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Even though dilute (unentangled) polymer solutions cannot act as gel-like sieving media, it has been shown that they can be used to separate DNA molecules in capillary electrophoresis. The separation then comes from sporadic, independent DNA–polymer collisions. We study polymer–polymer collisions in nanochannels (i.e., channels that are smaller than the normal size of the polymers), a situation where a polyelectrolyte is forced to migrate "through" isolated uncharged molecules during electrophoresis. We use Langevin dynamics simulations to explore the nature of these collisions and their effect on the net motion of the two polymer chains. We identify several types of collisions, including some that are unique to nanochannels. When the uncharged polymer is much larger than the polyelectrolyte, the system is reminiscent of gel electrophoresis, and we propose a modified empirical reptation model to explain the data, with an orientation factor that depends on the tube diameter. We also observe that the duration of a collision is a non-monotonic function of the polymer size ratio when the two chains are of comparable size, a surprising resonance-like phenomenon, which, combined with the asymmetric nature of molecular conformations during collision, suggests possible ratchet-like mechanisms that could be used to sort polyelectrolytes in nanodevices. [ABSTRACT FROM AUTHOR]

A simple empirical method is described that allows the assignment of absolute configurations of natural products containing chiral vicinal bromochloro (VBC) units, including the bromochloro substituted isoprenyl units present in the structures of antiproliferative halomon (1a) and its halogen-swapped isomer iso-halomon (1b) from the red alga, Portieria hornemannii, and callophycols A (3) and B (4) from Callophycus serratus. The relative configurations of 3 and 4, published in 2007, were incomplete: C-16 was left unassigned. It is now shown that the additivity of molar rotations, [M]D (herein, abbreviated [M])─a consequence of vant Hoffs principle of optical superposition─could be used to deconvolute rotatory contributions, designated as [MX] and [MY] of the two remotely spaced chiral substructures within 3 and 4 using simple arithmetic. Input of proxy values, [M Y1] and [MY2], for the two different VBC units in two equations for [MX] and application of a conditional test returns the same value for [MX] only when a proxy with the correct configuration is included. It is revealed that 3 and 4 have opposite configurations at the C-16 stereocenter: 16S and 16R, respectively. Two important implications lie in these findings: 3 and 4 appear to qualify as paired-regioisomers, coupled through a putative dyotropic rearrangement (DR), and the biosyntheses of other Callophycus secondary metabolites, now numbering over 50, are tightly controlled by stereoelectronic considerations including neighboring group interactions of the DR. It now appears, counter to earlier suggestions, that the chirality of Callophycus secondary metabolites, despite their high chemodiversity, are surprisingly highly conserved. Enantiofacial halogenation additions to the C═C double bonds of precursor alkenes appear to direct the formation of the remaining stereocenters at both the halogenated benzoate-decalin core and the distal VBC of 3 and 4. A consistent hypothesis is proposed to account for macrolactonizations in other Callophycus natural products including bromophycolides A and B. The conditional test of molar rotations was applied in a different context to understand the chiroptical properties and trends observed in the highly iodinated meroditerpenes, iodocallophycols A-E, also from Callophycus sp., resulting in the revision of the configuration of callophycol E from (10R,14R) to (10S,14S).

Molecular dynamics (MD) is the method of choice for understanding the structure, function, and interactions of molecules. However, MD simulations are limited by the strong metastability of many molecules, which traps them in a single conformation basin for an extended amount of time. Enhanced sampling techniques, such as metadynamics and replica exchange, have been developed to overcome this limitation and accelerate the exploration of complex free energy landscapes. In this paper, we propose Vendi Sampling, a replica-based algorithm for increasing the efficiency and efficacy of the exploration of molecular conformation spaces. In Vendi sampling, replicas are simulated in parallel and coupled via a global statistical measure, the Vendi Score, to enhance diversity. Vendi sampling allows for the recovery of unbiased sampling statistics and dramatically improves sampling efficiency. We demonstrate the effectiveness of Vendi sampling in improving molecular dynamics simulations by showing significant improvements in coverage and mixing between metastable states and convergence of free energy estimates for four common benchmarks, including Alanine Dipeptide and Chignolin. [ABSTRACT FROM AUTHOR]

Interpreting high-dimensional data from molecular dynamics simulations is a persistent challenge. In this paper, we show that for a small peptide, deca-alanine, metastable states can be identified through a neural net based on structural information alone. While processing molecular dynamics data, dimensionality reduction is a necessary step that projects high-dimensional data onto a low-dimensional representation that, ideally, captures the conformational changes in the underlying data. Conventional methods make use of the temporal information contained in trajectories generated through integrating the equations of motion, which forgoes more efficient sampling schemes. We demonstrate that EncoderMap, an autoencoder architecture with an additional distance metric, can find a suitable low-dimensional representation to identify long-lived molecular conformations using exclusively structural information. For deca-alanine, which exhibits several helix-forming pathways, we show that this approach allows us to combine simulations with different biasing forces and yields representations comparable in quality to other established methods. Our results contribute to computational strategies for the rapid automatic exploration of the configuration space of peptides and proteins. [ABSTRACT FROM AUTHOR]

Inferring the 3D structure and conformation of disordered biomolecules, e.g., single stranded nucleic acids (ssNAs), remains challenging due to their conformational heterogeneity in solution. Here, we use escape-time electrometry (ETe) to measure with sub elementary-charge precision the effective electrical charge in solution of short to medium chain length ssNAs in the range of 5–60 bases. We compare measurements of molecular effective charge with theoretically calculated values for simulated molecular conformations obtained from Molecular Dynamics simulations using a variety of forcefield descriptions. We demonstrate that the measured effective charge captures subtle differences in molecular structure in various nucleic acid homopolymers of identical length, and also that the experimental measurements can find agreement with computed values derived from coarse-grained molecular structure descriptions such as oxDNA, as well next generation ssNA force fields. We further show that comparing the measured effective charge with calculations for a rigid, charged rod—the simplest model of a nucleic acid—yields estimates of molecular structural dimensions such as linear charge spacings that capture molecular structural trends observed using high resolution structural analysis methods such as X-ray scattering. By sensitively probing the effective charge of a molecule, electrometry provides a powerful dimension supporting inferences of molecular structural and conformational properties, as well as the validation of biomolecular structural models. The overall approach holds promise for a high throughput, microscopy-based biomolecular analytical approach offering rapid screening and inference of molecular 3D conformation, and operating at the single molecule level in solution. [ABSTRACT FROM AUTHOR]

Despite recent advancement in 3D molecule conformation generation driven by diffusion models, its high computational cost in iterative diffusion/denoising process limits its application. Here, an equivariant consistency model (EC-Conf) was proposed as a fast diffusion method for low-energy conformation generation. In EC-Conf, a modified SE (3)-equivariant transformer model was directly used to encode the Cartesian molecular conformations and a highly efficient consistency diffusion process was carried out to generate molecular conformations. It was demonstrated that, with only one sampling step, it can already achieve comparable quality to other diffusion-based models running with thousands denoising steps. Its performance can be further improved with a few more sampling iterations. The performance of EC-Conf is evaluated on both GEOM-QM9 and GEOM-Drugs sets. Our results demonstrate that the efficiency of EC-Conf for learning the distribution of low energy molecular conformation is at least two magnitudes higher than current SOTA diffusion models and could potentially become a useful tool for conformation generation and sampling. Scientific Contributions: In this work, we proposed an equivariant consistency model that significantly improves the efficiency of conformation generation in diffusion-based models while maintaining high structural quality. This method serves as a general framework and can be further extended to more complex structure generation and prediction tasks, including those involving proteins, in future steps. Key points: A novel ultra-fast equivariant diffusion model, EC-Conf, was proposed for low-energy conformation generation by construction of a consistency process. Compared with other SOTA diffusion models running with thousands denoising steps, EC-Conf can achieve comparable quality with only one sampling step and keep improving with a few more sampling iterations. The efficiency of EC-Conf is at least two magnitudes higher than current SOTA diffusion models. The EC-Conf is universal and can be easily extended to various conformation generation tasks such as protein–ligand docking pose. [ABSTRACT FROM AUTHOR]

