Chain-end Modification Research Articles

Polysaccharides as a Hydrophilic Building Block of Amphiphilic Block Copolymers for the Conception of Nanocarriers.

Polysaccharides are gaining increasing attention for their relevance in the production of sustainable materials. In the domain of biomaterials, polysaccharides play an important role as hydrophilic components in the design of amphiphilic block copolymers for the development of drug delivery systems, in particular nanocarriers due to their outstanding biocompatibility, biodegradability, and structural versatility. The presence of a reducing end in polysaccharide chains allows for the synthesis of polysaccharide-based block copolymers. Compared with polysaccharide-based graft copolymers, the structure of block copolymers can be more precisely controlled. In this review, the synthesis methods of polysaccharide-based amphiphilic block copolymers are discussed in detail, taking into consideration the structural characteristics of polysaccharides. Various synthetic approaches, including reductive amination, oxime ligation, and other chain-end modification reactions, are explored. This review also focuses on the advantages of polysaccharides as hydrophilic blocks in polymeric nanocarriers. The structure and unique properties of different polysaccharides such as cellulose, hyaluronic acid, chitosan, alginate, and dextran are described along with examples of their applications as hydrophilic segments in the synthesis of amphiphilic copolymers to construct nanocarriers for sustained drug delivery.

Anionic polymerization of methyl methacrylate and chain-end modification via terminal-selective transesterification with bulky zincate

The anionic polymerization of methyl methacrylate (MMA) was investigated using dilithium tetra-tert-butylzincate (TBZL), which is a bulky zincate, as an initiator. Poly(methyl methacrylate) (PMMA) with a narrow molecular weight distribution was obtained by conducting the polymerization in toluene at −80 °C. Chain-end analysis revealed the formation of PMMA with a tert-butyl group at the α-end and a hydrogen atom at the ω-end. These results suggest the living nature of the present polymerization. However, a prolonged polymerization time or elevated temperature caused backbiting reactions. Postpolymerization modification of the formed PMMA was also investigated using TBZL as a transesterification catalyst. Chain-end analysis revealed that terminal-selective transesterification occurred only at the monomeric unit at the terminating chain end. Therefore, TBZL appears to play dual roles in the production of chain-end-modified PMMA: an initiator for anionic polymerization and a catalyst for terminal-selective transesterification.

Novel Chain-End Modification of Polymer Iodides via Reversible Complexation-Mediated Polymerization with Functionalized Radical Generation Agents.

The modification of polymer chain ends is important in order to produce highly functional polymers. A novel chain-end modification of polymer iodides (Polymer-I) via reversible complexation-mediated polymerization (RCMP) with different functionalized radical generation agents, such as azo compounds and organic peroxides, was developed. This reaction was comprehensively studied for three different polymers, i.e., poly (methyl methacrylate), polystyrene and poly (n-butyl acrylate) (PBA), two different functional azo compounds with aliphatic alkyl and carboxy groups, three different functional diacyl peroxides with aliphatic alkyl, aromatic, and carboxy groups, and one peroxydicarbonate with an aliphatic alkyl group. The reaction mechanism was probed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The combination of PBA-I, iodine abstraction catalyst and different functional diacyl peroxides enabled higher chain-end modification to desired moieties from the diacyl peroxide. The dominant key factors for efficiency in this chain-end modification mechanism were the combination rate constant and the amount of radicals generated per unit of time.

The influence of chain‐end functionalization and stereocomplexation on the degradation stability under alkaline condition

AbstractHydrolytic degradation of polylactides (PLAs) bearing cinnamic acid derivatives was conducted and their thermal degradation temperature at 10% weight loss (T10) and melting point temperature (Tm) were measured, to confirm that a PLA stereocomplex could be modified for use in a wide range of application. The improved T10 values of PLA films by chain end modification were maintained after the alkaline degradation. The increase in Tm by stereocomplex formation was also maintained after degradation with a slight change in the melting point of the attached homopolymer. The present results indicate the suitability of chain end modification for the additional functionality of PLA stereocomplex films.

