Ring-opening Copolymerization Of E-caprolactone Research Articles

Decisive Influence of Hydrophobic Side Chains of Polyesters on Thermoinduced Gelation of Triblock Copolymer Aqueous Solutions

A series of amphiphilic triblock copolymers composed of poly(ethylene glycol) (PEG) and poly(ε-caprolactone-co-5-alkyl δ-lactone)s bearing distinct alkyl side groups were synthesized via ring-opening copolymerization of ε-caprolactone and a small amount of various 5-alkyl δ-lactones using PEG as the macroinitiator and metal-free diphenyl phosphate as the catalyst. The analysis of 1H NMR, GPC, DSC, and XRD confirmed that the synthetic copolymers had similar molecular weights and bulk properties; nevertheless, they exhibited quite different aqueous behaviors in response to temperature variations. While the polyesters without side chains simply presented a free-flowing sol over the entire examined temperature range, those bearing methyl or n-propyl side groups underwent a sol–gel transition upon heating and harvested a reversed thermosensitive hydrogel (T-Gel). Meanwhile, the sol–gel transition temperature of the polymer/water system could be easily tailored by adjusting the content of the n-propyl side group. In contrast, the polyesters containing longer n-amyl side groups formed a normal hydrogel (N-Gel) exhibiting a gel–sol (suspension) transition upon heating. Their different aqueous behaviors stemmed from the difference in the hydrophilic–hydrophobic equilibrium of the amphiphilic copolymers. The sol–gel transitions of the thermosensitive hydrogels were attributed to the aggregation of micelles and the dehydration of PEG. The copolymers bearing n-propyl side groups had good cytocompatibility and were fairly stable in a phosphate buffered saline for 80 days, whereas the formed thermosensitive hydrogel (20 wt %) was rapidly degraded via surface erosion within half a month after subcutaneous injection into mice. Consequently, this study indicates that subtle variation in the length of hydrophobic side chains plays a decisive role in the physical gelation of PEG/polyester copolymers. In addition, the thermosensitive hydrogels have the potential for drug and cell delivery based on their good biocompatibility and biodegradability.

Ring-opening copolymerization of ε-caprolactone and δ-valerolactone by a titanium-based metal–organic framework

Copolymerization of ε-caprolactone and δ-valerolactone without any co-catalyst in a solvent-free medium under eco-friendly conditions using earth abundant Ti-metal based MOF, MIL-125.

Ring opening copolymerization of ε-caprolactone and diselenic macrolide carbonate for well-defined poly(ester-co-carbonate): kinetic evaluation and ROS/GSH responsiveness

Theoretical calculations agreed well with the experimental results. The competitive mechanism was proposed to clarify the composition and structure of the copolymers.

Ring-opening Copolymerization of ε-Caprolactone and δ-Valerolactone Catalyzed by a 2,6-Bis(amino)phenol Zinc Complex

In combination with methyllithium, a 2,6-bis(amino)phenol zinc complex 1 was used in the ring-opening polymerization of δ-valerolactone in the absence or presence of benzyl alcohol and showed high efficiency, mainly producing cyclic and linear polyvalerolactones, respectively. On the basis of homopolymerization, the ring-opening copolymerization of e-caprolactone and δ-valerolactone was investigated. The P(CL-co-VL) random copolymers, PCL-b-PVL and PVL-b-PCL diblock copolymers, were prepared by varying the feeding strategy (premixing or sequential feeding). The copolymer composition was adjusted by varying the feeding ratio of two monomers. The structure and thermal properties of obtained polymers were characterized by GPC, 1H-NMR, 13C-NMR, MALDI-TOF mass spectroscopy, and DSC, respectively.

