Ring-opening Polymerization Of Trimethylene Carbonate Research Articles

Determination of the individual block lengths of the block copolymers of Poly(trimethylene carbonate) by liquid chromatography at critical conditions

Amphiphilic block copolymers based on poly(trimethylene carbonate) (PTMC) have gained significant attention for biomedical applications owing to their unique degradation characteristics. Ring-opening polymerization (ROP) is the most widely employed method for polymerization of cyclic carbonates, especially for trimethylene carbonate (TMC). Herein, di- and tri-block copolymers of PTMC are synthesized by ROP of TMC using poly(ethylene glycol) monomethyl ether (MeO-PEG) or poly(ethylene glycol) (PEG) as a macro-initiator, respectively. The synthesized products are characterized by size-exclusion chromatography (SEC) and nuclear magnetic resonance spectroscopy (1H NMR) for their molar mass and chemical composition, respectively. However, these techniques are inconclusive about several pertinent aspects of the block copolymers, such as individual block length and unwanted homopolymer content. To address these limitations, liquid chromatography at critical conditions of both PEG and PTMC are employed. Chromatographic critical conditions for PTMC are reported for the first time in the current study. The analysis protocol successfully reveals the individual block lengths of both blocks of the block copolymers, along with the quantification of the unwanted homopolymers in the samples. The individual block lengths and the presence of homopolymers significantly affect the self-assembly capability and drug-loading capacity of amphiphilic block copolymers. Thus, the study divulges important information crucial for the development of structure-property correlations, which is essential for optimizing the performance of these block copolymers in biomedical applications.

Ring-Opening Polymerization of Trimethylene Carbonate with Phosphazene Organocatalyst.

Aliphatic polycarbonate (APC) compounds are an important class of biodegradable materials with excellent biocompatibility, good biodegradability, and low toxicity, and the study of these compounds and their modification products aims to obtain biodegradable materials with better performance. In this context, the ring-opening polymerization (ROP) of trimethylene carbonate (TMC) from a low nucleophilic organic superbase of phosphazene (t-BuP4) as a catalyst and benzyl alcohol (BnOH) as an initiator at room temperature was carefully studied to prepare poly(trimethylene carbonate) (PTMC) which is one of the most studied APC. 1H NMR and SEC measurements clearly demonstrate the presence of a benzyloxy group at the α-terminus of the obtained PTMC homopolymers while investigation of the polymerization kinetics confirms the controlled/living nature of t-BuP4-catalyzed ROP of TMC. On the basis of this, the block copolymerization of TMC and δ-valerolactone (VL)/ε-caprolactone (CL) was successfully carried out to give PTMC-b-PCL and PTMC-b-PVL copolymers. Furthermore, PTMC with terminal functionality was also prepared with the organocatalytic ROP of TMC through functional initiators. We believe that the present ROP system is a robust, highly efficient, and practical strategy for producing excellent biocompatible and biodegradable PTMC-based materials.

DFT Investigations on the Ring-Opening Polymerization of Trimethylene Carbonate Catalysed by Heterocyclic Nitrogen Bases

Organocatalysts for polymerization have known a huge interest over the last two decades. Among them, heterocyclic nitrogen bases are widely used to catalyse the ring-opening polymerization (ROP) of heterocycles such as cyclic carbonates. We have investigated the ring-opening polymerization of trimethylene carbonate (TMC) catalysed by DMAP (4-dimethylaminopyridine) and TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene) as case studies in the presence of methanol as co-initiator by Density Functional Theory (DFT). A dual mechanism based on H-bond activation of the carbonyl moieties of the monomer and a basic activation of the alcohol co-initiator has been shown to occur more preferentially than a direct nucleophilic attack of the carbonate monomer by the heterocyclic nitrogen catalyst. The rate-determining step of the mechanism is the ring opening of the TMC molecule, which is slightly higher than the nucleophilic attack of the TMC carbonyl by the activated alcohol. The calculations also indicate TBD as a more efficient catalyst than DMAP. The higher energy barrier found for DMAP vs. TBD, 23.7 vs. 11.3 kcal·mol−1, is corroborated experimentally showing a higher reactivity for the latter.