Dependence of Crystallization Behavior of Interacting Telechelic Poly(butylene succinate) Oligomer on Molecular Weight

A large spherulite structure deteriorates the mechanical properties of crystalline polymers, and therefore various methods have been explored to increase primary nucleation density. Recently, chain-end modification has been proposed as an effective approach for regulating polymer crystal nucleation. However, the relevant nucleation mechanism still requires investigation. Therefore, in this work, 2-ureido-4[1H]-pyrimidinone (UPy) units, which can form stacks via quadruple hydrogen bonds with each other, are introduced as end groups for the preparation of interacting telechelic poly(butylene succinate) (PBS-UPy) oligomers with different molecular weights (Mns). The crystallization, especially the nucleation behavior of PBS-UPy, is studied in detail by comparing with the corresponding pre-polymer, the hydroxyl-terminal PBS (PBS-OH). The thermal properties of PBS-UPy exhibit similar Mn-dependent tendency to those of PBS-OH, but with weaker total crystallization rate. The spherulite growth rate is significantly reduced, whereas the primary nucleation density is highly promoted, after introducing UPy groups. Further investigation reveals that the mechanism of UPy stacks’ influence on nucleation ability changes from inhibition to promotion with respect to Mn. Even under an inhibition of nucleation ability, the final nucleation density is obviously increased because of a significant decline of the growth rate. In addition, the change in the impact of UPy stacks on nucleation ability is speculated to originate from the memory expression feasibility of ordered conformation in the melt during crystallization.

Polymethylene Brushes via Surface-Initiated C1 Polyhomologation.

Surface-initiated polymerization reactions are a powerful tool to generate chain-end-tethered polymer brushes. This report presents a synthetic strategy that gives access to structurally well-defined hydrocarbon polymer brushes of controlled molecular weights, which can be further modified to generate more complex surface-attached polymer architectures. The hydrocarbon brushes reported in this study are polymethylene brushes that are obtained via surface-initiated C1 polyhomologation of dimethylsulfoxonium methylide. The strategy outlined here is based on the use of an alkylboronic acid pinacol ester initiator, which allows for controlled, unidirectional chain growth by monomer insertion into only the C-B bond of the initiator and which presents the polymerization active group at the growing polymer chain end. This surface-initiated C1 polyhomologation methodology is compatible with photopatterning strategies and can be used to generate micropatterned polymethylene brush films. Furthermore, conversion of the boronic ester chain-end functionalities to hydroxyl groups allows for selective chain-end modification and enables access to a variety of surface-anchored block copolymer architectures by chain extension via, for example, ring-opening or atom transfer radical polymerization chemistries.

Syntheses of benzhydryl 2-propanoyl-functionalized trithiocarbonates and its use as chain transfer agents in the RAFT polymerization of styrene

Abstract The preparation of three new benzhydryl 2-propanoyl-functionalized trithiocarbonate RAFT agents, benzhydryl 2-(ethylsulfanylthiocarbonylsulfanyl)propanoate, benzhydryl 2-(butylsulfanylthiocarbonylsulfanyl)propanoate, benzhydryl 2-(dodecylsulfanylthiocarbonylsulfanyl)propanoate is described. The RAFT polymerization of styrene, mediated by the appropriate benzhydryl 2-(alkylsulfanylthiocarbonylsulfanyl)propanoate as the chain transfer agent, with AIBN as initiator at 70 0C, proceeds via reversible-deactivation radical polymerization processes to produce the corresponding α-benzhydryl 2-propanoyl polystyrene derivative, with the benzhydryl ester group introduced at the α-terminus of the polymer chain. Polymerization kinetics measurements show that each RAFT polymerization reaction follows first order rate kinetics with respect to percentage monomer consumption and the number average molecular weights of the functionalized polymers increase linearly with the percentage monomer conversion to produce functionalized polymers with narrow molecular weight distributions. The percentage monomer conversion with time for each polymerization reaction was monitored by 1H NMR spectroscopy by evaluating the consumption of styrene with respect to polymerization time. Post-RAFT polymerization chain end modification of α-benzhydryl 2-propanoyl-functionalized polystyrene by the acid catalyzed ester hydrolysis reactions with concentrated sulfuric acid afforded the corresponding α-carboxyl functionalized polystyrene derivative, with the retention of the thiocarbonylthio moiety at the ω-terminus of the polymer chain. The benzhydryl 2-propanoyl-functionalized trithiocarbonate chain transfer agents and the different functionalized polystyrene derivatives were characterized by 1H NMR, 13C NMR and FTIR spectroscopy, size exclusion chromatography, thin layer chromatography and mass spectrometry measurements.

