Synthesis and characterization poly(ϵ-caprolactone-b-ethylene glycol-b-ϵ-caprolactone) ABA type block copolymers via “Click” chemistry and ring-opening polymerization

Synthesis of poly(?-caprolactone-b-ethylene glycol-b-?-caprolactone) ABA type block copolymer by “click” chemistry and ring-opening polymerization (ROP) was reported by using propargyl polyethylene glycol (propargyl-PEG) and terminally azido poly(?-caprolactone) ester (PCL-N₃). For this purpose, primarily propargyl-PEG was synthesized by using reaction of PEGs (3000 Da, 2000 Da, 1500 Da, 1000 Da, 600 Da ve 400 Da) and propargyl chloride. 3-azido-1-propanol was obtained by using chemical interaction of 3-chloro-1-propanol and sodium azide. Synthesis of PCL-N₃ was carried out by means of ROP of ?-caprolactone and 3-azido-1-propanol. Finally, poly(?-caprolactone-b-ethylene glycol-b-?-caprolactone) ABA type block copolymers were synthesized by using PCL-N₃ and propargyl-PEG. The primary parameters such as concentration, time, and temperature that influenced the reactions were assessed. The product characterization was achieved using NMR, FT-IR, GPC, elemental analysis, and fractional precipitation [non-solvent (petroleum ether-mL)/solvent (THF-mL)] techniques.     

Preparation of poly(ε-caprolactone)@attapulgite nanocomposites via a combination of controlled ring-opening polymerization and click chemistry

In this work, by a combination of controlled ring-opening polymerization (CROP) and click chemistry, we report a facile and useful method to synthesize linear poly(ε-caprolactone)@attapulgite nanocomposites with well-defined structures. For this, first, the chlorine-terminated attapulgite was prepared by the self-assembly of 3-chloropropyltrimethoxysilane from the surfaces of attapulgite. And then, the terminal chlorines of modified attapulgite were substituted with azido groups. As the second step, linear propargyl-terminated poly(ε-caprolactone) (PCLs) with different molecular weights were synthesized by the CROP of ε-CL monomer in toluene with stannous octoate as a catalyst and propargyl alcohol as an initiator. The structural characteristics of the obtained linear PCLs have been determined by ¹H NMR and gel permeation chromatography analysis. Finally, the azido-terminated attapulgite was reacted with propargyl-terminated PCLs via the click reaction.     

Synthesis and characterization of poly(ɛ-caprolactone)/Fe3o4 nanocomposites by in situ polymerization

A series of magnetic nanocomposites based on poly(?-caprolactone) (PCL) and Fe₃O₄ nanoparticles were prepared using a facile in situ polymerization method. The chemical structures of the PCL/Fe₃O₄ nanocomposites were characterized by Fourier transform infrared (FTIR) spectroscopy. Results of wide-angle X-ray diffraction (WAXD) showed that the incorporation of the Fe₃O₄ nanoparticles did not affect the crystallization structure of the PCL. Both scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to characterize the morphology and dispersion of the Fe₃O₄ nanoparticles within the as-synthesized nanocomposites. Results of differential scanning calorimetry (DSC) and polarizing optical microscopy (POM) showed that the crystallization temperature was raised and the spherulites size decreased by the presence of Fe₃O₄ nanoparticles in the nanocomposites due to the heterogeneous nucleation effect. The thermal stability of the PCL was depressed by incorporation of Fe₃O₄ nanoparticles from thermogravimetric analysis (TGA). The superparamagnetic behavior of the PCL/Fe₃O₄ nanocomposites was testified by the superconducting quantum interference device (SQUID) magnetometer analysis. The obtained biodegradable nanocomposites will have a great potential in magnetic resonance imaging contrast and targeted drug delivery.     

