C. Remzi Becer

Lignocellulosic biomass: a sustainable platform for the production of bio-based chemicals and polymers

The demand for petroleum dependent chemicals and materials has been increasing despite the dwindling of their fossil resources. As the dead-end of petroleum based industry has started to appear, todays modern society has to implement alternative energy and valuable chemical resources immediately. Owing to the importance of lignocellulosic biomass being the most abundant and bio-renewable biomass on earth, this critical review provides insights into the potential of lignocellulosic biomass as an alternative platform to fossil resources. In this context, over 200 value-added compounds, which can be derived from lignocellulosic biomass by various treatment methods, are presented with their references. Lignocellulosic biomass based polymers and their commercial importance are also reported mainly in the frame of these compounds. This review article aims to draw the map of lignocellulosic biomass derived chemicals and their synthetic polymers, and to reveal the scope of this map in todays modern chemical and polymer industry.

Self-healing and self-mendable polymers

Smart materials with the ability to repair themselves have been the focus of different fields of science and engineering. This mini-review provides an insight into the rapidly expanding area of research into smart materials with self-healing properties and also discusses both chemical (reversible and polymeric) and non-chemical (irreversible and microvascular) systems, with emphasis focused on the recent reports in the field.

Investigation into thiol-(meth)acrylate Michael addition reactions using amine and phosphine catalysts

This work describes a study into thiol–ene based Michael addition reactions. Different catalysts, primary and tertiary amines and phosphines, were investigated for the reaction of a range of thiols with dimers and oligomers of some (meth)acrylates. Primary and tertiary amines are efficient catalysts for the thiol–ene reaction, although these catalysts require several hours to reach high conversion. Moreover, the phosphine catalysts, dimethylphenylphosphine (DMPP) and tris-(2-carboxyethyl)phosphine (TCEP), were investigated in detail. DMPP is an efficacious catalyst yielding complete conversion in few minutes under optimized conditions. Importantly, the concentration of DMPP should be kept at catalytic levels to avoid the formation of by-products, originating from the addition of DMPP to the vinyl group. Furthermore, TCEP is an efficient catalyst for thiol–ene reactions in aqueous media when the pH of the medium is higher than 8.0 since at acidic pH the formation of by-products is observed.

Sequence-controlled multi-block glycopolymers to inhibit DC-SIGN-gp120 binding.

