Synthesis of Branched Polymers by Means of Living Anionic Polymerization, 9. Radical Coupling Reaction of 1,1‐Diphenylethylene‐Functionalized Polymers with Potassium Naphthalenide and Its Application to Syntheses of In‐Chain‐Functionalized Polymers and Star‐Branched Polymers

Radical coupling reactions of both 1,1‐diphenylethylene (DPE)‐chain‐end‐ and DPE‐in‐chain‐functionalized polymers with potassium naphthalenide have been studied under the conditions mainly in THF at –78°C. Chain‐end‐functionalized polymers having M̄_n values of less than 10 kg/mol were very efficiently coupled in more than 90% yield to afford the polymeric dianion that were dimeric coupled products with two 1,1‐diphenylalkyl anions in the middle of the chains. However, the dimer yield decreased with increasing the molecular weight. The dimer was obtained in 59% yield with use of the chain‐end‐functionalized polymer having M̄_n of 33.9 kg/mol. Well‐defined in‐chain‐functionalized polymers with two benzyl bromide and DPE moieties each have been successfully synthesized by the reaction of the polymeric dianion thus obtained with 1‐(4‐bromobutyl)‐4‐(tert‐butyldimethylsilyloxymethyl)benzene and 1‐[4‐(4‐bromobutyl)phenyl]‐1‐phenylethylene, respectively. The radical coupling reaction of in‐chain‐functionalized polymers with DPE (M̄_n ca. 20 kg/mol) with potassium naphthalenide also proceeded efficiently to afford the coupled products that were A₂A′₂ and A₂B₂ four‐arm star‐branched polymers with well‐defined structures (M̄_n ca. 40 kg/mol).     

Synthesis and Micellization of Star‐Shaped Poly(ethylene glycol)‐block‐Poly(ε‐caprolactone)

Summary: The relationship between the architecture of block copolymers and their micellar properties was investigated. Diblock, 3‐arm star‐shaped and 4‐arm star‐shaped block copolymers based on poly(ethylene glycol) and poly(ε‐caprolactone) were synthesized. Micelles of star‐shaped block copolymer in an aqueous solution were then prepared by a solvent evaporation method. The critical micelle concentration and the size of the micelles were measured by the steady‐state pyrene fluorescence method and dynamic light scattering, respectively. The CMC decreased in the order di‐, 3‐arm star‐shaped and 4‐arm star‐shaped block copolymer. The size of the micelles increased in the same order as the CMC. Theory also predicts that the formation of micelles becomes easier for 4‐arm star‐shaped block copolymers than for di‐ and 3‐arm star‐shaped block copolymers, which qualitatively agrees with the experiments.

     

New Star‐Branched Poly(acrylonitrile) Architectures: ATRP Synthesis and Solution Properties

Summary: Atom transfer radical polymerization (ATRP) has been chosen as “living”/controlled free radical polymerization system to synthesize a number of novel poly(acrylonitrile) (PAN) architectures. The reaction conditions for the synthesis of linear samples with control over molar mass and molar mass distribution have been investigated together with the possibility of obtaining copolymers of acrylonitrile with small quantities of methyl acrylate (max. 5 mol‐%). Well‐defined star polymers with 3, 4 and 6 arms have been successfully synthesized together with linear chains initiated by a bifunctional initiator and star‐branched polymers with a hyperbranched poly(ester amide) as core. Molar masses were determined by NMR and GPC with the latter leading to a significant over estimation. Solution viscosity studies indicated that the stiff structure of the PAN chains is still maintained in the homopolymer star architectures and that the incorporation of small quantities of methyl acrylate as comonomer has a stronger effect on chain flexibility than the incorporation of star‐branch points.