Molecular dynamic simulation along with experiments was used to study polycarbonate (PC) molecular conformation on composite interfacial properties. The interlaminar shear strength (ILSS) variations of composites with carbon fiber roughness were quite different between sized and unsized carbon fibers, which seem to conflict with the theory that rougher surface is harder to wet. By the results of molecular dynamic simulation, it was found that the conformation of PC molecules through solvent intervention could be higher, which is conducive to the formation of π–π stacking conformation between PC and carbon fibers and benefits the interface interaction, resultantly affecting the ILSS more when the carbon fiber surface area was low. When the specific surface area was high enough, the ILSS gets to a saturation value, because the fracture area changes from the interface to the matrix. It is concluded that the effects of sizing on ILSS varied with carbon fiber surface roughness, and the molecular conformation of the matrix affected by sizing or processing must be considered. Therefore, it is important to enhance the physical interactions with carbon fiber for thermoplastic resin matrixes. [ABSTRACT FROM AUTHOR]

Light‐emitting organic small molecules require high internal and external quantum efficiencies with excellent radiative characteristics for their potential application in next‐generation optoelectronics. Nonetheless, achieving high efficiency in solid states remains a formidable challenge, primarily owing to the non‐radiative processes. Therefore, conformational modulation in solid states is pivotal in influencing emission properties to mitigate non‐radiative decay. Notably, modifying intra‐ and intermolecular non‐covalent interactions (NCIs) is a promising strategy that can simultaneously realize rigidity and stabilization of flexible single bonds, thus suppressing reorganization energy associated with non‐radiative decay. Consequently, considerable emission enhancement is attainable through adept manipulation of NCIs, corresponding to systems ranging from single molecules to multimolecular networks in solid states. This review systematically summarizes and analyzes the influence of diverse NCIs in efficient light‐emitting organic small molecules. The effects of NCIs on single‐and multimolecular‐systems are discussed, based on the fundamentals of light emission mechanism and the correlation between molecular design strategy and photophysical properties. Additionally, strategic perspectives are provided for the advancement of future light‐emitting organic small molecules. Therefore, this review serves as a comprehensive molecular design library, providing an up‐to‐date overview of molecular design leveraging NCIs for efficient light‐emitting organic small molecules. [ABSTRACT FROM AUTHOR]

Molecular conformation is an important characteristic feature of chemistry and physics, which exists in organic molecules. Based on the hydrogen bonding (HB) regulating conformations, we proposed a scheme to switch the stimulated Raman scattering peak from the symmetric vibration mode of −CαH2 (2878 cm−1) to that of −CβH2 (2937 cm−1) of n-propanol (NPA) aqueous solution with a volume fraction of 0.55. The dominant association structure can be converted from NPA–NPA to NPA–H2O by the HB network between H2O and NPA, and the HB structures were investigated through density functional theory calculations. The changes in intramolecular vibrational modes have effect on the relative abundances of NPA molecules by intermolecular HBs. This study can be extended to explore other organic molecular conformations in mixing solutions. [ABSTRACT FROM AUTHOR]

Comprehensive Summary Salicylaldehyde Schiff base is a kind of important photochromism system, whose photochromism process is widely acknowledged to be co‐determined by the electronic structure and molecular conformation. Normally, salicylaldehyde Schiff base derivatives with α‐type structures tend to exhibit photochromism while those with β‐type structures tend to be photostable. However, more and more counterexamples are found, and the root cause of photochromism property of salicylaldehyde Schiff base is still unclear. In this work, a series of chiral salicylaldehyde Schiff bases and their racemates were prepared. The formers are photochromic while the latters are photostable. Influenced by Wallach's rule, the homochiral counterparts have looser packing modes than that of the racemic counterparts. Mechanism study revealed that the pressure should be the root cause of photochromism property. Close molecule packing can restrict the photochromism property effectively after being pressed, which also explains why the photochromism of salicylaldehyde Schiff base is usually observed in solid state. This work not only reports the unique photo‐responsive difference between the chiral salicylaldehyde Schiff bases and their racemates, more importantly, provides a new perspective to understand the influence of molecule pressure on their photophysical properties. [ABSTRACT FROM AUTHOR]

Tannery solid waste (TSW) contains 70–90% collagen by weight. The rapid extraction of collagen while preserving its original and unique triple-helical conformation has proved challenging. In this paper, an ionic liquid-synergistic dissolution and regeneration (IL-SDR) method was developed based on a TBAH/DMSO/H2O ternary (TDH) solvent for the rapid recovery of collagen from TSW under mild conditions. A solubility of 10.25% TSW and a collagen recovery yield of 51.2% were achieved in 30 minutes at room temperature. The original triplet helical conformation and the molecular weight of the collagen product were retained, confirmed via FT-IR, circular dichroism, and matrix-assisted laser desorption/ionization time-of-flight analysis. SEM was used to verify that dense and uniform pores could be formed within collagen by adjusting the DMSO content, and cytotoxicity and moisture retention tests demonstrated that the collagen produced via the IL-SDR process is comparable to natural collagen used in cosmetic and skincare applications. Moreover, the TDH solvent demonstrated excellent reproducibility across five cycles, achieving consistent solubility varying from 9.71% to 11.04%. EPR and 1H NMR showed that the OH– in TBAH induced the generation of DMSO˙ free radicals in the TDH solvent, and these radicals were indispensable for the dissolution of TSW. The DMSO content was positively correlated with the concentration of free radicals. A synergistic dissolution mechanism was proposed: DMSO˙ free radicals preferentially cleaved the terminal peptide chains, causing the collagen molecules to be exposed to DMSO. Subsequently, DMSO disrupted the original hydrogen bond network within the collagen molecules. Then, TBAH and DMSO formed hydrogen bonds with the collagen molecules, stabilizing the dissolved collagen and preventing the reformation of the hydrogen bond network between collagen molecules. This work provides an avenue for low-temperature and rapid dissolution of TSW, and reveals an in-depth, atypical dissolution mechanism for collagen-based materials during the IL-SDR process. [ABSTRACT FROM AUTHOR]

