Reversible Addition-fragmentation Chain Transfer Copolymerization Research Articles

Kinetics and scale inhibition application studies towards bulk and RAFT copolymerization of maleic anhydride and acrylic acid

Poly(maleic anhydride) (PMA) is commonly reckoned as a better water scale inhibitor than poly(acrylic acid) (PAA) since each maleic anhydride unit can supply two carboxylic acid groups. However, pure PMA is difficult to achieve because the steric effect of its monomer MA. Herein, we synthesize copoly(MA-AA) copolymer by bulk polymerization method (bulk-copoly(MA-AA)), which avoids the use of any solvents which have to be removed afterwards. In addition, we also synthesize copoly(MA-AA) by reversible addition-fragmentation chain transfer (RAFT) polymerization method to afford RAFT-copoly(MA-AA) with low polydispersity index (PDI) less than 1.2, and the performance of RAFT-copoly(MA-AA) in water scale inhibition is more excellent relative to bulk-copoly(MA-AA). We also synthesize other copoly(MA-AA) copolymers by varying the molar ratio of MA to AA to study the polymerization mechanism. Through the static scale inhibition experiment, it is concluded that when the concentration of copoly(MA-AA) is 80 mg/L, the scale inhibition performance of RAFT-copoly(MA-AA) can reach 96.50 % which is the best among the control samples. It is also found that only 1:1 alternating copolymerization of MA and AA could be achieved as demonstrated by 1H nuclear magnetic resonance spectra of the copolymers, evidencing the strong steric hindrance of MA for its homo-polymerization.

RAFT copolymerization of methyl methacrylate and di(ethylene glycol) methyl ether methacrylate in a hexylpyridinium ionic liquid

AbstractSmart polymers undergo significant physical or chemical changes in response to stimuli like temperature and pH. Achieving a narrow molecular weight distribution is crucial for their sensitivity. Reversible addition–fragmentation chain transfer (RAFT) in ionic liquids is an effective method for synthesizing such polymers due to its favorable kinetics and environmental benefits. Most studies use imidazolium ionic liquids, while pyridinium ionic liquids are less common despite their easy synthesis. This study reports the first successful RAFT copolymerization of di(ethylene glycol) methyl ether methacrylate (DEGMEMA) and methyl methacrylate in N‐hexylpyridinium hexafluorophosphate ([HPY][PF6]). Both linear and hyperbranched copolymers (Mn > 25,000) with narrow molecular weight distribution were synthesized, showing observable temperature responses and biocompatibility. The linear copolymers had a desirable dispersity (Ð) of less than 1.10, while the hyperbranched copolymer had a Ð of 2.034. The lower critical solution temperatures (LCSTs) of the copolymers were close to or below the LCST of PDEGMEMA (26°C). This study indicates that pyridinium ionic liquids can be explored as a suitable solvent for synthesizing methacrylate‐based smart polymers.

Self-healing amino acid-bearing acrylamides/n-butyl acrylate copolymers via multiple noncovalent bonds.

Four amino acid-bearing acrylamides, N-acryloyl-l-threonine (AThrOH), N-acryloyl-l-glutamic acid (AGluOH), N-acryloyl-l-phenylalanine (APheOH), and N-acryloyl-l, l-diphenylalanine (APhePheOH), were selected for copolymerization with n-butyl acrylate (nBA) to develop amino acid-based self-healable copolymers. A series of copolymers comprising amino acid-bearing acrylamides and nBA with tunable comonomer compositions and molecular weights were synthesized by free radical and reversible addition-fragmentation chain-transfer copolymerization. Self-healing and mechanical properties originated from the noncovalent bonds between the carboxyl, hydroxyl, and amide groups, and π-π stacking interactions among the amino acid residues in the side chains were evaluated. Among these copolymers, P(nBA-co-AGluOH) with suitable comonomer compositions and molecular weights (nBA : AGluOH = 82 : 18, Mn = 18 300, Mw/Mn = 2.58) exhibited good mechanical properties (modulus of toughness = 17.3 MJ m-3) and self-healing under ambient conditions. The multiple noncovalent bonds of P(nBA-co-AGluOH)s were also efficient in improving the optical properties with an enhanced refractive index and good transparency.