Synthesis of mono- and tetra-nuclear β-pyridylenolate zinc complexes and their catalysis toward the ring-opening copolymerization of ε-caprolactone and lactide

The synthesis of mono-nuclear β-pyridylenolate zinc complexes L12Zn (1) (L1 = (2-C5H4N)–CH=C(CH3)–O–) and L22Zn (2) (L2 = (2-C5H4N)–CH=C (2-CH3C6H5)–O–) were performed by the protonolysis of the corresponding β-pyridylenol bidentate ligands 1-(2-pyridinyl)-2-propanone (L1H) and 1-(2-methylphenyl)-2-(2-pyridinyl)-ethanone (L2H) with diethylzinc in a 2:1 M ratio, respectively. The unanticipated tetra-nuclear β-pyridylenolate zinc complex [L12Zn-μ-O (Et)ZnEt]2 (3) was isolated by the reaction of L1H with an equiv. of ZnEt2 and oxygenation with air. All the complexes were well characterized by single crystal X-ray crystallography. Complexes 1–3 were tested as an initiator for the ring opening polymerization (ROP) of ε-caprolactone and l-lactide. In the same conditions, 1 and 2 are shown inefficient for ROP due to the lack of suitable initiating group for polymerization, however, tetra-nuclear complex 3 is a highly active single-component initiator in the ROP of ε-caprolactone and l-lactide. Complex 3 was also researched for its catalytic activity in block (PCL-b-PLLA) and gradient (LA-grad-CL) copolymerization of ε-caprolactone and l-lactide.

Synthesis and post-functionalization of a degradable aliphatic polyester containing allyl pendent groups

Aliphatic polyesters have been widely used in environmental and biomedical engineering, but a lack of functional groups limits their applications. Here, we reported a facile approach to synthesize vinyl functional polyester via the ring opening copolymerization of ε-caprolactone (CL) and allyl glycidyl ether (AGE). NMR analysis confirmed the copolymeric structures and suggested that the copolymerization depended on the epoxide ring of AGE rather than vinyl group. The amount of AGE incorporated into the copolymers (FAGE) increased with the amount of epoxide monomer feed with a maximum incorporation of 16.7%. Increasing temperature helped AGE to incorporate into the copolymer, however, accompanying with lots amount of AGE homopolymers. The resulting copolymer was successfully post-functionalized by thiol-end click, epoxidation, and bromination reactions depending on the reactivity of pendent ally groups. This facile and efficient approach can be used to functionalize biodegradable polymers and synthesize some new polymers under mild conditions.

Enzymatic synthesis of poly(ε-caprolactone-co-ε-thiocaprolactone)

This study presents the successful enzymatic ring opening copolymerization of ε-caprolactone (ε-CL) and ε-thiocaprolactone (ε-TCL) catalyzed by Novozyme 435, immobilized lipase B from Candida antarctica. Various monomers feed ratio (from 0 to 100% in TCL content) were tested using two polymerization strategies. The first one is a direct one-step strategy, starting with both monomers mixed in the feed, while the two-steps strategy consists in a first step of ε-CL homopolymerization followed by a second step with ε-TCL addition in the medium and its polymerization from the previously formed PCL chains. The obtained copolymers have been fully characterized by NMR, DSC, SEC and MALDI-ToF MS spectroscopy. Main results of the one-step strategy showed a decrease in the final copolymer molar mass with the increase in ε-TCL content as well as minimum values of crystallinity and melting temperature for the 50:50 feed composition. An in-depth analysis of the MALDI-TOF mass spectra of the copolymers showed interesting patterns that suggest a micro-structuration of polymers from the one step strategy resulting from an uncommon multistep chain growth mechanism of trimers addition. The two-steps strategy produced copolymers showing a more blocky structure, as confirmed by their two distinct melting temperatures.

Ring-opening copolymerization of ε-caprolactone with 2,2-dimethyltrimethylene carbonate using N-heterocyclic carbene organocatalysts

Random copolymer of e-caprolactone with 2,2-dimethyltrimethylene carbonate has been synthesized by using N-heterocyclic carbene organocatalysts for the first time. A series of N-heterocyclic carbenes namely, imidazol-2-ylidenes substituted at 1,3 position by benzyl, isopropyl, ethyl and methyl were demonstrated to bring about the metal-free ring-opening copolymerization of e-caprolactone and 2,2-dimethyltrimethylene initiated by benzyl alcohol in THF. The influences of reaction conditions, such as monomer, catalyst, and initiator concentration, as well as reaction temperature and time on the copolymerization have been examined in detail. The results show that 1-isopropyl-3-benzyl imidazol-2-ylidene carbene was potent organic catalyst for the ring-opening copolymerization of cyclic esters to generate well-defined linear polyesters of controlled molecular weight and narrow polydispersity. 1H NMR spectral data of copolymer obtained showed that the polymerization mechanism is in agreement with the activated monomer mechanism.