Synthesis and micellar characterization of thermosensitive amphiphilic poly(ε-caprolactone)-b-poly(N-vinylcaprolactam) block copolymers

Poly(ε-caprolactone)-b-poly(N-vinylcaprolactam) (PCL-b-PVCL) block copolymers were synthesized as new biocompatible, thermosensitive, amphiphilic block polymers by a combination of ring-opening polymerization and reversible addition–fragmentation chain transfer (RAFT) polymerization, and their thermosensitive micellar behavior was examined. The PCL macro-chain-transfer agent was first synthesized by converting the end group of PCL-OH to O-ethyl xanthate, which was subsequently used for the RAFT polymerization of N-vinylcaprolactam. The critical micelle concentration of PCL-b-PVCL (M _n,NMR?=?56,300?g/mol, polydispersity index?=?1.18) was 0.026?mg/mL. The mean diameter of the PCL-b-PVCL micelles determined by transmission electron microscopy was 55?±?25?nm. The PCL-b-PVCL micelles exhibited repetitive aggregation and dispersion during reversible cooling and heating cycles between 20 and 40?°C due to the thermosensitive behavior of the PVCL shell. Overall, the PCL-b-PVCL block copolymers have potential applications in thermosensitive drug delivery applications.     

One-pot tandem ring-opening polymerization of N-sulfonyl aziridines and “click” chemistry to produce well-defined star-shaped polyaziridines

An effective approach for fast synthesis of well-defined star-shaped poly(2-methyl-N-tosylaziridine)s was developed by one-pot tandem ring-opening polymerization (ROP) of N-sulfonyl aziridines with trimethylsilyl azide (TMSN₃) and “click” reaction with alkynes. Azido terminated polyaziridines (α-N₃-PAzs) could be achieved via ROP of N-sulfonyl aziridines with TMSN₃ in the presence of organic superbases. The catalytic efficiency of organobases, including 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]-7-undecene (DBU), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), and N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA), was evaluated, and all of them except TBD afforded “living”/controlled ROP of 2-methyl-N-tosylaziridines (TsMAz). Star-shaped polyaziridines were then fastly synthesized by the one-pot tandem strategy. During the reaction process, PMDETA catalyzed ROP first, then was triggered to be a ligand by adding CuBr for “click” reaction. Well-defined 3- and 4-arm star P(TsMAz)s were successfully prepared, and subsequently desulfonylated to give star-shaped polypropylenimines (PPIs). PPI stars exhibited intrinsic photoluminescence properties from the polyamine arms.     

Preparation of new poly(ester triazole) and poly(amide triazole) by “click chemistry”

New dialkynyl monomers containing furan and ester or amide units were prepared via three step reactions from ethyl furan-2-carboxylate. Their click polymerization with either poly(ethylene glycol) diazide or poly(tetrahydrofuran) diazide catalyzed by Cu(I) led to corresponding amorphous poly(ester triazole) and poly(amide triazole) with molecular weights in the range of (7–11) × 10³ and with glass transition temperatures in the range of ?35 and ?19°C. The temperature at 5% wt loss (T ₁₀), determined from TGA of polyazomethines were in the range 345–365°C indicating their good thermal stability.     

Iodine-transfer polymerization and CuAAC “click” chemistry: A versatile approach toward poly(vinylidene fluoride)-based amphiphilic triblock terpolymers

