0/ [HDA salt]0 = 25). C

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Figure 3. 1H NMR spectra of PdMMLABn obtained by dMMLABn ROP from HDA/TBD (top) and HDA/DBU (bottom) and recorded in CDCl3 at 21 °C (see the main text for the a′ signal attribution).

condensation of HDA (void of any dMMLABn) in the experimental conditions used for the ROP process (DCM, 21 °C, [HDA]0 = 1.18 M, [HDA]0/[TBD]0 = 1). After 72 h, 1H NMR analysis of the crude medium revealed no sign of condensation discriminating then end-to-end secondary reactions. Subsequently, backbiting/reshuffling reactions possibly involved from transesterification of pendant benzyl ester functions by the activated hydroxyl end groups were evaluated by initiating the dMMLABn ROP (DCM, 21 °C, [dMMLABn]0 = 1.33 M, [dMMLABn]0/[initiator]0 = 25) from an unhydroxylated initiator, i.e., the 1-pyreneacetic acid/ TBD salt ([1-pyreneacetic acid]0/[TBD]0 = 1). After 72 h, SEC analysis of the as-obtained PdMMLABn revealed a monomodal chromatogram characterizing a sample of MnSEC = 3500 g/mol and a ĐM of 1.38. Such a result corroborates the hypothesis that both backbiting (intramolecular) and reshuffling (intermolecular) side reactions are mainly due to benzyl ester transesterification from the activated end-capping hydroxyl functions. Further analysis of the HDA/TBD-initiated PdMMLABn by MALDI-ToF enabled the identification of the side reactions

PdMMLABn produced from HDA/TBD indicate that transesterification reactions happened. Prolonging the reaction time for 120 h revealed a multimodal SEC chromatogram indicating both intra- and intermolecular secondary reactions (Figure S2). Interestingly, 1H NMR analysis of that highly transesterified PdMMLABn sample revealed the total disappearance of the methylene hydroxy protons (Ha)which should have been observed at around δ 3.62 ppm (cf. Figure S1)to the benefit of unexpected signals (Ha′) showing up at ca. δ 4.05 ppm (Figure 3). Such signals could come from transesterification reactions between the initially present (and activated) α-hydroxy group and either the propagating carboxylate function21 (by intra- or intermolecular end-toend processes) or a pending benzyl ester group (by backbiting or reshuffling reactions) (Scheme 4). To discriminate or validate the hypothesis that backbiting and end-to-end secondary reactions are or are not involved either intra- or intermolecularly during the ROP of dMMLABn from an HDA/TBD initiating system, two model reactions were realized. The propensity of end-to-end reactions was first studied by evaluating the capacity of TBD to catalyze the D

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one where a H+ is exchanged with a Na+. The observation of this second distribution is considered as the “fingerprint” of the presence of the carboxylic acid end-group,18,22 confirming the exclusive “O−alkyl” cleavage of the dMMLABn monomer. The HDA/DBU initiating system was found to function analogously to the HDA/TBD in terms of kinetics but producing PdMMLABn of narrower dispersities and higher molecular weights (Figure 2). The low propensity of such initiating group to induce transesterification reactions was investigated by analysis of the end-groups of a DP ∼ 25 polymer by 1H NMR spectroscopy (Figure 3, bottom). For this sample, methylene hydroxy protons (Ha) were indeed observed at δ = 3.62 ppm but with an intensity slightly lower than the one expected (1.61 rather than 2). Such small discrepancy is due to a low part of transesterification reaction that could be estimated to 10−15% by comparing the intensity of the methylene hydroxy protons to the signal showing up at δ = 4.05 ppm. MALDI-ToF confirms such a result by the presence of two populations. While the major one is typical of the as-expected PdMMLABn topology properly end-capped by both hydroxyl and carboxylic moieties, the small other distribution is characteristic of transesterified structures (Figure 5). The environment polarity has a tremendous impact on the β-lactone rate of polymerization.23−27 In accordance with the literature, substituting DCM (dipole moment μ = 1.6 D and dielectric constant ε = 8.9) by slightly less polar THF solvent (μ = 1.75 D, ε = 7.6) markedly increases the apparent rate constant of dMMLABn anionic polymerization (Figure 6a). The solvent effect on the polymerization of LA with the HDA/ DBU initiator was inconsistent with an anionic mechanism (Figure 6b). For the HDA/DBU-initiated ROP of LA ([LA]0 = 1.33 M; [LA]0/[HDA/DBU]0 = 43), the reaction was fastest in DCM and slightly slower in THF, consistent with the expected hydrogen-bonding process. To prove the efficiency of the HDA/DBU initiator in preparing PLA-b-PdMMLABn diblock copolymers, the latter were primarily synthesized in a “one-pot, two-step” process starting with the LA ROP, followed by the anionic ROP of dMMLABn. This order was chosen to limit the propension of dandling benzyl ester functions to be transesterified by the end-capping hydroxyl group since the nucleophilic character of primary alcohols (here on the HDA initiator) is more pronounced than the one of secondary alcohols (here on the