     

Tailored Synthesis of Triblock Co‐ and Terpolymers Composed of Synthetically Difficult Sequence Orders by Combining Living Anionic Polymerization with Specially Designed Linking Reaction

This study demonstrates the versatility and wider applicability of the recently developed methodology combining the living anionic polymerization with a specially designed linking reaction using the α‐phenylacrylate (or benzyl bromide) function, allowing the synthesis of triblock co‐ and terpolymers, which are otherwise difficut to be obtained by sequential addition of monomers during a sequential polymerization approach. With this methodology using styrene and four para‐substituted styrene derivatives with N‐cyclohexylimine, 4‐N,N‐dimethyl‐2‐oxazoline, 2,6‐di(tert‐butyl)‐4‐methylphenyl ester, and nitrile, 12 polymers among the 16 possible triblock terpolymers and 6 triblock copolymers were successfully synthesized. Furthermore, the synthesis of two tetrablock quarterpolymers was achieved by the same linking methodology. The polymers synthesized in this study are all well‐controlled in chain length, composition, which are difficult to be obtained by the sequential polymerization. In addition, they possess functional groups usable for the further modification and introduction of other functionalities.

     

Allyl End‐Functionalized Poly(ethylene oxide)‐block‐poly(methylidene malonate 2.1.2) Block Copolymers: Synthesis,Characterization, and Chemical Modification

Summary: Poly(ethylene oxide)‐block‐poly(methylidene malonate 2.1.2) block copolymer (PEO‐b‐PMM 2.1.2) bearing an allyl moiety at the poly(ethylene oxide) chain end was synthesized by sequential anionic polymerization of ethylene oxide (EO) and methylidene malonate 2.1.2 (MM 2.1.2). This allyl functional group was subsequently modified by reaction with thiol‐bearing functional groups to generate carboxyl and amino functionalized biodegradable block copolymers. These end‐group reactions, performed in good yields both in organic media and in aqueous micellar solutions, lead to functionalized PEO‐b‐PMM 2.1.2 copolymers which are of interest for cell targeting purposes.

Synthetic route to α‐allyl functionalized PEO‐b‐PMM 2.1.2 copolymers.     

Well‐defined N‐Isopropylacrylamide Dual‐Sensitive Copolymers with LCST ≈38 °C in Different Architectures: Linear,Block and Star Polymers

Reversible addition‐fragmentation chain transfer (RAFT) polymerization is used to prepare temperature‐ and pH‐sensitive statistical copolymers with lower critical solution temperature (LCST) close to 38 °C at pH 7.4 based on N‐isopropylacrylamide and methacrylic acid derivative comonomers with a pK_a close to 6. Statistical copolymers are re‐activated to prepare amphiphilic block copolymers and star polymers with cross‐linked core. The LCST is maintained by varying the architecture; however, the LCST originated behaviour changes due to self‐aggregation. Statistical copolymers and short block copolymers show complex aggregation, whereas mid‐size block copolymers and star polymers show shrinkage of aggregate dimensions. The pH of the medium has a profound impact on the self‐assembling behaviour of the different polymer architectures.     

Multi‐Responsive Supramolecular Double Hydrophilic Diblock Copolymer Driven by Host‐Guest Inclusion Complexation between β‐Cyclodextrin and Adamantyl Moieties

Well‐defined β‐CD‐terminated poly(N‐isopropylacrylamide) (β‐CD‐PNIPAM) was synthesized via a combination of atom transfer radical polymerization (ATRP) and click chemistry. Moreover, adamantyl‐terminated poly(2‐(diethylamino)ethyl methacrylate) (Ad‐PDEA) was synthesized by ATRP using an adamantane‐containing initiator. Host‐guest inclusion complexation between β‐CD and adamantyl moieties drives the formation of supramolecular double hydrophilic block copolymers (DHBC) from β‐CD‐PNIPAM and Ad‐PDEA. The obtained supramolecular PNIPAM‐b‐PDEA diblock copolymer exhibits intriguing multi‐responsive and reversible micelle‐to‐vesicle transition behavior in aqueous solution by dually playing with solution pH and temperatures.