Insight into the Alcohol-Free Ring-Opening Polymerization of TMC Catalyzed by TBD.

We report herein a study on the alcohol-free, ring-opening polymerization of trimethylene carbonate (TMC) in THF, catalyzed by 1,5,7-triazabicyclo [4.4.0] ec-5-ene (TBD) with ratios nTBD/nTMC ranging between 1/20 and 1/400. In all cases, the reaction proceeds very rapidly, even faster than in the presence of alcohol initiators, and provides PTMC with molecular weights up to Mn = 34,000 g mol−1. Characterization of the obtained PTMC samples by MALDI-TOF mass spectrometry, triple detection size exclusion chromatography and 1H NMR spectroscopy reveals the presence of both linear and cyclic polymer chains.

Use of samarium (III) acetate as initiator in ring-opening polymerization of trimethylene carbonate

In this work was evaluated the activity of samarium acetate (III) (Sm(OAc)3) as a possible initiator in the polymerization by ring opening of trimethylene carbonate (TMC). All polymerizations were carried out under solvent-free melt conditions in ampoules-like flasks, equipped with a magnetic stirrer. The effects of different parameters of reaction, such as molar ratio monomer to initiator, temperature and reaction time, on typical variables of polymers, e.g., conversion of TMC to poly(trimethylene carbonate) (PTMC), dispersity and molar mass, were analyzed. The molar ratio of monomer to initiator was varied between 0 and 1000 mol/mol and the temperature among 70 and 150 °C. Nuclear Magnetic Resonance (1H-NMR and HMBC) and Size Exclusion Chromatography (SEC) were used to characterize the polymers. The results indicate that the Sm(OAc)3 induces the polymerization of TMC to high conversion with number-average molecular weights of 3.11 × 103 to 38.40 × 103 Da. Based on the 1H-NMR end-group analysis of low-molecular-weight PTMC, it was proposed a coordination–insertion mechanism for the polymerization, with a breakdown of the acyl-oxygen bond of the TMC. In according to the kinetic study carried out, the polymerization rate is first-order with respect to monomer concentration with apparent rate constants of kap = 7.02 × 10−4 mol × L−1 × h−1.

Ring-opening polymerization of trimethylene carbonate to poly(trimethylene carbonate) diol over a heterogeneous high-temperature calcined CeO2 catalyst.

CeO2 calcined at 1273 K showed higher activity per surface area than other metal oxides in the ring-opening polymerization of trimethylene carbonate under neat conditions without any additives, providing metal-free and additive-free poly(trimethylene carbonate) diols with no ether bonds with high selectivity. It was demonstrated that CeO2 was a robust and reusable heterogeneous catalyst.

Main-chain biodegradable liquid crystal based on diosgenyl end-capped poly(trimethylene carbonate)

ABSTRACTMain-chain biodegradable liquid crystal based on c diosgenyl end-capped poly(trimethylene carbonate) [Dios-(TMC)n] was investigated. The novel liquid crystal was synthesized through ring-opening polymerization of trimethylene carbonate initiated by diosgenin, without adding any catalyst. The chemical structure of resulting polymers was confirmed by 1H NMR. The liquid crystalline properties were validated by X-ray diffraction, differential scanning calorimetry, and polarising optical microscopy. The results showed that the synthesized Dios-(TMC)n exhibited liquid crystallinity in particular temperature ranges because of the incorporation of the diosgenin moieties.

Polymerization of trimethylene carbonate and lactones in the presence of magnesium monoionolate: A comparative theoretical and experimental study

Using quantum-chemical calculations (DFT, program Priroda), the formation of a catalyst species on the basis of magnesium complexes with 2,6-di-tert-butyl-4-methylphenol is discussed. A comparative theoretical and experimental study of the ring-opening polymerization of trimethylene carbonate, 1,4-dioxanone, δ-valerolactone, and e-caprolactone in the presence of the monoionolate magnesium complex is performed. It is shown that the calculated values of activation barriers correlate with the observed order of activity of cyclic esters. The maximum rate of polymerization is exhibited by trimethylene carbonate.