Understanding how subtle structural differences between macrocyclic conformational isomers impact their properties and separation has garnered increasing attention in the field of supramolecular synthetic chemistry. In this work, a series of tetraphenylene (TPE)-embedded butterfly bis-crown ether macrocycles (BCE[n], n = 4–7), comprising two crown ether side rings and a TPE core, are synthesized through intramolecular McMurry coupling. Unexpectedly, the presence of flexible oligoethylene chains with varying lengths are found to influence molecular conformation via multiple intramolecular interactions, resulting in the formation of two stabilized conformers with specific semi-rigid symmetric/asymmetric structures (sym-BCE[n] and asym-BCE[n], n = 5, 6). Moreover, it is noteworthy that neither symmetric nor asymmetric conformers are present in the more rigid BCE[4] or the more flexible BCE[7]. Interestingly, these conformers display distinct fluorescence properties and host-guest binding abilities, and only sym-BCE[5] can serve as a host for chiral polymer binding, resulting in the formation of chiral supramolecular assemblies through host-guest interaction induced chirality. Moreover, both circular dichroism and circularly polarized luminescence signals of the obtained assemblies can be switched off by the addition of sodium ion, suggesting potential applications in the field of dynamic chiral materials. Understanding how structural differences impact the properties of macrocyclic conformational isomers has garnered attention in the field of supramolecular chemistry. Here, the authors synthesize tetraphenylene-embedded butterfly bis-crown ether macrocycles with conformers that display distinct fluorescence properties and host-guest binding abilities. [ABSTRACT FROM AUTHOR]

Quantum chemical (QC) property prediction is crucial for computational materials and drug design, but relies on expensive electronic structure calculations like density functional theory (DFT). Recent deep learning methods accelerate this process using 1D SMILES or 2D graphs as inputs but struggle to achieve high accuracy as most QC properties depend on refined 3D molecular equilibrium conformations. We introduce Uni-Mol+, a deep learning approach that leverages 3D conformations for accurate QC property prediction. Uni-Mol+ first generates a raw 3D conformation using RDKit then iteratively refines it towards DFT equilibrium conformation using neural networks, which is finally used to predict the QC properties. To effectively learn this conformation update process, we introduce a two-track Transformer model backbone and a novel training approach. Our benchmarking results demonstrate that the proposed Uni-Mol+ significantly improves the accuracy of QC property prediction in various datasets. Quantum chemical (QC) property prediction is crucial in computational chemistry. Here, the authors introduce Uni-Mol+, a deep model that uses iterative updates of 3D molecular conformations to improves the accuracy of QC property prediction. [ABSTRACT FROM AUTHOR]

Summary In this study, temperature‐dependent changes in the molecular conformation of curdlan were investigated using differential scanning calorimetry (DSC), microscopic observation, particle size analysis and molecular dynamics (MD) simulation. The DSC results showed that the gel formation temperature of curdlan is related to the glass transition temperature (Tg). The results of microscopic observation and particle size analysis showed that the curdlan particles swelled with increasing temperature, and the original rough and irregular surface morphology gradually became relatively smooth. The MD results show that the weak gel is the result of hydrogen bonds and hydrophobic interaction, whereas the strong gel is less affected by hydrogen bonds, and hydrophobic interaction is the main driving force. [ABSTRACT FROM AUTHOR]

The molecular conformation of giant molecule acceptors (GMAs) plays a significant role in regulating the intermolecular interactions and their photovoltaic performances in organic solar cells (OSCs). For the linear GMA GT‐l, the stronger homo‐molecular interaction causes its aggregation being weakly affected by the donor, thus forming an ordered molecular stacking and proper phase separation in its blend film. The star‐shaped GMA GT‐s‐based blend film shows a dominant hetero‐molecular interaction that suppresses the aggregation of the donor and acceptor, resulting in smaller phase separation and more uniform vertical phase distribution. While for another star‐shaped GMA GTs, the weakest hetero‐molecular interaction causes its blend film to form larger phase separation. Therefore, the GT‐l based OSC with PM6 as donor shows the highest charge mobilities, the fastest charge transfer (CT) process, reduced energy loss and less charge recombination, contributing to a higher power conversion efficiency (PCE) of 19.03%. Comparatively, the PCEs of the OSCs based on GTs and GT‐s are 18.05% and 17.58% respectively. Notably, all the three GMAs based OSCs show excellent thermal stability and long‐term storage stability. This study provides a facile strategy by tuning the linking unit and its connecting mode for designing highly efficient and stable organic photovoltaic materials. [ABSTRACT FROM AUTHOR]

Molecular brushes, known for their precise structure and multifunctional integration, prove essential in stabilizing Li metal anode (LMA). This review highlights their design, application, and crucial role in LMA. Examples and computational studies examining molecular brushes' conformation and dynamics in Li metal batteries (LMBs) are overviewed. Challenges and prospects are discussed, aiming to inspire advancements in high-performance LMBs. [Display omitted] Li-metal anode (LMA) has attracted significant attention as a prospective anode material for next-generation Li-metal batteries (LMBs). However, the development of LMBs is hampered by safety concerns, including the risk of short-circuiting, fire, and explosions. These safety issues derive mostly from undesirable reactions of the LMA during cycling, such as dendrite growth, dead Li formation, and volume changes. In response to these challenges, molecular brushes, characterized by their well-defined architecture and multifunction integration, have emerged as a valuable solution to stabilize LMA. This comprehensive review focuses on the design and application of molecular brushes in the field of LMBs, aiming to unveil their structure–function relationship and their pivotal role in enhancing stability of LMA. Moreover, we provide an overview of recent computational studies that have elucidated the conformation and dynamics of molecular brushes in LMBs. Finally, we discuss existing challenges and present future prospects with the goal of motivating the progress of high-performance LMBs. [ABSTRACT FROM AUTHOR]

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The pressure response of crystalline trans‐cinnamic acid is studied by means of Raman spectroscopy up to 6 GPa. Pressure application causes the reversible shift of all the observed Raman peaks to higher frequencies and changes in their relative intensities, with the intermolecular vibrational modes being by far more sensitive to pressurization compared to the intramolecular ones. The present high‐pressure Raman data indicate the structural stability of the trans‐cinnamic acid crystal and molecular conformation up to the highest pressure attained in the experiments, the importance of the hydrogen bonding, as well as the considerable strengthening of the intermolecular interactions at elevated pressures. [ABSTRACT FROM AUTHOR]

New fluorinated dibenzo-1,2,5,6-tetrathiocines 1 and 2 were synthesized by a novel condensation of 1,2-disulfenyl chlorides under the influence of elemental Cu, and structurally defined in the solid state, solution, and gas phase by single-crystal XRD, variable-temperature 19F NMR and NOESY, and DFT calculations. Crystalline 1 and 2 exhibited the C2h chair and C2 twist molecular conformations, respectively. Unlike 1 displayed only C⋯S shortened intermolecular contacts, crystal structure of 2 featured F⋯π, F⋯F, F⋯S and S⋯S contacts. In toluene solutions at 296 K, both twist and chair conformers were observed in the ∼1 : 1 and ∼7 : 1 ratios for 1 and 2, respectively. For 1, the twist ↔ chair conformer interconversion was practically temperature-independent, and for 2 revealed ΔH ∼3.5 kJ mol−1 and ΔS ∼4.4 J K−1 mol−1. With DFT, the PESs for twist–chair transformation and twist–twist racemization were analyzed and the TSs exhibiting twist–halfchair and boat conformations, respectively, were found. Several additional stationary points on the PESs, corresponding to hidden intermediates and bifurcation points and featuring twistboat and halfchair conformations were detected. In chloroform solution under sunlight, 1 underwent 1,2,5,6-tetrathiocine → 1,2,3,6-tetrathiocine isomerization whose product was characterized by XRD. [ABSTRACT FROM AUTHOR]