Hydrophilic Copolymers with Hydroxamic Acid Groups as a Protective Biocompatible Coating of Maghemite Nanoparticles: Synthesis, Physico-Chemical Characterization and MRI Biodistribution Study.

Superparamagnetic iron oxide nanoparticles (SPION) with a "non-fouling" surface represent a versatile group of biocompatible nanomaterials valuable for medical diagnostics, including oncology. In our study we present a synthesis of novel maghemite (γ-Fe2O3) nanoparticles with positive and negative overall surface charge and their coating by copolymer P(HPMA-co-HAO) prepared by RAFT (reversible addition-fragmentation chain-transfer) copolymerization of N-(2-hydroxypropyl)methacrylamide (HPMA) with N-[2-(hydroxyamino)-2-oxo-ethyl]-2-methyl-prop-2-enamide (HAO). Coating was realized via hydroxamic acid groups of the HAO comonomer units with a strong affinity to maghemite. Dynamic light scattering (DLS) demonstrated high colloidal stability of the coated particles in a wide pH range, high ionic strength, and the presence of phosphate buffer (PBS) and serum albumin (BSE). Transmission electron microscopy (TEM) images show a narrow size distribution and spheroid shape. Alternative coatings were prepared by copolymerization of HPMA with methyl 2-(2-methylprop-2-enoylamino)acetate (MMA) and further post-polymerization modification with hydroxamic acid groups, carboxylic acid and primary-amino functionalities. Nevertheless, their colloidal stability was worse in comparison with P(HPMA-co-HAO). Additionally, P(HPMA-co-HAO)-coated nanoparticles were subjected to a bio-distribution study in mice. They were cleared from the blood stream by the liver relatively slowly, and their half-life in the liver depended on their charge; nevertheless, both cationic and anionic particles revealed a much shorter metabolic clearance rate than that of commercially available ferucarbotran.

Polymeric Surfactants Bearing Divalent Carboxy Pendants for Stable Color Dispersions with High Redispersibility

Inkjet printing of ink requires dyes or pigments insoluble in water but uniformly dispersing as fine particles for a long period. In addition, redispersibility after solidification by solvent vaporization around the jetting heads is also important for performance. In this study, thus, a series of amphiphilic copolymers were prepared for a dispersant of inkjet using reversible addition fragmentation chain-transfer copolymerization of styrene (St), benzyl acrylate (BnA), and phenoxyethyl acrylate (PEA) as a hydrophobic monomer with acrylic acid (AA) and itaconic acid (IA) as a hydrophilic monomer. To understand the fundamental properties and potentials as a polymer dispersant, the surface parameters and rheology of the copolymers and their color dispersions in aqueous media were investigated. The aqueous solutions were typical Newtonian fluids, whereas the color dispersions were non-Newtonian fluids with shear-thinning properties and yield values ranging from 0.57 to 1.04 Pa. Although the surface parameters, such as surface tension (γ), molecular occupied area (Amin), and zeta potential (ζ), did not show clear correlation with polymer structures, their behaviors as a dispersant were significantly different. The color dispersants containing the copolymer of St or BnA as a hydrophobic monomer and IA and AMPS as hydrophilic monomers exhibited sufficient redispersion both for yellow and cyan inks, even after the aging test at 60 °C for 5 days, whereas other copolymers did not exhibit such superior performances. In addition, the color dispersions of the copolymer of St, IA, and AMPS (St-IA-AMPS) showed lower viscosity and yield value and became closer to Newtonian fluid compared with that of St, AA, and AMPS (St-AA-AMPS). Thus, St-IA-AMPS provided good redispersibility and avoided sedimentation. These results suggest that the most suitable dispersant for inkjet inks among the polymers investigated was the copolymer of St, IA, and AMPS.