Antifouling fluoropolymer-coated nanomaterials for 19F MRI.

We developed a multifunctional polymer coating for nanoparticles (NPs) that enables simultaneous detection by 19F MRI and shielding from blood plasma fouling. The coating is based on a water-soluble fluorinated poly(N-(2-fluoroethyl)acrylamide) (PFEAM) that shows high 19F MRI sensitivity, cytocompatibility and excellent antifouling properties, significantly outperforming polyethylene glycol. A proof-of-concept experiment was performed by synthesizing polymer-coated gold NPs that were successfully visualized by 19F MRI at magnetic fields close to the fields used in clinical practice. This universal approach can be used for coating and tracing of various NPs upon suitable polymer chain-end modification.

Synthetic Biodegradable Polymers with Chain End Modification: Polylactide, Poly(butylene succinate), and Poly(hydroxyalkanoate)

Abstract Of the various synthetic biodegradable polymers, polylactide, poly(butylene succinate), and poly(hydroxyalkanoate) have been widely studied and developed. This review focuses on studies of the chain end modification of these polymers. The selected research was categorized into initiators, chain end modification, including chain extending, and the degradation reaction. We cover the recent literature on this topic, and discuss the developing trends and challenges of biodegradable polymers.

Organocatalytic Michael Addition as a Method for Polyisobutylene Chain-End Functionalization.

Functionalization of polyolefins, in particular polyisobutylene, remains a relatively unexplored application for the Michael reaction. This work evaluates the potential of polyisobutylene acrylate (PIBA) chain-end modification via organocatalyzed thiol-Michael and aza-Michael additions. A series of chain-end functional polyisobutylene oligomers are prepared using "click" reactions of thiols or amines to PIBA in the presence of 0.02 equivalents of organocatalyst. Reaction kinetics and chain-end transformations are monitored using NMR spectroscopy and the macromolecular products are characterized by size exclusion chromatography. Further potential of this synthetic strategy is illustrated by thiol-Michael addition of thiols formed in situ via nucleophilic thiolactone ring opening. The obtained results provide an efficient method for the preparation of functional polyisobutylene oligomers that can be utilized in a broad range of potential applications.

Chain-End Modifications and Sequence Arrangements of Antimicrobial Peptoids for Mediating Activity and Nano-Assembly.