Advancements in flexible electronic technology, especially the progress in foldable displays and under‐display cameras (UDC), have created an urgent demand for high‐performance colorless polyimide (CPI). However, current CPIs lack sufficient heat resistance for substrate applications. In this work, four kinds of rigid spirobifluorene diamines are designed, and the corresponding polyimides are prepared by their condensation with 5,5′‐(perfluoropropane‐2,2‐diyl) bis(isobenzofuran‐1,3‐dione) (6FDA) or 9,9‐bis(3,4‐dicarboxyphenyl) fluorene dianhydride (BPAF). The rigid and conjugated spirobifluorene units endow the polyimides with higher glass transition temperature (Tg) ranging from 356 to 468 °C. Their optical properties are regulated by small side groups and spirobifluorene structure with a periodically twisted molecular conformation. Consequently, a series of CPIs with an average transmittance ranging from 75% to 88% and a yellowness index (YI) as low as 2.48 are obtained. Among these, 27SPFTFA‐BPAF presents excellent comprehensive performance, with a Tg of 422 °C, a 5 wt.% loss temperature (Td5) of 562 °C, a YI of 3.53, and a tensile strength (δmax) of 140 MPa, respectively. The mechanism underlying the structure‐property relationship is investigated by experimental comparison and theoretical calculation, and the proposed method provides a pathway for designing highly rigid conjugated CPIs with excellent thermal stability and transparency for photoelectric engineering. [ABSTRACT FROM AUTHOR]

Photo‐triggered phase transition is a new type of phase transition in which a photochromic crystal with a thermal phase transition transforms into an identical high‐temperature phase in a temperature region lower than the thermal phase transition temperature upon light irradiation. Here, we report a second crystal that exhibits a photo‐triggered phase transition, thereby demonstrating that the photo‐triggered phase transition is a general phenomenon that occurs in crystals. When the chiral salicylidenephenylethylamine crystal was irradiated with ultraviolet (UV) light, the photo‐triggered phase transition occurred in the temperature range −30 to −10 °C. The photo‐triggered phase transition is induced by local stress due to trans‐keto molecules produced by photoisomerization near the irradiated surface. Crystal cantilevers exhibited stepwise bending by the combination of the photo‐triggered phase transition and photoisomerization. Alternate irradiation with UV and visible light achieved locomotion of single crystals driven by repeated stepwise bending. Finally, a detailed comparison of photo‐triggered and non‐photo‐triggered phase transition crystals revealed that a sufficient molecular conformation change in affordable crystal voids, smooth photoisomerization, and most likely a chiral molecular arrangement are required for inducing the photo‐triggered phase transition. [ABSTRACT FROM AUTHOR]

Highly varying process conditions drive polymers into nonequilibrium molecular conformations. This has direct implications for the resulting structural and mechanical properties. This study rigorously investigated processing-property relations from a microscopic perspective. The corresponding models use a mesoscale molecular dynamics (MD) approach. Different loading conditions, including uniaxial and biaxial stretching, along with various cooling conditions, were employed to mimic process conditions on the micro-scale. The resulting intricate interplay between equi-biaxial stretching, orientation, and crystallization behavior in long polyethylene chains was reviewed. The study reveals notable effects depending on different cooling and biaxial stretching procedures. The findings emphasize the significance of considering distributions and directions of chain ordering. Local inspections of trajectories unveil that crystal growth predominantly occurs in regions devoid of entanglements. [ABSTRACT FROM AUTHOR]

Considering that regulation of thermally activated delayed fluorescence (TADF) and room temperature phosphorescence (RTP) is necessary for a fluorophore to survive and properly show its characteristic features, it is successfully shown herein that a carefully designed novel pyrene derivative can exhibit remarkable aggregation‐induced emission (AIE) overcoming the characteristic fast excitonic decay of pyrene compounds. Moreover, it is established that J‐aggregation in the red‐emitting molecular crystals of the compound reduces the singlet‐triplet energy gap (∆EST), allowing TADF with a very high photoluminescence quantum yield (PLQY) of 72%. Whereas, anisotropic grinding of the same crystals generates well‐defined microcrystals that show RTP as the nature of aggregation changes. Impressively, under isotropic hydrostatic pressure, the crystals show near‐infra‐red (NIR) emission with a very high piezochromic luminescence sensitivity of 46.2 nm GPa−1. The results have established that formation of stable H‐aggregates in the microcrystals is responsible for the ultra‐long RTP. A highly sophisticated full‐spectrum Mueller‐matrix analysis is used for the first time in such systems to demonstrate the details of the effect of perturbation (pressure) on molecular conformation. [ABSTRACT FROM AUTHOR]

A molecular design strategy for the precise regulation of full‐color‐tunable emission organic luminescence materials is not yet systematically established for pyrene chemistry. To fabricate color‐tunable and highly‐efficiency pyrene‐based emitters, this article presents novel pyrene‐based molecules with donating‐π‐accepting structures, which exhibit bright, relatively narrow‐band FWHM emission, broad color‐tunable from deep blue (439 nm) to orange‐red (599 nm) both in solution and in the solid state. Moreover, the compounds 2a, 2d–g exhibit typical aggregation‐induced emission (AIE) characteristics, with an enhanced fluorescence quantum yield in the solid state. The experimental results indicated that the presence of the sterically bulky meta‐substituted biphenyl adopts an out‐of‐plane twist conformation, which can strengthen the rigidity of the molecular conformation and suppress the intermolecular π–π stacking in the aggregated state, resulting in an enhanced emission in the solid state. The prepared pyrene‐based AIEgens are applied as fluorescent inks to write Chinese characters and art with a vivid pattern. Thus, this article not only presents an efficient molecular strategy to construct pyrene‐based AIEgen with broad color‐tunable emission properties for practical applications, but also display a powerful combination of the strong alliance between the advanced luminescent materials, art and Chinese traditional culture. [ABSTRACT FROM AUTHOR]

π‐Conjugated chiral nanorings with intriguing electronic structures and chiroptical properties have attracted considerable interests in synthetic chemistry and materials science. We present the design principles to access new chiral macrocycles (1 and 2) that are essentially built on the key components of main‐group electron‐donating carbazolyl moieties or the π‐expanded aza[7]helicenes. Both macrocycles show the unique molecular conformations with a (quasi) figure‐of‐eight topology as a result of the conjugation patterns of 2,2',7,7'‐spirobifluorenyl in 1 and triarylamine‐coupled aza[7]helicene‐based building blocks in 2. This electronic nature of redox‐active, carbazole‐rich backbones enabled these macrocycles to be readily oxidized chemically and electrochemically, leading to the sequential production of a series of positively charged polycationic open‐shell cyclophanes. Their redox‐dependent electronic states of the resulting multispin polyradicals have been characterized by VT‐ESR, UV/Vis‐NIR absorption and spectroelectrochemical measurements. The singlet (ΔES‐T=−1.29 kcal mol−1) and a nearly degenerate singlet‐triplet ground state (ΔES−T(calcd)=−0.15 kcal mol−1 and ΔES−T(exp)=0.01 kcal mol−1) were proved for diradical dications 12+2⋅ and 22+2⋅, respectively. Our work provides an experimental proof for the construction of electron‐donating new chiral nanorings, and more importantly for highly charged polyradicals with potential applications in chirospintronics and organic conductors. [ABSTRACT FROM AUTHOR]