Synthesis and enzymatic degradation of poly(ε-caprolactone-co-ethylene carbonate-co-ethylene oxide) copolymer

Poly(e-caprolactone-co-ethylene carbonate-co-ethylene oxide) (CL-co-EC-co-EO) copolymer was synthesized via ring-opening copolymerization of e-caprolactone (CL) and 1,3-dioxolan-2-one with a metal-free phosphazene catalyst (t-BuP4). The monomer conversion and molecular weight in CL-co-EC-co-EO copolymer were characterized by nuclear magnetic resonance and gel permeation chromatography, respectively. Moreover crystallization behavior of CL-co-EC-co-EO copolymer was investigated by differential scanning calorimeter and wide-angle X-ray diffraction. The enzymatic degradation of the copolymer has been investigated by quartz crystal microbalance with dissipation. Our studies demonstrate that as PCL content in the copolymer decreases, the degree of crystallinity and crystal size decrease, while the enzymatic degradation rate increases. The copolymer exhibits layer-by-layer degradation.

Synthesis, characterization, and micellization of PCL‐g‐PEG copolymers by combination of ROP and “Click” chemistry via “Graft onto” method

AbstractBiodegradable and biocompatible PCL‐g‐PEG amphiphilic graft copolymers were prepared by combination of ROP and “click” chemistry via “graft onto” method under mild conditions. First, chloro‐functionalized poly(ε‐caprolactone) (PCL‐Cl) was synthesized by the ring‐opening copolymerization of ε‐caprolactone (CL) and α‐chloro‐ε‐caprolactone (CCL) employing scandium triflate as high‐efficient catalyst with near 100% monomer conversion. Second, the chloro groups of PCL‐Cl were quantitatively converted into azide form by NaN3. Finally, copper(I)‐catalyzed cycloaddition reaction was carried out between azide‐functionalized PCL (PCL‐N3) and alkyne‐terminated poly(ethylene glycol) (A‐PEG) to give PCL‐g‐PEG amphiphilic graft copolymers. The composition and the graft architecture of the copolymers were characterized by 1H NMR, FTIR, and GPC analyses. These amphiphilic graft copolymers could self‐assemble into sphere‐like aggregates in aqueous solution with diverse diameters, which decreased with the increasing of grafting density. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Controlled thermal gelation of poly(ε-caprolactone)/poly(ethylene glycol) block copolymers by modifying cyclic ether pendant groups on poly(ε-caprolactone)

The control of the thermal gelation behavior of amphiphilic copolymers based on PEGylated hydrophobic polymers is important for applications in drug administration and controlled release. This paper studied a new method to control the thermal gelation behavior of the amphiphilic copolymers by structure modification of hydrophobic segments. A kind of triblock copolymer of PEG and modified poly(e-caprolactone) (PCL) with cyclic ether pendant groups, i.e. poly(e-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(e-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) triblock copolymers (PECT) were synthesized through the ring-opening copolymerization of e-caprolactone and 1,4,8-trioxa[4.6]spiro-9-undecanone (TOSUO) in the presence of poly(ethylene glycol). The structure and thermal gelation behavior of PECT were characterized by 1H NMR, FT-IR, GPC, XRD, DSC and DLS, etc. The study results indicated that the introduction of cyclic ether pendant groups on the PCL backbone not only reduced the crystallinity of PCL but also increased the hydrophilicity of the hydrophobic phase, which provides perfect dispersity of PECT in water and allows a more excellently controlled thermal gelation behavior than the PCL-PEG-PCL block copolymer. PECT powder can directly disperse in water to form a stable nanoparticle aqueous dispersion even with a high content of hydrophobic block (the weight ratio of PCL to PEG is nearly 3). Further, the PECT nanoparticle aqueous dispersion at higher concentration performed sol–gel–sol transition behavior with the temperature increasing from ambient or lower temperature, and the transition temperature and gelation behavior could be adjusted by the content of the cyclic ether pendant groups on the PCL segments. Significantly, avoiding the pre-quenching treatment that is needed for PCL-PEG-PCL gelation, the PECT nanoparticle aqueous dispersions, which are injectable fluids at ambient temperature and form a gel at 37 °C quickly, provide an injectable in situ gel system for clinical applications with the advantages of convenient dosage, administration, storage, and prescription. Therefore, the PECT thermal hydrogel system is expected to have potential applications in drug delivery and tissue engineering.