Scheme 4. Intramolecular Transesterification Reactions Possibly Involved during the dMMLABn ROP from a TBDActivated 12-Hydroxydodecanoic Acida

a

Intermolecular reactions are also involved but omitted for clarity (∗ represents the activated state of the hydroxyl end-group).

that take place in this polymerization. Figure 4 represents the MALDI-ToF analysis of a PdMMLABn sample obtained after 48 h of reaction (MnSEC = 2640 g/mol; ĐM of 2.34). The main population displayed regular spacings equal to the molar mass of benzylated dimethyl malolactonate repeat unit (Δm/z = 234 Th) but was assigned to be the result of transesterification side reactions. The main distribution indeed corresponds to a sodium charged chain, presumably initiated from the HDA moiety but 108 u lower than expected, i.e., if no transfer occurred. Because 108 u does correspond to the molar mass of a C7H8O group, such as benzyl alcohol, and as attested by an isotopic model, we postulate that this species originates from intramolecular transesterification from the activated alcohol end-group to a benzyl ester repeated pendant unit and substituting benzyl alcohol (see Scheme 4, “backbiting” process). Note here that intermolecular transesterifications are not excluded but are simply not observed by MALDI. Joined to the first population, a secondary minor population is observed higher in mass of 22 Th and corresponds to the first

Figure 4. MALDI-ToF MS spectrum of a PdMMLABn initiated by an HDA/TBD (MnSEC = 2640 g/mol, ĐM of 2.34). Inset: expansion of region from m/z 2460 to 2510 (bottom) and a simulated mass distribution (top). E

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Figure 5. MALDI-ToF MS spectrum of a PdMMLABn initiated by an HDA/DBU (MnSEC = 3100 g/mol, ĐM of 1.52). Inset: expansion of region from m/z 5980 to 6110 (bottom) and simulated mass distributions of untransesterified (top) and transesterified structures (middle).

Figure 6. Semilogarithmic plots of (a) dMMLABn and (b) LA homopolymerizations initiated with HDA/DBU in both DCM (dashed lines) and THF (solid lines). Values in parentheses represent the experimental DP calculated by 1H NMR analyses.

Table 1. Molecular Characterizations of PLA-b-PdMMLABn Copolymers and Corresponding PLA Macroinitiators Obtained in a “One-Pot, Two-Step” Process from an HDA/DBU Initiator in Dry THF first step: LA ROP

second step: dMMLABn ROP

entry

DPtha

polym time (min)

DPexpb

Mn,SEC PLAc (g/mol)/ĐM

DPtha

polym time (h)

DPexpb

Mn,SEC copoc (g/mol)/ĐM

1 2 3

20 40 100

45 60 120

20 40 105

5600/1.19 11600/1.24 31300/1.15

20 40 100

24 71 168

19 43 47

9600/1.37 19300/1.39 42400/1.17

a Theoretical targeted DP in PLA and PdMMLABn. bAs determined by 1H NMR analyses. cUncorrected molar mass and dispersity determined by SEC in THF using PS standards.

polymerization was intentionally stopped after 168 h of dMMLABn ROP since the magnetic stirrer was completely blocked in a highly viscous medium. Regardless of the composition, well-defined copolymers were obtained. Molar masses increased with the overall DP while monomodal SEC traces were observed with dispersity remaining low (1.17 < ĐM < 1.39), confirming the good control over the process (Figure 8 and Figure S3). Such control is however sullied by a slight asymmetry observed in the high molar mass region of each SEC chromatograms, indicating the occurrence of intermolecular transesterification reactions probably between lactoyl end-groups and benzyl ester functions.

PLA extremities). Polymerizations were then conducted in dry THF from the HDA/DBU initiator and for total DPs ranging from 40 to 200 ([LA]0 ∼ 1.5 mol L−1; [dMMLABn]0 ∼ 1.1 mol L−1; targeted DP in PdMMLABn = targeted DP in PLA; Table 1). Polymerization times were adapted in function of both LA and dMMLABn conversions as recorded by either SEC or FT-IR. Figure 7 shows a typical 1H NMR spectrum of the resulting copolymer (entry 1, Table 1). After purification, each copolymer has a molar ratio of LA/dMMLABn almost equal to the corresponding feed ratio at the exception of the highest targeted DP (entry 3, Table 1). In that specific case, the F

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Figure 7. 1H NMR spectrum of a PLA-b-PdMMLABn (entry 1, Table 1) recorded in CDCl3 at 21 °C. ∗ refers to DBU signals. Insets: 1H NMR zooms of end-groups and 13C NMR carbonyl region.

