Six-membered Cyclic Carbonate Monomer Research Articles

Selective Organocatalytic Preparation of Trimethylene Carbonate from Oxetane and Carbon Dioxide

The organocatalytic coupling of oxetanes and carbon dioxide (CO2) offers a sustainable route to poly(trimethylene carbonate)s and/or functional six-membered cyclic carbonate monomers. This transfor...

ROS-Responsive Chalcogen-Containing Polycarbonates for Photodynamic Therapy.

Reactive oxygen species (ROS)-responsive polymers have attracted attention for their potential in photodynamic therapy. Herein, we report the ROS-responsive aliphatic polycarbonates prepared by the ring-opening polymerization (ROP) of three six-membered cyclic carbonate monomers with ethyl selenide, phenyl selenide or ethyl telluride groups. Under catalysis of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), all three monomers underwent the controlled anionic ROP, showing a feature of equilibrium polymerization due to the bulky effect of 5,5-disubstituents. With PEG macroinitiator, three series amphiphilic block copolymers were prepared. They could form spherical nanoparticles of ∼100 nm, which were stable in neutral phosphate buffer but dissociated rapidly under triggering of H2O2. We studied the H2O2-induced oxidation profiles of selenide- or telluride-containing small molecules by 1H NMR and revealed the factors that affect the oxidation kinetics and products. On this basis, the oxidative degradation mechanism of the copolymer nanoparticles has been clarified. Under the same oxidative condition, the telluride-containing nanoparticle degraded with the fastest rate while the phenyl selenide-based one degraded most slowly. These ROS-responsive nanoparticles could load photosensitizer chlorin e6 (Ce6) and anticancer drug doxorubicin (DOX). Under red light irradiation, Ce6-sensitized production of 1O2 that triggered the degradation of nanoparticles, resulting in an accelerated payload release. In vitro cytotoxicity assays demonstrate that the nanoparticles coloaded with DOX and Ce6 exhibited a synergistic cell-killing effect to MCF-7 cells, representing a novel responsive nanoplatform for PDT and/or chemotherapy.

A Vinyl Ether-Functional Polycarbonate as a Template for Multiple Postpolymerization Modifications.

A highly-reactive vinyl ether-functionalized aliphatic polycarbonate and its block copolymer were developed as templates for multiple post-polymerization conjugation chemistries. The vinyl ether-functional six-membered cyclic carbonate monomer was synthesized by a well-established two-step procedure starting from 2,2-bis(hydroxymethyl)propionic acid. An organobase-catalyzed ring-opening polymerization of the synthesized monomer afforded polycarbonates with pendant vinyl ether functionalities (PMVEC). The vinyl ether moieties on the resulting polymers were readily conjugated with hydroxyl- or thiol-containing compounds via three different post-polymerization modification chemistries - acetalization, thio-acetalization, and thiol-ene reaction. Acetal-functionalized polycarbonates were studied in depth to exploit their acid-labile acetal functionalities. Acetalization of the amphiphilic diblock copolymer of poly(ethylene glycol) methyl ether (mPEG) and PMVEC, mPEG113-b-PMVEC13, with the model hydroxyl compound 4- methylbenzyl alcohol resulted in a maximum of 42% acetal and 58% hydroxyl side chain groups. Nonetheless, the amphiphilicity of the block polymer allowed for its self-assembly in water to afford nanostructures, as characterized via dynamic light scattering and transmission electron microscopy. The kinetics of acetal cleavage within the block polymer micelles were examined in acidic buffered solutions (pH 4 and 5). In addition, mPEG-b-PMVEC and its hydrolyzed polymer mPEG-b-PMHEC (i.e., after full cleavage of acetals) exhibited minimal cytotoxicity to RAW 264.7 mouse macrophages, indicating that this polymer system represents a biologically non-hazardous material with pH-responsive activity.

Studies on microwave-assisted ring-opening polymerization and property of poly(9-phenyl-2,4,8,10-tetraoxaspiro-[5,5]undcane-3-one)

Poly(9-phenyl-2,4,8,10-tetraoxaspiro-[5,5]undcane-3-one) (PPTC) was synthesized by the microwave-assisted ring-opening polymerization (MROP) of a six-membered cyclic carbonate monomer 9-phenyl-2,4,8,10-tetraoxaspiro-[5,5]undcane-3-one (PTC) with tin(II) 2-ethylhexanoate (Sn(Oct)2) or aluminum isopropoxide (Al(OiPr)3) as the catalysts. The obtained polycarbonates were further reduced by apalladium/carbonate catalyst (10% Pd/C) to afford partly deprotected polycarbonates containing hydroxyl groups (HPPTC). These two types of polycarbonates were characterized by 1H-NMR, Fourier transform infrared spectroscopy (FTIR), UV, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and automatic contact-angle measurements. The influence of the feed molar ratio of monomer-to-catalyst, the microwave irradiation power and the reaction time on the polymerization was also studied. The experimental results showed that HPPTC possessed significantly higher hydrophilicity and water absorption rate than PPTC.