This study presents the synthesis and properties of linear PVDF-based amphiphilic triblock terpolymers with PS and PEO, [PVDF-b-PS-b-PEO], by adopting a procedure that involves: (a) iodine-transfer polymerization (ITP) of VDF with 1-iodoperfluorohexane (C₆F₁₃I) serving as chain-transfer agent (CTA) to afford C₆F₁₃-PVDF-I, (b) ITP of styrene with the C₆F₁₃-PVDF-I macromolecular-CTA to obtain C₆F₁₃-PVDF-b-PS-I diblock copolymer, (c) end-group exchange from iodo- to azido-group by nucleophilic substitution reaction with NaN_3, and (d) copper-catalyzed azide-alkyne cycloaddition (CuAAC) with alkyne-terminated PEO to achieve C₆F₁₃-PVDF-b-PS-b-PEO triblock terpolymers. The ¹H and ¹⁹F NMR spectroscopy confirmed the presence of all blocks, while gel permeation chromatography traces showed the living nature of ITP technique. The self-assembly of these terpolymers was investigated in films (atomic force microscopy and DSC), as well as in aqueous and organic solvents (DLS). The analysis of crystalline phases based on the FTIR spectroscopy indicated the conversion of PVDF α-phase into α + β-phases and β + γ-phases upon the incorporation of PS and PEO blocks, respectively. The synthesized amphiphilic copolymers were evaluated (fluorescence spectroscopy) as carriers of small hydrophobic molecules in water. © 2019 Wiley Periodicals, Inc. J. Polym. Sci. 2020 , 58, 163–171     

Synthesis and characterization of poly(ethylene glycol) based β-cyclodextrin polymers

A series of novel water soluble β-cyclodextrin (βCD) polymers has been synthesized from functionalized poly(ethylene glycol) (PEG). The chemical composition of the polymers has been characterized by ¹H NMR and the βCD content is found to be between 48 and 33% (w/w). The molecular weight has been determined by Size Exclusion Chromatography (SEC) and depends on the ratio between βCD and PEG, varying from 2.1 × 10⁴ to 8.6 × 10⁴ g mol^?1. The physico chemical properties have been characterized by differential scanning calorimetry (DSC), viscometry and isothermal titration calorimetry (ITC). ITC shows that the polymers have association constants comparable to βCD with different guest molecules, indicating a good accessibility of the CDs.     

Synthesis and characterization of alternating fluorene–thiophene copolymers bearing ethylene glycol side-chains

Abstract  

New alternating fluorene–thiophene copolymers are introduced bearing polar ethylene glycol-carboxylate functionalities on the thiophene ring to achieve enhanced solubility in polar solvents. Suzuki polycondensation was applied to synthesize a set of three polymers with differing lengths of the ethylene glycol side-chains. The polymers are thermally stable up to temperatures of 300 °C. Solutions of the polymers in CHCl₃ show an absorption maximum at approximately 397 nm and a luminescence maximum of 472 nm in solutions with quantum yield of 30%. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) levels have been determined to be at −5.7 and −2.6 eV, respectively.     

Synthesis of poly(ε-caprolactone) diols and EO-CL block copolymers and their characterization by liquid chromatography and MALDI-TOF-MS

Polymers of ε-caprolactone were synthesized by microwave-assisted polymerization initiated with polyethylene glycols (PEG 200 and PEG 300) and monodisperse diols (mono-, di-, tri-, tetra- and hexaethylene glycol) and tin octoate as catalyst. These polymers were characterized by different chromatographic techniques (SEC, LAC and LCCC) and MALDI-TOF-MS. A comparison with commercially available polycaprolactone diols with molecular weight 530 and 830 showed that the new polymers had a much higher content of triblock structures, while the commercial samples contained considerable amounts of diblocks.     

Synthesis and characterization of aba-type block copolymer of poly(ϵ-caproplactone) with poly(ethylene glycol), by mean of activation end groups

Poly(?-caprolactone)-b-poly(ethylene glycol)-b-poly(?-caprolactone) (PCL-b-PEG-b-PCL) triblock copolymer were synthesized by mean anionic activation of the hydroxyl end groups of poly(ethylene glycol) in presence of diphenylmethylsodium. Copolymers were characterized by SEC, FT-IR and ¹H-NMR spectroscopy, TGA and DSC. Size exclusion chromatographic analysis of obtained copolymers indicated incorporation of CL monomer into PEG without formation of PCL homopolymer. Characterization by FT-IR and ¹H NMR spectroscopy of the resulting polymeric products, with respect to their structure, end-groups and composition, showed that they are best described as ester-ether-ester triblock copolymers, whose compositions can be adjusted changing the feeding molar ratio of PEG to CL. The thermal stability of triblock copolymers was less that PEG precursor, but higher that PCL homopolymer. Analysis by mean DSC showed that all copolymers were semi-crystalline and their thermal behavior depending on their composition.     

