Hyperbranched Research Articles

Bioreducible Amphiphilic Hyperbranched Polymer-Drug Conjugate for Intracellular Drug Delivery.

This paper reports synthesis of a bioreducible hyperbranched (HB) polymer by A2+B3 approach from commercially available dithiothreitol (DTT) (A2) and an easily accessible trifunctional monomer (B3) containing three reactive pyridyl-disulfide groups. Highly efficient thiol-activated disulfide exchange reaction leads to the formation of the HB polymer (Mw = 21000; Đ = 2.3) with bioreducible disulfide linkages in the backbone and two different functional groups, namely, hydroxyl and pyridyl-disulfide in the core and periphery, respectively, of the HB-polymer. Postpolymerization functionalization of the hydroxyl-groups with camptothecin (CPT), a topoisomerase inhibitor and known anticancer drug, followed by replacing the terminal pyridyl-disulfide groups with oligo-oxyethylene-thiol resulted in easy access to an amphiphilic HB polydisulfide-CPT conjugate (P1) with a very high drug loading content of ∼40%. P1 aggregated in water (above ∼10 μg/mL) producing drug-loaded nanoparticles (Dh ∼ 135 nm), which showed highly efficient glutathione (GSH)-triggered release of the active CPT. Mass spectrometry analysis of the GSH-treated P1 showed the presence of the active CPT drug as well as a cyclic monothiocarbonate product, which underpins the cascade-degradation mechanism involving GSH-triggered cleavage of the labile disulfide linkage, followed by intramolecular nucleophilic attack by the in situ generated thiol to the neighboring carbonate linkage, resulting in release of the active CPT drug. The P1 nanoparticle showed excellent cellular uptake as tested by confocal fluorescence microscopy in HeLa cells by predominantly endocytosis mechanism, resulting in highly efficient cell killing (IC50 ∼ 0.6 μg/mL) as evident from the results of the MTT assay, as well as the apoptosis assay. Comparative studies with an analogous linear polymer-CPT conjugate showed much superior intracellular drug delivery potency of the hyperbranched polymer.

Rapid polythioether synthesis and thioether network formation using thiol-yne chemistry of electron-deficient alkynes

The preparation of polythioethers has gained importance again after the development of click chemistry reactions. The thiol-X reactions, i.e., thiol-ene reactions based on free radical mechanism facilitated by light or heat, and thiol-Michael and thiol-epoxy reactions, which are the main synthetic pathways for the synthesis of polymers (linear, hyperbranched (HB), and network) with thioether linkages and meet most of the features of click reactions strategy, have currently been revisited. For a while, our group has focused on synthesizing linear, HB, and network polythioethers based on electron-deficient alkyne-containing precursors. We have shown that electron-deficient alkyne-containing monomers and polymers offer a suitable platform for thiol-Michael (i.e., thiol-yne) click reactions to yield linear, HB, and network structures rapidly under ambient conditions. The central structure in these polythioether syntheses is electron-deficient alkyne bonds of acetylenedicarboxylates, which are then reacted with dithiols in chloroform through an organobase 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) at ambient temperatures. Moreover, acetylenedicarboxylates are functionalized using copper-free azide-alkyne cycloaddition reaction followed by reacting with multifunctional allyl and SH derivatives through thiol-ene photopolymerization resulting in polymeric networks with thioether linkages. This feature article highlights our contribution to the synthesis of linear, HB, and network polythioether based on various electron-deficient alkyne precursors.

Shape matters: Effect of amphiphilic polymer topology on antibacterial activity and hemocompatibility

