Hydrophobic Pendant Research Articles

Self-Sorting of Amphiphilic Copolymers for Self-Assembled Materials in Water: Polymers Can Recognize Themselves.

Amphiphilic random copolymers bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic alkyl pendants showed dynamic self-sorting behavior, that is, self-recognition, under competitive conditions in aqueous media. The self-sorting universally takes place not only in water but also in hydrogels and on the material surfaces, according to encoded information originating from the primary structure of composition and pendants. Binary blends of the copolymers with different composition or alkyl pendants readily induced composition- or alkyl pendant-dependent self-sorting to simultaneously provide discrete and size-controlled micelles with hydrophobic cores. Surprisingly, the micelles reversibly keep exchanging polymer chains exclusively between identical polymer micelles even in the presence of different counterparts. Owing to the dynamic self-sorting behavior, ABA-triblock copolymers comprising the amphiphilic random copolymer A segments and a hydrophilic PEG chain B segment further provided hydrogels with self-healing yet selectively adhesive properties.

Self‐assembly of amphiphilic ABA random triblock copolymers in water

ABSTRACTSelf‐assembly of amphiphilic ABA random triblock copolymers in water serves as a novel approach to create unique structure micelles connected with flexible linkages. The ABA triblock copolymers consist of amphiphilic random copolymers bearing hydrophilic poly(ethylene glycol) and hydrophobic dodecyl pendants as the A segments and a hydrophilic poly(ethylene oxide) (PEO) as the middle B segment. The A block is varied in dodecyl methacrylate content of 20%–50% and degree of polymerization (DP) of 100‐200. By controlling the composition and DP of the A block, various architectures can be tailor‐made as micelles in water: PEO‐linked double core unimer micelles, PEO‐looped unimer or dimer micelles, and multichain micelles. Those PEO‐linked or looped micelles further exhibit thermoresponsive solubility in water. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 313–321

A Novel PAA Derivative with Enhanced Drug Efficacy in Pancreatic Cancer Cell Lines.

Nanoparticles have been shown to be effective drug carriers in cancer therapy. Pancreatic cancer forms dense tumours which are often resistant to drug molecules. In order to overcome such multidrug resistance, new drug entities, novel delivery systems and combination therapy strategies are being explored. In this paper, we report the design and synthesis of a poly(allylamine)-based amphiphile modified with hydrophobic naphthalimido pendant groups. Bisnaphthalimide compounds have been shown to possess anticancer activity. The potential of this polymer to encapsulate, solubilize and enhance drug (5-fluorouricil and bis-(naphthalimidopropyl)-diaminooctane) cytotoxicity in BxPC-3 cells was evaluated. Our studies showed that the insoluble drugs could be formulated up to 4.3 mg mL−1 and 2.4 mg mL−1 inside the amphiphiles, respectively. Additionally, the novel poly(allylamine)-naphthalimide carrier resulted in an amplification of cytotoxic effect with drug treatment after 24 h, and was capable of reduction of 50% cell population at concentrations as low as 3 μg mL−1.

Interaction between human serum albumin and cholesterol-grafted polyglutamate as the potential carriers of protein drugs

Currently there is no successful platform technology for the sustained release of protein drugs. It seems inevitable to specifically develop new materials for such purpose, and hence the understanding of protein–material interactions is highly desirable. In this study, we synthesized cholesterol-grafted polyglutamate (PGA-g-Chol) as a hydrophobically-modified polypeptide, and thoroughly characterized its interaction with a model protein (human serum albumin) in the aqueous solution by using circular dichroism, fluorescence methods, and light scattering. With the protein concentration fixed at 5 μmol/L, adding PGA-g-Chol polymers into the solution resulted in continuous blue shift of the protein fluorescence (from 339 to 332 nm), until the polymer molar concentration reached the same value as the protein. In contrast, the un-modified polyglutamate polymers apparently neither affected the protein microenvironment nor formed aggregates. Based on the experimental data, we proposed a physical picture for such protein–polymer systems, where the polymer first bind with the protein in a 1:1 molar ratio via a fraction of their hydrophobic pendant cholesterol resides along the polymer chain. In this protein/polymer complex, there are excess unbound cholesterol residues. As the polymer concentration increases, the polymers form multi-polymer aggregates around 200 nm in diameter via the same hydrophobic cholesterol residues. The protein/polymer complex also participate in the aggregation via their excess cholesterol residues, and consequently the proteins are encapsulated into the nanoparticles. The encapsulation was also found to increase the thermal stability of the model protein.

Nanostructured Materials via the Pendant Self-Assembly of Amphiphilic Crystalline Random Copolymers.