The use of stable carbene‐CO2 adducts for the polymerization of trimethylene carbonate

ABSTRACTThe synthesis of poly(trimethylene carbonate) via carbene catalyzed ring‐opening polymerization (ROP) was investigated. The N‐heterocyclic carbenes were protected as CO2‐adducts to improve their handling (e.g., carbene generation without base). The influence of catalyst structure, different solvents and microwave radiation on conversion, molecular weight and end groups was investigated to gain an insight into the reaction mechanism. Different NHC structures were investigated for their catalytic activity toward the ROP of trimethylene carbonate. The analytic studies were performed by using NMR spectroscopy, SEC and ESI‐IMS mass spectrometry. It was found that the reaction can be performed in acetonitrile, toluene, THF and CH2Cl2. Synthesis in CH2Cl2 allows the best control over the resulting polymer with regards to polydispersity and molecular weight. Microwave radiation accelerates the reaction at 80 °C. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 820–829

Structure-directing star-shaped block copolymers: Supramolecular vesicles for the delivery of anticancer drugs

Amphiphilic polycarbonate/PEG copolymer with a star-like architecture was designed to facilitate a unique supramolecular transformation of micelles to vesicles in aqueous solution for the efficient delivery of anticancer drugs. The star-shaped amphipilic block copolymer was synthesized by initiating the ring-opening polymerization of trimethylene carbonate (TMC) from methyl cholate through a combination of metal-free organo-catalytic living ring-opening polymerization and post-polymerization chain-end derivatization strategies. Subsequently, the self-assembly of the star-like polymer in aqueous solution into nanosized vesicles for anti-cancer drug delivery was studied. DOX was physically encapsulated into vesicles by dialysis and drug loading level was significant (22.5% in weight) for DOX. Importantly, DOX-loaded nanoparticles self-assembled from the star-like copolymer exhibited greater kinetic stability and higher DOX loading capacity than micelles prepared from cholesterol-initiated diblock analogue. The advantageous disparity is believed to be due to the transformation of micelles (diblock copolymer) to vesicles (star-like block copolymer) that possess greater core space for drug loading as well as the ability of such supramolecular structures to encapsulate DOX. DOX-loaded vesicles effectively inhibited the proliferation of 4T1, MDA-MB-231 and BT-474 cells, with IC50 values of 10, 1.5 and 1.0mg/L, respectively. DOX-loaded vesicles injected into 4T1 tumor-bearing mice exhibited enhanced accumulation in tumor tissue due to the enhanced permeation and retention (EPR) effect. Importantly, DOX-loaded vesicles demonstrated greater tumor growth inhibition than free DOX without causing significant body weight loss or cardiotoxicity. The unique ability of the star-like copolymer emanating from the methyl cholate core provided the requisite modification in the block copolymer interfacial curvature to generate vesicles of high loading capacity for DOX with significant kinetic stability that have potential for use as an anti-cancer drug delivery carrier for cancer therapy.

Organocatalytic Ring-Opening Polymerization of Trimethylene Carbonate To Yield a Biodegradable Polycarbonate

In this laboratory experiment, students work in pairs to synthesize a simple aliphatic polycarbonate via ring-opening polymerization of trimethylene carbonate using 1,8-diazabicyclo[5.4.0]undec-7-ene and thiourea as organocatalysts. Following polymer isolation, students cool the material in a dry ice/acetone bath to observe its glass-transition behavior. This experiment is convenient to perform under teaching laboratory conditions and reinforces key concepts learned in second-year undergraduate organic chemistry, for example, nucleophilic acyl substitution, transesterification reactions, and Lewis acidity–basicity. Additionally, the experiment introduces students to polymer chemistry, heterocycles, materials science, and green chemistry. It also covers interesting concepts that are less frequently encountered at the undergraduate level such as biomimetic chemistry, bifunctional catalysis, and polymer–glass transitions.