PLA‐b‐SMA as an Amphiphilic Diblock Copolymer for Encapsulation of Lipophilic Cargo

AbstractThe encapsulation of active pharmaceutical ingredients (APIs) within drug delivery systems such as polymeric nanoparticles (PNPs) vastly improves the therapeutic efficiency of the incorporated APIs. PNPs synthesized using amphiphilic block copolymers are efficient drug delivery systems as the hydrophobic block facilitates the encapsulation of lipophilic components and the hydrophilic block constitutes the hairy corona of the PNP that stabilizes the nanocarriers against aggregation in solution. Poly(styrene‐alt‐maleic acid) (SMA) is an attractive polymer for the hydrophilic corona of PLA‐based nanoparticles as it allows for post polymerization functionalization and aids in the prevention of NP aggregation. The synthesis of a novel PLA‐b‐SMA block copolymer, via sequential ring opening polymerization (ROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization, is presented. PLA macro‐CTAs, synthesized via ROP, can be chain extended via RAFT copolymerization of styrene and maleic anhydride to yield PLA‐b‐SMAnh and via RAFT polymerization of N‐vinylpyrrolidone to yield PLA‐b‐PVP block copolymers. Controlled hydrolysis of the anhydride moieties converts PLA‐b‐SMAnh into PLA‐b‐SMA. Monodisperse PLA‐b‐SMA and PLA‐b‐PVP nanoparticles (NPs) ranging in diameter between 60 and 220 nm are prepared. The lipophilic fluorescent dye DiI is encapsulated within the NPs successfully and these fluorescent NPs are used in a preliminary cell uptake study.

Zwitterionic Amino Acid-Derived Polyacrylates as Smart Materials Exhibiting Cellular Specificity and Therapeutic Activity.

The synthesis of new amino acid-containing, cell-specific, therapeutically active polymers is presented. Amino acids served as starting material for the preparation of tailored polymers with different amino acids in the side chain. The reversible addition-fragmentation chain-transfer (RAFT) polymerization of acrylate monomers yielded polymers of narrow size distribution (Đ ≤ 1.3). In particular, glutamate (Glu)-functionalized, zwitterionic polymers revealed a high degree of cytocompatibility and cellular specificity, i.e., showing association to different cancer cell lines, but not with nontumor fibroblasts. Energy-dependent uptake mechanisms were confirmed by means of temperature-dependent cellular uptake experiments as well as localization of the polymers in cellular lysosomes determined by confocal laser scanning microscopy (CLSM). The amino acid receptor antagonist O-benzyl-l-serine (BzlSer) was chosen as an active ingredient for the design of therapeutic copolymers. RAFT copolymerization of Glu acrylate and BzlSer acrylate resulted in tailored macromolecules with distinct monomer ratios. The targeted, cytotoxic activity of copolymers was demonstrated by means of multiday in vitro cell viability assays. To this end, polymers with 25 mol % BzlSer content showed cytotoxicity against cancer cells, while leaving fibroblasts unaffected over a period of 3 days. Our results emphasize the importance of biologically derived materials to be included in synthetic polymers and the potential of zwitterionic, amino acid-derived materials for cellular targeting. Furthermore, it highlights that the fine balance between cellular specificity and unspecific cytotoxicity can be tailored by monomer ratios within a copolymer.

Mathematical Description of the RAFT Copolymerization of Styrene and Glycidyl Methacrylate Using the Terminal Model.

A mathematical model for the kinetics, composition and molar mass development of the bulk reversible addition-fragmentation chain transfer (RAFT) copolymerization of glycidyl methacrylate (GMA) and styrene (St), at several GMA molar feed fractions at 103 °C, in the presence of 2-cyano isopropyl dodecyl trithiocarbonate as the RAFT agent and 1,1′-azobis(cyclohexane carbonitrile), as the initiator, is presented. The copolymerization proceeded in a controlled manner and dispersities of the copolymers remained narrow even at high conversions. Experimental data and calculated profiles of conversion versus time, composition versus conversion and molar mass development for the RAFT copolymerization of St and GMA agreed well for all conditions tested, including high-conversion regions. The kinetic rate constants associated with the RAFT- related reactions and diffusion-controlled parameters were properly estimated using a weighted nonlinear multivariable regression procedure. The mathematical model developed in this study may be used as an aid in the design and upscaling of industrial RAFT polymerization processes.