Accurate prediction of molecular properties is fundamental in drug discovery and development, providing crucial guidance for effective drug design. A critical factor in achieving accurate molecular property prediction lies in the appropriate representation of molecular structures. Presently, prevalent deep learning–based molecular representations rely on 2D structure information as the primary molecular representation, often overlooking essential three-dimensional (3D) conformational information due to the inherent limitations of 2D structures in conveying atomic spatial relationships. In this study, we propose employing the Gram matrix as a condensed representation of 3D molecular structures and for efficient pretraining objectives. Subsequently, we leverage this matrix to construct a novel molecular representation model, Pre-GTM, which inherently encapsulates 3D information. The model accurately predicts the 3D structure of a molecule by estimating the Gram matrix. Our findings demonstrate that Pre-GTM model outperforms the baseline Graphormer model and other pretrained models in the QM9 and MoleculeNet quantitative property prediction task. The integration of the Gram matrix as a condensed representation of 3D molecular structure, incorporated into the Pre-GTM model, opens up promising avenues for its potential application across various domains of molecular research, including drug design, materials science, and chemical engineering. [ABSTRACT FROM AUTHOR]

This paper reports five novel PDI dimer type electron transport materials (ETMs) employing o‐indoloquinoxaline (o‐Iq), m‐indoloquinoxaline (m‐Iq), and cibalackrot (Ci) groups as the core building blocks and presents the twisted structures of PDI dimers coded as PDI‐NHR‐o‐Iq, PDI‐o‐Iq, PDI‐NHR‐m‐Iq, PDI‐m‐Iq and PDI‐NHR‐Ci dyes (see Scheme 1 and 2). We have systematically compared their photophysical, electrochemical, and optoelectronic properties with respect to the reference dye (2PDI‐NHR), which is directly connected of two PDI planes. Their calculated HOMO‐LUMO energy levels are sufficient for charge transfer to the perovskite material so that structure‐photovoltaic performance relationship of synthesized ETM dyes can be evaluated. When the binding position of indoloquinoxaline group between PDI rings are changed from o‐ to m‐ positions, most of the photophysical and electrochemical properties of PDI dimer are dramatically changed, finally improving the photovoltaic performances. [ABSTRACT FROM AUTHOR]

The development of semiconducting polymers with good processability in green solvents and competitive electrical performance is essential for realizing sustainable large‐scale manufacturing and commercialization of organic electronics. A major obstacle is the processability‐performance dichotomy that is dictated by the lack of ideal building blocks with balanced polarity, solubility, electronic structures, and molecular conformation. Herein, through the integration of donor, quinoid and acceptor units, an unprecedented building block, namely TQBT, is introduced for constructing a serial of conjugated polymers. The TQBT, distinct in non‐symmetric structure and high dipole moment, imparts enhanced solubility in anisole—a green solvent—to the polymer TQBT‐T. Furthermore, PTQBT‐T possess a highly rigid and planar backbone owing to the nearly coplanar geometry and quinoidal nature of TQBT, resulting in strong aggregation in solution and localized aggregates in film. Remarkably, PTQBT‐T films spuncast from anisole exhibit a hole mobility of 2.30 cm2 V‐1 s‐1, which is record high for green solvent‐processable semiconducting polymers via spin‐coating, together with commendable operational and storage stability. The hybrid building block emerges as a pioneering electroactive unit, shedding light on future design strategies in high‐performance semiconducting polymers compatible with green processing and marking a significant stride towards ecofriendly organic electronics. [ABSTRACT FROM AUTHOR]

Context: Conformation generation, also known as molecular unfolding (MU), is a crucial step in structure-based drug design, remaining a challenging combinatorial optimization problem. Quantum annealing (QA) has shown great potential for solving certain combinatorial optimization problems over traditional classical methods such as simulated annealing (SA). However, a recent study showed that a 2000-qubit QA hardware was still unable to outperform SA for the MU problem. Here, we propose the use of quantum-inspired algorithm to solve the MU problem, in order to go beyond traditional SA. We introduce a highly compact phase encoding method which can exponentially reduce the representation space, compared with the previous one-hot encoding method. For benchmarking, we tested this new approach on the public QM9 dataset generated by density functional theory (DFT). The root-mean-square deviation between the conformation determined by our approach and DFT is negligible (less than about 0.5Å), which underpins the validity of our approach. Furthermore, the median time-to-target metric can be reduced by a factor of five compared to SA. Additionally, we demonstrate a simulation experiment by MindQuantum using quantum approximate optimization algorithm (QAOA) to reach optimal results. These results indicate that quantum-inspired algorithms can be applied to solve practical problems even before quantum hardware becomes mature. Methods: The objective function of MU is defined as the sum of all internal distances between atoms in the molecule, which is a high-order unconstrained binary optimization (HUBO) problem. The degree of freedom of variables is discretized and encoded with binary variables by the phase encoding method. We employ the quantum-inspired simulated bifurcation algorithm for optimization. The public QM9 dataset is generated by DFT. The simulation experiment of quantum computation is implemented by MindQuantum using QAOA. [ABSTRACT FROM AUTHOR]

Stout beer was selected as the research object to screen angiotensin-converting enzyme (ACE) inhibitory peptides. The peptide sequences of stout beer were identified using ultra-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry with de novo, and 41 peptides were identified with high confidence. Peptide Ranker was used to score the biological activity and six peptides with a score ≥ 0.5 were screened to predict their potential ACE inhibitory (ACEI) activity. The toxicity, hydrophilicity, absorption, and excretion of these peptides were predicted. In addition, molecular docking between the peptides and ACE revealed a significant property of the peptide DLGGFFGFQR. Furthermore, molecular docking conformation and molecular dynamics simulation revealed that DLGGFFGFQR could be tightly bound to ACE through hydrogen bonding and hydrophobic interaction. Lastly, the ACEI activity of DLGGFFGFQR was confirmed using in vitro evaluation and the IC50 value was determined to be 24.45 μM. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the impact of different ultrasonic power and time pretreatments on the structures and gel properties of the flaxseed gum and soybean protein isolate composite gel induced by TG enzyme. Methods: The structural characteristics, molecular conformation, and micro-network structures of the composite gel under varying ultrasonic conditions were analyzed using a texture analyzer, laser particle size meter, circular dichroism (CD), fluorescence spectrum, and scanning electron microscope (SEM). Results: The 50% power ultrasound pretreatment for 10 min could significantly improve the hardness, adhesiveness, chewiness, cohesiveness and water-holding property of the composite gel, and reduce its adhesiveness. After 50% power ultrasound pretreatment for 10 min, the α-helix and β-turn content of composite gel proteins decreased, and the content of β-folding and irregular curls increased, and the fluorescence intensity increased, which was conducive to the improvement of the functional properties of the gel. The microstructure of the composite gel became ordered from disorder, the network density increased, the pore diameter became smaller, and the pore wall was thickened. While after increasing the ultrasound power to 80%, the gel properties fluctuated only slightly and the microstructure was destroyed. Conclusion: 50% power ultrasound pretreatment for 10 min can significantly improve the gel properties and network structure of TG enzyme cross-linked flaxseed gum-soybean protein isolate composite. [ABSTRACT FROM AUTHOR]

