End-group Fidelity Research Articles

Acid-Enhanced Photoiniferter Polymerization under Visible Light.

Photoiniferter (PI) is a promising polymerization methodology, often used to overcome restrictions posed by thermal reversible addition-fragmentation chain-transfer (RAFT) polymerization. However, in the overwhelming majority of reports, high energy UV irradiation is required to effectively trigger photolysis of RAFT agents and facilitate the polymerization, significantly limiting its potential, scope, and applicability. Although visible light PI has emerged as a highly attractive alternative, most current approaches are limited to the synthesis of lower molecular weight polymers (i.e. 10,000 g/mol), and typically suffer from prolonged reaction times, extended induction periods, and higher dispersities when high activity CTAs (photoiniferters), such as trithiocarbonates, are employed. Herein, an acid-enhanced PI polymerization is introduced that efficiently operates under visible light irradiation. The presence of small amounts of biocompatible citric acid fully eliminates the lengthy induction period (21 hours) by enhancing photolysis, rapidly consuming the CTA, and accelerating the reaction rate, yielding polymers with narrow molar mass distributions (Ð ~1.1), near-quantitative conversions (>97 %), and high end-group fidelity in just two hours. A particularly noteworthy aspect of this work is the possibility to target very high degrees of polymerization (i.e. DP=3,000) within short timescales (i.e. less than five hours) without compromising the control over the dispersity (Ð ~1.1). The versatility of the technique is further demonstrated through the synthesis of well-defined diblock copolymers and its compatibility to various polymer classes (i.e. acrylamides, acrylates, methacrylates), thus establishing visible-light PI as a robust tool for polymer synthesis.

Xanthate Disulfide-Mediated RAFT Polymerization Toward Oxygen Tolerance.

In recent years, the fully oxygen-tolerant reversible addition-fragmentation chain transfer (RAFT) polymerization has been emerging as a versatile and powerful tool for preparing well-defined polymers. In this contribution, the symmetrical diethyl xanthogen disulfide (XD) is successfully used as an initiator, chain transfer agent, and termination (iniferter) agent to directly regulate the open-to-air RAFT polymerization. The high end-group fidelity of polymer demonstrated by nuclear magnetic resonance (1H-NMR) and matrix-assisted laser desorption/ionization time-of-flight mass spectra indicates that sulfur-centered xanthate radical can initiate and regulate RAFT polymerization of methacrylate (MA) under open conditions. It is believed that sulfur-centered xanthate radical initiation strategy provides a powerful and minimalist tool for fully oxygen-tolerant RDRPs.

Synthesis of linear and crosslinked isosorbide-containing poly(β-thioether ester) via amine-catalyzed thiol-Michael addition

In this work, the amine-catalyzed thiol-Michael reaction of isosorbide or isomannide-derived dithiols as Michael-donors, with some diacrylates and dimethacrylates as Michael-acceptors, is reported. In a first part, different amines (1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU), dimethylaminopyridine (DMAP), Amberlyst® A-21 and hexylamine (HA)) were tested as catalysts for reactions involving diacrylates and dimethacrylates in acetonitrile, respectively. Molecular weight taken as the relevant criterion, DBU and DMAP were found to be equally efficient for polymerization with acrylates while DBU was the most efficient one with methacrylates. A library of polymers differing from the structure of the used diacrylate (some of them derived from isosorbide or isomannide) or dimethacrylate was prepared, with fair molecular weights and Tg varying from –22 to +32 °C. Then oligomers with controlled molecular weight and good end group fidelity were prepared, and were further used in a two-stage crosslinking reaction to prepare soft and elastic biobased crosslinked polymers via thiol-Michael addition.

Scalable Approach to Molecular Motor-Polymer Conjugates for Light-Driven Artificial Muscles.