Poly(N-substituted glycine) “peptoids” are an interesting class of peptidomimics that can resist proteolysis and mimic naturally found antimicrobial peptides (AMPs), which exhibit wide spectrum activity against bacteria. This work investigates the possibility of modifying peptoid AMP mimics (AMPMs) with aliphatic lipid “tails” to generate “lipopeptoids” that can assemble into micellar nanostructures, and evaluates their antimicrobial activities. Two families of AMPMs with different distributions of hydrophobic and cationic residues were employed—one with a uniform repeating amphiphilicity, the other with a surfactant-like head-to-tail amphiphilicity. To further evaluate the interplay between self-assembly and activity, the lipopeptoids were variously modified at the AMPM chain ends with a diethylene glycol (EG2) and/or a cationic group (Nlys-Nlys dipeptoid) to adjust amphiphilicity and chain flexibility. Self-assembly was investigated by critical aggregation concentration (CAC) fluorescence assays and dynamic light scattering (DLS). The structure of a key species was also verified by small-angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-EM). To screen for antibacterial properties, we measured the minimum inhibitory concentrations (MIC) against S. aureus, E. coli, and P. aeruginosa. We found that certain combinations of lipid tail and AMPM sequences exhibit increased antibacterial activity (i.e., decreased MICs). Perhaps counter-intuitively, we were particularly interested in increased MICs in combination with low CACs. Concealing antimicrobial interactions due to packing of AMPMs in nano-assemblies could pave the way to AMPMs that may be “inert” even if unintentionally released and prevent microbes from gaining resistance to the lipopeptoids. Overall, incorporation of EG2 significantly improved lipopeptoids packing while the hydrophobic tail length was found to have a major influence over the MIC. One particular sequence, which we named C15-EG2-(kss)4, exhibited a very low CAC of 34 μM (0.0075 wt.%) and a significantly increased MIC above values for the unmodified AMPM. With the sequence design trends uncovered from this study, future work will focus on discovering more species such as C15-EG2-(kss)4 and on investigating release mechanisms and the potency of the released lipopeptoids.

RAFT polymerization of styrene mediated by naphthyl-functionalized trithiocarbonate RAFT agents

New oxazolyl benzhydryl and oxazolyl benzyl-functionalized trithiocarbonate RAFT agents, 1-(butylsulfanylthiocarbonylsulfanyl)-1-[4-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)phenyl]-1-phenylmethane and 2-[4-((butylsulfanylthiocarbonylsulfanyl)methyl)phenyl]-4,5-dihydro-4,4-dimethyloxazole, were prepared and employed as chain transfer agents in RAFT polymerization reactions. The RAFT polymerization of styrene, mediated by the appropriate oxazolyl-functionalized trithiocarbonate RAFT agent with AIBN as initiator at 70 °C, proceeded via controlled/living polymerization processes to produce the corresponding α-oxazolyl-functionalized polystyrene derivative, with the oxazolyl group introduced at the α-terminus of the polymer chain and the absence of any unfunctionalized polystyrene. Post-RAFT polymerization chain end modification of α-oxazolyl-functionalized polystyrene by acid-catalyzed hydrolysis reactions with dilute hydrochloric acid afforded the corresponding α-carboxyl-functionalized polystyrene derivative, with the retention of the butylsulfanylthiocarbonylsulfanyl moiety at the ω-terminus of the polymer chain. Polymer kinetic measurements show that each RAFT polymerization reaction follows first-order rate kinetics with respect to the percentage monomer consumption. The oxazolyl-functionalized benzhydryl fragmentation radical provides better control of the re-initiation of the polymerization of styrene than the oxazolyl-functionalized benzyl fragmentation radical. After consumption of the RAFT agent, the number average molecular weights of the functionalized polymers increases linearly with the percentage monomer conversion to produce α-oxazolyl-functionalized polystyrene derivatives with narrow molecular weight distributions. New oxazolyl benzhydryl and oxazolyl benzyl-functionalized trithiocarbonate RAFT agents, 1-(butylsulfanylthiocarbonylsulfanyl)-1-[4-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)phenyl]-1-phenylmethane and 2-[4-((butylsulfanylthiocarbonylsulfanyl)methyl)phenyl]-4,5-dihydro-4,4-dimethyloxazole, were prepared and employed as chain transfer agents in RAFT polymerization reactions. The RAFT polymerization of styrene, mediated by 1-(butylsulfanylthiocarbonylsulfanyl)-1-[4-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)phenyl]-1-phenylmethane or 2-[4-((butylsulfanylthiocarbonylsulfanyl)methyl)phenyl]-4,5-dihydro-4,4-dimethyloxazole as chain transfer agents with AIBN as the initiator at 70 °C, proceeds via a controlled/living polymerization process to produce the corresponding α-oxazolyl-functionalized polystyrene derivative, with the oxazolyl group introduced at the α-terminus of the polymer chain.

