Thermoresponsive Helical Dendronized Poly(phenylacetylene)s: Remarkable Stabilization of Their Helicity via Photo-Dimerization of the Dendritic Pendants.

Dynamic helical polymers can change their helicity according to external stimuli due to the low helix-inversion barriers, while helicity stabilization for polymers is important for applications in chiral recognition or chiral separations. Here, we present a convenient methodology to stabilize dynamic helical conformations of polymers through intramolecular cross-linking. Thermoresponsive dendronized poly(phenylacetylene)s (PPAs) carrying 3-fold dendritic oligoethylene glycol pendants containing cinnamate moieties were synthesized. These polymers exhibit typical features of dynamic helical structures in different solvents, that is, racemic contracted conformations in less polar organic solvents and predominantly one-handed stretched helical conformations in highly polar solvents. This dynamic helicity can be enhanced through selective solvation by increasing the polarity of the organic solvents or simply via their thermally mediated dehydration in water. However, through photocycloaddition of the cinnamate moieties between the neighboring pendants via UV irradiation, these dendronized PPAs adopt stable helical conformations either below or above their phase transition temperatures in water, and their helical conformations can even be retained in less polar organic solvents. Spectroscopic and atomic force microscopy measurements demonstrate that photocycloaddition between the cinnamate moieties occurs on the individual molecular level, and this is found to be helpful in restraining the photodegradation of the PPA backbones. Molecular dynamics simulations reveal that the spatial orientation of the pendants along the rigid polyene backbone is crucial for the photodimerization of cinnamates within one helix pitch.

Upper Critical Solution Temperature-Type Responsive Cyclodextrins with Characteristic Inclusion Abilities.

Water-soluble and thermoresponsive macrocycles with stable inclusion toward guests are highly valuable to construct stimuli-responsive supramolecular materials for versatile applications. Here, we develop such macrocycles - ureido-substituted cyclodextrins (CDs) which exhibit unprecedented upper critical solution temperature (UCST) behavior in aqueous media. These novel CD derivatives showed good solubility in water at elevated temperature, but collapsed from water to form large coacervates upon cooling to low temperature. Their cloud points are greatly dependent on concentration and can be mediated through oxidation and chelation with silver ions. Significantly, the amphiphilicity of these CD derivatives is supportive to host-guest binding, which affords them inclusion abilities to guest dyes. The inclusion complexation remained nearly intact during thermally induced phase transitions, which is in contrast to the switchable inclusion behavior of lower critical solution temperature (LCST)-type CDs. Moreover, ureido-substituted CDs were exploited to co-encapsulate a pair of guest dyes whose fluorescence resonance energy transfer process can be switched by the UCST phase transition. We therefore believe these novel thermoresponsive CDs may form a new strategy for developing smart macrocycles and allow for exploring smart supramolecular materials.

Confined Microenvironments from Thermoresponsive Dendronized Polymers.

Confined microenvironments in biomacromolecules arising from molecular crowding account for their well-defined biofunctions and bioactivities. To mimick this, synthetic polymers to form confined structures or microenvironments are of key scientific value, which have received significant attention recently. To create synthetic confined microenvironments, molecular crowding effects and topological cooperative effects have been applied successfully, and the key is balance between self-association of structural units and self-repulsion from crowding-induced steric hindrance. In this article, formation of confined microenvironments from stimuli-responsive dendronized polymers carrying densely dendritic oligoethylene glycols (OEGs) moieties in their pendants is presented. These wormlike thick macromolecules exhibit characteristic thermoresponsive properties, which can provide constrained microenvironments to encapsulate effectively guest molecules including dyes, proteins, or nucleic acids to prevent their protonation or biodegradation. This efficient shielding effect can also mediate chemical reactions in aqueous phase, and even enhance chirality transferring efficiency. All of these can be switched off simply through the thermally-induced dehydration and collapse of OEG dendrons due to the amphiphilicity of OEG chains. Furthermore, the switchable encapsulation and release of guests can be greatly enhanced when these dendronized polymers are used as major constituents for fabricating bulk hydrogels or nanogels, which provide a higher-level confinement.

A Supramolecular-Based Dual-Wavelength Phototherapeutic Agent with Broad-Spectrum Antimicrobial Activity Against Drug-Resistant Bacteria.