The integration of molecular machines and motors into materials represents a promising avenue for creating dynamic and functional molecular systems, with potential applications in soft robotics or reconfigurable biomaterials. However, the development of truly scalable and controllable approaches for incorporating molecular motors into polymeric matrices has remained a challenge. Here, it is shown that light-driven molecular motors with sensitive photo-isomerizable double bonds can be converted into initiators for Cu-mediated controlled/living radical polymerization enabling the synthesis of star-shaped motor-polymer conjugates. This approach enables scalability, precise control over the molecular structure, block copolymer structures, and high-end group fidelity. Moreover, it is demonstrated that these materials can be crosslinked to form gels with quasi-ideal network topology, exhibiting light-triggered contraction. The influence of arm length and polymer structure is investigated, and the first molecular dynamics simulation framework to gain deeper insights into the contraction processes is developed. Leveraging this scalable methodology, the creation of bilayer soft robotic devices and cargo-lifting artificial muscles is showcased, highlighting the versatility and potential applications of this advanced polymer chemistry approach. It is anticipated that the integrated experimental and simulation framework will accelerate scalable approaches for active polymer materials based on molecular machines, opening up new horizons in materials science and bioscience.

Influence of chirality on protein corona formation of low-fouling chiral poly(2-oxazoline) coated nanoparticles

Low-fouling polymers play a crucial role in the development of therapeutic nanoparticles (NPs), which are commonly described as nanomedicines. These hydrophilic polymers are typically designed to favourably alter the protein corona that forms around a NP by reducing the binding of opsonins, resulting in reduced immune recognition and clearance. The polymer specific proteome of the corona is mainly dictated by the physicochemical properties of the polymer and several parameters such as hydrophilicity and charge have been explored to regulate its composition. To date, there has been little attention given to the influence of the chirality of the hydrophilic polymer on the composition of the corona. Water-soluble poly(2,4-dialkyl-2-oxazoline)s (PdOx) are a unique synthetic polymer class to explore the effect of chirality as they can be rendered optically active if enantiopure monomers are used for their synthesis. Herein we prepared two water-soluble poly(2,4-dimethyl-2-oxazoline)s (PdMeOx) of different handedness, alongside racemic PdMeOx and the well-established low-fouling structural isomer poly(2-ethyl-2-oxazoline) (PEtOx). All polymers were equipped with sulphur-containing xanthate moieties with high end-group fidelity, which enabled anchoring to gold nanoparticles (AuNPs) as a useful handle for evaluation of the polymer-specific fouling. It was revealed that a hard corona formed after exposing the coated AuNP to human plasma proteins as investigated by dynamic light scattering, SDS-PAGE and PierceTM bicinchoninic acid protein assay (BCA) revealing a similar protein adsorption between PEtOx and all three PdMeOx. Moreover, a detailed proteomics study using liquid chromatography coupled to mass spectrometry (LC–MS/MS) was performed and analysed by label-free quantitation (LFQ). Overall, the PdMeOx systems showed similar human plasma protein corona profiles compared to the PEtOx control. However, between the R- and S-PdMeOx enantiomers differences in protein population abundances were observed, suggesting the propensity for specific interaction of chiral PdOx with different elements of the proteome. Overall, the present study introduces PdMeOx as a chiral, low fouling polymer system, which can reduce protein fouling in a similar magnitude to the PEtOx control. Importantly, we provide a first insight into how changes in the chirality of PdMeOx can influence the components of the protein corona, which will inform the future design of PdOx nanotherapeutics.

A Single Amino Acid Able to Promote High-Temperature Ring-Opening Polymerization by Dual Activation.

Amino acids are indispensable compounds in the body, performing several biological processes that enable proper functioning. In this work, it is demonstrated that a single amino acid, taurine, is also able to promote the ring-opening polymerization (ROP) of several cyclic monomers under industrially relevant conditions. It is shown that the unique zwitterionic structure of taurine, where the negatively charged sulfonic acid group and the protonated amine group are separated by two methylene groups, not only provides high thermal stability but also leads to a dual activation mechanism, which is corroborated by quantum mechanical calculations. This unique mechanism allows for the synthesis of polylactide of up to 50kDa in bulk at 180 °C with good end-group fidelity using a highly abundant catalyst. Furthermore, cytotoxicity tests confirm that PLLA synthesized with taurine is non-toxic. Moreover, it is demonstrated that the presence of taurine does not have any detrimental effect on the thermal stability of polylactide, and therefore polymers can be used directly without any post-polymerization purification. It is believed that the demonstration that a simple structure composed of a single amino acid can promote polymerization can bring a paradigm shift in the preparation of polymers.