Figure 8. SEC traces of PLA (dashed line) and corresponding PLA-b-PdMMLABn (solid line) (entry 1, Table 1). Molecular structures are presented with a carboxylate end-group since those have been demonstrated stable even after precipitation of the sample.20 13 C NMR analyses evidenced the blocky structure of all PLA-b-PdMMLABn diblock copolymers by presenting the carbonyl signature of both PLA and PdMMLABn homosequences. As illustrated by Figure 7 (left inset), the intense signal showing up at δ = 169.61 ppm corresponds to the PLA carbonyls while both less intense signals appearing at δ = 167.38 ppm and δ = 172.99 ppm are attributed to the two types of carbonyl groups on the malolactonate repeating units. In addition, NMR DOSY analyses were performed on a PLA-bPdMMLABn (entry 2, Table 1) and compared to a PLA homopolymer (DP = 40). These experiments were performed in DMSO-d6 (Figure 9 and Figure S4). As expected, only one diffusion coefficient was determined (D = 2.0 × 10−11 m2 s−1) that was different from that of PLA (D = 3.2 × 10−10 m2 s−1).

We then attempted to realize the copolymerizations in a “one-pot, one-step” process. Experimental polymerization conditions were kept identical to the ones used for the “onepot, two-step” reactions. Practically, symmetrical structures were targeted (DPthPLA = DPthPdMMLABn) while both monomer concentrations were kept constant (1.1 M < [LA]0 = [dMMLABn]0 < 1.2 M). Table 2 summarizes the molecular characterizations of three PLA-b-PdMMLABn copolymers obtained for total DPs of 50−200. As compared to the “one-pot, two-step” process, the “onestep” approach is characterized by a slower kinetics. Such a difference in (co)polymerization rate is probably due to the fact that the carboxylate end-group participates simultaneously as dMMLABn propagating site and hydroxyl PLA end-group G

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Figure 9. DOSY-NMR spectrum (recorded in DMSO-d6) of a PLA-b-PdMMLABn (entry 2, Table 1) obtained in a “one-pot, two-step” process.

Table 2. Molecular Characterizations of PLA-b-PdMMLABn Copolymers Obtained in a “One-Pot, One-Step” Process from a HDA/DBU Initiator in Dry THF DPtha

DPexpb

Mn,SECc (g/mol)/ĐM

entry

PLA

PdMMLABn

polym time (h)

PLA

PdMMLABn

PLA-b-PdMMLABn

1 2 3

25 50 100

25 50 100

23.5 72 168

18 35 106

17 31 107

6500/1.44 12450/1.46 26000/1.76

a Theoretical targeted DP in PLA and PdMMLABn. bAs determined by 1H NMR analyses. cUncorrected molar mass and dispersity determined by SEC in THF using PS standards.

(ConvLA ∼ 35% and ConvdMMLABn ∼ 40% as determined by 1H NMR on the crude), the copolymerization was quenched by precipitating the polymer in heptane leading to a PdMMLABnb-(PLA)2 of MnSEC = 6300 g/mol and a ĐM of 1.24. The functional group of bis-MPA provides a sensitive marker for the spectroscopic analysis since methylene groups are very sensitive to the substitution of the neighboring hydroxy groups.28,29 1H NMR spectroscopy showed that the efficiency of initiation of both LA and dMMLABn was quantitative affording a well-defined triblock structure polymer (MnPLA = 2500 g/mol and MnPdMMLABn = 2340 g/mol; Figure S5). Similarly, a 4-arm copolymer composed of three blocks of PdMMLABn and one sequence of PLA has been obtained from citric acid (Figure 12). Citric acid was first dispersed in THF, and 3 equiv of DBU base ([citric acid]0/[DBU]0 = 1/3) was necessary to allow the salt to fully solubilize in THF after a few minutes. 75 equiv of LA and 75 equiv of dMMLABn (presolubilized in THF) were then quickly added to the citric acid/DBU solution ([LA]0 = 0.94 M; [dMMLABn]0 = 0.94 M). After 23 h (ConvLA ∼ 25%; ConvdMMLABn ∼ 50% as determined by 1H NMR on the crude), the copolymerization was quenched by precipitating the polymer in heptane, leading to a (PdMMLABn)3-b-PLA of MnSEC = 7200 g/mol and a ĐM of 1.65. The broadness of the SEC chromatogram might be explained by a slow initiation of the LA ROP from the