Understanding the intricate relationship between polymer architecture and biological activity is critical for advancing the development of antibacterial polymers. In this study, we systematically investigated the antibacterial properties and hemocompatibility of 27 different synthetic polymers prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. The antibacterial activities of these polymers were probed against two gram-negative bacteria, namely Pseudomonas aeruginosa PAO1 and Escherichia coli K12. Furthermore, the antibacterial efficacy and hemocompatibility of synthetic polymers were correlated with their polymer topology, encompassing linear (LPs), hyperbranched (HPs), and star polymers (SPs), characterized by varying hydrophobic compositions (20 %, 25 %, and 30 %). HPs were prepared using two types of crosslinking monomer (acrylate vs. acrylamide). The [crosslinker]:[RAFT agent] ratio in the synthesis of HPs greatly affect their hemocompatibility, while the type of crosslinker had a negligible impact. HPs showed a remarkable 2- to 4-fold enhancement in hemocompatibility compared to LPs at the same hydrophobic ratio. Interestingly, SPs with a low hydrophobic ratio, did not display toxicity towards red blood cells, while maintaining similar potent antibacterial activities as LPs and HPs. Overall, SPs exhibited superior bioactivity compared to HPs and LPs (SPs > HPs > LPs), demonstrating that the manipulation of polymer topology offers a promising avenue for enhancing the performance of synthetic antibacterial polymers.

Facile Synthesis of Functionalised Hyperbranched Polymers for Application as Novel, Low Viscosity Lubricant Formulation Components.

A novel, previously unreported, method for synthesising hyperbranched (HB) materials is detailed. Their use as additives to produce lubricant formulations that exhibit enhanced levels of wear protection and improved low-temperature oil viscosity and flow is also reported. The lubricant formulations containing HB additives were found to exhibit both significantly lower viscosities and improved in-use film-forming properties than the current industry standard formulations. To achieve this, alkyl methacrylate oligomers (predominantly dimers and trimers) were synthesised using catalytic chain transfer polymerisation. These were then used as functional chain transfer agents (CTA) to control the polymerisation of divinyl benzene (DVB) monomers to generate highly soluble, high polydispersity HB polymers. The level of dimer/trimer purification applied was varied to define its influence on both these HB resultant structures and the resultant HB additives’ performance as a lubricant additive. It was shown that, while the DVB acted as the backbone of the HB, the base oil solubility of the additive was imparted by the presence of the alkyl chains included in the structure via the use of the oligomeric CTAs.

Amphiphilic P(OEGMA-co-DIPAEMA) Hyperbranched Copolymer/Magnetic Nanoparticle Hybrid Nanostructures by Co-Assembly

This work presents the utilization of amphiphilic poly(oligo(ethylene glycol) methyl methacrylate)-co-poly(2-(diisopropylamino)ethyl methacrylate), P(OEGMA-co-DIPAEMA), hyperbranched (HB) copolymers, forming polymeric aggregates in aqueous media, as building nanocomponents and nanocarriers for the entrapment of magnetic cobalt ferrite nanoparticles (CoFe2O4, MNPs), and the hydrophobic drug curcumin (CUR) in their hydrophobic domains. Dynamic light scattering (DLS) and cryogenic transmission electron microscopy (cryo-TEM) techniques were used to evaluate the multifunctional hybrid nanostructures formed in aqueous media by co-assembly of the components and their solution properties. Magnetic nanoparticles (MNPs) or MNPs/CUR were co-assembled effectively with pre-existing polymer aggregates, leading to well-defined hybrid nanostructures. Magnetophoresis experiments revealed that the hybrid nanostructures retain the magnetic properties of MNPs after their co-assembly with the hyperbranched copolymers. The hybrid nanostructures demonstrate a significant colloidal stability under physiological conditions. Furthermore, MNPs/CUR-loaded aggregates displayed considerable fluorescence as demonstrated by fluorescence spectroscopy. These hybrid nanostructures could be promising candidates for drug delivery and bio-imaging applications.

Topological-skeleton controlled chirality expression of supramolecular hyperbranched and linear polymers

The topology of polymers plays an essential role in their chemical, physical and biological properties. However, their effects on chirality-related functions remain unclear. Here, we reported the topology-controlled chirality expression in the chiral supramolecular system for the first time. Two topological supramolecular polymers, hyperbranched (HP) and linear (LP) supramolecular polymers produced by the host–guest interactions of branched and linear monomers, respectively, exhibited completely different chirality expressions despite the same molecular chirality of their monomers. Significantly, due to the branch points and strong steric hindrance existing in HP, cis-HP showed an enhanced and sign-inverted Cotton effect in the n–π* bands compared with cis-LP, as a result that the distinctive chirality induction and transfer were controlled by the topological skeletons. This topology-controlled chirality induction and transfer in the photoswitchable supramolecular polymers not only enables us to elucidate the in-depth effects of topology on the chiral expression in biopolymers but also inspires the design of chiroptical and bioinspired materials.