With the ever-increasing threat posed by the multi-drug resistance of bacteria, the development of non-antibiotic agents for the broad-spectrum eradication of clinically prevalent superbugs remains a global challenge. Here, we demonstrate the simple supramolecular self-assembly of structurally defined graphene nanoribbons (GNRs) with a cationic porphyrin (Pp4N) to afford unique one-dimensional wire-like GNR superstructures coated with Pp4N nanoparticles. This Pp4N/GNR nanocomposite displays excellent dual-modal properties with significant reactive-oxygen-species (ROS) production (in photodynamic therapy) and temperature elevation (in photothermal therapy) upon light irradiation at 660 and 808 nm, respectively. This combined approach proved synergistic, providing an impressive antimicrobial effect that led to the complete annihilation of a wide spectrum of Gram-positive, Gram-negative, and drug-resistant bacteria both in vitro and in vivo. The study also unveils the promise of GNRs as a new platform to develop dual-modal antimicrobial agents that are able to overcome antibiotic resistance.

Self-immolative colorimetric, fluorescent and chemiluminescent chemosensors.

Self-immolative chemistry features a cascade of disassembly reactions in response to external stimuli, which provides great opportunities to design new self-immolative chemosensors with advanced performance and/or functions. Self-immolative spacers in these chemosensors not only facilitate the linkage of designed triggers to various chromophores or fluorophores, but can also be used to solve inherent problems associated with native chemosensors, such as low reactivities, poor stabilities and slow response times. Their capacity for stimuli-responsive release through operation of a self-immolative reaction further enables integration of sophisticated functions into chemosensors, including signal amplification, enzyme activity localization, and drug monitoring. Significant advances have been made in the field of self-immolative chemosensors, leading to intriguing applications to sensitive detection of analytes, bioimaging and cancer theranostics. This tutorial review summarizes this recent progress with a focus on their design strategies and sensing mechanisms.

Thermoresponsive cyclodextrins with benzenesulfonamide showing tunable inhibition for carbonic anhydrase.

Monodisperse thermoresponsive cyclodextrins appended with benzenesulfonamides were demonstrated to reversibly regulate the enzymatic activity of carbonic anhydrase, which was found to be dependent on both scaffold effect and thermoresponsiveness.

Hierarchical assembly of thermoresponsive helical dendronized poly(phenylacetylene)s through photo-crosslinking of the thermal aggregates.

Supramolecular assembly of helical homopolymers to form stable chiral entities in water is highly valuable for creating chiral nanostructures and fabricating chiral biomaterials. Here we report on thermally induced supramolecular assembly of helical dendronized poly(phenylacetylene)s (PPAs) in aqueous solutions, and their in-situ photo-crosslinking at elevated temperatures to afford crosslinked nano-assemblies with hierarchical structures and stabilized helicities. These helical dendronized homopolymers carry cinnamate-cored dendritic oligoethylene glycol (OEG) pendants, which exhibit characteristic thermoresponsive behavior. Their thermal aggregation confers hexagonal packing of the polymer chains, and simultaneously resulting in enhancement of their chiralities. Assisted by radial amphiphilicity and worm-like molecular geometry, these dendronized PPAs form supramolecular twisted fibers, spheroid particles or toroids via thermal aggregation. Through UV photoirradiation above their cloud points (Tcps), cycloaddition of cinnamate moieties from the dendritic pendants promotes intermolecular crosslinking of dendronized PPA chains within the thermal aggregates, and simultaneously, the dynamic morphologies and supramolecular chirality from the dendronized PPAs through thermally induced aggregation can be fixed. In addition, photo-crosslinking can be occurred solely within individual aggregates due to the protection of densely packed dendritic OEGs. Therefore, various crosslinked assemblies from the dendronized homopolymers with tailorable morphologies and stabilized chirality are fabricated by tuning their thermally induced dynamic aggregations followed by in-situ photo-crosslinking. We believe that this work paves a convenient route to fabricate chiral assemblies with stabilized morphologies and fixed chiralities from dynamic helical homopolymers through intermolecular crosslinking, which can be promising for various chiral applications.

Visible Light [2 + 2] Cycloadditions of Thermoresponsive Dendronized Styryltriazines To Exhibit Tunable Microconfinement.

Visible light-triggered photochemical reactions in aqueous media are highly valuable to tailor molecular structures and properties in an ecofriendly manner. Here we report visible light-induced catalyst-free [2 + 2] cycloadditions of thermoresponsive dendronized styryltriazines, which show tunable microconfinement to guest dyes in aqueous media. These dendronized styryltriazines are constituted of conjugated mono- or tristyryltriazines, which carry hydrophilic dendritic oligoethylene glycol (OEG) pendants. They underwent efficient [2 + 2] cycloadditions to form dendronized cyclobutane dimers or oligomers in water through irradiation with visible light of 400 nm, and their cycloaddition behavior was dominated by dendritic architectures and solvent conditions. Dendronization with dendritic OEGs also afforded them characteristic thermoresponsive properties with tunable phase transition temperatures in the range 36-65 °C, which can be further modulated through photocycloaddition of styryltriazine chromophores. Importantly, dendronized styryltriazines can form tunable microenvironments in aqueous media, which encapsulate hydrophobic solvatochromic Nile red to exhibit variable photophysical properties. The encapsulated guest dye can be simultaneously released through noninvasive visible light-induced [2 + 2] cycloaddition reactions.

