Reversible Conformation Research Articles

Rational Design of High-Performance Photocontrolled Molecular Switches Based on Chiroptical Dimethylcethrene: A Theoretical Study.

The reversible photo-induced conformation transition of a single molecule with a [5]helicene backbone has garnered considerable interest in recent studies. Based on such a switching process, one can build molecular photo-driven switches for potential applications of nanoelectronics. But the achievement of high-performance reversible single-molecule photoswitches is still rare. Here, we theoretically propose a 13,14-dimethylcethrene switch whose photoisomerization between the ring-closed and ring-open forms can be triggered by ultraviolet (UV) and visible light irradiation. The electronic structure transitions and charge transport characteristics, concurrent with the photo-driven electrocyclization of the molecule, are calculated by the non-equilibrium Green's function (NEGF) in combination with density functional theory (DFT). The electrical conductivity bears great diversity between the closed and open configurations, certifying the switching behavior and leading to a maximum on-off ratio of up to 103, which is considerable in organic junctions. Further analysis confirms the evident switching behaviors affected by the molecule-electrode interfaces in molecular junctions. Our findings are helpful for the rational design of organic photoswitches at the single-molecule level based on cethrene and analogous organic molecules.

Photoinduced Reversible Disentanglement-Entanglement Transition in partially miscible azobenzene polymer blends

Entanglements, an intrinsic feature of long chains, are critical to the rheological and mechanical properties of polymers. Adding low molecular weight solvents or oligomers into entangled polymers can reduce the entanglements, but the entanglement cannot recover without removing the solvents. Reversible control of the entanglement degree is still a big challenge. In this work, we introduce the azobenzene polymer (Pazo) with reversible photoswitchable side-chain conformation as dynamic diluent into entangled poly(butyl methacrylate) (PBMA) to form a partially miscible blend system. The reduction of entanglement of PBMA by trans-Pazo is similar to a typical solvent, while an unexpectedly stronger tube dilation effect was found for cis-Pazo. Cis-Pazo/PBMA blends exhibit a stronger dependence of plateau modulus on PBMA content, GN(φ)∼φ4.5, which is significantly different from the well-established relation GN(φ)∼φ2 for polymer solutions and blends. The cis-Pazo can disentangle PBMA at a much lower concentration (∼55 %) than the trans-Pazo (>70 %). Pazo content of 55 %–70 % can induce a completely unentangled state of PBMA in Pazo/PBMA blends when Pazo is in the cis state after UV light irradiation, and the entanglement can recover when it is transformed to the trans state. Adding azobenzene polymer does not alter the activation energy of the re-entanglement process.

Photoresponsive Viscoelasticity of the Granular Materials of Azobenzene-Bearing Molecular Nanoparticles.

The large sizes of granular particles lead to their slow diffusive dynamics and significant interparticle friction, bringing enormous difficulty to tune the mechanical properties and processability of the granular materials (GMs). Herein, 1 nm polyhedral oligomeric silsesquioxane (POSS) particles functionalized with azobenzene are designed as structural units, and the obtained GMs show unique photoswitchable viscoelasticity. The azobenzene group can undergo a reversible trans-cis conformation switch while the π-π stacking among the azobenzene fragments is only favored by the trans-conformation due to molecular geometrical requirements. The POSS units from neighboring assemblies close pack to form microdomains, and the POSS is under confinement by both the supramolecular bonding and the other POSS in the microdomains. The simultaneous breaking of the two types of confinement is difficult and, therefore, the free diffusion of POSS is hindered, leading to the elasticity of the GMs of trans-POSS. For cis-POSS, the interparticle supramolecular interaction is weak and the POSS unit can undergo free diffusion, contributing to their high flowability at room temperature. The photoswitching viscoelasticity of GMs is further used for self-healing and photoswitchable adhesion. This work paves new pathways for the regulation of material viscoelasticity and the design of GM-based smart materials.

Reversible Molecular Conformation Transitions of Smectic Liquid Crystals for Light/Bias-Gated Transistor Memory.