Stepwise Gradient Copolymers of n-Butyl Acrylate and Isobornyl Acrylate by Emulsion RAFT Copolymerizations

Gradient copolymers of n-butyl acrylate (nBA) and isobornyl acrylate (IBA) were prepared using reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization. Gradient copolymerizations were conducted using stepwise monomer addition such that the system was monomer-starved. Using the stepwise monomer addition process with a fixed comonomer ratio during the polymerization allows for pre-specified gradient compositions to be obtained. The structural properties of copolymers were confirmed via kinetic investigations and two-dimensional chromatography. 1H nuclear magnetic resonance (NMR) characterization revealed the gradient behavior of the prepared copolymers. The degree of change in monomer composition along the copolymer chain strongly affects the thermal properties of the final polymer product. Thus, gradient copolymers were examined to determine how the strength of the gradient impacts the glass-transition temperature (Tg). Comparisons were also made between the gradient copolymers and their corresponding statistical copolymers and homopolymers. Differential scanning calorimetry analysis of gradient copolymers demonstrated that such copolymers had much broader glass-transition regions compared to homopolymers and statistical copolymers. Furthermore, both the midpoint of the transition (i.e., Tg) and the breadth of the transition were found to be predeterminable through a judicious choice of the comonomer feed composition and the steepness of the comonomer feed in the subsequent monomer additions.

Comprehensive studies of continuous flow reversible addition–fragmentation chain transfer copolymerization and its application for photoimaging materials

Thorough studies of RAFT copolymerization in a continuous flow to gain deeper insights into kinetics, reactivity, and applicability were conducted with monomers and solvents utilizable for chemically amplified resist systems.

Facile Synthesis of CO2‐Responsive Nano‐Objects: Batch versus Semi‐Batch RAFT Copolymerization

Back Cover: In article number 2000765 by San H. Thang, Anchao Feng, Zhao Wang, and co-workers, a series of well-defi ned CO2-responsive statistical, gradient and block copolymer nano-objects are synthesized through batch, semi-batch and stepwise reversible addition-fragmentation chain transfer (RAFT) polymerization. In aqueous solution, the copolymers can self-assemble into various aggregates before CO2 stimulus. Upon bubbling CO2, the gradient copolymers prefer to form nanosheet-like structures, while the block and statistical copolymers with similar molar mass can only form larger vesicles with thinner membrane thickness or disassemble.

Kinetic analysis of continuous reaction data for RAFT and free radical copolymerization with acrylic and styrenic monomers

Free radical (FR) and Reversible Addition Fragmentation Chain Transfer (RAFT) copolymerization rates for styrenic monomers in bulk and aqueous reactions were accelerated by acrylic comonomers, whose own rates were both delayed and decreased. The effect was found with styrenics as low as 0.6% by mole, and is directly observable from Automatic Continuous Online Monitoring of Polymerization reactions (ACOMP) data. Rapid radical transfer from acrylic to styrenic comonomer, through lower energy radical resonance stabilization in styrenics, was the suspected cause. FR and RAFT rates were equal, suggesting that FR termination controlled radical concentrations and rates. Despite strongly changing concentrations of initiator and comonomer radicals during reactions, the Quasi-Steady-State Approximation was demonstrated to hold. While rates were identical, molecular weights showed the characteristic increase with conversion for RAFT and decrease for FR. A new, generalized method for reactivity ratio determination was found and acceleration/deceleration behavior was consistently interpreted within a penultimate model.