FPGA-based CCD signal acquisition and transmission system design.

In order to facilitate the analysis and processing of optical signals, an FPGA-based CCD signal acquisition and data transmission system is designed in this work. The system uses an FPGA as the main control device, the TCD1304DG/AP chip as the optical signal detector, and the CYUSB3KIT-003 development board product by Cypress for data transmission. Verilog and Python languages are employed for modular design and on-board verification. Through the coordination of each module, the system successfully achieves CCD signal data acquisition and transmission.

Machine learning identifies exosome features related to hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most malignant tumors with a poor prognosis. There is still a lack of effective biomarkers to predict its prognosis. Exosomes participate in intercellular communication and play an important role in the development and progression of cancers. Methods: In this study, two machine learning methods (univariate feature selection and random forest (RF) algorithm) were used to select 13 exosome-related genes (ERGs) and construct an ERG signature. Based on the ERG signature score and ERG signature-related pathway score, a novel RF signature was generated. The expression of BSG and SFN, members of 13 ERGs, was examined using real-time quantitative polymerase chain reaction and immunohistochemistry. Finally, the effects of the inhibition of BSG and SFN on cell proliferation were examined using the cell counting kit-8 (CCK-8) assays. Results: The ERG signature had a good predictive performance, and the ERG score was determined as an independent predictor of HCC overall survival. Our RF signature showed an excellent prognostic ability with the area under the curve (AUC) of 0.845 at 1 year, 0.811 at 2 years, and 0.801 at 3 years in TCGA, which was better than the ERG signature. Notably, the RF signature had a good performance in the prediction of HCC prognosis in patients with the high exosome score and high NK score. Enhanced BSG and SFN levels were found in HCC tissues compared with adjacent normal tissues. The inhibition of BSG and SFN suppressed cell proliferation in Huh7 cells. Conclusion: The RF signature can accurately predict prognosis of HCC patients and has potential clinical value.

Supramolecular Chiral Assembly of Symmetric Molecules with an Extended Conjugated Core.

C3-symmetric molecules carrying a conjugated diacetylene (DA) core are found to self-assemble into well-defined supramolecular fibers with enhanced supramolecular chirality in both organic and aqueous solutions. The conjugated core affords these amphiphiles characteristic fluorescence properties, which can be quenched partially due to the aggregation. Integration of the C3-symmetry with the conjugation provides these novel molecules strong aggregation tendency through solvent-mediated π-π stacking with preferential supramolecular chirality, which is predominately related to steric hindrance from their dipeptide pendants. Highly uniform supramolecular fibers of P and M handedness with thickness consistent in the dimensions of individual C3 molecules are obtained. The increase of concentrations induces these fibers to wrap together to form supramolecular fibrous bundles. Topochemical polymerization of the DA moieties can transform these supramolecular fibers into stable covalent polymers. We therefore believe that self-assembly of these C3-symmetric molecules with extended conjugated DA cores provides new prospects for the construction of supramolecular helical fibers through enhanced π-π stacking and creates a convenient strategy to furnish covalent chiral polymers of hierarchical structures through supramolecular assembly.

Multiple-Responsive Dendronized Hyperbranched Polymers.

By combining topological structures of hyperbranched polymers with dendronized polymers, a series of hyperbranched poly(acylhydrazone)s pendanted with 3-fold branched dendritic oligoethylene glycol (OEG) units were efficiently prepared through A2 + B3 polycondensation. The constituents of these dendritic polymers can be mediated through dynamic covalent acylhydrazones. Owing to the dense OEG pendants, these dendronized hyperbranched polymers are biocompatible and thermoresponsive, and their cloud points (T cps) can be modulated by the branched architecture, solution pH, and addition of a third component. Cell viability in the presence of these hyperbranched poly(acylhydrazone)s can be maintained above 80%. Based on the unique dendritic architecture with rich acylhydrazine groups, dynamic hydrogels cross-linked via acylhydrazone linkages with good mechanical property were prepared, which inherit the characteristic thermoresponsive behavior of the polymer precursors and also show remarkable self-healing properties. This novel kind of topological polymers and their corresponding hydrogels with dynamic and multiple smart properties may have promising applications as biomaterials.

Stimuli-responsive zwitterionic block copolypeptides: poly(N-isopropylacrylamide)-block-poly(lysine-co-glutamic acid).