A base–conjugate-acid pair for living/controlled ring-opening polymerization of trimethylene carbonate through hydrogen-bonding bifunctional synergistic catalysis

The ring-opening polymerization (ROP) of trimethylene carbonate (TMC) using a base–acid binary organocatalyst system of 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) and Bronsted acid trifluoromethanesulfonic acid (TFA) with benzyl alcohol (BnOH) as the initiator has been investigated. The MTBD and its conjugate-acid pair H-bonding bifunctional synergistic activation mechanism was demonstrated by NMR measurements, and the living/controlled nature of MTBD/TFA catalyzed ROP of TMC was confirmed by the kinetic and chain extension experiments. The controlled ROP of TMC with the optimal molar ratio of MTBD/TFA = 2/1 proceeded to afford well-defined PTMC with narrow molecular weight distributions (Mw/Mn ∼ 1.1). The molecular weights determined by 1H NMR are in precise agreement with the theoretical values. 1H NMR, SEC, and MALDI-ToF MS measurements confirmed the structure of the obtained homopolymer PTMC. In addition, a diblock copolymer consisting of poly(trimethylene carbonate) and poly(L-lactide) (PTMC-b-PLLA) was synthesized successfully by the MTBD/TFA binary catalyst system.

Bifunctional imidodiphosphoric acid-catalyzed controlled/living ring-opening polymerization of trimethylene carbonate resulting block, α,ω-dihydroxy telechelic, and star-shaped polycarbonates

Bifunctional imidodiphosphoric acid-catalyzed controlled/living ring-opening polymerization of trimethylene carbonate resulting block, α,ω-dihydroxy telechelic, and star-shaped polycarbonates

Phosphoramidic acid catalyzed controlled/living ring-opening polymerization of trimethylene carbonate

The ring-opening polymerization (ROP) of trimethylene carbonate (TMC) catalyzed by phosphoramidic acid (PAA) and initiated with benzyl alcohol (BnOH) has been investigated. The polymerization conditions were optimized to afford well-defined polytrimethylene carbonates (PTMCs). The molecular weight of the obtained PTMC with the [TMC]0/[BnOH]0/[PAA]0 ratio of 40:1:1 was analyzed by 1H NMR, Mn = 4180 g mol−1, showed good agreement with that estimated from the initial ratio, Mn = 3830 g mol−1. The kinetics and chain extension experiments have been carried out to further justify the controlled/living nature of this polymerization. The 1H NMR, SEC, and MALDI-TOF MS measurements were applied to analyze the obtained PTMCs.

Discrete Cationic Zinc and Magnesium Complexes for Dual Organic/Organometallic‐Catalyzed Ring‐Opening Polymerization of Trimethylene Carbonate

We describe herein an original approach for the efficient immortal ring-opening polymerization (iROP) of trimethylene carbonate (TMC) under mild conditions using dual-catalyst systems combining a discrete cationic metal complex with a tertiary amine. A series of new zinc and magnesium cationic complexes of the type [{NNO}M](+) [anion](-) ({NNO}(-) = 2,4-di-tert-butyl-6-{[(2'-dimethylaminoethyl)methylamino]methyl}phenolate; M = Zn, [anion](-) = [B(C(6)F(5))(4)](-) (2), [H(2)N-{B(C(6)F(5))(3)}(2)](-) (3), and [EtB(C(6)F(5))(3)](-) (4); M = Mg, [anion](-) = [H(2)N{B(C(6)F(5))(3)}(2)](-) (7)) have been prepared from the corresponding neutral compounds [{NNO}ZnEt] (1) and [{NNO}-Mg(nBu)] (6). Compounds 2-4 and 7 exist as free ion pairs, as revealed by (1)H, (13)C, (19)F, and (11) B NMR spectroscopy in THF solution, and an X-ray crystallographic analysis of the bis(THF) adduct of compound 7, 7⋅(THF)(2). The neutral complexes 1 and 6, in combination with one equivalent or an excess of benzyl alcohol (BnOH), initiate the rapid iROP of TMC, in bulk or in toluene solution, at 45-60 °C (turnover frequency, TOF, up to 25-30,000 mol(TMC)⋅mol(Zn)⋅h(-1) for 1 and 220-240,000 mol(TMC)⋅mol(Mg)⋅h(-1) for 6), to afford H-PTMC-OBn with controlled macromolecular features. ROP reactions mediated by the cationic systems 2/BnOH and 7/BnOH proceeded much more slowly (TOF up to 500 and 3000 mol(TMC)⋅mol(Zn or Mg)⋅h(-1) at 110 °C) than those based on the parent neutral compounds 1/BnOH and 6/BnOH, respectively. Use of original dual organic/organometallic catalyst systems, obtained by adding 0.2-5 equiv of a tertiary amine such as NEt(3) to zinc cationic complexes [{NNO}Zn](+) [anion](-) (2-4), promoted high activities (TOF up to 18,300 mol(TMC)⋅mol(Zn)⋅h(-1) at 45 °C) giving H-PTMC-OBn with good control over the M(n) and M(w)/M(n) values. Variation of the nature of the anion in 2-4 did not significantly affect the performance of these catalyst systems. On the other hand, the dual magnesium-based catalyst system 7/NEt(3) proved to be poorly effective.