Preparation and characterization of composites using blends of divinylbenzene‐based hyperbranched and linear functionalized polymers

AbstractIn this study, hyperbranched polymers were explored as matrix modifiers to create E‐glass fiber (GF) reinforced polymer composites with enhanced mechanical properties. Hyperbranched polymers have lower viscosities than their linear equivalents, potentially providing enhanced fiber wet out leading to improved stress transfer. Hyperbranched (HB), hydrogenated hyperbranched (H‐HB), and linear functional (LF) divinyl benzene were blended with linear polystyrene (LP) to form a range of composite matrix formulations. Blends of the HB and LP polymers were used since the neat hyperbranched polymers alone proved to be highly brittle when formed into a film. A neat LP‐GF composite was also prepared as control. Of the three matrix modifiers considered, only the H‐HB provided an improvement in mechanical properties in comparison to LP‐GF. With the addition of 10 and 20 wt% H‐HB, respectively, the flexural modulus increased by 25% (p < 0.05) and 36% (p < 0.05) and flexural strength increased by 15% (p < 0.05) and 31% (p < 0.005). The enhanced mechanical properties were attributed to better fiber wetting along with crystallization observed with the addition of 20 wt% H‐HB. The non‐reactive ethyl (CH2CH3) chain end group of the macromolecular H‐HB resulted in a plasticizing effect, which in turn improved its wettability. The LP:HB polymer blends, on the other hand, underwent crosslinking due to the presence of the vinyl (CHCH2) chain ends leading to poor wettability in comparison to the LP:H‐HB and LP:LF blended films and hence lower mechanical properties.

Rapid Hyperbranched Polythioether Synthesis Through Thiol‐Michael Addition Reaction

ABSTRACTIn this study, two types of hyperbranched (HB) polythioether could readily be achieved in a short time at ambient temperature through a thiol‐Michael addition reaction. Dimethyl acetylenedicarboxylate (DMADC) or methyl propiolate (A2) and trimethylolpropane tris(3‐mercaptopropionate) (B3) monomers were reacted using an organobase 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD) as a catalyst in chloroform at room temperature to provide subsequent HB polythioethers. The effect of TBD concentration on the polymerization was studied for the DMDAC case monitoring the molecular weight evolution against time. HB polythioethers were characterized using spectroscopic (nuclear magnetic resonance) and chromatographic (gel permeation chromatography with refractive index and light‐scattering detectors) techniques. © 2020 Wiley Periodicals, Inc. J. Polym. Sci. 2020, 58, 824–830

Universal Relationships in Hyperbranched Polymer Architecture for Batch and Continuous Step Growth Polymerization of AB2-Type Monomers

Design and control of hyperbranched (HB) polymer architecture by way of reactor operation is key to a successful production of higher-valued HB polymers, and it is essential in order to clarify the fundamental structural characteristics formed in representative types of reactors. In this article, the irreversible step growth polymerization of AB2 type monomer is investigated by a Monte Carlo simulation method, and the calculation was conducted for a batch and a continuous stirred-tank reactor (CSTR). In a CSTR, a highly branched core region consisting of units with large residence times is formed to give much more compact architecture, compared to batch polymerization. The universal relationships, unchanged by the conversion levels and/or the reactivity ratio, are found for the mean-square radius of gyration Rg2, and the maximum span length LMS. For batch polymerization, the g-ratio of Rg2 of the HB molecule to that for a linear molecule conforms to that for the random branched polymers represented by the Zimm-Stockmayer equation. A single linear equation represents the relationship between Rg2 and LMS, both for batch and CSTR. Appropriate process control in combination with the chemical control of the reactivity of the second B-group promises to produce tailor-made HB polymer architecture.

Preparation and Evaluation of Antimicrobial Hyperbranched Emulsifiers for Waterborne Coatings.