One‐Pot Synthesis of Dual Supramolecular Associative PMMA‐Based Copolymers and the Precise Thermal Property Tuning

AbstractDual supramolecular associative polymers have attracted attention for efficient physical property modification. Herein, a one‐pot synthesis of dual supramolecular associative poly(methyl methacrylate)‐based copolymers via reversible addition fragmentation chain transfer (RAFT) copolymerization using a novel methacrylate‐type monomer (coded as UP‐MA) bearing a urea bond and a pendant pyridine group is demonstrated. UP‐MA is synthesized by reacting 4‐picolylamine and 2‐isocyanatoethyl methacrylate. The subsequent RAFT copolymerization of UP‐MA and methyl methacrylate (MMA) can be performed by directly adding MMA, a chain transfer agent, and a radical initiator into the reaction solution of UP‐MA. The estimated values of radical reactivity ratio (r) for UP‐MA and MMA are close to unity, attaining a nearly ideal random sequence of the dual supramolecular associative units in the copolymer chain. By blending a metal salt into the random copolymer, coordination bonds between the salt and the pyridine groups are formed, and the urea groups simultaneously form hydrogen bonds, generating a dual supramolecular associative network. Precise tuning of the thermal property is realized by changing the fraction of the metal salt and associative groups in the copolymers.

Delocalization of Hydrophobicity using Random/Statistical Copolymers: A Facile Tactic towards Developing High-performance X-ray Contrast Media for Real-time Image-guided Radiation Therapy

Traditional X-ray contrast media (XRCM) suffers from rapid renal clearance (half-life < 30 min), leading to a narrow acquisition time window for the X-ray computed tomography (CT) after intravenous (IV) administration, and limiting the operation time for the potential real-time CT-guided radiation therapy. Real-time image-guided radiation therapy can improve tumor-specific radiation dosages while sparing healthy tissue and critical structures. To broaden operational time and improve performance of XRCM, the next-generation XRCM with long blood residence time, high contrast efficiency, specific biodistribution, facile access to dual or multiple diagnostic imaging modalities, and biocompatibility is desirable. We report a simple strategy for preparing iodinated nano-XRCM for CT-PET dual imaging through intra/intermolecular self-assembly of random/statistical amphiphilic iodocopolymers (ICPs). ICPs were synthesized from reversible addition-fragmentation chain transfer (RAFT) copolymerization of triiodobenzoyl acrylate and oligo(ethylene oxide) acrylate monomers. The controlled RAFT copolymerization allowed for installation of DOTA moieties to chelate 64Cu radionuclides, enabling CT and positron emission tomography (PET) dual imaging and targeted radiotherapy. An EMT6 breast cancer mouse model (C57BL/6 mice) was used for in vivo biodistribution evaluation using 185 kBq of 64Cu-DOTA-ICP (45 mg/mouse) in 75 μL saline injected via the tail vein of C57BL/6 mice weighing 20–25 g (n = 4/group). The mice were euthanized at 1, 4, 24, and 48 h post-injection, and organs were collected, weighed, and counted in a well gamma counter. Intra/intermolecular self-assembly of ICPs formed nano-XRCM particles with ultrahigh iodine concentration (up to ca. 300 mg/mL), low viscosity (4.75 cSt at 37 °C), long term thermodynamic stability (> 6 months), and the identical hydrodynamic size of ca. 10 nm independent of the degree of polymerization. The resulting ICP-based nano-XRCMs showed excellent biocompatibility and exhibited long blood circulation time over 2 days with adequate tumor accumulation and low non-specific accumulation after single IV administration, allowing ample operation time for potential real-time CT image-guided radiation therapy application. Furthermore, the micro-CT imaging showed clear tumor contrast 6 days post-injection. The simple synthetic methodology allows the construction of multi-functional theranostic agents by incorporating diverse moieties. The ICP-based nano-XRCMs demonstrated extended blood residence time, high contrast efficiency, tumor specific accumulation, and biocompatibility for potential real-time image-guided radiotherapy application. Clear tumor contrast 6 days post-injection allowed convenient monitoring, which could be important for future studies of therapeutic effect.