Nanoporous poly(ether sulfone) from polylactide-b-poly(ether sulfone)-b-polylactide precursor

We report a route to synthesize polylactide-b-poly(ether sulfone)-b-polylactide (PLA-b-PES-b-PLA) containing PES and PLA, which provide a mechanically robust framework and a sacrificial template for pore formation, respectively. High-molar mass PES terminated with fluorine groups was synthesized by the step-growth nucleophilic aromatic substitution (SNAr) reaction, and the chain ends were transformed into benzylic hydroxyl groups by chain end modification. Growth of the PLA using the hydroxyl groups as initiating sites via chain-growth ring opening transesterification polymerization (ROTEP) produced the target triblock copolymer. Although the step-growth polymerization produced a PES middle block with high dispersity, small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) analyses indicated the formation of an ordered lamellar morphology. We further demonstrated that a nanoporous PES with slit-like pores could be obtained by selective removal of the PLA.

A photo-selective chain-end modification of polyacrylate-iodide and its application in patterned polymer brush synthesis

A photo-selective chain-end modification of polyacrylate-iodide (polymer-I) was developed. The method was used to generate chain-end patterned polymer brushes.

Chain-End Functionalization with a Saccharide for 10 nm Microphase Separation: “Classical” PS-b-PMMA versus PS-b-PMMA-Saccharide

Microphase-separated structures of block copolymers (BCPs) have attracted much attention as template materials for bottom-up nanofabrication. At the same time, chain-end modification has become a leading facile and efficient technique for fine-tuning the morphologies of microphase-separated structures generated from BCPs. Herein, we describe the preparation of well-defined polystyrene-block-poly(methyl methacrylate)s (PS-b-PMMAs) bearing highly hydrophilic mono/oligosaccharide moieties at their PMMA chain ends (SM-mono/oligosaccharides) as well as the impact of the mono/oligosaccharide on microphase separation behavior. PS-b-PMMAs were terminal-selectively transesterified using the titanium alkoxide of 6-azido-1-hexanol to introduce azido groups into the side chains of the terminal MMA units. The azido-functionalized PS-b-PMMAs were subsequently click reacted with ethynyl-functionalized mono/oligosaccharides to yield SM-mono/oligosaccharides. Small-angle X-ray scattering and microscopy experiments reveal ...

Enhancing Temporal Control and Enabling Chain-End Modification in Photoregulated Cationic Polymerizations by Using Iridium-Based Catalysts.

Gaining temporal control over chain growth is a key challenge in the enhancement of controlled living polymerizations. Though research on photocontrolled polymerizations is still in its infancy, it has already proven useful in the development of previously inaccessible materials. Photocontrol has now been extended to cationic polymerizations using 2,4,6-triarylpyrylium salts as photocatalysts. Despite the ability to stop polymerization for a short time, monomer conversion was observed over long dark periods. Improved catalyst systems based on Ir complexes give optimal temporal control over chain growth. The excellent stability of these complexes and the ability to tune the excited and ground state redox potentials to regulate the number of monomer additions per cation formed allows polymerization to be halted for more than 20 hours. The excellent stability of these iridium catalysts in the presence of more nucleophilic species enables chain-end functionalization of these polymers.

Sequential synthesis of well-defined poly(vinyl acetate)-block-polystyrene and poly(vinyl alcohol)-block-polystyrene copolymers using difunctional chloroamide-xanthate iniferter

The sequential synthesis of well-defined poly(vinyl acetate)-block-polystyrene copolymer (PVAc-b-PS) and poly(vinyl alcohol)-block-polystyrene copolymer (PVA-b-PS) is challenging due to inactive vinyl acetate monomer and active styrene monomer. In this study, sequential polymerizations of vinyl acetate and styrene monomer were carried out by reversible addition-fragmentation chain transfer (RAFT) and atom transfer radical polymerization (ATRP) using an innovative amide based difunctional chloroamide-xanthate iniferter [S-(1-((3-(2-chloropropanamido)propyl) amino)-1-oxopropan-2-yl) O-ethyl xanthate]. Synthesized difunctional iniferter was very stable under basic condition and allowed the sequential reactions without chain-end modification and purification steps. Synthesized iniferter was first used for xanthate-mediated RAFT polymerization of VAc, followed by ATRP of styrene to achieve controlled molecular weight of PVAc-b-PS with lower polydispersity (≤1.3). Then, PVAc-b-PS was successfully converted to the corresponding PVA-b-PS by hydrolysis. Synthesized block copolymers were characterized by size exclusion chromatography, nuclear magnetic resonance spectroscopy, transmission electron microscopy, and dynamic light scattering.