Nosocomial infections are a major problem in medical health care. To solve this problem, a series of antimicrobial waterborne paints were prepared by using antimicrobial hyperbranched (HB) emulsifiers. The HB-emulsifiers were prepared by polymerizing AB2 monomers obtained in a one-step reaction of bis(hexamethylene)triamine and carbonyl biscaprolactam. The blocked isocyanate end groups (B groups) of the HB-polymer were utilized to introduce tertiary amino groups through the reaction with compounds comprising either a hydroxyl or a primary amino group and a tertiary amino group. Quaternization of the tertiary amines with 6 different alkyl bromides resulted in 12 amphiphilic cationic species. The 12 emulsifiers showed the successful inhibition and killing of 8 bacterial and 2 fungal strains. The killing efficacy increased with increasing alkyl chain length. The octyl-functionalized compound was chosen for suspension polymerizations because of the good compromise between killing and emulsifying properties. With this emulsifier, aqueous poly(methacrylate) suspensions were prepared, which were stable and had excellent killing properties.

Cytomembrane Infused Polymer Accelerating Delivery of Myelin Antigen Peptide to Treat Experimental Autoimmune Encephalomyelitis.

While there has been extensive development of soluble epitope-specific peptides to induce immune tolerance for the treatment of autoimmune diseases, the clinical efficacy of soluble-peptides-based immunotherapy was still uncertain. Recent strategies to develop antigen carriers coupled with peptides have shown promising results in preclinical animal models. Here we developed functional amphiphilic hyperbranched (HB) polymers with different grafting degrees of hydrophobic chains as antigen myelin antigen oligodendrocyte glycoprotein (MOG) peptide carriers and evaluated their ability to induce immune tolerance. We show that these polymers could efficiently deliver antigen peptide, and the uptake amount by bone marrow dendritic cells (BMDCs) was correlated with the hydrophobicity of polymers. We observe that these polymers have a higher ability to activate BMDCs and a higher efficacy to induce antigen-specific T cell apoptosis than soluble peptides, irrespective of hydrophobicity. We show that intravenous injection of polymer-conjugated MOG peptide, but not soluble peptide, markedly treats the clinical symptoms of experimental autoimmune encephalomyelitis in mice. Together, these results demonstrate the potential for using amphiphilic HB polymers as antigen carriers to deliver peptides for pathogenic autoreactive T cell deletion/tolerance strategies to treat autoimmune disorders.

Hybrasurfs-A New Class of Hyperbranched Surfactants.

A hyperbranched (HB) polyester carrying peripheral allyl groups was prepared by melt-condensation of a suitably designed AB2 monomer bearing two allyl ester groups and one hydroxyl group. The periphery of the hyperbranched polymer was co-clicked with two different organic thiols, namely, hexadecane thiol and 3-mercaptopropionic acid, using the thiol-ene reaction. Three different samples with varying mole fractions of the hydrophilic carboxylic acid groups were prepared; the conformational adaptability of the hyperbranched polymer backbone permitted these amphiphilic systems to form Janus structures that exhibit surfactant-like properties and, therefore, we have termed them hybrasurfs. These polymers behave like clusters of surfactants that have been stitched at the waist by the HB polymer backbone; the Langmuir isotherms revealed the formation of a monolayer, and in two of the samples having higher mole fractions of hexadecyl segments a weak inflection in the isotherm is seen. This suggests a densification, typically implying the crystallization of the alkyl segment at the air-water interface. The monolayers were transferred onto a substrate, and their heights were estimated using atomic force microscopy; the values thus obtained were in reasonable agreement with the expected value. The water contact angles of the substrates bearing the transferred monolayers of the three different samples (transferred at two different points along the isotherm) were measured; it was seen that the sample carrying the highest mole fraction of hexadecyl chains exhibited a significantly larger contact angle when compared to that of the other two samples. Interestingly, these hybrasurfs also formed vesicles in water and were shown to encapsulate water-soluble dyes, such as Eosin Y. Thus, this class of readily accessible amphiphilic HB polymers that behave as a cluster of surfactants opens some interesting possibilities for further exploration.