Synthesis and protonolysis of neutral aluminum dihydride compounds stabilized by tridentate-substituted pyrrolyl ligands: Synthesis, structural characterization and ring-opening polymerization of ?-caprolactone

A series of aluminum compounds containing tridentate pyrrolyl ligands were obtained from related aluminum dihydride compounds via protonolysis. Treatment of tetranuclear aluminum compound [C₄H₂N{2,5-(CH₂NMe₂)₂}Al₂H₅]₂ (1) with two equivalents of [C₄H₃N{2,5-(CH₂NMe₂)₂}] in methylene chloride at 0 °C led to the formation of [C₄H₂N{2,5-(CH₂NMe₂)₂}]AlH₂ (2). Similarly, when the deuterated aluminum compound 1D was used, the corresponding aluminum compound [C₄H₂N{2,5-(CH₂NMe₂)₂}]AlD₂ (2D) could be isolated. The reaction of 2 with one or two equivalents of phenylethyne, triphenylmethanethiol, 2,6-diisopropylaniline, or triphenylsilanol generated mononuclear aluminum compounds [[C₄H₂N{2,5-(CH₂NMe₂)₂}]AlRR′ (3, R = -CCPh, R′ = H; 4, R = R′ = -CCPh; 5, R = -SCPh₃, R′ = H; 6, R = R′ = -SCPh₃; 7, R = -NH(2,6-ⁱPr₂Ph), R′ = H; 8, R = R′ = -NH(2,6-ⁱPr₂Ph); 9, R = -OSiPh₃, R′ = H; 10, R = R′ = -OSiPh₃). Related Al-D compounds of 3, 5, 7 and 9 were also synthesized and corresponding IR spectroscopic data well matched in comparison of the stretching frequencies of Al-H and Al-D. The molecular structures of 2D, 4, 5, 5D, 7, and 10 have been determined by X-ray crystallography. Compounds 2, 5, and 7 initiated the ring-opening polymerization of ?-caprolactone and produced high-molecular weight of poly-?-caprolactone.     

A novel strategy for synthesis of amphiphilic π-shaped copolymers by RAFT polymerization

The amphiphilic π-shaped copolymers with narrow molecular weight distribution (M_w/M_n = 1.04-1.09) based on polystyrene (PSt) and poly(ethylene glycol) have been synthesized successfully. The reversible addition-fragmentation transfer (RAFT) polymerization of St in the presence of dibenzyl trithiocarbonate and N,N′-azobis(isobutyronitrile) (AIBN) yielded macro RAFT agent PSt-SC(S)S-PSt, subsequent reaction with excess maleic anhydride (MAh) at 80 °C in tetrahydrofuran afforded the PSt-MAh-SC(S)S-MAh-PSt. It was used as RAFT agent in the RAFT polymerization of St, and finally the amphiphilic π-shaped copolymers were obtained by the reaction of MAh with hydroxyl-terminated poly(ethylene glycol methyl ether) at 90 °C for 48 h. Their structures were confirmed by FT-IR and ¹H NMR spectra, and their molecular weight and molecular weight distribution were measured by gel permeation chromatography.     