In recent years, organic photonic field-effect transistors have made remarkable progress with the rapid development of conjugated polycrystalline materials. Liquid crystals, with their smooth surface, defined layer thickness, and crystalline structures, are commonly used for these advantages. In this work, a series of smectic liquid crystalline molecules, 2,9-didecyl-dinaphtho-thienothiophene (C10-DNTT), 2,7-didecyl-benzothieno-benzothiopene (C10-BTBT), 3,9-didecyl-dinaphtho-thiophene (C10-DNT), and didecyl-sexithiophene (C10-6T), have been used in photonic transistor memory, functioning as both hole-transport channels and electron traps to investigate systematically the reasons and mechanisms behind the memory behavior of smectic liquid crystals. After thermal annealing, C10-BTBT and C10-6T/C10-DNTT are homeotropically aligned from the smectic A and smectic X phases, respectively. The 3D-ordered structure of these smectic-aligned crystals contributed to efficient photowriting and electrical erasing processes. Among them, the device performance of C10-BTBT was particularly significant, with a memory window of 21 V. The memory ratio could reach 1.5 × 106 and maintain a memory ratio of over 3 orders after 10,000 s, contributing to its smectic A structure. Through the research, we confirmed the memory and light/bias-gated behaviors of these smectic liquid crystalline molecules, attributing them to reversible molecular conformation transitions and the inherent structural inhomogeneity inside the polycrystalline channel layer.

Designer pseudopeptides: autofluorescent polygonal tubes via Phe-zipper and triple helix.

Chemists are increasingly turning to biology for inspiration to develop novel and superior synthetic materials. Here, we present an innovative peptide design strategy for tubular assembly. In this simple design, a phenylene urea unit is introduced as an aglet at the N-terminus of the peptide. When α-amino isobutyric acid (Aib) is the first residue and phenylalanine (Phe) is the second residue from the phenylene urea entity, it induces an edge-to-face π-π interaction resulting in a turn conformation. The peptides with a unique reverse turn conformation associate to form polygonal peptide tubes via a Phe-zipper arrangement, as evidenced by microscopic and single crystal X-ray studies. Ultra-microscopic imaging revealed that the tubular assembly is hexagonal, square, and triangular in shape. This hierarchical assembly reveals the interplay between π-π interactions and hydrogen bonding. In another design, pseudopeptide 5, wherein a Phe-Phe (FF) unit is linked to phenylene urea, formed polygonal tubes via a triple helical arrangement. Interestingly, the extension of this design to the bis-urea core resulted in vesicular assembly. These supramolecular polygonal tubes and vesicles showed autofluorescence, which allowed confocal imaging. The observed fluorescence is an additional advantage for applications in biological and medical sciences.

Complex Materials with Stochastic Structural Patterns: Spiky Colloids with Enhanced Charge Storage Capacity.

Self-assembled materials with complex nanoscale and mesoscale architectureattract considerable attention in energy and sustainability technologies. Their high performance can be attributed to high surface area, quantum effects, and hierarchical organization. Delineation of these contributions is, however, difficult because complex materials display stochastic structural patterns combining both order and disorder, which is difficult to be consistently reproduced yet being important for materials' functionality. Their compositional variability make systematic studies even harder. Here, a model system of FeSe2 "hedgehog" particles (HPs) was selected to gain insight into the mechanisms of charge storage n complex nanostructured materials common for batteries and supercapacitors. Specifically, HPs represent self-assembled biomimetic nanomaterials with a medium level of complexity; they display an organizational pattern of spiky colloids with considerable disorder yet non-random; this patternt is consistently reproduced from particle to particle. . It was found that HPs can accommodate ≈70× greater charge density than spheroidal nano- and microparticles. Besides expanded surface area, the enhanced charge storage capacity was enabled by improved hole transport and reversible atomic conformations of FeSe2 layers in the blade-like spikes associated with the rotatory motion of the Se atoms around Fe center. The dispersibility of HPs also enables their easy integration into energy storage devices. HPs quadruple stored electrochemical energy and double the storage modulus of structural supercapacitors.

Fused-Ring Electron-Acceptor Single Crystals with Chiral 2D Supramolecular Organization for Anisotropic Chiral Optoelectronic Devices.