Acid-triggered radical polymerization of vinyl monomers

Reversible addition–fragmentation chain-transfer (RAFT) polymerization is one of the most versatile and robust controlled radical polymerization methods owing to its broad material scope and high tolerance to various functionalities and impurities. However, to operate RAFT polymerization, a constant supply of radicals is required, typically via exogenous thermal radical initiators that are not only challenging to transport and store, but also primarily responsible for termination and end-group heterogeneity. Here we present an acid-triggered RAFT polymerization that operates in the dark and without any conventional radical initiator. Abundant acids (for example, sulfuric acid) are shown to have a dual role initiating and accelerating the polymerization. The polymers prepared have low dispersity and high end-group fidelity. The method is compatible with a wide range of vinyl monomers and solvents, and can be applied to the synthesis of well-controlled high molecular weight block copolymers, as well as to free radical polymerization.

Enhanced synthesis of multiblock copolymers via acid-triggered RAFT polymerization.

The synthesis of multiblock copolymers has emerged as an efficient tool to not only reveal the optimal way to access complex structures and investigate polymer properties but also to ascertain the end-group fidelity of a given polymerization methodology. Although reversible addition-fragmentation chain-transfer (RAFT) polymerization is arguably the most dominant strategy employed, its success is often hampered by the unavoidable and excessive use of radical initiators which results in increased termination and loss of end-group fidelity. In this work, we employ acid in RAFT polymerization to enhance the synthesis of multiblock copolymers. By the addition of a small amount of acid, a 4-fold decrease in the overall required radical initiator concentration was achieved, enabling the synthesis of a range of well-defined multiblock copolymers with various degrees of polymerization (DP) per block. The acid enhances the propagation rate, minimizing the initiator concentration. In all cases, near-quantitative monomer conversion was obtained (>97%) for every iterative block formation step. Notably, and in contrast to conventional RAFT approaches, the tailing to low molecular weight was significantly suppressed and the dispersity was maintained nearly constant (i.e. in most cases Đ = 1.1-1.2), thus indicating minor termination events and side reactions during acid-enhanced synthesis. The possibility to synthesize multiblocks consisting of methacrylates, acrylates, and acrylamides was also demonstrated. This work presents an advancement in the synthesis of well-defined multiblock copolymers and more broadly, RAFT polymers with high end-group fidelity.

Precise Synthesis of Tetrablock Copolymers of Different Acrylamide Derivatives via Iterative Aqueous Cu(0)-Mediated Polymerization

The accessibility of specific synthesis of tetrablock copolymers is reported. In a specific synthesis, four acrylamide monomers are gradually added using an iterative aqueous Cu(0)-mediated reversible-deactivation radical polymerization (RDRP) method. Essential to the success of this approach is the ability to design and polymerize ABCD copolymer sequence with no need for immediate purification steps. The simple in-situ sequential polymerization method allowed for essentially perfect control of accurately well-defined tetrablock copolymers, which are composed of four tiny blocks, each of which contains an average of ten functional monomer units of acrylamide derivatives, resulting in a variety of functional groups. While the final molecular weight distributions have very narrow despersities (Đ < 1.10), the efficient successive chain extension polymerization proceeded with high monomer conversions (>99%), delivering excellent block purification in a short period of time. The tetrablock poly(NIPAM-DMA-HEAA-DEA) was characterized by NMR and GPC and showed beneficial end-group fidelity, allowing quantitative monitoring of the system’s alive nature after each synthetic cycle. Importantly, these one-pot syntheses are carried out at a below temperature of 0.0 °C in water as the solvent and can be implemented for applications of molecular biology. We also investigate the potential for a copper-amide complex to develop with acrylamide monomer, which could have an adverse effect on the end group’s functioning. Finally, we believe that this approach makes it easier to create a novel category of advanced polymeric materials.