Versatile self-assembly systems to nanostructured materials in both solid and solution were developed with common amphiphilic random copolymers bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic crystalline octadecyl pendants. The copolymers efficiently induced precision self-assembly of the pendants to provide not only core-crystalline, thermoresponsive micelles and vesicles in water and reverse micelles in hexane but also sub-10 nm lamellar or spherical microphase separation structure in solid. Typically, the solid random copolymers with 50-80 mol % octadecyl units formed lamellar structure of a hydrophilic PEG layer and a hydrophobic, crystalline octadecyl layer. Importantly, the domain spacing is about 5 nm, much smaller than that generally obtained with conventional block copolymers. The domain structure is controlled by composition, independent of chain length. The copolymers further gave various thermoresponsive, compartmentalized materials in aqueous and organic media, where the 3D structure can be also controlled by the composition and sample preparation protocols.

Programmed Self-Assembly Systems of Amphiphilic Random Copolymers into Size-Controlled and Thermoresponsive Micelles in Water

We report programmed self-assembly systems of amphiphilic random copolymers bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic alkyl pendants into size-controlled and thermoresponsive micelles in water. This system affords simultaneous and precise control of the size, aggregation numbers, and cloud point (Cp) of micelles in water by primary structure (pendant alkyl groups, composition, and chain length) that is programmed in the copolymers. Typically, random copolymers bearing PEG and alkyl pendants (butyl, octyl, dodecyl, and octadecyl groups) universally induce intermolecular self-assembly in water to produce uniform size micelles (<10 nm). The size is just determined by the content and alkyl pendant length of the hydrophobic monomers, independent of main chain length (below critical length for self-folding): The size increased with increasing the content and the pendant length. Design of hydrophobic alkyl groups with tuning composition allow us to widely control the size (molecular weight:...

Small neutral Gd(iii) tags for distance measurements in proteins by double electron-electron resonance experiments.

Spin labels containing a Gd(iii) ion have become important for measuring nanometer distances in proteins by double electron-electron resonance (DEER) experiments at high EPR frequencies. The distance resolution and sensitivity of these measurements strongly depend on the Gd(iii) tag used. Here we report the performance of two Gd(iii) tags, propargyl-DO3A and C11 in DEER experiments carried out at W-band (95 GHz). Both tags are small, uncharged and devoid of bulky hydrophobic pendants. The propargyl-DO3A tag is designed for conjugation to the azide-group of an unnatural amino acid. The C11 tag is a new tag designed for attachment to a single cysteine residue. The tags delivered narrower distance distributions in the E. coli aspartate/glutamate binding protein and the Zika virus NS2B-NS3 protease than previously established Gd(iii) tags. The improved performance is consistent with the absence of specific hydrophobic or charge-charge interactions with the protein. In the case of the Zika virus NS2B-NS3 protease, unexpectedly broad Gd(iii)-Gd(iii) distance distributions observed with the previously published charged C9 tag, but not the C11 tag, illustrate the potential of tags to perturb a labile protein structure and the importance of different tags. The results obtained with the C11 tag demonstrate the closed conformation in the commonly used linked construct of the Zika virus NS2B-NS3 protease, both in the presence and absence of an inhibitor.

Simultaneous trapping of Cr(III) and organic dyes by a pH-responsive resin containing zwitterionic aminomethylphosphonate ligands and hydrophobic pendants

A novel functionalized resin containing hydrophilic motifs of aminomethylphosphonate and hydrophobic pendant of 6-(biphenyl-4-yloxy)hexyl has been synthesized. The resin has been utilized as a sorbent for the simultaneous removal of Cr(III) as well as several organic dyes from aqueous solutions. At an initial Cr(III) concentration of 1.0ppm, the metal uptake was almost ≈100% in 20min at pH 5 and 25°C. The experimental results were evaluated by Langmuir, Freundlich, and Temkin isotherm models. By using 0.1M HNO3 solution, the adsorbed Cr(III) ions were desorbed effectively. Interestingly, the resin demonstrated remarkable efficacy in simultaneous and complete removal of Cr(III) and several dyes including methyl orange, eriochrome black T, rhodamine B, methyl red and methylene blue from their mixture. The resin has also been remarkably effective in the removal of several toxic metal ions from a real industrial wastewater. As such, the resin may have applications for international environmental management in the water technology.