Supramolecular chiral organization gives π-conjugated molecules access to fascinating specific interactions with circularly polarized light (CPL). Such a feature enables the fabrication of high-performance chiral organic electronic devices that detect or emit CPL directly. Herein, it is shown that chiral fused-ring electron-acceptor BTP-4F single-crystal-based phototransistors demonstrate distinguished CPL discrimination capability with current dissymmetry factor exceeding 1.4, one of the highest values among state-of-the-art direct CPL detectors. Theoretical calculations prove that the chirality at the supramolecular level in these enantiomeric single crystals originates from chiral exciton coupling of a unique quasi-2Dsupramolecular organization consisting of interlaced molecules with opposite helical conformation. Impressively, such supramolecular organization produces a higher dissymmetry factor along the preferred growth direction of the chiral single crystals in comparison to that of the short axis direction. Furthermore, the amplified, inverted, and also anisotropic current dissymmetry compared to optical dissymmetry is studied by finite element simulations. Therefore, a unique chiral supramolecular organization that is responsible for the excellent chiroptical response and anisotropic electronic properties is developed, which not only enables the construction of high-performance CPL detection devices but also allows a better understanding of the structure-property relationships in chiral organic optoelectronics.

Cryo-EM structures of LHCII in photo-active and photo-protecting states reveal allosteric regulation of light harvesting and excess energy dissipation.

The major light-harvesting complex of photosystem II (LHCII) has a dual regulatory function in a process called non-photochemical quenching to avoid the formation of reactive oxygen. LHCII undergoes reversible conformation transitions to switch between a light-harvesting state for excited-state energy transfer and an energy-quenching state for dissipating excess energy under full sunshine. Here we report cryo-electron microscopy structures of LHCII in membrane nanodiscs, which mimic in vivo LHCII, and in detergent solution at pH 7.8 and 5.4, respectively. We found that, under low pH conditions, the salt bridges at the lumenal side of LHCII are broken, accompanied by the formation of two local α-helices on the lumen side. The formation of α-helices in turn triggers allosterically global protein conformational change, resulting in a smaller crossing angle between transmembrane helices. The fluorescence decay rates corresponding to different conformational states follow the Dexter energy transfer mechanism with a characteristic transition distance of 5.6 Å between Lut1 and Chl612. The experimental observations are consistent with the computed electronic coupling strengths using multistate density function theory.

Synthesis of ESIPT fluorophores with two intramolecular H-bonding functionalities: Reversible mechanofluorochromism and conformation controlled solid state fluorescence efficiency

We have synthesized two new ESIPT fluorophores (1-((E)-((E)-((2-hydroxyphenyl)(phenyl)methylene)hydrazono)methyl) naphthalen-2-ol (Naph-2-OH) and 5-(diphenylamino)-2-((E)-((E)-((2-hydroxyphenyl)(phenyl) methylene)hydrazono)methyl) phenol (TPA-2-OH)) with two unsymmetrical intramolecular H-bonding functionalities and investigated the solid-state structural assembly and fluorescence properties. The crystal structure analysis confirmed the formation of strong intramolecular H-bonding and twisted molecular conformation. The nonplanar twisted molecular conformation produced well separated molecules in the crystal lattice that lead to strongly enhanced emission ((λmax = 538 nm, Φf = 5.2% (Naph-2-OH), λmax = 562 nm, Φf = 13.4% (TPA-2-OH)). Density functional theoretical (DFT) calculation supported the fluorescence tuning and intramolecular charge transfer (ICT) from TPA donor to imine acceptor. Both Naph-2-OH and TPA-2-OH showed mechanical crushing and heating induced reversible fluorescence switching due to the reversible phase transformation between crystalline and amorphous state.

