Thermoresponsive Helical Poly(phenylacetylene)s

Poly­(phenylacetylene) (PPA) bearing dendritic oligo­(ethylene glycol) (OEG) as pendants was synthesized, and its thermoresponsiveness and helical conformation were investigated. Despite the steric hindrance of the bulky pendants in the homopolymer PPA-OEG, the chirality could be efficiently transferred from pendant alanine moieties to PPA main chain through ester linkage. In order to examine the steric effect of pendants on chiral transformation, a model PPA homopolymer PPA-Boc which carries less bulky moieties was prepared for comparison. The chiroptical properties of these thermoresponsive PPAs were further investigated by varying temperature to examine the effects of their thermoresponsiveness. In addition, PPA copolymers PPA-BDY bearing OEG dendron and fluorescent boradiazaindacene (BDY) chromophore showed excellent thermoresponsive properties and interesting fluorescence enhancement at elevated temperatures. To investigate the rigidity effects of polymer backbone on the thermally induced fluorescence enhancement, a nonchiral polymer carrying the same pendants but with polymethacrylate as the backbone (PMA-OEG) was prepared. It was found that the chiroptical and fluorescence properties of these PPAs are dependent not only on their chemical structures but also on the thermoresponsiveness

Thermo-Gelling Dendronized Chitosans for Modulating Protein Activity

Regulation of protein activity is important in their applications for biomedicine and therapeutics. Here, an approach for the regulation of protein bioactivity through molecular confinement provided by oligoethylene glycol (OEG)-based dendronized chitosan (DCS) hydrogels is reported. Structural effects on their thermoresponsiveness are investigated. The highly transparent hydrogels are formed from thermoresponsive DCSs through their thermal dehydration and exhibit an intriguing reversible sol–gel transition property when triggered at physiological temperatures. The thermo-gelling behavior and mechanical strength of these hydrogels are investigated, and possible effects from hydrophobicity of the OEG dendrons, grafting rates of the dendrons on the chitosan main chain, and solid content of polymers are examined. These DCS hydrogels are found to have lamellar morphologies and can provide characteristic hydrophobicity microenvironments formed through the crowded OEG dendrons, which show a higher level of confinement to guest proteins. This allows the DCS hydrogels remarkable activity protection capability to proteins. Furthermore, these DCS hydrogels inherit the degradability from chitosan, allowing protein release from these hydrogels through the controllable ways without impairing their activities

How Big Is Big Enough? Effect of Length and Shape of Side Chains on the Single-Chain Enthalpic Elasticity of a Macromolecule

Polymers with a carbon–carbon (C–C) backbone are an important class of polymers, which can be regarded as the derivatives of polyethylene (PE). To investigate the effect of side chains on the single-chain enthalpic elasticity (SCEE) of polymers with a C–C backbone, several polymers with pendants or side chains of different lengths and shapes have been studied by single-molecule AFM. We find that both length and shape of the side chains count: only the side chains that are both long and bulky (i.e., bulky dendrons of second or higher generation as side chains) affect the SCEE. Thus, only rare polymers have special SCEE. For the vast majority of polymers, the SCEE is identical to that of PE, which means that the SCEE is determined by the nature of the C–C backbone. It is expected that this conclusion can also be popularized to all polymers with various backbones. This study is an important update to the understanding of polymers at the single-chain level

Thermoresponsive Dendronized Polypeptides Showing Switchable Recognition to Catechols

A new class of thermoresponsive dendronized polypeptides was prepared through highly efficient oxime ligation between oxyamino-substituted polylysines and aldehyde-cored oligoethylene glycol (OEG) dendrons. Their secondary structures and thermoresponsive behavior were investigated. Because of the dendritic structures and stable oxime linkage, these OEG-based dendronized polypeptides exhibited fast and fully reversible phase transitions in neutrally aqueous solutions, and their phase transition temperatures can be controlled around physiological temperatures. The effect of OEG dendronization on secondary structures of polypeptides were examined to check their prominent dendritic shielding effect, steric hindrance, and thermally driven phase transitions. To further extend the functions and potential applications of these stimuli-responsive dendronized polypeptides, phenylboronic acid moieties were introduced to achieve the corresponding dendronized copolymers, which were utilized to specifically recognize catechol-containing compounds such as alizarin red S or dopamine. These copolypeptides showed a significant enhancement to bind to catechols when comparing to monomeric phenylboronic acid. Furthermore, this enhanced binding can be switched surprisingly by thermally driven phase transitions or through addition of competitive catechols, which makes this class of dendronized polypeptides as unique scaffolds for selective and reversible recognition of catechols