     

Living Metathesis Polymerization of Diethyl Di‐2‐butynyl Malonate by Molybdenum‐Based Ternary Catalysts

The living polymerization of diethyl di‐2‐butynyl malonate (DEDBM) was achieved with a MoOCl₄‐based ternary catalyst, MoOCl₄—Bu₄Sn—EtOH, to give a polymer with five‐ and six‐membered rings in the main chain. In contrast, the polymerization of diethyl dipropargyl malonate (DEDPM) with the same catalyst led to gelation. Block copolymers were obtained from DEDBM and other substituted acetylenes such as 1‐chloro‐1‐octyne. Poly(DEDBM) forms a condensed monomolecular membrane at the air–water interface.     

Polythiophene Diblock Copolymer with Different Solvent Affinities of the Side‐Chain Substituents: Solvatochromism and Effect on the Electronic Conjugation

A new diblock copolymer composed of a regioregular block of poly[3‐[2‐(2‐methoxyethoxy)ethoxy]methylthiophene], bearing as side‐chain a hydrophilic substituent, and a regioregular block of poly[3‐(1‐octyloxy)thiophene], is prepared and characterized. The properties are compared with those of a related copolymer composed of poly(3‐hexylthiophene) and poly(3‐alkoxythiophene) blocks. The solvatochromic properties of these materials in solution are investigated by absorption and emission spectroscopy upon gradual addition of a poor solvent, and compared with those of the parent regioregular homopolymers. The experimental results are interpreted in terms of electronic interactions between the blocks. It is found that the different hydrophilicity of the side chain plays a crucial role for the electronic communication between blocks in poly(3‐alkylthiophene)‐block‐poly(3‐alkoxythiophene) copolymers.

     

Poly[2,7‐(9,9‐dihexylfluorene)]‐block‐Poly(2‐vinylpyridine) Rod–Coil Star‐block Copolymers: Synthesis,Micellar Structures,and Photophysical Properties

The first successful synthesis of conjugated rod–coil star block copolymer, (PF‐b‐P2VP)_n, containing conjugated poly[2,7‐(9,9‐dihexylfluorene)] (PF), and coil‐like poly(2‐vinylpyridine) (P2VP) by combining a Suzuki coupling reaction and living anionic polymerization is reported. With increasing methanol content in THF/methanol mixtures (PF‐b‐P2VP)_n symmetric star‐block copolymers maintain spherical micelles, but PF‐b‐P2VP asymmetric diblock copolymers vary from spherical micelles to vesicles. Both the absorption and emission spectra of PF‐b‐P2VP blue shift with increasing methanol content, suggesting an “H‐type” aggregation. However, (PF‐b‐P2VP)_n star‐block exhibits no shift in absorption but a red shift in the emission spectra, indicating a different type of aggregation. These results suggest the significance of polymer architectures on microphase‐separated morphologies and photophysical properties.

     

Synthesis,Characterization, and Investigation of Thermosensitive Star‐Shaped Poly(2‐isopropyl‐2‐oxazolines) Based on Carbosilane Dendrimers

Star‐shaped poly(2‐isopropyl‐2‐oxazolines) with dramatically hydrophobic dendrimer core are synthesized using carbosilane dendrimers of first to third generations as macroinitiators. It is observed that half of the initiator functional groups are incorporated in polymerization process. The polymerization degree of polyoxazoline arms is about 25. Strong arm folding results in small molecule dimensions in both aqueous and organic solutions. Thermosensitive properties are studied for second generation‐based star solution with the concentration of 0.00095 g cm⁻³. Model linear poly(2‐isopropyl‐2‐oxazolines) are investigated for comparison. Carbosilane dendrimer core interaction leads to the formation of different types of aggregates at low temperatures. The temperatures of the beginning (T ₁ = 42–43 °C) and finishing (T ₂ = 50 °C) of phase separation are determined. It is shown that macromolecule compactization and aggregation take place even far from the phase transition interval and alternately prevail on heating.