The highly selective and sensitive fluorescent detection of SO2 based on an emissive quinoline derivative probe

Sulfur dioxide (SO2) is a common global air pollutant that can cause serious air pollution and lead to a variety of severe diseases. In this study, a tripodal quinoline-based derivative T with two reversible conformations is synthesized. T demonstrates highly selective, sensitive fluorescent SO2 detection in solution. As SO2 is added into a dioxane/water solution, the sensor T purple emission rapidly changes to a green color in a strongly acidic environment. T showed high sensitivity and selectivity toward H2SO4 and SO2 detecting with good detection limits as low as 0.098 μM and 5.438 μM, respectively. The fluorescence sensing process is successfully confirmed via FT-IR, NMR, and ESI-Ms spectrum. Furthermore, DFT calculation reveals the potentially reversible conformation transfer mechanism and selective, sensitive fluorescence sensing behavior driven by host-guest and multiple hydrogen bonding interactions in solution.

Simultaneous Profiling of Chromosome Conformation and Gene Expression in Single Cells.

Rapid development in single-cell chromosome conformation capture technologies has provided valuable insights into the importance of spatial genome architecture for gene regulation. However, a long-standing technical gap remains in the simultaneous characterization of three-dimensional genomes and transcriptomes in the same cell. We have described an assay named Hi-C and RNA-seq employed simultaneously (HiRES), which integrates in situ reverse transcription and chromosome conformation capture (3C) for the parallel analysis of chromatin organization and gene expression. Here, we provide a detailed implementation of the assay, using mouse embryos and cerebral cortices as examples. The versatility of this method extends beyond these two samples, with the potential to be used in various other cell types. Key features • A multi-omics sequencing approach to profile 3D genome structure and gene expression simultaneously in single cells. • Compatible with animal tissues. • One-tube amplification of both DNA and RNA components. • Requires three days to complete.

Controlled Growth of Millimeter Scale ZIF-8 Single Crystal in Organic Solvents: Reversible Structural Conformation Investigated by Single-Crystal XRD at Various Temperatures

Controlled Growth of Millimeter Scale ZIF-8 Single Crystal in Organic Solvents: Reversible Structural Conformation Investigated by Single-Crystal XRD at Various Temperatures

Assembly of Helical Nanostructures: Solvent-Induced Morphology Transition and Its Effect on Cell Adhesion.

Being able to precisely manipulate both the morphology and chiroptical signals of supramolecular assemblies will help to better understand the natural biological self-assembly mechanism. Two simple l/d-phenylalanine-based derivatives (L/DPFM) have been designed, and their solvent-dependent morphology evolutions are illustrated. It was found that, as the content of H2 O in aqueous ethanol solutions was increased, LPFM self-assembles first into right-handed nanofibers, then flat fibrous structures, and finally inversed left-handed nanofibers. Assemblies in ethanol and H2 O exhibit opposite conformations and circular dichroism (CD) signals even though they are constructed from the same molecules. Thus, the morphology-dependent cell adhesion and proliferation behaviors are further characterized. Left-handed nanofibers are found to be more favorable for cell adhesion than right-handed nanostructures. Quantitative AFM analysis showed that the L929 cell adhesion force on left-handed LPFM fibers is much higher than that on structures with inversed handedness. Moreover, the value of cell Young's modulus is lower for left-handed nanofibrous films, which indicates better flexibility. The difference in cell-substrate interactions might lead to different effects on cell behavior.

Enantiomeric Resolution and Enantiomer Isolation of H2 TPPS4 J-Aggregate from Aqueous Solution Is Enabled by Vortexes.

Protonated achiral H2 TPPS4 spontaneously self-arranges at acids pH and high ionic strength to build mesoscopic J-aggregates that are intrinsically chiral. According to the symmetry rule aggregation leads to a racemate that, however, can be unbalanced by chemical (chiral pollutants) or physical stimuli (as vortexing the solution). Vortexing the title racemate, in principle, might either induce chiral separation or chiral enrichment. Indeed, herein it is shown that vortices enable the resolution of this racemic solution exploiting the tendency to deposit, onto the quartz cuvette walls, of the enantiomer favored by the stirring sense. Simultaneously, over time, it was found that the opposite chiral conformation becomes prevalent in solution realizing a significant enantiomeric resolution. Therefore, after removing all stirring-favored chiral J-aggregate from the solution, the recovering and isolating of the desired enantiomers from the cuvette walls was successfully obtained without complex procedures. In this sense, it has been demonstrated that the stirring forces are executively able to fulfil the chiral separation in H2 TPPS4 J-aggregates, employed as model of a self-assembled system in aqueous solution.