Effect of aliphatic chain length on the chemical structures of low molecular weight hyperbranched polyesters

AbstractLow molecular weight hyperbranched (HB) polyesters were synthesized via melt polymerization from trimethylolpropane and three aliphatic dicarboxylic acids, namely, succinic acid (SA), adipic acid (AA) and dodecanedioic acid (DA). The degrees of branching (DBs) ranged between 30% and 75% depending on the monomer ratio. Their DB, cyclic index and terminal index were all determined, indicating that the shorter chain HB polyesters PE-SA and PE-AA showed a greater degree of intramolecular cyclization, compared to the longer aliphatic chains within PE-DA. The HB polyesters form stable colloidal suspensions in buffered aqueous media and were found to be pH responsive. The stability of the colloidal suspensions is enhanced by two factors: (1) increasing the aliphatic chain length and (2) increasing the pH of the solution for the same HB polyester.

Thermal Energy Storage Using Poly(ethylene glycol) Incorporated Hyperbranched Polyurethane as Solid–Solid Phase Change Material

For efficient energy storage, hyperbranched (HB) architecture was adopted to prepare a series of HB polyurethanes via A2 + B3 approach with isocyanate terminated poly(ethylene glycol) (PEG) as branching unit and phloroglucinol (PG) as aromatic core. The chemical structure of the HB polymer was confirmed using FTIR and NMR. The gel permeation chromatography and solution viscosities indicate polymers of moderately high molecular weights. The thermal behavior and crystalline properties were investigated using differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction, and polarized optical microscopy. A high fusion enthalpy of 146.6 J g–1 at transition temperature of 56 °C was achieved. Thermal stability was found to be quite high (up to 300 °C), and thermal reliability was retained with no chemical degradation after thermal cycling. The polymer exhibited crystalline to amorphous phase change above the transition temperatures and back, which makes it attractive as a polymeric phase chan...

Synthesis of functionalized CNTs/hyperbranched polyester nanocomposites

Carbon nanotubes (CNTs) were unzipped using the modified Hummer method to prepare the CNTs-GO microstructure (see Fig. 1). A new type of CNTs-GO-H20 nanocomposite has been synthesized by grafting hyperbranched (HB) polyester (Boltorn H20) brushes on the CNTs-GO by coupling agent (KH560). The morphology of CNTs-GO-H20 was characterized by FTIR, TEM, XPS and TGA. The FT-IR data and XPS data evidenced that CNTs-GO-H20 nanocomposites were synthesized successfully. The addition of CNTs improved the thermal stability of the nanocomposites. The TEM data showed that the CNTs-GO microstructure was also prepared. These electrochemical measurements results indicated that coatings provided greater protection against corrosion behavior. Moreover, the nanocomposite material improved corrosion resistance of the coating.

Tunable Permittivity in High-Performance Hyperbranched Polyimide Films by Adjusting Backbone Rigidity

Currently, low-dielectric polyimides (PIs) such as fluorinated or porous PIs exhibit a low-dielectric property but have undesirable mechanical and/or thermal properties. Therefore, it is crucial to find a more considerate method that could lower the permittivity, while maintaining or improving the mechanical and thermal properties. Herein, a series of hyperbranched (HB) PI films were synthesized by adjusting the content of the rigid diamine, 2,2′-dimethylbenzidine (DMBZ). The dielectric properties of the HBPIs were accordingly tuned, that is, the permittivity of the resulting HBPIs decreased with increasing the DMBZ fraction owing to the enlarged free volume and the hindered dipole orientations afforded by the rigid DMBZ. The maximum mechanical strength of the resulting HBPIs located at the formulation made using 50% DMBZ and 50% ODA. At this formulation, the optimal comprehensive performances were achieved, that is, excellent tensile strength (124.1 MPa), desirable thermal stability (5% weight loss tempe...