Controlling the Chain Folding for the Synthesis of Single-Chain Polymer Nanoparticles Using Thermoresponsive Polymers

Synthetic polymer single-chain nanoparticles (SCNPs) are an emerging new class of nanomaterials that possess similar folded structures as natural proteins. However, most SCNPs reported so far are p...

Controlled surface modification of silicone rubber by gamma-irradiation followed by RAFT grafting polymerization

The formation of biofilms on the surface of some biomaterials causes problems that can have a negative impact on human health. Various studies have been carried out for the modification of polymeric biomaterials; however, with conventional methods of modifying surfaces with radiation-induced grafts, obtaining uniformly distributed grafts over the entire surface is not facilitated, so the mechanical properties are strongly affected by the modification. In this study, silicone rubber (SR) films were modified with 2-hydroxyethyl methacrylate (HEMA) and with oligo(ethylene glycol) methyl ether methacrylate, Mn = 300 g mol−1 (OEGMA300) using the oxidative pre-irradiation method with gamma-irradiation followed by reversible addition-fragmentation chain transfer (RAFT) grafting polymerization. The copolymers of SR-g-PHEMA and SR-g-poly(HEMA-co-OEGMA300) were synthesized with various grafting percentages and these could be adjusted to obtain a thin grafted layer. The grafted samples were characterized by FTIR-ATR spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), light microscopy, swelling in water, contact angle, and dynamic mechanical analysis (DMA); in addition, the non-grafted polymer formed in the RAFT copolymerization reactions was analyzed by gel permeation chromatography (GPC) and nuclear magnetic resonance spectroscopy (NMR). The results confirmed the presence of PHEMA and poly(HEMA-co-OEGMA300) on the surface of SR films, uniformly grafted by the use of a chain transfer agent (CTA). The uniform layer of hydrophilic grafts in the SR films generates a surface capable of forming a water barrier on the surface, without significantly compromising the elastic properties of the SR; furthermore, the grafted thin layer was capable of loading biologically active molecules like curcumin. Modified SR films loaded with curcumin may decrease the possibility of biofilm formation. The described approach of oxidative gamma pre-irradiation followed by RAFT controlled grafting may be of interest for the modification of biomaterials in a controlled way, in the case of silicone for instance for catheters or aesthetic implants.

Surface modification of multiwalled carbon nanotubes via surface RAFT copolymerization method and capecitabine-loaded anticancer hydrogel for controlled drug delivery in stomach

ABSTRACT In our work, reversible addition-fragmentation chain transfer (RAFT)/carbon nanotube (CNT)/acrylic acid (AA)/acrylamide (AAm) nanocomposite was synthesized by living radical polymerization. The structure and surface morphology of the synthesized RAFT-CNT-Hydrogel nanocomposites were analyzed by FTIR, 1HNMR, SEM, TEM, XRD, and TGA/DTG techniques. The results indicated that PAA/AAm chains grafted with CNT by RAFT polymerization. RAFT-CNT-Hydrogel nanocomposites for drug release investigated in different buffers resulted in a strong pH-sensitive behavior. In total, the obtained hydrogel drug-delivery systems are presented a proper effect versus stomach cancer in vitro and in vivo, and it can be used as candidates for controlled release of anticancer drugs in stomach with exalted remedial agents.

Caspofungin Functionalized Polymethacrylates with Antifungal Properties.

We describe the synthesis of hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) (PmPEGMA) and hydrophobic poly(methyl methacrylate) (PMMA) caspofungin conjugates by a post-polymerization modification of copolymers containing 10 mol % pentafluorophenyl methacrylate (PFPMA), which were obtained via reversible addition-fragmentation chain transfer copolymerization. The coupling of the clinically used antifungal caspofungin was confirmed and quantified in detail by a combination of 1H-, 19F- and diffusion-ordered NMR spectroscopy, UV-vis spectroscopy, and size exclusion chromatography. The trifunctional amine-containing antifungal was attached via several amide bonds to the hydrophobic PMMA, but sterical hindrance induced by the mPEGMA side chains prohibited intramolecular double functionalization. Both polymer-drug conjugates revealed activity against important human-pathogenic fungi, that is, two strains of Aspergillus fumigatus and one strain of Candida albicans (2.5 mg L-1 < MEC < 8 mg L-1, MIC50 = 4 mg L-1), whereas RAW 264.7 macrophages as well as HeLa cells remained unaffected at these concentrations.