Controllable ring‐opening polymerization of trimethylene carbonate catalyzed by aliphatic tertiary amines in the presence of benzyl alcohol or F127

AbstractWith the increased awareness of avoiding residue metals, the field of organocatalysts is attracting more attention. Aliphatic tertiary amines, such as triethylamine (TEA), N, N, N, N‐tetramethylethylenediamine (TMEDA) and 1,1,4,7,7‐pentamethyldiethylenetriamine (PMDTA), have low boiling points which allow their easy elimination after a chemical reaction. Here, we used these aliphatic tertiary amines to catalyze ring‐opening polymerizations (ROPs) of trimethylene carbonate (TMC). In the presence of benzyl alcohol, the catalytic activities of the tertiary amines were in the order of TEA < TMEDA < PMDTA. Correlation between the molecular weight of polycarbonates and monomer conversions was linear, suggesting the polymerization was controlled. The polymerization pathway was presumed to follow an alcohol‐activated mechanism according to the end‐group fidelity determined using 1H NMR spectroscopy. The ROP of TMC was also successfully initiated by PEO99‐PPO65‐PEO99 (F127) under the catalysis of the tertiary amines, producing well‐defined PTMCn‐F127‐PTMCn copolymers with narrow dispersity (ca 1.2) and with thermosensitive properties in aqueous solution. Furthermore, copolymerizations of TMC with acryloyl‐containing cyclic carbonate were catalyzed by the tertiary amines in the presence of F127. No crosslinking reactions were detected. Our results demonstrate that the aliphatic tertiary amines have the potential to catalyze TMC homo‐ or copolymerization featuring controllable structure and composition under mild conditions. Copyright © 2012 Society of Chemical Industry

Bis(phosphinimino)methanide borohydride complexes of the rare-earth elements as initiators for the ring-opening polymerization of trimethylene carbonate: combined experimental and computational investigations

Bis(phosphinimino)methanide bisborohydride complexes of lanthanum, yttrium and lutetium, [{CH(PPh2NSiMe3)2}La(BH4)2(THF)] (1) and [{CH(PPh2NSiMe3)2}Ln(BH4)2] (Ln = Y (2), Lu (3)), have been investigated in the ring-opening polymerization (ROP) of trimethylene carbonate (TMC). All three initiators afforded linear poly(trimethylene carbonate)s (PTMCs) in toluene at 23 °C. 1H NMR analyses of the polycarbonates revealed the formation of α-hydroxy,ω-formate telechelic PTMCs, as previously observed in the ROP of TMC initiated by [Sm(BH4)3(THF)3]. This suggested the non-reduction of the carbonyl of the carbonate group in the active species by the BH3 moiety, as hinted by this same prior experimental work. Formation of α,ω-dihydroxy PTMCs, resulting from the reduction of the carbonyl, is also likely and cannot be ruled out from experimental data. DFT investigations, focused on the initiation step, supported two energetically (thermodynamically and kinetically) favorable and similar reaction pathways leading to two distinct end-functionalized PTMCs. Depending on whether reduction of the carbonyl occurred or not, α,ω-dihydroxy or α-hydroxy,ω-formate telechelic PTMCs were predicted, respectively. Although these two calculated feasible approaches are very close in energy, the formation of the latter heterofunctionalized α-hydroxy,ω-formate telechelic PTMCs is slightly preferred computationally. This first in silico study on the mechanism of the ROP of a cyclic carbonate revealed several features without any precedent in the ROP of a cyclic ester (ε-caprolactone or lactide). An easily accessible (no activation barrier) intermediate in which BH3 is trapped by the intracyclic oxygen of a non-opened TMC ring has been located for the first time. The low activation barrier for the opening of the TMC ring that proceeds without B–H activation is predicted to be competitive, affording the thermodynamically less stable BH3 adduct. Finally, trapping of BH3 by the nitrogen of the {CH(PPh2NSiMe3)2}− ligand, in agreement with previous findings, highlights again the valuable role of this bisphosphiniminomethanide ligand.