Thymine-functionalized amphiphilic biodegradable copolymers for high-efficiency loading and controlled release of methotrexate

In this study, a novel thymine-functionalized six-membered cyclic carbonate monomer (TAC) was synthesized by the Michael-addition reaction between thymine and acryloyl carbonate (AC). The corresponding functional amphiphilic block copolymer mPEG-b-PTAC was further successfully synthesized by ring-opening polymerization using immobilized porcine pancreas lipase (IPPL) as the catalyst and mPEG as the macroinitiator. Meanwhile, mPEG-b-P(TAC-co-DTC) and mPEG-b-PDTC were also synthesized by the same enzymatic methods for comparison on different TAC contents. The structures of monomer and copolymers were characterized by 1H-NMR, 13C-NMR and FTIR. All the amphiphilic block copolymers could self-assemble to form nano-sized micelles in aqueous solution. Transmission electron microscopy (TEM) observation showed that the micelles dispersed in spherical shape with nano-size before and after MTX loading. 1H-NMR and FTIR results confirmed the successful formation of multiple hydrogen-bonding interactions between exposed thymine groups of hydrophobic PTAC segments and 2,6-diaminopyridine (DAP) groups of MTX molecules, which resulting in the higher drug loading capacity and the pH-sensitive drug release behavior. MTT assays also indicated lower toxicity of copolymer but higher potent cytotoxic activity of MTX-loaded copolymer against HeLa cells.

Synthesis of high molecular flexibility polycarbonates for solid polymer electrolytes

A new self-plasticizing aliphatic polycarbonate comprising flexible alkyl and alkyl ether side groups was designed and synthesized from six-membered cyclic carbonate monomers with the aim of producing a material with high molecular flexibility (low Tg) and concomitant high ionic conductivity when used as a polymer electrolyte. The Tg of the novel polycarbonate was determined to be −49.4°C at a molecular weight of 34 400gmol−1, which is the lowest reported Tg to date for a substituted poly(trimethylene carbonate). UV-crosslinked polymer electrolytes were produced based on this novel material together with LiTFSI salt and showed ionic conductivities in the range of 2×10−8 to 2×10−7Scm−1 at room temperature and 1×10−6 to 1×10−5Scm−1 at 100°C. The limited ionic conductivities of these electrolytes indicate that high molecular flexibility alone does not guarantee fast ion transport in solid polymer electrolytes and that other factors, such as the polarity of the polymer host material, will also influence the transport properties of the electrolyte.

Ring-Closing Depolymerization: A Powerful Tool for Synthesizing the Allyloxy-Functionalized Six-Membered Aliphatic Carbonate Monomer 2-Allyloxymethyl-2-ethyltrimethylene Carbonate

Ring-closing depolymerization is demonstrated to be a powerful synthetic methodology for the formation of six-membered functional aliphatic carbonate monomers, providing a rapid, straightforward, inexpensive, and green route for obtaining six-membered functional aliphatic carbonate monomers at a scale greater than 100 g. The utility of this technique was observed via the synthesis of the allyloxy-functionalized six-membered cyclic carbonate monomer 2-allyloxymethyl-2-ethyltrimethylene carbonate (AOMEC). The synthesis was performed in a one-pot bulk reaction, starting from trimethylolpropane allyl ether, diethyl carbonate, and NaH, resulting in a final AOMEC yield of 63%. The synthetic methodology is based upon the reversible nature of this class of polymers. The anionic environment produced by NaH was observed to be sufficient to mediate the monomer equilibrium concentration; thus, an additional catalyst is not required to induce depolymerization. 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) was demonstrated to be a very active catalyst for the ring-opening polymerization (ROP) of AOMEC, resulting in a rapid (kpapp = 28.2 s–1) and controlled polymerization with a low dispersity (Đ = 1.2). The availability and activity of the functionality of poly(AOMEC)s were established through subsequent postpolymerization functionalization via the UV-initiated thiol–ene chemistry of poly(AOMEC) with 1-dodecanethiol and benzophenone as a radical initiator. The functionalization proceeded with high control and with a linear relation between the molecular weight and conversion of the unsaturation, revealing the high orthogonality of the reaction and the stability of the carbonate backbone. Hence, as a synthetic methodology, depolymerization provides a straightforward and simple approach for the synthesis of the highly versatile functional carbonate AOMEC. In addition, formation of the monomer does not require any solvents, reactive ring-closing reagents, or transition-metal-based depolymerization catalysts, thereby providing a “greener” route for obtaining functional carbonate monomers and polymers.