High-Affinity N-(2-Hydroxypropyl)methacrylamide Copolymers with Tailored N-Acetyllactosamine Presentation Discriminate between Galectins.

N-Acetyllactosamine (LacNAc; Galβ4GlcNAc) is a typical disaccharide ligand of galectins. The most abundant members of these human lectins, galectin-1 (Gal-1) and galectin-3 (Gal-3), participate in a number of pathologies including cancerogenesis and metastatic formation. In this study, we synthesized a series of fifteen N-(2-hydroxypropyl)methacrylamide (HPMA)-based glycopolymers with varying LacNAc amounts and presentations and evaluated the impact of their architecture on the binding affinity to Gal-1 and Gal-3. The controlled radical reversible addition-fragmentation chain transfer copolymerization technique afforded linear polymer precursors with comparable molecular weight (Mn ≈ 22,000 g mol-1) and narrow dispersity (D̵ ≈ 1.1). The precursors were conjugated with the functionalized LacNAc disaccharide (4-22 mol % content in glycopolymer) prepared by enzymatic synthesis under catalysis by β-galactosidase from Bacillus circulans. The structure-affinity relationship study based on the enzyme-linked immunosorbent assay revealed that the type of LacNAc presentation, individual or clustered on bi- or trivalent linkers, brings a clear discrimination (almost 300-fold) between Gal-1 and Gal-3, reaching avidity to Gal-1 in the nanomolar range. Whereas Gal-1 strongly preferred a dense presentation of individually distributed LacNAc epitopes, Gal-3 preferred a clustered LacNAc presentation. Such a strong galectin preference based just on the structure of a multivalent glycopolymer type is exceptional. The prepared nontoxic, nonimmunogenic, and biocompatible glycopolymers are prospective for therapeutic applications requiring selectivity for one particular galectin.

Asymmetrically Substituted Poly(diitaconates) Obtained by Reversible Addition‐Fragmentation Chain Transfer (RAFT) Polymerization: Synthesis, Copolymerization Parameters, and Antimicrobial Activity

AbstractAsymmetrically substituted poly(diitaconate) copolymers are synthesized from 1‐((N‐tert‐butoxycarbonyl)‐2‐aminoethyl)‐4‐propyl diitaconate (PrIA) and different comonomers (N,N‐dimethyl‐acrylamide, DMAA; acrylic acid; or ((N‐tert‐butoxycarbonyl)‐2‐aminoethyl)methacrylate) by reversible addition–fragmentation chain transfer polymerization (RAFT). The RAFT copolymerization parameters of PrIA and DMAA are rDMAA = 0.49 and rPrIA = 0.17, compared to rDMAA = 0.52 and rPrIA = 0.54 obtained by free radical copolymerization (FRP). Thus, the RAFT process has a stronger trend to alternating polymerization than the FRP process. The polydispersity index of the RAFT copolymers is around 1.2–1.8, compared to 2.8–2.9 for the corresponding FRP copolymers. After removal of the tert‐butoxycarbonyl protective groups, antimicrobially active synthetic mimics of antimicrobial peptides are obtained. The thus activated poly(PrIA‐co‐DMAA) copolymers (repeat unit ratio 1:1) have an increasing activity against Escherichia coli and Staphylococcus aureus with increasing molar mass. The RAFT copolymers are slightly more active and less toxic than comparable FRP polymers, leading to a higher selectivity for bacteria over mammalian cells. Higher molar fractions of PrIA in poly(PrIA‐co‐DMAA) copolymers (up to 80 mol%) do not increase their antimicrobial activity; reduction of the BuIA content in poly(BuIA‐DMAA) (down to 10 mol%) leads to a loss of activity against both E. coli and S. aureus.