Organic Phase-Change Memory Transistor Based on an Organic Semiconductor with Reversible Molecular Conformation Transition.

Phase-change semiconductor is one of the best candidates for designing nonvolatile memory, but it has never been realized in organic semiconductors until now. Here, a phase-changeable and high-mobility organic semiconductor (3,6-DATT) is first synthesized. Benefiting from the introduction of electrostatic hydrogen bond (S···H), the molecular conformation of 3,6-DATT crystals can be reversibly modulated by the electric field and ultraviolet irradiation. Through experimental and theoretical verification, the tiny difference in molecular conformation leads to crystalline polymorphisms and dramatically distinct charge transport properties, based on which a high-performance organic phase-change memory transistor (OPCMT) is constructed. The OPCMT exhibits a quick programming/erasing rate (about 3 s), long retention time (more than 2h), and large memory window (i.e., large threshold voltage shift over 30V). This work presents a new molecule design concept for organic semiconductors with reversible molecular conformation transition and opens a novel avenue for memory devices and other functional applications.

Polymer elastomer near plastic-to-rubber critical transition produces enhanced elastocaloric effects

Solid-state cooling technology based on elastocaloric effects has shown potential advantages over traditional vapor-compression cooling systems owing to its high energy efficiency and zero greenhouse gas emissions. However, a lack of strategies for improving the elastocaloric activity of polymers remains the main obstacle to their commercialization since the elastocaloric effect was first investigated by J.P. Joule in natural rubber. Herein, we demonstrate that polymer elastomers with molecular chains near molecular-structure-induced plastic-rubber critical transitions exhibit superior elastocaloric activity through reversible conformational changes. As the content of ethyl side groups in the soft block of polystyrene- b -poly(ethylene- co -butylene)- b -polystyrene decreases from 33 to 8 mol %, the adiabatic temperature change increases from −4.3 to −16.3 K, and the isothermal entropy change increases from 38.5 to 173.3 J kg −1 K −1 , which thus shows the highest polymer elastocaloric activity near room temperature. This strategy could promote the commercialization of elastocaloric polymers in solid-state cooling applications. • Polymers near plastic-rubber critical transition show reversible conformations • Over a 3-fold increment in the elastocaloric activity close to room temperature • The lowest limit value of cooling temperature decreased from 275 to 262 K Solid-state cooling technologies are expected to be a net-zero potential alternative to vapor-compression cooling systems. Here, Shixian Zhang et al. demonstrate a strategy to enhance the cooling performance of solid polymers. This strategy could be widely applied in polymer systems to reach polymers’ solid-state cooling.

Aptamer-Functionalized Nanodevices for Dynamic Manipulation of Membrane Receptor Signaling in Living Cells.

The capacity to regulate the signaling amplitude of membrane receptors in a user-defined manner would open various opportunities for precise biological study and therapy. While partial agonists enabled downtuning of cellular responses, they required esoteric optimization of the ligand-receptor interface, limiting their practical applications. Herein, we developed an aptamer-functionalized, tweezer-like nanodevice to dynamically modulate the cellular behavior through control over the distance between receptors in the dimer with no need to involve complicated structural analysis. By combining a reversible conformation switch with aptamer-based molecular recognition, this nanodevice showed excellent performance on dynamic regulation of CD28 receptor-mediated T cell immunity. With the modular design, this nanodevice could be extended to dynamically modulate the activity of other membrane receptors (e.g., c-Met), expecting to offer a new paradigm for precise study and manipulation of specific molecular events in complex biological systems.