Rheological properties of hydroxyl‐terminated and end‐capped aliphatic hyperbranched polyesters

ABSTRACTThe rheological behavior of two series of aliphatic hyperbranched (HB) polyesters, based on 2,2‐bis(hydroxymethyl)propionic acid (bis‐MPA) and di‐trimethylol propane (Di‐TMP) as a tetrafunctional core, was studied. The effect of the size (pseudo‐generation number, from second to eight) and structure on the melt rheological properties was investigated for a series of hydroxyl‐terminated HB polyesters. In addition, the influence of the nature and degree of modification of the terminal OH groups in a series of fourth‐generation polyesters end‐capped with short and long alkyl chains and some aryl groups on the rheological properties was analyzed. The time–temperature superposition procedure was applied for the construction of master curves and for the analysis of the rheological properties of HB polyesters. The data obtained from WLF analysis of the HB polyesters showed that the values of the thermal coefficient of expansion of free volume αf and the fractional free volume at the glass transition temperature, fg, increase with increasing size of the HB polyesters. It was shown that the modified HB polyesters exhibited lower Tg and TG′=G″ temperatures, above which viscous became dominant over elastic behavior. From an analysis of the master curves of the modified HB polyesters, it was observed that with increasing degree of modification, both storage and loss modules and complex dynamic viscosity and apparent energy for viscoelastic relaxation decrease, because of reduced intermolecular hydrogen interactions. They do not exhibit a plateau of rubbery behavior, which confirms that no entanglements are present and that the molar masses are below the critical molar mass. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41479.

Polyurethane molded foams with high content of hyperbranched polyols from soybean oil

This paper examines the feasibility of using polyols from vegetable oils as base polyols (i.e. with 50% or more in a blend with petrochemical polyols) for flexible molded polyurethane foams. A series of hyperbranched (HB) polyols were synthesized by transesterification of hydroxy fatty acid methyl esters and different modifiers to control viscosity, hydrophilicity, molecular weight, and functionality. All HB polyols had hydroxyl numbers around 85 mg KOH/g, with the exception of one which was 105 mg KOH/g. When mixed with petrochemical polyols with OH numbers 35 and 28 mg KOH/g, the HB polyols acted primarily as high molecular weight crosslinkers that increased the stiffness of the polymeric network and the load-bearing properties but decreased the tensile strength, elongation, and tear strength. However, most of the foams met the targeted tensile and tear strength values while some of the foam formulations provided satisfactory elongation. The best mechanical properties were obtained from foams with phthalic anhydride-modified HB polyols. It was demonstrated that flexible molded foams with satisfactory properties can be obtained with 50% and 65% of HB soy polyols in a blend with PPO polyols.

Phase transition behaviours of a single dendritic polymer.

Dendritic polymers with highly branching structures exhibit many unique properties. In this paper, a computational study using the Wang-Landau sampling technique is carried out to reveal the phase transition behaviours of dendritic homopolymers with various branching structures. Two types of dendritic homopolymers, dendrimers/dendrigrafts (D/D) and hyperbranched (HB) polymers are studied. It is found that with increasing degree of branching in the dendritic polymer, the liquid-solid (LS) transition temperature increases and the coil-globule (CG) transition becomes weak. Additionally, under similar degrees of branching and polymerization, D/D polymers have a higher LS transition temperature than HB polymers. The reason is that the D/D polymers have greater regularity in the radial distribution of the branching units, which facilitates monomer packing during the LS transition. The distinctive internal unit distribution at various temperatures is quantitatively analysed. Our results show the importance of dendritic polymer structure regularity in phase transition behaviours and are valuable in guiding the structural design of dendritic macromolecules for functionalization applications.

A thiol‐ene clickable hyperbranched polyester via a simple single‐step melt trans‐esterification process

ABSTRACTSelf‐condensation of AB2 type monomers (containing one A‐type and two B‐type functional groups) generates hyperbranched (HB) polymers that carry numerous B‐type end‐groups at their molecular periphery; thus, development of synthetic methods that directly provide quantitatively transformable peripheral B groups would be of immense value as this would provide easy access to multiply functionalized HB systems. A readily accessible AB2 monomer, namely diallyl, 5‐(4‐hydroxybutoxy)isophthalate was synthesized, which on polymerization under standard melt‐transesterfication conditions yielded a peripherally clickable HB polyester in a single step; the allyl groups were quantitatively reacted with a variety of thiols using the facile photoinitiated “thiol‐ene” reaction to generate a wide range of derivatives, with varying solubility and thermal properties. Furthermore, it is shown that the peripheral allyl double bonds can also be readily epoxidized using meta‐chloroperoxybenzoic acid to yield interesting HB systems, which could potentially serve as a multifunctional cross‐linking agent in epoxy formulations. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40248.