Synthesis and characterization of aluminum and zinc complexes supported by pyrrole-based ligands and catalysis of the aluminum complexes toward the ring-opening polymerization of ?-caprolactone

Reaction of quinolin-8-amine with 1H-pyrrole-2-carbaldehyde or 5-tert-butyl-1H-pyrrole-2-carbaldehyde catalyzed by HCO₂H forms N-((1H-pyrrol-2-yl)methylene)quinolin-8-amine (≡ HL, 3a) or N-((5-tert-butyl-1H-pyrrol-2-yl)methylene)quinolin-8-amine (≡ HL′, 3b). Treatment of 3a and 3b respectively with AlMe₃ or AlEt₃ in toluene affords corresponding aluminum complexes LAlMe₂ (4a), L′AlMe₂ (4b) and LAlEt₂ (4c). Reaction of 3a and 3b with an equivalent of ZnEt₂ in toluene generates L₂Zn and L′₂Zn, respectively. A related compound N-((1H-pyrrol-2-yl)methylene)-2-(3,5-dimethyl-1H-pyrazol-1-yl)benzenamine (≡ HL″, 7) was prepared by reaction of 2-(3,5-dimethyl-1H-pyrazol-1-yl)benzenamine with 1H-pyrrole-2-carbaldehyde in the presence of HCO₂H. Reaction of 7 with AlMe₃ gives L″₂AlMe (8), and with ZnEt₂ yields L″₂Zn (9). All new compounds were characterized by NMR spectroscopy and elemental analysis. The structures of complexes 4b, 5b and 8 were additionally characterized by single crystal X-ray diffraction analyses. Complexes 4a-4c, and 8 were proved to be active catalysts for the ring-opening polymerization (ROP) of ?-caprolactone (?-CL) in the presence of BnOH. The kinetic study of the polymerization reactions catalyzed by 4a and 8 was performed.     

Solubility of naphthalene in aqueous solutions of poly(ethylene glycol)–poly(propylene glycol)–poly(ethylene glycol) triblock copolymers and (2-hydroxypropyl)cyclodextrins

The solubility of naphthalene was investigated in aqueous solutions of triblock copolymers poly(ethylene glycol)–poly(propylene glycol)–poly(ethylene glycol) (PEG–PPG–PEG) and (2-hydroxypropyl)cyclodextrins. The results with solutions of the individual solubilizers were as expected: the solubility enhancement was much higher with a micelle-forming copolymer than with the non-micellizing one and with (2-hydroxypropyl)--cyclodextrin (HPBCD) than with (2-hydroxypropyl)--cyclodextrin (HPACD). Although the formation of inclusion complexes between HPACD and PEG and between HPBCD and PPG is well established, the naphthalene solubility in mixed solutions does not significantly deviate from that predicted for a mixture of independent solubilizers. Thus the interactions between HPCD and PEG–PPG–PEG copolymers are not strong enough to disrupt micelles and aggregates formed by those copolymers. In fact, slight synergetic deviations were observed with the micellizing copolymer, indicating the existence of ternary naphthalene/HPCD/copolymer interactions. For pharmaceutical applications, it is important that the solubilization efficacy of PEG–PPG–PEG copolymers and that of cyclodextrins modified by the 2-hydroxypropyl group would not be compromised if these two types of solubilizers were co-administered.     

Nanosized Micelles Self-Assembled from amphiphilic dextran-graft-methoxypolyethylene glycol/poly(ε-caprolactone) copolymers

A series of amphiphilic copolymers, dextran-graft-methoxypolyethylene glycol/poly(ε-caprolactone) (Dex-g-mPEG/PCL) were synthesized by grafting both PCL and mPEG chains to dextran, and subsequently the micellar self-assembly behavior of resultant copolymers was investigated. PCL was designed by using Fmoc-protected valine other than organometallic catalyst as the initiator to ring-opening polymerize ε-caprolactone (CL) in view of the safety demand as well as the extra application potential resulting from -NH₂ group introduced after Fmoc deprotection. All the copolymers were characterized by ¹H NMR, FT-IR and GPC measurements. The prepared copolymers are capable of self-assembling into nanosized spherical micelles in aqueous solution with the diameter of around 100-200 nm determined by TEM image and DLS measurement. The critical micellar concentration (CMC) of the graft copolymers is in the range of 10-100 mg/L determined by the fluorescence robe technique using pyrene. The result also indicated that the CMC of self-assembled micelles could be adjusted by controlling the degree of substitution of mPEG and PCL, and these micelles may find great potential as drug carriers in biomedical fields.     