Controlled biomolecules separation by CO2-responsive block copolymer membranes

The intelligent responsive membranes have aroused much attention due to their distinctive capability to reversibly change separation performances under the stimulation of ambient environment. Especially, the responsive membranes derived from block copolymers, which have regular nanoporous structures, display great potential in high-precision controllable separation. Herein, we use CO2 gas as the non-toxic, mild stimulus, and develop the responsive membranes from a block copolymer of poly(2-diethylaminoethyl methacrylate)-block-polystyrene (PDEAEMA-b-PS) by the selective swelling method. The membranes exhibit a bi-continuous nanoporous structure and the surfaces and pore walls are rich with CO2-responsive PDEAEMA chains. Based on the reversible conformation transition of PDEAEMA chains between the collapsed state and extended state upon CO2/N2 stimulation, the membranes achieve the controllable regulation on the water permeances from ∼100 to ∼2100 L⋅h−1⋅m−2⋅bar−1, also realize the blocking/passing switch for varied proteins. More importantly, the extended PDEAEMA chains shrink the effective pore size down to less than 5 nm, moving the separation scope from ultrafiltration to tight-ultrafiltration. Thus, the membranes are capable to separate macromolecular proteins with small molecule polypeptide and vitamin with high separation efficiencies, demonstrating their application prospect in precise separation and fractionation of biomolecules.

Regenerable bacterial killing–releasing ultrathin smart hydrogel surfaces modified with zwitterionic polymer brushes

Abstract Building long-lasting antimicrobial and clean surfaces is one of the most effective strategies to inhibit bacterial infection, but obtaining an ideal smart surface with highly efficient, controllable, and regenerative properties still encounters many challenges. Herein, we fabricate an ultrathin brush–hydrogel hybrid coating (PSBMA-P(HEAA-co-METAC)) by integrating antifouling polyzwitterionic (PSBMA) brushes and antimicrobial polycationic (P(HEAA-co-METAC)) hydrogels. The smart bacterial killing–releasing properties can be achieved independently by the opposite volume and conformation changes between the swelling (shrinking) of P(HEAA-co-METAC) hydrogel layer and the shrinking (swelling) of PSBMA brushes. The friction test reveals that both METAC and SBMA components support great lubrication. By tuning the initial organosilane (BrTMOS:KH570) ratios, the prepared PSBMA-P(HEAA-co-METAC) coating exhibits different antibacterial abilities from single “capturing–killing” to versatile “capturing–killing–releasing.” Most importantly, 99% of the bacterial-releasing rate can be easily achieved via 0.5 M NaCl treatment. This smart surface not only possesses long-lasting antibacterial performance, only ∼1.09 × 105 cell·cm−2 bacterial residue even after 72 h exposure to bacteria solutions, but also can be regenerated and triggered between water and salt solution multiple times. This work provides a new way to fabricate antibacterial smart hydrogel coatings with bacterial “killing–releasing” functions and shows great potential for biomedical applications.

Structure-activity relationships of mitochondria-targeted tetrapeptide pharmacological compounds

Mitochondria play a central role in metabolic homeostasis, and dysfunction of this organelle underpins the etiology of many heritable and aging-related diseases. Tetrapeptides with alternating cationic and aromatic residues such as SS-31 (elamipretide) show promise as therapeutic compounds for mitochondrial disorders. In this study, we conducted a quantitative structure-activity analysis of three alternative tetrapeptide analogs, benchmarked against SS-31, that differ with respect to aromatic side chain composition and sequence register. We present the first structural models for this class of compounds, obtained with Nuclear Magnetic Resonance (NMR) and molecular dynamics approaches, showing that all analogs except for SS-31 form compact reverse turn conformations in the membrane-bound state. All peptide analogs bound cardiolipin-containing membranes, yet they had significant differences in equilibrium binding behavior and membrane interactions. Notably, analogs had markedly different effects on membrane surface charge, supporting a mechanism in which modulation of membrane electrostatics is a key feature of their mechanism of action. The peptides had no strict requirement for side chain composition or sequence register to permeate cells and target mitochondria in mammalian cell culture assays. All four peptides were pharmacologically active in serum withdrawal cell stress models yet showed significant differences in their abilities to restore mitochondrial membrane potential, preserve ATP content, and promote cell survival. Within our peptide set, the analog containing tryptophan side chains, SPN10, had the strongest impact on most membrane properties and showed greatest efficacy in cell culture studies. Taken together, these results show that side chain composition and register influence the activity of these mitochondria-targeted peptides, helping provide a framework for the rational design of next-generation therapeutics with enhanced potency.