activator. For high targeted DP, the diminishing overall activity favors the propensity of the benzyl ester functions to be attacked by the propagating PLA hydroxy groups, increasing considerably the copolymer dispersity (entry 3, Table 2). When lower DPs are targeted (entries 1 and 2, Table 2), the polymerization is reasonably controlled with ĐM < 1.46. 1 H NMR spectroscopy clearly indicates the presence of both PLA and PdMMLABn block units characterized by a quite similar mole fraction whatever the targeted DP. As for the “one-pot, two-step” process, 13C NMR and NMR DOSY analyses evidenced the blocky structure of PLA-b-PdMMLABn copolymers by presenting the carbonyl signature of both PLA and PdMMLABn homosequences (Figure 10a) and one single diffusion coefficient (Figure 10b). Finally, multiarm polymer topologies such as Y-shaped and 4-arm structures were also prepared in a “one-pot, one-step” process. The Y-shaped-based copolymers composed by two PLA blocks and one PdMMLABn sequence have been obtained from 2,2′-(bishydroxymethyl)propionic acid (bisMPA) (Figure 11). Bis-MPA was first suspended in a solution of DBU in THF ([bis-MPA]0/[DBU]0 = 1). After ≈10 min at room temperature, the solution became homogeneous, indicating the effective formation of the bis-MPA/DBU salt. 50 equiv of LA and 25 equiv of dMMLABn (presolubilized in THF) were then quickly added to the bis-MPA/DBU solution ([LA]0 = 1.89 M; [dMMLABn]0 = 0.94 M). After 22 h H

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Figure 10. (a) 13C NMR analysis (zoomed between 166 and 175 ppm) and (b) DOSY-NMR spectrum (recorded in DMSO-d6) of a PLA-bPdMMLABn (entry 2, Table 2) obtained in a “one-pot, one-step” process.

multiblock copolymers, via “one-pot, two-step” and “one-pot, one-step” processes. We demonstrate that the DBU-based carboxylate moieties selectively polymerize the 4-membered lactone (dMMLABn) via O−alkyl bond cleavage, involving an anionic ROP mechanism, as well as activate the hydroxyl groups, allowing the hydroxyl groups to selectively polymerize the 6-membered lactone (LA), via a O−acyl bond cleavage, involving a H-bonding ROP mechanism. Simultaneous and independent copolymerization is thus achieved, making the “one-pot, one-step” approach possible, despite it being slower

dandling alcohol of the citric acid due to either its nature (tertiary alcohol) or its sterically encumbered environment.

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CONCLUSION This work addresses a challenging topic in polymer chemistry, namely, multiblock copolymer synthesis via a “one-pot, onestep” approach. In this study, we show that heterofunctional initiators bearing both hydroxyl group(s) and DBU-based carboxylate moietie(s) are efficient initiators for the copolymerization of lactones of different ring sizes, yielding I

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Julien De Winter: 0000-0003-3429-5911 Olivier Coulembier: 0000-0001-5753-7851 Notes

The authors declare no competing financial interest. The bioprofiling platform was supported by the European Regional Development Fund and the Walloon Region, Belgium.

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ACKNOWLEDGMENTS This work was supported by the Science Policy Office of the Belgian Federal Government (PAI 7/5) and by a grant from the Belgian FRFC-FNRS (no. 2.4508.12). The UMONS MS laboratory acknowledges the Fonds National de la Recherche Scientifique (FRS-FNRS) for its contribution to the acquisition of the Waters QToF Premier mass spectrometer and for continuing support. O.C. is Research Associates of the F.R.S.FNRS.

Figure 11. Generation of Y-shaped triblock copolymer from bisMPA/DBU salt.

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Figure 12. Preparation of 4-arm block copolymer from citric acid/ DBU salt.

than the “one-pot, two-step” process. Furthermore, we investigate side reactions that occur, such as various transesterifications, via NMR and MALDI-ToF analyses. Finally, we go on to synthesize various multiblock architectures, such as Yshaped and 4-arm block copolymers of (PLA) x -b(PdMMLABn)y. This work thus expands the scope of “onepot, one-step” multiblock copolymer synthesis by providing a straightforward and direct access to multiblock copolymers and joins the various other methodologies in the preparation of block copolymers from lactones.30−37

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.9b01282. Figures S1−S6, experimental protocols, SEC, 1H and DOSY NMR characterizations (PDF) J

DOI: 10.1021/acs.macromol.9b01282 Macromolecules XXXX, XXX, XXX−XXX

Article

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DOI: 10.1021/acs.macromol.9b01282 Macromolecules XXXX, XXX, XXX−XXX