Synthesis and characterization of biodegradable pH-sensitive hydrogels based on poly(?-caprolactone), methacrylic acid, and poly(ethylene glycol)

In this work, a novel biodegradable pH-sensitive hydrogel based on poly(?-caprolactone) (PCL), methoxpoly(ethylene glycol) (MPEG) and methacrylic acid (MAA) was prepared by UV-initiated free radical polymerization. The resulting macromonomers and hydrogels were characterized by FTIR and/or ¹H NMR. Swelling behaviour and pH sensitivity of the hydrogels were studied in detail. With increase in pH of aqueous medium from 1.2 to 7.2, swelling ratio of the hydrogels increased accordingly. The hydrolytic degradation behaviour was also investigated. The prepared biodegradable pH-sensitive hydrogel based on PCL, MPEG, and MAA might have great potential application in smart drug delivery system.     

Synthesis and characterization of a novel amphiphilic biodegradable β-cyclodextrin/poly(γ-benzyl L-glutamate) copolymer

β-Cyclodextrin/poly(γ-benzyl L-glutamate) (β-CD-PBLG) copolymers were synthesized by ring-opening polymerization of N-carboxy-γ-benzyl L-glutamate anhydride (BLG-NCA) in N,N-dimethylformamide (DMF) initiated by mono-amino-β-cyclodex-trin(H2N-β-CD). The structures of the copolymers were confirmed by IR, 1H NMR and GPC. The fluorescence technique was used to determine the critical micelle concentrations (CMC) of copolymer miceU solution, the diameter and the distribution of micelles were characterized by DLS. The results showed that BLG-NCA could be initiated by H2N-β-CD to produce copolymer. The nano-micells were formed by these copolymers in water.     

Synthesis,characterization, and solution behavior of well-defined double hydrophilic linear amphiphilic poly (N-isopropylacrylamide)-b-poly (ε-caprolactone)-b-poly (N-isopropylacrylamide) triblock copolymers

Well-defined linear dihydrophilic amphiphilic ABA-type triblock copolymers of ε-caprolactone (CL) and N-isopropylacrylamide (NIPAAm) have successfully been synthesized with a high yield by combining the ring opening polymerization (ROP) and xanthate-mediated reversible addition-fragmentation chain transfer (RAFT) polymerization methods. The resulted block copolymer shows the formation of micelles in water as supported by light scattering. The critical micelle concentration (cmc) value of the micelle increases with the increase in the chain length of the poly (N-isopropylacrylamide) (PNIPAAm) block. Cloud point of the block copolymers decreases with the decrease in the PNIPAAm chain length. The TGA analysis shows a one-step degradation and a lower thermal stability of the triblock copolymer than the PNIPAAm. The DSC analysis of the triblock copolymer shows the lowering of glass transition temperature (T _g), and melting temperature (T _m) peaks possibly due to the partial miscibility of the poly (ε-caprolactone) (PCL) block with the amorphous PNIPAAm block through the interaction of ester groups of PCL with the amide groups of PNIPAAm. The XRD pattern of the triblock copolymer shows a broad peak due to the suppression of the crystallization of PCL block owing to the mixing of PNIPAAm block with the PCL block.     

Design of phosphonate analogs of short peptides by “click” chemistry

Methods were developed for the first time for the modification of the natural neuropeptides Ile–Gly–Leu and Leu–Gly–Leu simultaneously with the phosphonate moiety and the triazole ring or solely with the triazole ring by means of click chemistry. All of the peptidomimetics synthesized were isolated as a mixture of diastereomers and were characterized by spectroscopic methods.