Evaluating Catalyst Performance in Synthesizing Hydroxyl-Terminated Polybutadiene by Ring-Opening-Metathesis Polymerization

AbstractHydroxyl-terminated polybutadiene (HTPB) can be synthesized by ring-opening metathesis polymerization (ROMP) in a one-step process using cyclooctadiene in the presence of a hydroxyl-functionalized chain-transfer agent (CTA). However, previous studies have shown that the presence of primary alcohols can lead to the degradation of some ruthenium catalysts and that the hydroxyl end groups may be converted into aldehydes. Here we compare the performance of five ruthenium-based catalysts — Grubbs first-, second-, and third-generation catalysts (G1, G2, and G3, respectively), Hoveyda–Grubbs Z-selective catalyst (HGZ), and Hoveyda–Grubbs second-generation catalyst (HG2) — in ROMP with a CTA containing primary alcohols. We found that HTPB can be rapidly synthesized in a single step using G3 while avoiding end-group isomerization (2.2% aldehyde formation after full conversion is reached in 5 min). This result suggests that G3 may enable a more effective approach to synthesizing HTPB that avoids protecting groups but still maintains high end-group fidelity.

Cocontinuous Nanostructures by Microphase Separation of Statistically Cross-Linked Polystyrene/Poly(2-vinylpyridine) Networks.

Cocontinuous polymeric nanostructures have drawn considerable attention due to their ability to combine distinct, percolation-dependent properties of two different polymer domains. Randomly end-linked copolymer networks (RECNs) have previously been shown to support the formation of disordered cocontinuous nanostructures across wide composition windows in a robust way. However, achieving highly efficient linking of telechelic polymers with excellent end-group fidelity often requires complex synthetic routes. As an alternative, we study here statistically cross-linked copolymer networks (SCCNs) composed of polystyrene and poly(2-vinylpyridine) (PS and P2VP) with cross-linkable allyl pendent groups that are conveniently synthesized by controlled radical copolymerization. Via selective extraction of P2VP, coupled with gravimetry, small-angle X-ray scattering, and electron microscopy, we find disordered cocontinuous phases across wide composition ranges (up to ≈ 35 wt %), approaching values previously determined for RECNs. Remarkably, even for samples that appear to exhibit full percolation, a substantial fraction of P2VP (≈ 20-30 wt %) cannot be removed, which we ascribe to short strands between nearby cross-linkers that are physically embedded within PS domains. The resulting PS porous monoliths with residual surface P2VP layers enable facile surface modification to resist protein adsorption and templating of porous gold nanostructures.

Photocatalytic ATRP Depolymerization: Temporal Control at Low ppm of Catalyst Concentration.

A photocatalytic ATRP depolymerization is introduced that significantly suppresses the reaction temperature from 170 to 100 °C while enabling temporal regulation. In the presence of low-toxicity iron-based catalysts and under visible light irradiation, near-quantitative monomer recovery could be achieved (up to 90%), albeit with minimal temporal control. By employing ppm concentrations of either FeCl2 or FeCl3, the depolymerization during the dark periods could be completely eliminated, thus enabling temporal control and the possibility to modulate the rate by simply turning the light "on" and "off". Notably, our approach allowed preservation of the end-group fidelity throughout the reaction, could be carried out at high polymer loadings (up to 2M), and was compatible with various polymers and light sources. This methodology provides a facile, environmentally friendly, and temporally regulated route to chemically recycle ATRP-synthesized polymers, thus opening the door for further opportunities.

Chemoselectivity Streamlines the Approach to Linear and Y-Shaped Thiol-Polyethers Starting from Thiocarboxylic Acids.