Glycan–protein interactions are essential for many physiological processes including cell–cell recognition, cell adhesion, cell signalling, pathogen identification, and differentiation. Dendritic cell-specific intercellular adhesion molecule3-grabbing non-integrin (DC-SIGN; CD209) is a C-type lectin (carbohydrate-binding protein) present on both macrophages and dendritic cell subpopulations and plays a critical role in many cell interactions. DC-SIGN binds to microorganisms and host molecules by recognizing surface-rich mannose-containing glycans through multivalent glycan– protein interactions and serves as a target for several viruses, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Carbohydrate-binding proteins (CBP) have been suggested as potential microbicides for the prevention of HIV infection. However, the isolation of natural CBPs is relatively difficult because of their hydrophilic nature and low affinity for the virus. 4] Thus, synthetic lectins are of interest for carbohydrate recognition studies. Alternatively, noncarbohydrate inhibitors of mammalian lectins can be used to prevent the interaction between DC-SIGN and gp120. The structures of these multivalent ligands have a great effect on carbohydrate binding to lectins, and the use of linear polymers to effectively inhibit lectin binding has been demonstrated by several research groups. Synthetic polymer chemistry has developed rapidly in recent years. Currently, polymerization of functional monomers with the desired chain length, structure, and composition is straightforward; whereas producing polymers with monomer sequence control remains challenging, which has implications for the controlled folding of synthetic macromolecules. There are a few recent reports where sufficient control has been achieved in controlling the monomer sequence along the polymer chain. To the best of our knowledge, this is the first report where some control over the relative position of the sugars is exhibited and their binding to the human lectin DC-SIGN is demonstrated. We have used a controlled polymerization technique, single-electron transfer living radical polymerization (SET-LRP), to polymerize glycomonomers, which are prepared by copper catalyzed azide–alkyne click (CuAAC) reaction prior to polymerization. A series of glycomonomers were prepared by reaction of 3-azidopropylacrylate (APA) and alkylated mannose, glucose, and fucose using a Fischer–Helferich glycosylation. This was performed using CuSO4 and sodium ascorbate in a methanol/water mixture (see the Supporting Information). SET-LRP of the glucose monomer (GluA) was performed in dimethylsulfoxide (DMSO) using a copper(0)/copper(II) and tris[2-(dimethylamino)ethyl]amine (Me6TREN)-derived catalyst. Polymerization reached over 90 % monomer conversion in six hours whilst maintaining a narrow molecular weight distribution with increasing molecular weight. (Supporting Information, Figure S4). The obtained polymers were characterized by size exclusion chromatography (SEC) and MALDI-TOF mass spectroscopy (MS) or high-resolution electrospray ionization mass spectroscopy (HR-ESI MS), which indicated very high chain-end fidelity allowing for sequential monomer addition. We designed a polymerization reaction starting with one equivalent of initiator (I) and two equivalents of mannose glycomonomer (ManA; Figure 1a). ManA was fully consumed after 12 hours; then two equivalents of GluA in DMSO were added to the reaction mixture and GluA was consumed in 16 hours. Two equivalents of ManA in DMSO were subsequently added to the reaction mixture, and this cycle was continued until six short blocks of glycopolymers were produced (the degree of polymerization (DP) = 2 for each block, (mannose)2-(glucose)2-(mannose)2-(glucose)2(mannose)2-(glucose)2). No purification steps were required prior to addition of the subsequent monomer. The conversion of the first four blocks, as analyzed by H NMR spectroscopy, reached 100 %, shown by the complete disappearance of vinyl groups at 5.7–6.5 ppm. The glycomonomers were dissolved in purged DMSO prior to their addition and this resulted in further dilution of the reaction mixture upon each monomer addition. Traces of vinyl groups could still be detected after [*] Q. Zhang, J. Collins, A. Anastasaki, Dr. C. R. Becer, Prof. D. M. Haddleton Department of Chemistry, University of Warwick Gibbet Hill Road, Coventry, CV4 7AL (UK) E-mail: d.m.haddleton@warwick.ac.uk Homepage: http://www.warwick.ac.uk/go/polymers Dr. R. Wallis Department of Biochemistry, University of Leicester Leicester, LE1 9HN (UK) Dr. D. A. Mitchell Clinical Sciences Research Institute, Warwick Medical School, University of Warwick Coventry, CV2 2DX (UK) [**] We acknowledge financial support from the University of Warwick and the China Scholarship Council. Equipment used in this research was funded by the Innovative Uses for Advanced Materials in the Modern World (AM2) with support from AWM and ERDF. D.M.H. is a Royal Society/Wolfson Fellow and C.R.B. is a Science City Senior Research Fellow. Dr. Christopher N. Scanlan has provided the gp120. Supporting information for this article (syntheses of all materials and details of the characterization methods) is available on the WWW under http://dx.doi.org/10.1002/anie.201300068. Angewandte Chemie

High-Affinity Glycopolymer Binding to Human DC-SIGN and Disruption of DC-SIGN Interactions with HIV Envelope Glycoprotein

Noncovalent interactions between complex carbohydrates and proteins drive many fundamental processes within biological systems, including human immunity. In this report we aimed to investigate the potential of mannose-containing glycopolymers to interact with human DC-SIGN and the ability of these glycopolymers to inhibit the interactions between DC-SIGN and the HIV envelope glycoprotein gp120. We used a library of glycopolymers that are prepared via combination of copper-mediated living radical polymerization and azide−alkyne [3+2] Huisgen cycloaddition reaction. We demonstrate that a relatively simple glycopolymer can effectively prevent the interactions between a human dendritic cell associated lectin (DC-SIGN) and the viral envelope glycoprotein gp120. This approach may give rise to novel insights into the mechanisms of HIV infection and provide potential new therapeutics.