Self‐Assembly of Amphiphilic Random Copolyacrylamides into Uniform and Necklace Micelles in Water

Amphiphilic random copolyacrylamides bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic dodecyl pendants induce precision self‐assembly to produce quite small uniform and/or necklace micelles (≈10 nm) in water. The size, structure, and thermoresponsive properties of the micelles are controlled by the primary structure (composition and chain length) of the copolymers. For this, random copolymers with different composition, chain length, and molecular weight distribution are synthesized by iron‐catalyzed living or free radical copolymerization of PEG acrylamide and dodecyl acrylamide (DAAm). The copolymers with controlled molecular weight (degree of polymerization: ≈40) intermolecularly self‐assemble and/or self‐fold to form uniform (multichain or unimer) micelles in water; the size increases with increasing hydrophobic DAAm content (19–57 mol%: Mw = 43 900–191 000). In contrast, random copolymers with relatively small DAAm content (&lt;35 mol%) and broad molecular weight distribution provide both uniform and necklace micelles in water.

Polymer nanoassemblies with hydrophobic pendant groups in the core induce false positive siRNA transfection in luciferase reporter assays

Poly(ethylene glycol)-conjugated polyethylenimine (PEG-PEI) is a widely studied cationic polymer used to develop non-viral vectors for siRNA therapy of genetic disorders including cancer. Cell lines stably expressing luciferase reporter protein typically evaluate the transfection efficacy of siRNA/PEG-PEI complexes, however recent findings revealed that PEG-PEI can reduce luciferase expression independent of siRNA. This study elucidates a cause of the false positive effect in luciferase assays by using polymer nanoassemblies (PNAs) made from PEG, PEI, poly-(l-lysine) (PLL), palmitate (PAL), and deoxycholate (DOC): PEG-PEI (2P), PEG-PEI-PAL (3P), PEG-PLL (2P’), PEG-PLL-PAL (3P’), and PEG-PEI-DOC (2PD). In vitro transfection and western blot assays of luciferase using a colorectal cancer cell line expressing luciferase (HT29/LUC) concluded that 2P and 2P’ caused no luciferase expression reduction while hydrophobically modified PNAs induced a 35–50% reduction (3P’<2PD<3P). Although cell viability remained stagnant, 3P triggered cellular stress responses including increased membrane porosity and decreased ATP and cellular protein concentrations. Raman spectroscopy suggested that hydrophobic groups influence PNA conformation changes, which may have caused over-ubiquitination and degradation of luciferase in the cells. These results indicate that hydrophobically modified PEG-PEI induces cellular distress causing over-ubiquitination of the luciferase protein, producing false positive siRNA transfection in the luciferase assay.

Clathrin-Independent Killing of Intracellular Mycobacteria and Biofilm Disruptions Using Synthetic Antimicrobial Polymers.

Current membrane targeting antimicrobials fail to target mycobacteria due to their hydrophobic membrane structure, ability to form drug-resistant biofilms, and their natural intracellular habitat within the confines of macrophages. In this work, we describe engineering of synthetic antimicrobial polymers (SAMPs) derived from biocompatible polyamides that can target drug-sensitive and drug-resistant mycobacteria with high selectivity. Structure-activity relationship studies revealed that reduced hydrophobicity of cationic pendants induces enhanced and selective permeabilization of mycobacterial membranes. The least hydrophobic SAMP (TAC1) was found to be the most active with maximum specificity toward mycobacteria over E. coli, S. aureus, and mammalian cells. Membrane perturbation studies, scanning electron microscopy, and colony PCR confirmed the ability of TAC1 to induce membrane lysis and to bind to the genomic material of mycobacteria, thereby inducing mycobacterial cell death. TAC1 was most effective in perfusing and disrupting the mycobacterial biofilms and was also able to kill the intracellular mycobacteria effectively without inducing any toxicity to mammalian cells. Cellular uptake studies revealed clathrin independent uptake of TAC1, thereby allowing it to escape hydrolytic lysosomal degradation and effectively kill the intracellular bacteria. Therefore, this manuscript presents the design and selective antimycobacterial nature of polyamide polymers with charged hydrophobic pendants that have ability to disrupt the biofilms and kill intracellular mycobacteria.

Macromol. Rapid Commun. 18/2016

Back Cover: An amphiphilic statistical copolymer forms micellar aggregates in water that can entrap drug molecules and release selectively at acidic pH. This is ascribed to the slow hydrolysis of the β-thiopropionate linkage that connects the hydrophobic pendant chains to the backbone of the polymer. Further details can be found in the article by P. Pramanik, D. Halder, S. S. Jana,* and S. Ghosh* on page 1499.