Modulated release from implantable ocular silicone oil tamponade drug reservoirs.

ABSTRACTComplicated cases of retinal detachment can be treated with silicone oil tamponades. There is the potential for silicone oil tamponades to have adjunctive drug releasing behaviour within the eye, however the lipophilic nature of silicone oil limits the number of drugs that are suitable, and drug release from the hydrophobic reservoir is uncontrolled. Here, a radiometric technique was developed to accurately measure drug solubility in silicone oil and measure release into culture media. All‐trans retinoic acid (atRA), a lipophilic drug known to act as an anti‐proliferative within the eye, was used throughout this work. Chain‐end modification of polydimethylsiloxane with atRA produced a polydimethylsiloxane retinoate (PDMS‐atRA), which was used as an additive to silicone oil to modify the solvent environment within the silicone oil and the distribution coefficient. Blends of PDMS‐atRA and silicone oil containing different concentrations of free atRA were produced. The presence of PDMS‐atRA in silicone oil had a positive effect on atRA solubility and the longevity of release in vitro. The drug release period was independent of atRA starting concentration and dependent on the PDMS‐atRA concentration in the blend. A clinically relevant release period of atRA over 7 weeks from a silicone oil blend with PDMS‐atRA was observed. © 2018 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 938–946

Synthesis of Poly(N-H benzamide)-b-poly(lauryl methacrylate)-b-poly(N-H benzamide) symmetrical triblock copolymers by combinations of CGCP, SARA ATRP, and SA ATRC

We design a novel ABA type triblock copolymer (triBCP) by performing efficient synthetic methods of chain-growth condensation polymerization (CGCP), supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP), and styrenics-assisted atom transfer radical coupling (SA ATRC). A well-defined poly(3-(N-(octyloxy)benzyl benzamide) having a 2-bromo-2-phenylacetate effective ATRP initiating site (i.e., POOBBA-BrPA) through CGCP following quantitative chain end modifications, was firstly synthesized. The POOBBA-BrPA macroinitiator then conducted chain extension with lauryl methacrylate (LMA) via SARA ATRP to obtain the POOBBA-b-PLMA-Br diBCP (Mn = 8800 and Mw/Mn = 1.15). This was followed by SA ATRC of POOBBA-b-PLMA-Br with a high extent of coupling (xc = 0.85, Mn = 15300, and Mw/Mn = 1.26). The obtained triBCP was further purified and the selective removal of the protecting group yielded poly(N-H benzamide)-b-poly(lauryl methacrylate)-b-poly(N-H benzamide) (i.e., PNHBA-b-PLMA-b-PNHBA) was conducted. The characterization of these copolymers was performed using 1H NMR, GPC, FT-IR, TGA, DSC, AFM and SAXS.

Recyclable Telechelic Cross-Linked Polybutadiene Based on Reversible Diels–Alder Chemistry

Chain-end modification of low molar mass polybutadienes allowed the formation of thermoreversible networks based on the Diels–Alder chemistry. Furan telechelic polybutadienes with various chain length were first synthesized. Addition of a bis-maleimide (BM) compound to the liquid polymer led to the formation of elastomeric networks. Properties of this material were highly affected by the chain length of the polymer precursor and the cross-linking density, monitored by changing the quantity of the BM compound. Finally, the capacity of recycling of the rubber was shown by remolding the used material over five cycles without mechanical properties loss.