This study aimed to address the issue of the low solubility in the model drug probenecid (PRO) and its impact on bioavailability. Two salts of probenecid (PRO), 4-aminopyridine (4AMP), and 4-dimethylaminopyridine (4DAP) were synthesized and characterized by PXRD, DSC, TGA, FTIR, and SEM. The crystal structures of the two salts were determined by SCXRD, demonstrating that the two salts exhibited different hydrogen bond networks, stacking modes, and molecular conformations of PRO. The solubility of PRO and its salts in a phosphate-buffered solution (pH = 6.8) at 37 °C was determined, the results showed that the solubility of PRO salts increased to 142.83 and 7.75 times of the raw drug, respectively. Accelerated stability experiments (40 °C, 75% RH) showed that the salts had good phase stability over 8 weeks. Subsequently, Hirshfeld surface (HS), atom in molecules (AIM), and independent gradient model (IGM) were employed for the assessment of intermolecular interactions. The analyses of salt-forming sites and principles were conducted using molecular electrostatic potential surfaces (MEPs) and pKa rules. The lattice energy (EL) and hydration-free energy (EHF) of PRO and its salts were calculated, and the relationships between these parameters and melting points and the solubility changes were analyzed. [ABSTRACT FROM AUTHOR]

Macrocycles are important drug leads with many advantages including the ability to target flat and featureless binding sites as well as to act as molecular chameleons and thereby reach intracellular targets. However, due to their complex structures and inherent flexibility, macrocycles are difficult to study structurally, and there are limited structural data available. Herein, we use the cryo-EM method MicroED to determine the novel atomic structures of several macrocycles that have previously resisted structural determination. We show that structures of similar complexity can now be obtained rapidly from nanograms of material and that different conformations of flexible compounds can be derived from the same experiment. These results will have an impact on contemporary drug discovery as well as natural product exploration.

The voltage-gated potassium channel KV1.3 is an important therapeutic target for the treatment of autoimmune and neuroinflammatory diseases. The recent structures of KV1.3, Shaker-IR (wild-type and inactivating W434F mutant) and an inactivating mutant of rat KV1.2-KV2.1 paddle chimera (KVChim-W362F+S367T+V377T) reveal that the transition of voltage-gated potassium channels from the open-conducting conformation into the non-conducting inactivated conformation involves the rupture of a key intra-subunit hydrogen bond that tethers the selectivity filter to the pore helix. Breakage of this bond allows the side chains of residues at the external end of the selectivity filter (Tyr447 and Asp449 in KV1.3) to rotate outwards, dilating the outer pore and disrupting ion permeation. Binding of the peptide dalazatide (ShK-186) and an antibody-ShK fusion to the external vestibule of KV1.3 narrows and stabilizes the selectivity filter in the open-conducting conformation, although K+ efflux is blocked by the peptide occluding the pore through the interaction of ShK-Lys22 with the backbone carbonyl of KV1.3-Tyr447 in the selectivity filter. Electrophysiological studies on ShK and the closely-related peptide HmK show that ShK blocks KV1.3 with significantly higher potency, even though molecular dynamics simulations show that ShK is more flexible than HmK. Binding of the anti-KV1.3 nanobody A0194009G09 to the turret and residues in the external loops of the voltage-sensing domain enhances the dilation of the outer selectivity filter in an exaggerated inactivated conformation. These studies lay the foundation to further define the mechanism of slow inactivation in KV channels and can help guide the development of future KV1.3-targeted immuno-therapeutics.

Understanding and controlling protein motion at atomic resolution is a hallmark challenge for structural biologists and protein engineers because conformational dynamics are essential for complex functions such as enzyme catalysis and allosteric regulation. Time-resolved crystallography offers a window into protein motions, yet without a universal perturbation to initiate conformational changes the method has been limited in scope. Here we couple a solvent-based temperature jump with time-resolved crystallography to visualize structural motions in lysozyme, a dynamic enzyme. We observed widespread atomic vibrations on the nanosecond timescale, which evolve on the submillisecond timescale into localized structural fluctuations that are coupled to the active site. An orthogonal perturbation to the enzyme, inhibitor binding, altered these dynamics by blocking key motions that allow energy to dissipate from vibrations into functional movements linked to the catalytic cycle. Because temperature jump is a universal method for perturbing molecular motion, the method demonstrated here is broadly applicable for studying protein dynamics.

Nuclear magnetic resonance (NMR) spectroscopy is one of the indispensable techniques in chemistry because it enables us to obtain accurate information on the chemical, electronic, and dynamic properties of molecules. Computational simulation of the NMR spectra requires time-consuming density functional theory (DFT) calculations for an ensemble of molecular conformations. For large flexible molecules, it is considered too high-cost since it requires time-averaging of the instantaneous chemical shifts of each nuclear spin across the conformational space of molecules for NMR timescales. Here, we present a Gaussian process/deep kernel learning-based machine learning (ML) method for enabling us to predict, average in time, and analyze the instantaneous chemical shifts of conformations in the molecular dynamics trajectory. We demonstrate the use of the method by computing the averaged 1H and 13C chemical shifts of each nuclear spin of a trefoil knot molecule consisting of 24 para-connected benzene rings (240 atoms). By training ML model with the chemical shift data obtained from DFT calculations, we predicted chemical shifts for each conformation during dynamics. We were able to observe the merging of the time-averaged chemical shifts of each nuclear spin in a singlet 1H NMR peak and two 13C NMR peaks for the knot molecule, in agreement with experimental measurements. The unique feature of the presented method is the use of the learned low-dimensional deep kernel representation of local spin environments for comparing and analyzing the local chemical environment histories of spins during dynamics. It allowed us to identify two groups of protons in the knot molecule, which implies that the observed singlet 1H NMR peak could be composed of the contributions from protons with two distinct local chemical environments. [ABSTRACT FROM AUTHOR]

Ubiquitin phosphorylation at Ser65 increases the population of a rare C-terminally retracted (CR) conformation. Transition between the Major and CR ubiquitin conformations is critical for promoting mitochondrial degradation. The mechanisms by which the Major and CR conformations of Ser65-phosphorylated (pSer65) ubiquitin interconvert, however, remain unresolved. Here, we perform all-atom molecular dynamics simulations using the string method with swarms of trajectories to calculate the lowest free-energy path between these two conformers. Our analysis reveals the existence of a Bent intermediate in which the C-terminal residues of the β5 strand shift to resemble the CR conformation, while pSer65 retains contacts resembling the Major conformation. This stable intermediate was reproduced in well-tempered metadynamics calculations but was less stable for a Gln2Ala mutant that disrupts contacts with pSer65. Lastly, dynamical network modeling reveals that the transition from the Major to CR conformations involves a decoupling of residues near pSer65 from the adjacent β1 strand.

RNA origami is a method for designing RNA nanostructures that can self-assemble through co-transcriptional folding with applications in nanomedicine and synthetic biology. However, to advance the method further, an improved understanding of RNA structural properties and folding principles is required. Here we use cryogenic electron microscopy to study RNA origami sheets and bundles at sub-nanometre resolution revealing structural parameters of kissing-loop and crossover motifs, which are used to improve designs. In RNA bundle designs, we discover a kinetic folding trap that forms during folding and is only released after 10 h. Exploration of the conformational landscape of several RNA designs reveal the flexibility of helices and structural motifs. Finally, sheets and bundles are combined to construct a multidomain satellite shape, which is characterized by individual-particle cryo-electron tomography to reveal the domain flexibility. Together, the study provides a structural basis for future improvements to the design cycle of genetically encoded RNA nanodevices.