Pendant dual sulfonated poly(arylene ether ketone) proton exchange membranes for fuel cell application

Abstract Poly(arylene ether ketone) (PAEK) possessing carboxylic groups at the pendant position is synthesized, and the substitution degree of pendant carboxylic groups is controlled by adjusting the ratio of 4,4-bis(4-hydroxyphenyl)valeric acid and 2,2-bis(4-hydroxyphenyl)propane. Dual sulfonated 3,3-diphenylpropylamine (SDPA) is grafted onto PAEK as a proton-conducting moiety via the amidation reaction with carboxylic groups. The transparent and flexible membranes with different degrees of sulfonation are fabricated so that we can test and compare their structure and properties with a commercial Nafion ® 115 membrane for PEMFC applications. All prepared PAEK-SDPA membranes exhibit good oxidative and hydrolytic stability from Fenton's and high temperature water immersion test. SAXS analysis illustrates an excellent phase separation between the hydrophobic backbone and hydrophilic pendant groups, resulting in big ionic clusters. The proton conductivity was measured at different relative humidity, and its behavior was analyzed by hydration number of the membrane. Among a series of membranes, some samples (including B20V80-SDPA) show not only higher proton conductivity, but also higher integrated cell performance than those of Nafion ® 115 at 100% relative humidity, and thus we expect these to be good candidate membranes for proton exchange membrane fuel cells (PEMFCs).

PH-Triggered Sustained Drug Delivery from a Polymer Micelle having the β-Thiopropionate Linkage.

The synthesis, micellar aggregation, and pH-triggered intracellular drug delivery ability of an amphiphilic statistical copolymer (P2) are studied. Two methacrylate derivatives, one containing a hydrophilic pendant and the other containing a hydrophobic pendant chain, are copolymerized to produce P2. The hydrophobic pendant chain is linked to the polymer backbone by a β-thiopropionate linkage, known to undergo slow hydrolysis at mild acidic pH. P2 forms a multimicellar cluster in water with a critical aggregation concentration of 0.02 mg mL(-1) and encapsulates a hydrophobic guest such as pyrene, Nile red, or the anti-cancer drug doxorubicin (Dox). Sustained release of the entrapped Dox (80% after 100 h) is noticed at pH 5.2, while release is significantly slower (35% after 100 h) at pH 7.4. Acidic hydrolysis of the β-thiopropionate linkage leading to the reduction of the hydrophobicity is established as the cause for micellar disassembly and triggered drug release. Cell-culture studies with the human breast cancer cell line, MCF-7, reveal biocompatibility of P2 (below 150 μg mL(-1) ). It is further tested for intracellular delivery of Dox. MCF-7 cells remain healthy at pH 7.4 but become unhealthy at pH 5.2 when treated with a Dox-loaded P2 micelles.

Precision Self-Assembly of Amphiphilic Random Copolymers into Uniform and Self-Sorting Nanocompartments in Water

Self-assembly of amphiphilic molecules in water is a cornerstone to build compartmentalized materials toward unique functions, whereas it is yet challenging to create uniform, discrete, and size-controlled nanocompartments. This paper is to report that precision random copolymers, amphiphilic with hydrophilic poly(ethylene glycol) (PEG) and hydrophobic dodecyl pendants, induce precision self-assembly and self-recognition in water to form uniform, tunable, and self-sorting nanoparticles with inner-core hydrophobic compartments covered by PEG chains; the copolymers have been obtained via living or free radical copolymerization. The nanoparticles allow the on-target and predictable control of size, molecular weight, and aggregation number by tuning the primary structure of the copolymers; even mixtures of the copolymers with different composition underwent self-sorting to provide size-controlled discrete compartments.

Influence of the secondary structure on the AIE-related emission behavior of an amphiphilic polypeptide containing a hydrophobic fluorescent terminal and hydrophilic pendant groups

AIE-related emission of polypeptide containing an AIE-active terminal is correlated with secondary structures (α-helix, β-sheet and random coil) of the peptide chains.

Single-chain crosslinked star polymers via intramolecular crosslinking of self-folding amphiphilic copolymers in water