     

β‐Cyclodextrin‐Based Star Amphiphilic Copolymers: Synthesis,Characterization, and Evaluation as Artificial Channels

14‐arm amphiphilic star copolymers are synthesized according to different strategies. First, the anionic ring polymerization of 1,2‐butylene oxide (BO) initiated by per(2‐O‐methyl‐3,6‐di‐O‐(3‐hydroxypropyl))‐β‐CD (β‐CD’OH₁₄) and catalyzed by t‐BuP₄ in DMF is investigated. Analyses by NMR and SEC show the well‐defined structure of the star β‐CD’‐PBO₁₄. To obtain a 14‐arm poly(butylene oxide‐b‐ethylene oxide) star, a Huisgen cycloaddition between an α‐methoxy‐ω‐azidopoly(ethylene oxide) and the β‐CD’‐PBO₁₄,whose end‐chains are beforehand alkyne‐functionalized, is performed. In parallel, 14‐arm star copolymers composed of butylene oxide‐b‐glycidol arms are successfully synthesized by the anionic polymerization of ethoxyethylglycidyl ether (EEGE) initiated by β‐CD’‐PBO₁₄ with t‐BuP₄. The deprotection of EEGE units is then performed to provide the polyglycidol blocks. These amphiphilic star polymers are evaluated as artificial channels in lipid bilayers. The effect of changing a PEO block by a polyglycidol block on the insertion properties of these artificial channels is discussed.     

Synthesis of Star‐Comb Double Crystalline Diblock Copolymer of Poly(ε‐caprolactone)‐block‐poly(l‐lactide): Effect of Chain Topology on Crystallization Behavior

A series of highly branched star‐comb poly(ε‐caprolactone)‐block‐poly(l ‐lactide) (scPCL‐b‐PLLA) are successfully achieved using star‐shaped hydroxylated polybutadiene as the macroinitiator by a simple “grafting from” strategy. The ration of each segment can be controlled by the feed ratio of comonomers. These star‐comb double crystalline copolymers are well‐defined and expected to illustrate the influences of the polymer chain topology by comparing with their counterparts in linear‐shaped, star‐shaped, and linear‐comb shape. The crystallization behaviors of PCL‐b‐PLLA copolymers with different architectures are investigated systematically by means of wide‐angle X‐ray diffraction, differential scanning calorimetry, and polarized optical microscopy analysis. It is shown that the comb branched architectures promote the crystallization behavior of each constituent significantly. Both crystallinity and melting temperature greatly raise from linear to comb‐shaped copolymers. Compared to linear‐comb topology, the star‐comb shape presents some steric hindrance of the graft points, which decrease the crystallinity of scPCL‐b‐PLLA. Effects of copolymer composition and chain topology on the crystallization are studied and discussed.

     

Synthesis,Sequential Crystallization and Morphological Evolution of Well‐Defined Star‐Shaped Poly(ε‐caprolactone)‐b‐poly(L‐lactide) Block Copolymer

Summary: Well‐defined star‐shaped poly(ε‐caprolactone)‐b‐poly(L ‐lactide) copolymers (PCL‐b‐PLLA) were synthesized via sequential block copolymerization, and their molecular weights and arm length ratio could be accurately controlled. Both differential scanning calorimetry and wide angle X‐ray diffraction analysis indicated that the crystallization of both the PLLA and PCL blocks within the star‐shaped PCL‐b‐PLLA copolymer could be adjusted from the arm length of each block, and both blocks mutually influenced each other. The sequential isothermal crystallization process of both the PLLA and PCL blocks within the PCL‐b‐PLLA copolymers was directly observed with a polarized optical microscope, and the isothermal crystallization of the PCL segments was mainly templated by the existing spherulites of PLLA. Moreover, the PLLA blocks within the star‐shaped PCL‐b‐PLLA copolymer progressively changed from ordinary spherulites to banded spherulites when the arm length ratio of PCL to PLLA was increased while concentric spherulites were observed for the linear analog. Significantly, these novel spherulites with concentric or banded textures and the morphological evolution of the spherulites have been observed for the first time in the PCL‐b‐PLLA block copolymers.