Classifying reliably active and inactive molecular conformations of wildtype (WT) and mutated oncogenic proteins is a key, ongoing challenge in molecular cancer studies. Here, we probe the GTP-bound K-Ras4B conformational dynamics using long-time atomistic molecular dynamics (MD) simulations. We extract and analyze the detailed underlying free energy landscape of WT K-Ras4B. We use two key reaction coordinates, labeled d1 and d2 (i.e., distances coordinating the Pβ atom of the GTP ligand with two key residues, T35 and G60), shown to correlate closely with activities of WT and mutated K-Ras4B. However, our new K-Ras4B conformational kinetics study reveals a more complex network of equilibrium Markovian states. We show that a new reaction coordinate is required to account for the orientation of acidic K-Ras4B sidechains such as D38 with respect to the interface with binding effector RAF1 and rationalize the activation/inactivation propensities and the corresponding molecular binding mechanisms. We use this understanding to unveil how a relatively conservative mutation (i.e., D33E, in the switch I region) can lead to significantly different activation propensities compared with WT K-Ras4B. Our study sheds new light on the ability of residues near the K-Ras4B—RAF1 interface to modulate the network of salt bridges at the binding interface with the RAF1 downstream effector and, thus, to influence the underlying GTP-dependent activation/inactivation mechanism. Altogether, our hybrid MD-docking modeling approach enables the development of new in silico methods for quantitative assessment of activation propensity changes (e.g., due to mutations or local binding environment). It also unveils the underlying molecular mechanisms and facilitates the rational design of new cancer drugs. [ABSTRACT FROM AUTHOR]

The aggregation morphologies of conjugated polymers in solutions and solid films are important for their optoelectronic applications. Due to the amorphous state of the polymers, it remains a great challenge to determine their conformations in either liquids or solids. Herein, a ps/fs synchronized 2D IR technique is applied to investigate the molecular conformations of a high-mobility n-type low-bandgap copolymer, N2200, dissolved in CHCl3 and CCl4, and in solid films cast from both solutions by the vibrational cross-angle method. In CCl4, the polymer forms more aggregates and folds more and the backbone dihedral angle of C–C(NDI)/C–S(Thiophene) of its average conformation is about 10° more distorted than that in CHCl3 and the most stable conformation for a free molecule. Anti-intuitively, the solid films cast from both solutions have the same molecular conformation, and the conformation is similar to that of the polar CHCl3 rather than the conformation of the less polar CCl4. The results imply that the interaction between the polymer backbones is probably stronger than its interaction with CCl4, which can naturally guide the rearrangement of polymer chains during the evaporation of solvent molecules. This work also implies that the balance and competition between the polymer/polymer interaction and the polymer/solvent interaction seem to be the dominant factors responsible for what morphology can form in a solid film cast from solution. It is not always true that different molecular conformations must exist in solid films grown from different solutions with different polarity or different extents of aggregates with different conformations. [ABSTRACT FROM AUTHOR]

Conventional gas–liquid phase transitions feature a coexistence line that has a monotonic and positive slope in line with our intuition that cooling always leads to condensation. Here, we study the inverse phenomenon, condensation of adsorbed organic molecules into dense domains upon heating. Our considerations are motivated by recent experiments [Aeschlimann et al., Angew. Chem., Int. Ed. 60, 19117–19122 (2021)], which demonstrate the partial dissolution of an ordered molecular monolayer and the mobilization of molecules upon cooling. We introduce a simple lattice model in which each site can have three states corresponding to unoccupied and two discernible molecular conformations. We investigate this model through Monte Carlo simulations, mean-field theory, and exact results based on the analytical solution of the Ising model in two dimensions. Our results should be broadly applicable to molecules with distinct conformations that have sufficiently different entropies or heat capacities. [ABSTRACT FROM AUTHOR]

Abstract The envelope (E) protein of the Japanese encephalitis virus (JEV) is a key protein for virus infection and adsorption of host cells, which determines the virulence of the virus and regulates the intensity of inflammatory response. The mutation of multiple aa residues in the E protein plays a critical role in the attenuated strain of JEV. This study demonstrated that the Asp to Gly, Ser, and His mutation of the E389 site, respectively, the replication ability of the viruses in cells was significantly reduced, and the viral neuroinvasiveness was attenuated to different degrees. Among them, the mutation at E389 site enhanced the E protein flexibility contributed to the attenuation of neuroinvasiveness. In contrast, less flexibility of E protein enhanced the neuroinvasiveness of the strain. Our results indicate that the mechanism of attenuation of E389 aa mutation attenuates neuroinvasiveness is related to increased flexibility of the E protein. In addition, the increased flexibility of E protein enhanced the viral sensitivity to heparin inhibition in vitro, which may lead to a decrease in the viral load entering brain. These results suggest that E389 residue is a potential site affecting JEV virulence, and the flexibility of the E protein of aa at this site plays an important role in the determination of neuroinvasiveness.

Stimulus-responsive organic room temperature phosphorescence (RTP) materials are a class of materials that show emission property changes when subjected to diverse environmental stimuli. The change of molecular stacking modes and intermolecular interactions can result in mechanical stimulus-induced emission switching behaviour. The underlying mechanism of mechanoresponsive luminescent material is still unclear. Herein, based on density functional theory and time-dependent density functional theory calculations, the photophysical properties with response to hydrostatic pressure of RTP molecules in crystal are theoretically studied. Excited state dynamic processes are investigated by using quantum mechanics and molecular mechanics method coupled with thermal vibration correlation function method. Results show that the increase of pressure can blue-shift the RTP emissions which is mainly caused by the change of molecular conformation and the increase of bending vibration frequency. Under 2 Gpa, large spin–orbit coupling effect is determined, remarkable radiative and non-radiative decay processes are achieved. At 0.6 Gpa, a small non-radiative decay rate from T1 to S0 is obtained, high efficiency and long lifetime (more than 10 times the other pressures) are realised. Through further analysing the staking modes, reorganisation energies and SOC constants, relationships between molecular structures and RTP properties are determined, hydrostatic pressure responsive mechanism is revealed. [ABSTRACT FROM AUTHOR]

Electrokinetic force has been the major choice for driving the translocation of molecules through a nanopore. However, the use of this approach is limited by an uncontrollable translocation speed, resulting in non-uniform conductance signals with low conformational sensitivity, which hinders the accurate discrimination of the molecules. Here, we show the use of inertial-kinetic translocation induced by spinning an in-tube micro-pyramidal silicon nanopore fabricated using photovoltaic electrochemical etch-stop technique for biomolecular sensing. By adjusting the kinetic properties of a funnel-shaped centrifugal force field while maintaining a counter-balanced state of electrophoretic and electroosmotic effect in the nanopore, we achieved regulated translocation of proteins and obtained stable signals of long and adjustable dwell times and high conformational sensitivity. Moreover, we demonstrated instantaneous sensing and discrimination of molecular conformations and longitudinal monitoring of molecular reactions and conformation changes by wirelessly measuring characteristic features in current blockade readouts using the in-tube nanopore device. The authors report a strategy to achieve high S/N ratio signal readout in single molecule sensing by incorporating the inertial forces as a new channel for independently controlling the translocation parameters with high precision. [ABSTRACT FROM AUTHOR]