Synthesis of novel zwitterionic block copolypeptides, poly(N-isopropylacrylamide)-block-poly(L-glutamic acid-co-L-lysine) [PNiPAM(n)(PLG(x)-co-PLLys(y))m , where n is the number-average degree of polymerization (DP(n)) of PNiPAM block, x and y are the mole fraction of glutamic acid and lysine residues, respectively, and m is the total DP(n) of the peptide block], and their stimuli-responsiveness to temperature and pH variation in aqueous solutions are described. Initiated with the amino-terminated poly(N-isopropylacrylamide) (PNiPAM(n)-NH2), ring-opening polymerization (ROP) of a mixture of gamma-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA), and Boc-L-lysine N-carboxyanhydride (BLLys-NCA) afforded the block copolypeptides PNiPAM(n)(PBLG(x)-co-PBLLys(y))m, with a poly(N-isopropylacrylamide) block together with a random copolypeptide block, which was then deprotected with HBr/trifluoroacetic acid into the double hydrophilic block copolypeptides, PNiPAM(n)(PLG(x)-co-PLLys(y))m. Their block ratios and lengths, as well as the amino acid residue ratios in the random copolypeptide block are varied (n = 360, x = 0.4-0.5, y = 0.4-0.6, and m = 220-252). The secondary structures of the copolypeptides in aqueous solution at different pH conditions were examined. Phase transitions in aqueous solutions induced by both pH and temperature variation were investigated by (1)H NMR spectroscopy. The transitions induced by temperature were also explored by turbidity measurements using UV/vis spectroscopy for their lower critical aggregation temperature (LCAT) determination. Furthermore, these aggregation processes were followed by dynamic light scattering measurements.

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.

Metal-Ion-Mediated Supramolecular Assembly of C3 -Peptides.

An investigation on a supramolecular assembly of C3 -molecules benzene-1,3,5-tricarboxamides carrying tetrapeptide Gly-Ala-Gly-Ala pendants promoted by hydrogen bonding and metal ion coordination is described. A Gly-Ala peptide sequence was selected as it is the most abundant repeating unit in silkworm silk, and known to form ß-sheets through efficient intermolecular hydrogen bonds. These C3 -peptides formed long helical fibers in solvents mainly owing to strong hydrogen bonding. However, in the presence of divalent metal ions, chirality of these helical fibers was enhanced through metal coordination and could be transformed into nanospheres with an excess amount of the ions. Different metal ions show different tendencies to mediate the supramolecular chirality, which can even be inverted according to coordination differences.

Dendronized supramolecular polymers.

Supramolecular polymers formed from topological building blocks pave a new avenue for creating novel supramolecular structures and functional materials. Dendronized supramolecular polymers (DSPs) combine the topological characteristics of dendronized polymers and a dynamic nature from supramolecular chemistry, and are promising for the formation of supramolecular structures and functional assemblies. These topological supramolecular polymers have a characteristic cylindrical shape, high rigidity, multivalency, as well as inherent thickness. These structural characteristics make them ideal candidates for supramolecular assembly. DSPs can be formed through non-covalent interactions, such as hydrogen bonding, π-π stacking, and metal coordination, and classified into main-chain, side-chain and block types. This feature article will summarize methodologies for the preparation of homo- and block DSPs with a focus on their supramolecular structure formation. Particular attention is put on the structural effects of DSPs on their supramolecular assembly.

Thermoresponsive supramolecular dendronized polymers.

Combining the concepts of supramolecular polymers and dendronized polymers provides the opportunity to create bulky polymers with easy structural modification and tunable properties. In the present work, a novel class of side-chain supramolecular dendronized polymethacrylates is prepared through the host-guest interaction. The host is a linear polymethacrylate (as the backbone) attached in each repeat unit with a ß-cyclodextrin (ß-CD) moiety, and the guest is constituted with three-fold branched oligoethylene glycol (OEG)-based first-(G1) and second-generation (G2) dendrons with an adamantyl group core. The host and guest interaction in aqueous solution leads to the formation of the supramolecular polymers, which is supported with (1)H NMR spectroscopy and dynamic light scattering measurements. The supramolecular formation was also examined at different host/guest ratios. The water solubility of hosts and guests increases upon supramolecular formation. The supramolecular polymers show good solubility in water at room temperature, but exhibit thermoresponsive behavior at elevated temperatures. Their thermoresponsiveness is thus investigated with UV/Vis and (1)H NMR spectroscopy, and compared with their counterparts formed from individual ß-CD and the OEG dendritic guest. The effect of polymer concentration and molar ratio of host/guest was examined. It is found that the polar interior of the supramolecules contribute significantly to the thermally-induced phase transitions for the G1 polymer, but this effect is negligible for the G2 polymer. Based on the temperature-varied proton NMR spectra, it is found that the host-guest complex starts to decompose during the aggregation process upon heating to its dehydration temperature, and this decomposition is enhanced with an increase of solution temperature.