Single-chain crosslinked star polymers with multiple hydrophilic short arms and a hydrophobic core were created as novel microgel star polymers of single polymer chains. The synthetic process involves the intramolecular crosslinking of self-folding amphiphilic random copolymers in water. For this process, amphiphilic random copolymers bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic olefin pendants were synthesized by ruthenium-catalyzed living radical copolymerization of PEG methyl ether methacrylate, dodecyl methacrylate and hydroxyl-functionalized methacrylates, and the in situ or postesterification of the hydroxyl pendants of the resulting copolymers with methacryloyl chloride. The olefin-bearing copolymers with 20–40 mol% hydrophobic units efficiently self-folded because of hydrophobic interactions in water. These folded structures were then crosslinked intramolecularly using a free radical initiator or a ruthenium catalyst to selectively yield single-chain crosslinked star polymers, whereas a counterpart containing 50 mol% hydrophobic units induced bimolecular aggregation in water to give double-chain crosslinked star polymers. The primary structure of the star polymers can be precisely controlled with random copolymer precursors. Owing to the PEG arm units, the star polymers further showed thermosensitive solubility in water. Single-chain crosslinked star polymers with hydrophilic and thermoresponsive poly(ethylene glycol) short arms and a hydrophobic core were created as novel microgel star polymers of single polymer chains via the intramolecular crosslinking of self-folding amphiphilic random copolymers in water. For this, well-controlled amphiphilic random copolymers bearing hydrophobic olefin pendants were synthesized as self-folding precursors by ruthenium-catalyzed living radical polymerization and the subsequent introduction of olefin units. The copolymers with 20–40 mol% hydrophobic units efficiently gave single-chain crosslinked star polymers in water.

Enhancing the water stability of Al-MIL-101-NH2 via postsynthetic modification.

The resistance of metal-organic frameworks towards water is a very critical issue concerning their practical use. Recently, it was shown for microporous MOFs that the water stability could be increased by introducing hydrophobic pendant groups. Here, we demonstrate a remarkable stabilisation of the mesoporous MOF Al-MIL-101-NH2 by postsynthetic modification with phenyl isocyanate. In this process 86 % of the amino groups were converted into phenylurea units. As a consequence, the long-term stability of Al-MIL-101-URPh in liquid water could be extended beyond a week. In water saturated atmospheres Al-MIL-101-URPh decomposed at least 12-times slower than the unfunctionalised analogue. To study the underlying processes both materials were characterised by Ar, N2 and H2 O sorption measurements, powder X-ray diffraction, thermogravimetric and chemical analysis as well as solid-state NMR and IR spectroscopy. Postsynthetic modification decreased the BET equivalent surface area from 3363 to 1555 m(2) g(-1) for Al-MIL-101-URPh and reduced the mean diameters of the mesopores by 0.6 nm without degrading the structure significantly and reducing thermal stability. In spite of similar water uptake capacities, the relative humidity-dependent uptake of Al-MIL-101-URPh is slowed and occurs at higher relative humidity values. In combination with (1) H-(27) Al D-HMQC NMR spectroscopy experiments this favours a shielding mechanism of the Al clusters by the pendant phenyl groups and rules out pore blocking.

Zwitterionic ammonium and neutral amino molecules as cathode interlayer for inverted polymer solar cells

Cathode interlayer is essential to inverted bulk heterojunction polymer solar cells (PSCs). A series of zwitterionic ammonium and neutral amino organic molecules are introduced into inverted PSCs as cathode interlayer and power conversion efficiency (PCE) as high as 8.07% is demonstrated. Compared to the devices without interlayer, all the devices exhibit significant improvements of the device parameters by reducing the work function of indium tin oxide (ITO) cathode. It is striking that the devices with neutral amino molecules as interlayer exhibit remarkably higher PCEs than the devices with zwitterionic ammonium molecules as interlayer. We attribute the improved performance to the better photoactive morphology induced by the hydrophobic properties of the neutral amino derivatives through research of ultraviolet photoelectron spectroscopy, atomic force microscopy, and contact angle measurements. Interestingly, the PCEs of the inverted PSCs with cathode interlayer are positively correlated with the hydrophobic properties of the interlayer materials, since devices with neutral amino molecules or molecules with a more hydrophobic alkyl pendant (piperidine) as interlayer exhibit higher PCEs. These results pave the way to the design of effective cathode interlayer materials.

Functional spaces in star and single-chain polymers via living radical polymerization

This article reviews recent advances in the creation of functional spaces with core-functionalized star polymers and single-chain folding/crosslinked polymers via living radical polymerization. Various core-functionalized star polymers were efficiently prepared with functional linking agents and monomers to perform unique functions. For example, they can serve as nanoreactors for active and robust catalysis in organic reactions and polymerization and as nanocapsules for selective and stimuli-responsive molecular recognition. Single-chain folding polymers were obtained from the self-folding of amphiphilic random copolymers bearing hydrophilic poly(ethylene glycol) chains and hydrophobic alkyl pendants in water, resulting in unimer micelles with dynamic hydrophobic domains. The folded structure could be further fixed via the intramolecular crosslinking of the hydrophobic interior. In addition, cation template-assisted cyclopolymerization and concurrent tandem living radical polymerization with in situ monomer transesterification were also developed for the one-pot synthesis of cyclopolymers with large in-chain cavities and gradient and sequence-controlled copolymers.