     

New Functionalized Anionic Initiators Prepared from Substituted 1,1‐Diphenylethylene Derivatives with Acetal‐Protected Monosaccharides and Their Application to Chain‐Multi‐Functionalized Polymers with Glucose and Galactose Molecules

Living anionic polymerizations of methyl methacrylate, tert‐butyl methacrylate, 2‐(perfluorobutyl)ethyl methacrylate, tert‐butyl acrylate, and ethylene oxide were carried out with functionalized initiators prepared from substituted 1,1‐diphenylethylene (DPE) derivatives with two and four acetal‐protected α‐D ‐glucofuranose and α‐D ‐galactopyranose residues and carbanionic species such as sec‐butyllithium (sec‐BuLi), cumylpotassium, lithium and potassium naphthalenides. In certain cases, either LiCl or diethylzinc was used as an additive to control the polymerization. Several new well‐defined chain‐end‐ and in‐chain‐functionalized polymers with two and four glucose and two galactose molecules were successfully synthesized by these living polymerizations followed by deprotection. We have proposed a promising iterative methodology based on a convergent approach, with which novel two dendritic substituted DPE derivatives with four and eight acetal‐protected D ‐glucofuranose residues can successively be synthesized. With use of the functionalized anionic initiators prepared from such dendritic DPE derivatives and sec‐BuLi in the polymerization of methyl methacrylate, well‐defined chain‐end‐functionalized poly(methyl methacrylate)s with four and eight glucose molecules were synthesized.

     

Synthesis of AB2 3‐ and AB4 5‐Miktoarm Star Copolymers Initiated from Dendritic Tri‐ and Penta‐Functional Initiators by Combination of Ring‐Opening Polymerization of ε‐Caprolactone and Nitroxide‐Mediated Radical Polymerization of Styrene

Summary: Well‐defined AB₂ 3‐ and AB₄ 5‐miktoarm star copolymers were prepared by combination of ring‐opening polymerization (ROP) and nitroxide‐mediated radical polymerization (NMRP) using dendritic tri‐ and penta‐functional initiators. Initially, two kinds of dendritic initiators having one benzylic OH and two or four TEMPO‐based alkoxyamine moieties were prepared. Using them, ROP of ε‐caprolactone was carried out at room temperature to give poly(ε‐caprolactone)s carrying two or four alkoxyamine moieties. NMRP of styrene from the poly(ε‐caprolactone)s was carried out at 120 °C to give AB₂ 3‐ and AB₄ 5‐miktoarm star copolymers, which were analyzed by ¹H NMR and SEC. The increased linearly with conversion and the were in the range 1.10–1.37, showing that well‐defined AB₂ 3‐ and AB₄ 5‐miktoarm star copolymers were formed.

Well‐defined AB₂ 3‐ and AB₄ 5‐miktoarm star copolymers were prepared by combination of ring‐opening polymerization (ROP) and nitroxide‐mediated radical polymerization (NMRP) using dendritic tri‐ and penta‐functional initiators.     

Synthesis of Heterobifunctional Thiol‐poly(lactic acid)‐b‐poly(ethylene glycol)‐hydroxyl for Nanoparticle Drug Delivery Applications