Codendrimer from Polyamidoamine (PAMAM) and Oligoethylene Dendron as a Thermosensitive Drug Carrier

The efficient synthesis of codendrimer PAMAM-co-OEG (<b>PAG</b>) and its properties in aqueous solution, including particle size and thermosensitivity, are described. <b>PAG</b> is synthesized with well-defined structure through the “attach to” route. In the aqueous solutions, <b>PAG</b> forms unimer and multimolecular aggregates with the respective particle sizes of approximately 8 and 200 nm, depending on the concentration. <b>PAG</b> shows thermosensitive behavior with sharp and fast transition, and the lower critical solution temperature is 38.2 °C. The suitability of codendrimer <b>PAG</b> as the thermosensitive carrier is evaluated with methotrexate (MTX) as the model drug. MTX is encapsulated in <b>PAG</b> with the drug-loading capacity of 39%, among which 30% of MTX is encapsulated in PAMAM core. The release behavior of MTX mediated by temperature is investigated with focus on the effects around the LCST of <b>PAG</b>

Comblike Thermoresponsive Polymers with Sharp Transitions: Synthesis, Characterization, and Their Use as Sensitive Colorimetric Sensors

The synthesis and thermoresponsive behavior of two structural novel comblike polymers are presented, which are constituted by polymethacrylates main chain with dendritic oligoethylene glycol (OEG) side groups spaced with a linear hydrophobic alkyl [PG1(A)] or hydrophilic OEG unit [PG1(G)]. The design of this comblike architecture is to retain the unique thermoresponsive behavior of OEG-based dendritic polymers and, on the other side, to eliminate the tremendous synthesis effort for the dendronized polymer analogues. Their thermoresponsive behavior was investigated with UV/vis and temperature-varied ¹H NMR spectroscopy to determine their apparent LCSTs and follow chain dehydration process, respectively. These polymers show sharp and fast transitions with small hystereses. The phase transition temperatures are located in between 27 and 34 °C, which is in the vicinity of physiological temperature, and these transition temperatures are independent of polymer concentration. The thermoresponsiveness of these polymers is also compared with the corresponding macromonomers as well as the densely packed dendronized polymer analogues reported previously, focusing on chemical structure and architecture effects. It was found that the more hydrophobic polymer PG1(A) could form denser aggregates than that of the more hydrophilic polymer PG1(G). On the basis of the exceptional thermoresponsive behavior of these comblike polymers, this architecture is utilized for fabricating polymer sensors. Random copolymerization of the macromonomers with the monomer bearing solvatochromic dye moiety (Disperse Red 1) affords the thermoresponsive copolymers which act as sensitive dual-sensors for both temperature and pH value

ILQINS Hexapeptide, Identified in Lysozyme Left-Handed Helical Ribbons and Nanotubes, Forms Right-Handed Helical Ribbons and Crystals

Amyloid fibrils are implicated in over 20 neurodegenerative diseases. The mechanisms of fibril structuring and formation are not only of medical and biological importance but are also relevant for material science and nanotechnologies due to the unique structural and physical properties of amyloids. We previously found that hen egg white lysozyme, homologous to the disease-related human lysozyme, can form left-handed giant ribbons, closing into nanotubes. By using matrix-assisted laser desorption ionization mass spectrometry analysis, we here identify a key component of such structures: the ILQINS hexapeptide. By combining atomic force microscopy and circular dichorism, we find that this fragment, synthesized by solid-phase peptide synthesis, also forms fibrillar structures in water at pH 2. However, all fibrillar structures formed possess an unexpected right-handed twist, a rare chirality within the corpus of amyloid experimental observations. We confirm by small- and wide-angle X-ray scattering and molecular dynamics simulations that these fibrils are composed of conventional left-handed β-sheets, but that packing stresses between adjacent sheets create this twist of unusual handedness. We also show that the right-handed fibrils represent a metastable state toward β-sheet-based microcrystals formation