RING-OPENING POLYMERIZATION OF LACTONE IN THE PRESENCE OF BENZYL ALCOHOL CATALYZED BY ALIPHATIC TERTIARY AMINE

In order to study the structure and the catalytic activity of aliphatic tertiary amines,the ring-opening polymerizations of trimethylene carbonate(TMC) and L-lactide(L-LA) were catalyzed by aliphatic tertiary amines,including triethylamine(TEA),N,N,N′,N′-tetramethylethylenediamine(TMEDA),1,1,4,7,7-pentamethyldiethylenetriamine(PMDTA) and 4-(dimethylamino)pyridine(DMAP),using benzyl alcohol as initiator in THF at 55℃.Studies revealed the catalytic activity of these tertiary amines was increased according to the order:TEA TMEDA≈PMDTA DMAP.The relationships of polymer molecular weight with the conversion of monomer were linear,which were consistent with a living polymerization character.Finally,the plausible polymerization pathway was through an alcohol-activating mechanism.Aliphatic tertiary amines which were abundant in source and cheap in price were suitable for catalyzing the ring-opening bulk polymerization of lactone in low temperature because of their low boiling point,being liquid under ordinary conditions and being easy to get rid of.

Enzymatic Ring-Opening Polymerization of Trimethylene Carbonate with Macrodiol: Synthesis of Block Poly(ester-co-carbonate) for Biomaterial Preparation

Novozym 435-catalyzed ring-opening polymerization (ROP) of trimethylene carbonate (TMC) with telechelic hydroxylated poly[(R)-3-hydroxybutyrate] [PHB-diol; Mn = 3000 g/mol (GPC)] as initiator gave ...

Self-Assembly and Photo-Cross-Linking of Eight-Armed PEG-PTMC Star Block Copolymers

Eight-armed poly(ethylene glycol)-poly(trimethylene carbonate) star block copolymers (PEG-(PTMC)(8)) linked by a carbamate group between the PEG core and the PTMC blocks were synthesized by the metal-free, HCl-catalyzed ring-opening polymerization of trimethylene carbonate using an amine-terminated eight-armed star PEG in dichloromethane. Although dye solubilization experiments, nuclear magnetic resonance spectroscopy, and dynamic light scattering clearly indicated the presence of aggregates in aqueous dispersions of the copolymers, no physical gelation was observed up to high concentrations. PEG-(PTMC(9))(8) was end-group-functionalized using acryloyl chloride and photopolymerized in the presence of Irgacure 2959. When dilute aqueous dispersions of PEG-(PTMC(9))(8)-Acr were UV irradiated, chemically cross-linked PEG-PTMC nanoparticles were obtained, whereas irradiation of more concentrated PEG-(PTMC(9))(8)-Acr dispersions resulted in the formation of photo-cross-linked hydrogels. Their good mechanical properties and high stability against hydrolytic degradation make photo-cross-linked PEG-PTMC hydrogels interesting for biomedical applications such as matrices for tissue engineering and controlled drug delivery systems.