The molecular conformation, crystalline morphology, and properties of photochromic organic crystals can be controlled through photoirradiation, making them promising candidates for functional organic materials. However, photochromic porous molecular crystals with a networked framework structure are rare due to the difficulty in maintaining space that allows for photo‐induced molecular motion in the crystalline state. This study describes a photo‐responsive single crystal based on hydrogen‐bonded (H‐bonded) network of dihydrodimethylbenzo[e]pyrene derivative 4BDHP. A crystal composed of H‐bonded undulate layers, 4BDHP‐2, underwent photo‐isomerization in the crystalline state due to loose stacking of the layers. Particularly, enantio‐pure crystal (S,S)‐4BDHP‐2 allowed to reveal the structure of the photoisomerized crystal, in which the closed form (4BDHP) and open form (4CPD) were arranged alternately with keeping crystalline periodicity, although side reactions were also implied. The present proof‐of‐concept system of a photochromic framework that retains crystalline periodicity after photo‐isomerization may provide new light‐driven porous functional materials. [ABSTRACT FROM AUTHOR]

The envelope (E) protein of the Japanese encephalitis virus (JEV) is a key protein for virus infection and adsorption of host cells, which determines the virulence of the virus and regulates the intensity of inflammatory response. The mutation of multiple aa residues in the E protein plays a critical role in the attenuated strain of JEV. This study demonstrated that the Asp to Gly, Ser, and His mutation of the E389 site, respectively, the replication ability of the viruses in cells was significantly reduced, and the viral neuroinvasiveness was attenuated to different degrees. Among them, the mutation at E389 site enhanced the E protein flexibility contributed to the attenuation of neuroinvasiveness. In contrast, less flexibility of E protein enhanced the neuroinvasiveness of the strain. Our results indicate that the mechanism of attenuation of E389 aa mutation attenuates neuroinvasiveness is related to increased flexibility of the E protein. In addition, the increased flexibility of E protein enhanced the viral sensitivity to heparin inhibition in vitro, which may lead to a decrease in the viral load entering brain. These results suggest that E389 residue is a potential site affecting JEV virulence, and the flexibility of the E protein of aa at this site plays an important role in the determination of neuroinvasiveness. [ABSTRACT FROM AUTHOR]

Polymorphism‐dependent cytotoxicity and cellular uptake of drug molecules have been studied for the past two decades. However, the visualization of polymorph‐dependent cellular uptake and cytotoxicity using microscopy imaging techniques has not yet been reported. The luminescent polymorph is an ideal candidate to validate the above hypothesis. Herein, we report the polymorph‐dependent cellular uptake, cytotoxicity, and bio‐imaging functions of polymorphs 1Y and 1R of a naphthalimide‐phenothiazine dyad. These polymorphs show different luminescence colors in the solid state and exhibit aggregation‐induced enhanced emission (AIEE) in the DMSO‐Water mixture. Bioimaging, cytotoxicity assay, and fluorescence‐activated cell sorting (FACS) studies revealed that these polymorphs show different levels of cytotoxicity, cellular uptake, localization, and imaging potential. Detailed photophysical, morphological, and biological studies revealed that the difference in molecular conformation in these polymorphs enables them to form aggregates of different sizes and morphology, which leads to the differential uptake of these into the cells and consequently shows different cytotoxicity and imaging potentials. [ABSTRACT FROM AUTHOR]

The ternary complexes of the zinc(II), [Zn(met)(gly)(Cl)2] (1), and [Zn(met)(hist)(Cl)2] (2) are synthesized and illustrated utilizing spectroscopic and analytical measurements, and the geometry of the complexes has been identified to be octahedral. The Coats Red fern approach was employed to enumerate the thermodynamic and kinetic variables for both the Zn(II) complexes' decomposition. The quantum chemical variables were estimated utilizing the molecular orbital conformations' energy distribution, which was derived from optimal geometric shapes to test the stabilization of both complexes. DNA‐binding investigations by UV–Vis absorption, fluorescence, and viscosity were all exploited to examine the bonding properties between Zn(II) complexes and ct‐DNA, and a groove mode of bonding was established. The interactions between complexes and BSA/HSA were investigated by employing absorption and emission spectroscopic methods. The results demonstrate that complexes have a powerful ability to diminish BSA and HSA luminescence intensity, and overall associating mode is predominantly a static quenching process. The cytotoxic effect of the two Zn(II) complexes was additionally examined in human breast adenocarcinoma (MCF‐7 and MDA‐MB‐231) cell lines by employing the MTT technique. The IC50 values for every cell line were derived. Each of the two complexes was functional in both cell lines. [ABSTRACT FROM AUTHOR]

In the Alzheimer’s disease (AD) brain, the microtubule-associated protein tau aggregates into paired helical filaments in which each protofilament has a C-shaped conformation. In vitro assembly of tau fibrils adopting this fold is highly valuable for both fundamental and applied studies of AD without requiring patient-brain extracted fibrils. To date, reported methods for forming AD-fold tau fibrils have been irreproducible and sensitive to subtle variations in fibrillization conditions. Here, we describe a route to reproducibly assemble tau fibrils adopting the AD fold on the multi-milligram scale. We investigated the fibrillization conditions of two constructs and found that a tau (297–407) construct that contains four AD phospho-mimetic glutamate mutations robustly formed the C-shaped conformation. 2D and 3D correlation solid-state NMR spectra show a single predominant set of chemical shifts, indicating a single molecular conformation. Negative-stain electron microscopy and cryo-EM data confirm that the protofilament formed by 4E-tau (297–407) adopts the C-shaped conformation, which associates into paired, triple, and quadruple helical filaments. In comparison, NMR spectra indicate that a previously reported construct, tau (297–391), forms a mixture of a four-layered dimer structure and the C-shaped structure, whose populations are sensitive to the environmental conditions. The determination of the NMR chemical shifts of the AD-fold tau opens the possibility for future studies of tau fibril conformations and ligand binding by NMR. The quantitative assembly of tau fibrils adopting the AD fold should facilitate the development of diagnostic and therapeutic compounds that target AD tau. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs), which are the hubs of lipid metabolism, play a critical role in maintaining cellular energy homeostasis. The construction of advanced photosensitizers (PSs) capable of manipulating LD‐mediated cell fate regulation is highly desirable though rarely reported. In this study, a near‐infrared emissive PS (DPCMP) with LDs specificity was synthesized and successfully applied to induce ferroptosis and apoptosis. DPCMP exhibited typical aggregation‐induced emission characteristics owing to its twisted molecular conformation. Excellent biocompatibility and suitable lipophilicity allowed DPCMP to specifically stain the LDs in living cells. Under white light illumination, the DPCMP displayed potent reactive oxygen species (ROS) generation capacity through both type I and II photochemistry. The massive accumulation of lethal ROS generated by DPCMP‐mediated photosensitization initiated lipid peroxidation, impaired cellular redox homeostasis, and led to endoplasmic reticulum oxidative stress, ultimately inhibiting cellular proliferation via concurrent ferroptosis and apoptosis in both living cancer cells and multicellular tumor spheroids. [ABSTRACT FROM AUTHOR]