The glycopolymer code: synthesis of glycopolymers and multivalent carbohydrate-lectin interactions.

Glycopolymers are becoming more and more important in understanding biological interactions due to their unique recognition properties. Macromolecules with different chain lengths, compositions and architectures provide enormous diversity in the formation of primary and secondary structures that have a major effect on multivalent binding to lectins. It is crucial to control the precise structure of macromolecules to achieve specific and selective carbohydrate-lectin binding. The use of advanced synthesis techniques to prepare well-defined glycopolymers and selected advanced analytical techniques to study multivalent interactions are highlighted in this Feature Article.

Synthetic polymeric nanoparticles by nanoprecipitation

Nanoprecipitation is applied for the first time as a general concept for manufacturing nanoparticles of versatile hydrophobic polymer classes. As a result, polymer molecules self-assemble into nanospheres or irregularly shaped nanoparticles during the transition from the dissolved state to the solid state while using different solvents and methods for the conversion.

Dendritic cell lectin-targeting sentinel-like unimolecular glycoconjugates to release an anti-HIV drug.

A series of cyclodextrin-based glycoconjugates, including glycoclusters and star glycopolymers, were synthesized via combination of CuAAC Huisgen coupling and copper-mediated living radical polymerization. These glycoconjugates showed high affinity binding to the human transmembrane lectin DC-SIGN and act as inhibitors to prevent the binding of HIV envelope protein gp120 to DC-SIGN at nanomolar concentrations. The star block glycopolymers showed high loading capacity of hydrophobic anticancer and anti-HIV drugs, indicating promising applications in HIV-therapeutic and smart drug delivery.

Synthesis and modification of thermoresponsive poly(oligo(ethylene glycol) methacrylate) via catalytic chain transfer polymerization and thiol–ene Michael addition

Various poly(oligo(ethylene glycol) methyl ether methacrylate)s (POEGMEMAs) have been prepared by Catalytic Chain Transfer Polymerization (CCTP) using a range of OEGMEMA monomers (molecular weight from 180 to 1100 g mol−1). The chain transfer constants of bis(boron difluorodimethylglyoximate) cobalt(II) (CoBF) were determined and are reported for each monomer. The copolymerization of POEGMEMA (Mn = 475 g mol−1) with diethylene glycol methyl ether methacrylate (DEGMEMA) yielded thermoresponsive polymers. The lower critical solution temperatures (LCSTs) of the polymer chains can be tuned by the copolymer composition over the range 30 °C to 95 °C. In addition, the presence of the vinylic end-group, characteristic of CCT polymerization, provided further scope for post-synthetic modification via thiol–ene click chemistry, through nucleophilic Michael addition with various functional thiol compounds such as 2-mercaptoethanol, 3-mercaptopropionic acid, benzyl mercaptan and 1-dodecanethiol. The thiol–ene reaction was rigorously tested, optimized and characterized in this study in terms of solvents and most importantly the choice of the catalyst: dimethyl phenyl phosphine, tertiary amine or hexylamine. The optimum conditions reported allow near-quantitative functionalization of these macromonomers without significant side reactions. The effect of the end-group on the LCST has also been investigated, as well as thermal stability temperature of the copolymers.

Absolut “copper catalyzation perfected”; robust living polymerization of NIPAM: Guinness is good for SET-LRP

The controlled polymerization of N-isopropyl acrylamide (NIPAM) is reported in a range of international beers, wine, ciders and spirits utilizing Cu(0)-mediated living radical polymerization (SET-LRP). Highly active Cu(0) is first formed in situ by the rapid disproportionation of [Cu(I)(Me6-Tren)Br] in the commercial water–alcohol mixtures. Rapid, yet highly controlled, radical polymerization follows (Đ values as low as 1.05) despite the numerous chemicals of diverse functionality present in these solvents e.g. alpha acids, sugars, phenols, terpenoids, flavonoids, tannins, metallo-complexes, anethole etc. The results herein demonstrate the robust nature of the aqueous SET-LRP protocol, underlining its ability to operate efficiently in a wide range of complex chemical environments.