Unprecedented Access to Functional Biodegradable Polymers and Coatings

The ever-growing biomedical technology such as tissue engineering, regenerative medicine, and controlled drug release intimately relies on the development of advanced functional biomaterials. Here, we report on versatile and robust synthesis of novel vinyl sulfone (VS)-functionalized biodegradable polymers that offer unprecedented access to advanced functional biodegradable polymers and coatings through selective Michael-type conjugate reaction with thiol-containing molecules. VS-functionalized biodegradable polymers including poly(ε-caprolactone) (PCL), poly(l-lactide) (PLA), and poly(trimethylene carbonate) (PTMC) were conveniently prepared with controlled molecular weights and functionalities through ring-opening copolymerization of ε-caprolactone (ε-CL), l-lactide (LA), or trimethylene carbonate (TMC) with a new cyclic carbonate monomer, vinyl sulfone carbonate (VSC), in toluene at 110 °C using isopropanol as an initiator and stannous octoate as a catalyst. Interestingly, these VS-functionalized biodegradable polymers allowed quantitative modification, without aid of a catalyst, with various thiol-containing molecules including 2-mercaptoethanol, cystamine, cysteine, GRGDC peptide, and thiolated poly(ethylene glycol) (PEG-SH) at a ligand-SH/VS molar ratio of 2/1 in DMF at room temperature, confirming that the Michael-type conjugate addition to VS is highly selective and tolerant to most other functional groups including hydroxyl, carboxyl, and amine. Remarkably, results of contact angle measurements, X-ray photoelectron spectroscopy (XPS), and fluorescence studies showed that biodegradable coatings based on these VS-functionalized polymers allowed direct, efficient, and clean (without catalyst and byproduct) surface functionalization with thiol-containing molecules in aqueous conditions, which is unprecedented and opens a new avenue to surface functionalization of medical implants as well as cell and tissue scaffolds. The preliminary cell culture studies using MG6 cells showed that unmodified VS-functionalized PCL films, similar to tissue culture plate, could well support cell attachment and growth, indicating that VS-functionalized PCL film is nontoxic and biocompatible. The surface of VS-functionalized PCL films could be elegantly engineered with thiolated nonfouling polymers (e.g., PEG and glycol chitosan) or cell adhesive motif (GRGDC peptide) to control cell attachment and growth. We are convinced that these vinyl sulfone-functionalized biodegradable polymers have a tremendous potential in biomedical engineering.

Dual Catalytic System for Combination of Chain and Step Polymerizations: Ring-Opening Polymerization of ϵ-Caprolactone and Successive Dehydration Polycondensation with Dicarboxylic Acid Using the Same Catalyst

We demonstrate a new system for the combination of chain and step polymerizations in which scandium trifluoromethanesulfonate [Sc(OTf)3] catalyzes both polymerization modes. Ring-opening polymerization of ϵ-caprolactone initiated from a diol was carried out in acetonitrile at 45 °C (Mn =1.2 × 103−3.6 × 103, Mw/Mn = 1.3). After removing acetonitrile under reduced pressure, bulk polycondensation with methylsuccinic acid was performed at 100 °C for 15 h to give the polyester in an excellent yield (92−94%): Mn and Mw/Mn were respectively 1.4 × 104 and 1.9. To check whether transesterification occurred or not during the two polymerizations, 13C NMR measurement was carried out in CDCl3. Suppressed transesterification was also supported from reductive cleavage of polyester containing disulfide linkage synthesized using ring-opening copolymerization of ϵ-caprolactone and successive polycondensation with 3,3′-dithiopropionic acid. Reversibly, chemoselective polycondensation of dicarboxylic acid containing a hydroxyl group and a diol and subsequent ring-opening copolymerization initiated from the pendent hydroxyl groups were also demonstrated using Sc(OTf)3 as the dual catalyst.