Thiol-functionalized polyethers, especially poly(ethylene oxide) (PEO), have extensive applications in biomedicine and materials sciences. Herein, we report a simple one-pot synthesis of α-thiol-ω-hydroxyl polyethers through ring-opening polymerization (ROP) of epoxides using thiocarboxylic acid initiators followed by in situ aminolysis. The efficient and chemoselective metal-free Lewis pair catalyst avoids transthioesterification thus achieving well-controlled molar mass, low dispersity, and high end-group fidelity. Kinetic and calculation results demonstrated a fast-initiation mode of the ROP for the strong nucleophilicity of the thiocarboxylate anion and its weak interaction with Lewis acid. The method is expanded for α-thiol-ω-dihydroxyl (Y-shaped) PEO by virtue of the stability of thioester during the ROP. The thiol functionality in linear/Y-shaped PEO is further corroborated by the intensified interaction with gold surface and the resultant protein resistance behavior.

Photo Fenton RAFT Polymerization of (Meth)Acrylates in DMSO Sensitized by Methylene Blue.

A novel open-to-air photo RAFT polymerization of a series of acrylate and methacrylate monomers mediated by matching chain transfer agent irradiated by far-red light in DMSO is reported. Hydroxyl radical (•OH) generated from methylene blue (MB) sensitized decomposition of H2 O2 via photo-Fenton like-reaction is used for polymerization initiation. The "living/control" characteristic is evidenced by kinetic study, in which a pseudo first order curve and linearly increases of molecular weight with the increase of monomer conversion are observed. The living end-group fidelity is characterized by MALDI-TOF-MS and 1 H NMR results, and confirmed by successful chain extension. The temporary controllability is proved by light on/off switch experiment. This article is protected by copyright. All rights reserved.

Reversed Controlled Polymerization (RCP): Depolymerization from Well-Defined Polymers to Monomers

Controlled polymerization methods are well-established synthetic protocols for the design and preparation of polymeric materials with a high degree of precision over molar mass and architecture. Exciting recent work has shown that the high end-group fidelity and/or functionality inherent in these techniques can enable new routes to depolymerization under relatively mild conditions. Converting polymers back to pure monomers by depolymerization is a potential solution to the environmental and ecological concerns associated with the ultimate fate of polymers. This perspective focuses on the emerging field of depolymerization from polymers synthesized by controlled polymerizations including radical, ionic, and metathesis polymerizations. We provide a critical review of current literature categorized according to polymerization technique and explore numerous concepts and ideas which could be implemented to further enhance depolymerization including lower temperature systems, catalytic depolymerization, increasing polymer scope, and controlled depolymerization.

Chemical Recycling of Polymethacrylates Synthesized by RAFT Polymerization.

Reversing controlled radical polymerization and regenerating the monomer has been a long-standing challenge for fundamental research and practical applications. Herein, we report a highly efficient depolymerization method for various polymethacrylates synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization. The depolymerization process, which does not require any catalyst, exhibits near-quantitative conversions of up to 92%. The key aspect of our approach is the utilization of the high end-group fidelity of RAFT polymers to generate chain-end radicals at 120 °C. These radicals trigger a rapid unzipping of the polymethacrylates. The depolymerization product can be utilized to either reconstruct the linear polymer or create an entirely new insoluble gel that can also be subjected to depolymerization. Our depolymerization strategy offers a promising route towards the development of sustainable and efficient recycling methods for complex polymer materials.

Atom-Transfer Radical Polymerization of a SuFExable Vinyl Monomer and Polymer Library Construction via SuFEx Click Reaction

The advancement in the synthesis of functional polymeric materials has greatly benefited from the development of functionalized monomers and effective polymerization methods. Here, inspired by the controlled radical polymerization and the new generation of click chemistry, sulfur(VI) fluoride exchange (SuFEx), we introduce a SuFExable vinyl monomer, 4-vinylbenzenesulfonyl fluoride (VBSF), which shows a good balance of stability and reactivity and can readily undergo organocatalytic atom-transfer radical polymerization under visible light with good controls and high end-group fidelity, while retaining the sulfonyl fluoride groups intact. Moreover, poly(VBSF) can be further modified with high efficiency via SuFEx reactions with various aryl silyl ethers, thus allowing a rapid construction of a functional polymer library in a click fashion.