Biocompatible, amphiphilic block copolymers, such as poly(lactic acid)‐b‐poly(ethylene glycol) (PLA‐b‐PEG), that can be conjugated to targeting ligands, therapeutics, and imaging agents are required for the development of polymeric nanoparticle drug delivery systems. Synthesis of targetable, heterobifunctional X‐PLA‐b‐PEG‐Y has required the use of heterobifunctional PEG, which involves specialty equipment to synthesize and is expensive to purchase. Herein, a new method for the synthesis of bifunctional HS‐PLA‐b‐PEG‐OH is described. The approach takes advantage of polymer solution properties to improve a critical purification step, and uses inexpensive and readily available PEG‐diol as a starting material. In the method demonstrated here, the ring‐opening polymerization of PLA is initiated by both ends of a cleavable bifunctional initiator. PEG is conjugated to each PLA end, resulting in a high molecular weight intermediate which is simple to purify from the excess PEG, with recoveries that are nearly three times higher than when a monofunctional initiator is used. Following purification, the triblock copolymer is cleaved to produce the final HS‐PLA‐b‐PEG‐OH product, in which both polymer ends are reactive. Moreover, the polymers successfully stabilize nanoparticles produced by Flash NanoPrecipitation. Importantly, the synthesis method can be adopted by non‐polymer experts.     

Synthesis of Diverse Asymmetric α,ω‐Dienes Via the Passerini Three‐Component Reaction for Head‐to‐Tail ADMET Polymerization

The Passerini three‐component reaction is applied to synthesize, in a one‐step procedure, diverse asymmetric α,ω‐dienes containing an acrylate and a terminal olefin. Such monomers are well known to undergo head‐to‐tail acyclic diene metathesis (ADMET) polymerization due to the high cross‐metathesis selectivity between acrylates and terminal olefins. Additionally, amphiphilic block copolymers are synthesized using a monofunctional PEG₄₈₀ monoacrylate, which acts as a selective chain‐transfer agent during the polymerization process. Thus, control over the molecular weight of the amphiphilic ADMET polymers is shown by using different ratios of mono­mer and chain‐transfer agent. All the polymers are thoroughly characterized, and their ability to form nanoparticles in aqueous solution is studied.

     

Enhanced Preparation of Alkoxyamine‐Functionalized Poly(p‐phenylene)s and Their Use as Macroinitiators for the Synthesis of Stimuli‐Responsive Coil‐Rod‐Coil Block Copolymers

Herein, the enhanced preparation of alkoxyamine‐functionalized poly(p–phenylene)s (PPP) via Suzuki polycondensation (SPC) using microwave irradiation is described. Microwave heating effects a drastic decrease of reaction times compared to conventional heating. By varying the diboronic acid esters within the polymerization process different chain lengths of PPPs ( = 1900?3600 g mol^?1) could be prepared. In addition, by exchange of the catalyst and base either preferably mono‐ or bis‐alkoxyamine‐terminated PPPs could be obtained. These macroinitiators are then applied for the nitroxide‐mediated radical polymerization (NMRP) of N–isopropylacrylamide (NIPAAm) to form PNIPAAm‐b‐PPP‐b‐PNIPAAm block copolymers ( = 24 900–38 400 g mol^?1, / = 1.54–1.67).     

Use of Original ω‐Perfluorinated Dithioesters for the Synthesis of Well‐Controlled Polymers by Reversible Addition‐Fragmentation Chain Transfer (RAFT)

A series of five fluorinated dithioesters PhC(S)SRCH₂C_nF_2n+1 (where R represents an activating spacer and n = 6 or 8) was obtained in fair to high yields (57–88%). These transfer agents were successfully used in reversible addition‐fragmentation transfer (RAFT) of styrene (S), methyl methacrylate (MMA), ethyl acrylate (EA) and 1,3‐butadiene. Well‐chosen fluorinated dithioesters were able to lead to a good control of the radical polymerization of these monomers (i.e., molar masses of the produced polymers increased linearly with the monomer conversion and the polydispersity indexes ranging between 1.1 and 1.6 remained low). The relationship between the structures of the dithioesters and the living behavior of the radical polymerization of these above monomers is discussed and it is shown that the nature of the R group influences the living behavior from different contributions to radical stabilization. Furthermore, the RAFT process also yielded PMMA‐b‐PS and PEA‐b‐PS block copolymers bearing a fluorinated moiety.