Thermoresponsive Dendronized Poly(phenylacetylene)s via Dynamic Covalent Chemistry Showing Multiple-Responsive Chirality

Helical polymers with dynamic chirality are interesting not only for understanding the relationship between polymer structure and chiral conformation but also for developing responsive chiral polymeric materials. We report here the synthesis and characterization of a homologous series of dendronized poly(phenylacetylene)s (PPAs) via both macromonomer and grafting-to routes. These copolymers consist of achiral units carrying dendritic oligoethylene glycol (OEG) pendants and chiral units of dynamic imines formed from aldehydes and amino acids, which combine the constitutional dynamic chemistry (Schiff base) in the pendants with the conformational dynamic PPA backbones. Dendritic OEG pendants endow these copolymers with characteristic thermoresponsive behavior. The principles for modulating the helicity of these dendronized copolymers were examined, and factors including molecular structures (copolymer compositions and pendant linkage via ester or amide), solution pH, and thermally induced phase transitions have been investigated. These copolymers adopt tailored helicities in the presence of additional amino acids through multiple interaction balances between the copolymers and the amino acids. We believe that the methodology developed in this work will pave a convenient way to afford optically inactive copolymers or active polymers with featured dynamic helicity

Light-Controlled Shrinkage of Large-Area Gold Nanoparticle Monolayer Film for Tunable SERS Activity

The two-dimensional (2D) monolayer gold nanoparticle (Au NP) film is of significant interest and importance in both fundamental and practical applications including optoelectronic devices, sensing, catalysis, and surface-enhanced Raman spectroscopy (SERS). Because of the weak physical interaction, the conventional monolayer Au NP film fabricated at the oil–water interface was unstable, easily breakable, and difficultly transferred. In the present work, we report on a simple and effective chemical cross-linking strategy at the air–water interface to achieve a large-scale monolayer gold nanoparticle film with intelligently tunable size of nanogaps, and excellent free-standing and easily transferable properties. In our strategy, acrylamide, a polymerizable molecule, was first modified on the surface of Au NPs for subsequent self-assembly into a monolayer film at the liquid–liquid interface. Through photopolymerization of acrylamide, a chemically cross-linked film was formed with closely packed nanoparticles, highly macroscopic uniformity, and excellent free-standing property, which allowed it to be easily transferred from the air–water interface onto various solid substrates while maintaining its integrity. It is interesting to find that the macroscopic film underwent an <i>in situ</i> shrinkage under irradiation of UV-light, and its area shrinkage ratio is close to 55% (equal to 2.2 times) of that from non-cross-linked counterparts. More importantly, UV-light-controlled <i>in situ</i> shrinkage of the Au NP film would lead to intelligently, precisely tuned nanogaps less than 0.5 nm between neighboring Au NPs for maximal amplification of SERS signals, and the macroscopic uniformity of the films ensured the reproducible performance of SERS signals, providing an ideal candidate for SERS applications

OEGylated Cyclodextrins Responsive to Temperature, Redox, and Metal Ions

The present work provides a versatile access for “smart” cyclodextrins (CDs) that are responsive to temperature, redox, and metal ions. These CDs are modified with oligoethylene glycols through thiol–ene click chemistry, which are inherently thermoresponsive in aqueous solutions. At the same time, their thermoresponsiveness is tunable through oxidation or metal ion chelation of thioether moieties. Significantly, these stimuli-responsive CDs retained strong inclusion abilities to guest dyes, and the inclusion complexation can be tuned by thermally induced phase transitions, oxidation, as well as metal chelation. The stimuli-responsive complexation with dyes allows to fabricate colorimetric/fluorescent sensors for temperature or for soft metal ions, such as Ag⁺ and Hg²⁺. With multiple responsiveness integrated in one material, these monodisperse CDs have formed a new class of stimuli-responsive macrocycles, which can reversibly encapsulate and release guest species through multiple switches