Oxygen-Enhanced Atom Transfer Radical Polymerization through the Formation of a Copper Superoxido Complex.

In controlled radical polymerization, oxygen is typically regarded as an undesirable component resulting in terminated polymer chains, deactivated catalysts, and subsequent cessation of the polymerization. Here, we report an unusual atom transfer radical polymerization whereby oxygen favors the polymerization by triggering the in situ transformation of CuBr/L to reactive superoxido species at room temperature. Through a superoxido ARGET-ATRP mechanism, an order of magnitude faster polymerization rate and a rapid and complete initiator consumption can be achieved as opposed to when unoxidized CuBr/L was instead employed. Very high end-group fidelity has been demonstrated by mass-spectrometry and one-pot synthesis of block and multiblock copolymers while pushing the reactions to reach near-quantitative conversions in all steps. A high molecular weight polymer could also be targeted (DPn = 6400) without compromising the control over the molar mass distributions (Đ < 1.20), even at an extremely low copper concentration (4.5 ppm). The versatility of the technique was demonstrated by the polymerization of various monomers in a controlled fashion. Notably, the efficiency of our methodology is unaffected by the purity of the starting CuBr, and even a brown highly-oxidized 15-year-old CuBr reagent enabled a rapid and controlled polymerization with a final dispersity of 1.07, thus not only reducing associated costs but also omitting the need for rigorous catalyst purification prior to polymerization.

Organocatalyzed Ring-Opening Polymerization of (S)-3-Benzylmorpholine-2,5-Dione.

A 3-benzylmorpholine-2,5-dione monomer is synthesized from the natural amino acid l-phenylalanine and characterized by means of nuclear magnetic resonance and infrared spectroscopy, electrospray ionization mass spectrometry, and elemental analysis. Subsequent to preliminary polymerization studies, a well-defined poly(ester amide) homopolymer is synthesized via ring-opening polymerization using a binary catalyst system comprising1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and a 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea (TU) cocatalyst with a feed ratio of M/I/DBU/TU = 100/1/1/10. Kinetic studies reveal high controllability of the dispersities and molar masses up to conversions of almost 80%. Analysis by mass spectrometry hints toward excellent end-group fidelity at these conditions. In consequence, utilization of hydroxyl-functionalized poly(ethylene glycol) and poly(2-ethyl-2-oxazoline) as macroinitiators results in amphiphilic block copolymers. Bulk miscibility of the building blocks is indicated by differential scanning calorimetry investigations. As more and more promising new drugs are based on hydrophobic molecules featuring aromatic moieties, the novel polyesteramides seem highly promising materials to be used as potential drug delivery vehicles.

Simple and safe liquid seal approach to oxygen-tolerant ATRP

Trace oxygen is fatal to the conventional reversible deactivation radical polymerization (RDRP), so it is necessary to eliminate the influence of oxygen through some strict deoxygenation operations or by adding external components (post-treatment required). Here, we report the effective barrier of oxygen dissolution in an open system built by a liquid seal. Two different liquid seal materials, liquid paraffin and lithium grease, are used in this work. Lithium grease materials can stably isolate oxygen at a high stirring speed (450 rpm) to intensify the heat and mass transfer processes during the reaction. An effective atom transfer radical polymerization (ATRP) could be assisted by simply adding liquid seal materials with a thickness of 5 mm, providing polymers with high conversion (≥90 %), controlled molecular weight, narrow molecular weight distribution (Mw/Mn ≤ 1.15) and high end-group fidelity. With this liquid seal strategy, dozens of grams of the polymer were obtained, which is expected to have potential industrial applications under ambient atmosphere and conditions.