Synthesis and hydrolytic degradation of aliphatic polycarbonate based on dihydroxyacetone

The six-membered cyclic carbonate monomer, 2,2-dimethoxy-1,3-propanediol carbonate based on dihydroxyacetone with methanol ketal protected carbonyl group, was prepared by a two-step reaction including protection and ring-closing, starting from dihydroxyacetone. The ring-opening polymerization of 2,2-dimethoxy-1,3-propanediol carbonate was carried out in bulk at 110–140°C initiated by stannous octanoate to give polycarbonate, poly(2,2-dimethoxypropane-1,3-diol carbonate). The effects of different reaction conditions including different catalyst, reaction temperature, molar ratio of monomer to initiator and polymerization time on the polymerization were investigated. Polycarbonate was obtained with the yield of 58.9–91.0%. The number average molecular weight of polycarbonate was in the range of 1.43 × 104 to 13.82 × 104 with polydispersity indexes from 1.31 to 1.91. The protecting ketal group was partly removed by hydrolysis using 50% trifluroacetic acid as a catalyst to give a functional polycarbonate containing 70% ketone carbonyl group, which improved the hydrophilicity of initial polycarbonate. The in vitro degradation tests were carried out in a phosphate buffer solution with pH 7.4 at 37°C, which showed that the modified polycarbonate degraded completely after 5 days.

2-Amino-1,3-propane diols: a versatile platform for the synthesis of aliphatic cyclic carbonate monomers

Starting from commercially available 2-amino-1,3-propane diols, a variety of functional cyclic carbonate monomers were synthesized through a general two-step strategy. First the amino group was chemo-selectively reacted with a diverse set of electrophiles to result in functional diol intermediates (1), which were then cyclized in an intramolecular fashion to generate a series of functional aliphatic six-membered cyclic carbonate monomers (2). The unique feature of this approach is its ability to install concurrently two different functional groups. This includes a specific tethered functional group and a second functional group, which are installed in the monomer-forming reactions. Selected monomers were subjected to organo-catalytic ring opening polymerization to produce well-defined homopolymers and copolymers (ĐM ≥ 1.5) with controlled composition. Primary amine containing polymers were also readily accessed via post-polymerization acidolysis of a tBoc-derived monomer (2k). This approach will provide direct access to functional biodegradable polymers and impact the development of next-generation materials for biomedical and environmentally friendly products.

Reduction-sensitive core-cross-linked mPEG–poly(ester-carbonate) micelles for glutathione-triggered intracellular drug release

A functionalized six-membered cyclic carbonate monomer containing a protected thiol group, 2-(2,4-dinitrophenylthio)ethyl-5-methyl-2-oxo-1,3-dioxane-5-carboxylate (MTC), was prepared. Ring-opening polymerization (ROP) of MTC and L-lactide (LA) initiated by monohydroxyl poly(ethylene glycol) (mPEG) was successfully performed with controlled polymer molecular weight and molecular weight distribution. The structures of the obtained monomer and copolymers were confirmed by NMR and FTIR. After deprotection under mild conditions, the amphiphilic block copolymer was self-assembled into micelles in aqueous solution. By oxidation of the free thiol groups in the PMTC segments, the micelles with the cross-linked core were formed, and the enhanced stability against disruptive conditions was demonstrated by dynamic light scattering (DLS) measurement in the presence of DMF. Doxorubicin (DOX) was loaded into the micelles as a model drug. The in vitro DOX release behaviors indicated that cross-linking of the micelle cores resulted in a slow drug release and this process was greatly accelerated by adding glutathione (GSH) solution with comparable concentrations to intracellular levels in tumor cells. The cross-linked micelles were demonstrated to be efficiently internalized into the cells. Faster intracellular DOX release was observed by confocal laser scanning microscopy (CLSM) in the GSH pretreated MCF-7 cells than in the unpretreated MCF-7 cells. In vitro MTT assay revealed that the cross-linked micelles were biocompatible with L929 cells and MCF-7 cells. As expected, DOX-loaded cross-linked micelles showed higher cellular proliferation inhibition towards glutathione pretreated MCF-7 cells than that towards the unpretreated ones at various GSH concentrations. These results indicated that the bioreducible core-cross-linked micelles can be used as drug carriers for intelligent drug delivery.

Synthesis and polymerization of alkyl halide-functional cyclic carbonates

To increase the diversity in functional aliphatic polycarbonates, a series of novel chloro- and bromo-functional six-membered cyclic carbonate monomers were synthesized. Despite asymmetry in the monomer functionalities, homopolymerization of the monomers afforded semicrystalline polycarbonates with a high tendency to crystallize from the melt and/or on precipitation from a THF solution. Melting points were found in the 90–105 °C or 120–155 °C range for polymers comprising methyl or ethyl moieties, respectively, in the backbone. The monomers were further copolymerized with trimethylene carbonate to form random copolymers. Even among some of these random copolymers elements of semicrystallinity were found as confirmed by melting endotherms in DSC. The results clearly show that the incorporation of alkyl halide functionalities in aliphatic polycarbonates may lead to materials with a high ability to form crystallites, even in random copolymers, likely driven by polar interactions due to the presence of the halide functionalities.

Novel biodegradable aliphatic poly(butylene succinate-co-cyclic carbonate)s with functional carbonate building blocks. 1. Chemical synthesis and their structural and physical characterization.

This study presents chemical synthesis, structural, and physical characterization of novel biodegradable aliphatic poly(butylene succinate-co-cyclic carbonate)s P(BS-co-CC) bearing functional carbonate building blocks. First, five kinds of six-membered cyclic carbonate monomers, namely, trimethylene carbonate (TMC), 1-methyl-1,3-trimethylene carbonate (MTMC), 2,2-dimethyl-1,3-trimethylene carbonate (DMTMC), 5-benzyloxytrimethylene carbonate (BTMC), and 5-ethyl-5-benzyloxymethyl trimethylene carbonate (EBTMC), were well prepared from ethyl chloroformate and corresponding diols at 0 degrees C in THF solution with our modified synthetic strategies. Then, a series of new P(BS-co-CC)s were synthesized at 210 degrees C through a simple combination of poly-condensation and ring-opening-polymerization (ROP) of hydroxyl capped PBS macromers and the prepared carbonate monomers, and titanium tetra-isopropoxide Ti(i-OPr)4 was used as a more suitable catalyst of 5 candidate catalysts which could concurrently catalyze poly-condensation and ROP. By means of NMR, GPC, FTIR, and thermal analytical instruments, macromolecular structures and physical properties have been characterized for these aliphatic poly(ester carbonate)s. The experimental results indicated that novel biodegradable P(BS-co-CC)s were successfully synthesized with number average molecular weight Mn ranging from 24.3 to 99.6 KDa and various CC molar contents without any detectable decarboxylation and that the more bulky side group was attached to a cyclic carbonate monomer, the lower reactivity for its copolymerization would be observed. The occurrences of 13C NMR signal splitting of succinyl carbonyl attributed to the BS building blocks could be proposed due to the randomized sequences of BS and CC building blocks. FTIR characterization indicated two distinct absorption bands at 1716 and 1733 approximately 1735 cm(-1), respectively, stemming from carbonyl stretching modes for corresponding BS and CC units. With regard to their thermal properties, it is seen that the synthesized P(BS-co-CC)s exhibited thermal degradation temperatures 10 approximately 20 degrees C higher than that of PBS. On the basis of the synthesized P(BS-co-BTMC)s, new aliphatic poly(butylene succinate-co-5-hydroxy trimethylene carbonate)s were further synthesized, bearing hydrophilic hydroxyl pendant functional groups through an optimized Pd/C catalyzed hydrogenation. These semi-crystalline new biodegradable aliphatic copolymers with tunable physical properties and functional carbonate building blocks might be expected as potential new biomaterials.

Synthesis of Six-Membered Cyclic Carbonate Monomers by Disproportionation of 1,3-Bis(alkoxycarbonyloxy)propanes and Their Polymerization

Synthesis of Six-Membered Cyclic Carbonate Monomers by Disproportionation of 1,3-Bis(alkoxycarbonyloxy)propanes and Their Polymerization