Chirality Detection in Scanning Tunneling Microscopy Data Using Artificial Intelligence.

Enantiospecific effects play an uprising role in chemistry and technical applications. Chiral molecular networks formed by self-assembly processes at surfaces can be imaged by scanning probe microscopy (SPM). Low contrast and high noise in the topography map often interfere with the automatic image analysis using classical methods. The long SPM image acquisition times restrain Artificial Intelligence-based methods requiring large training sets, leaving only tedious manual work, inducing human-dependent errors and biased labeling. By generating realistic looking synthetic images, the acquisition of real datasets is avoided. Two state-of-the-art object detection architectures are trained to localize and classify chiral unit-cells in a regular molecular chiral network formed by self-assembly of linear molecular bricks. The comparison of different architectures and datasets demonstrates that the training on purely synthetic data outperforms models trained using augmented datasets. A Faster R-CNN model trained solely on synthetic data achieved an excellent mean average precision of 99% on real data. Hence this approach and the transfer to real data show high success, also highlighting the high robustness against experimental noise and different zoom levels across the full experimentally reasonable parameter range. The generalizability of this idea is demonstrated by achieving equally high performance on a different structure, too.

In-situ sequential crystallization of fenofibrate and tristearin - Understanding the distribution of API in particles and stability of solid lipid microparticles from the perspective of crystallization.

In-situ API crystallization in carrier matrices has attracted extensive attention in recent years for its advantages over traditional preparation processes. However, due to the lack of systemic research on molecular self-assembly behaviors, the products obtained by in-situ crystallization suffer from the problems of polymorphic transformation and drug expulsion during storage, limiting its industrial application. This paper investigates the in-situ sequential crystallization behavior of tristearin (SSS) and fenofibrate (FEN), utilizing SSS as the carrier and FEN as the API. It was found that the behavior of mixed crystallization significantly differs from single-component crystallization, including direct formation of stable form of SSS and the rapid crystallization of FEN. During the crystallization process, the melting FEN promotes the movement of SSS molecules, while the sliding of SSS lamellae, in turn, provides a mechanical stimulus to enhance the nucleation of FEN. Based on the observed synergistic crystallization behavior, the distribution and stability of the API within FEN solid lipid microparticles (SLMs) during storage were evaluated, while also examining the stability variations in SLMs formulated at different cooling rates and drug loading concentrations. The findings indicate that the initial nucleated FEN results in a decrease in the surrounding molten FEN and the irregularity of the SSS lamellas, thereby preventing the remaining molten FEN from achieving complete crystallization within a brief period. Due to the compatibility between FEN and SSS, some SSS may blend with the molten FEN, potentially resulting in further crystallization during storage and consequently increasing the risk of drug expulsion.

Air Corrosion of Layered Cathode Materials for Sodium-Ion Batteries: Cation Mixing and a Practical Suppression Strategy.

Layered oxide cathodes of sodium-ion batteries (SIBs) are considered promising candidates due to their fascinating high capacity, good cyclability, and environmental friendliness. However, the air sensitivity of layered SIB cathodes causes high electrode manufacturing costs and performance deterioration, hampering their practical application. Herein, a commercial O3-type layered Na(Ni1/3Fe1/3Mn1/3)O2 (NNFM) material is adopted to investigate the air corrosive problem and the suppression strategy. We reveal that once the layered material comes in contact with ambient air, cations migrate from transition metal (TM) layers to sodium layers at the near surface, although Na+ and TM ions show quite different ion radii. Experimental results and theoretical calculations show that more Ni/Na disorder occurs in the air-exposed O3-NNFM materials, owing to a lower Ni migration energy barrier. The cation mixing results in detrimental structural distortion, along with the formation of residual alkali species on the surface, leading to high impedance for Na+ diffusion during charge/discharge. To tackle this problem, an ultrathin and uniform hydrophobic molecular layer of perfluorodecyl trimethoxysilane is assembled on the O3-NNFM surface, which significantly suppresses unfavorable chemistry and structure degradation during air storage. The in-depth understanding of the structural degradation mechanism and suppression strategy presented in this work can facilitate high-energy cathode manufacturing from the perspective of future practical implementation and commercialization.

Cystine-cored diphenylalanine appended peptide-based self-assembled fluorescent nanostructures direct redox-responsive drug delivery.

Fabrication of stimuli-responsive superstructure capable of delivering chemotherapeutics directly to the cancer cell by sparing healthy cells is crucial. Herein, we developed redox-responsive hollow spherical assemblies through self-assembly of disulfide-linked cysteine-diphenylalanine (SN). These fluorescent hollow spheres display intrinsic green fluorescence, are proteolytically stable and biocompatible, and allow for real-time monitoring of their intracellular entry. The disulfide bond facilitates selective degradation in the presence of high glutathione (GSH) concentrations, prevalent in cancer cells. We achieved efficient encapsulation (68.72%) of the anticancer drug doxorubicin (Dox) and demonstrated GSH-dependent, redox-responsive drug release within cancerous cells. SN-Dox exhibited a 20-fold lower effective concentration (2.5 µM) for compromising breast cancer cell viability compared to non-malignant cells (50 µM). The ability of SN-Dox to initiate DNA damage signaling and trigger apoptosis was comparable to that of the unencapsulated drug. Our findings highlight the potential of SN for creating site-specific drug delivery vehicles for sustained therapeutic release.

Observing the Dynamics of an Electrochemically Driven Active Material with Liquid Electron Microscopy.

Electrochemical liquid electron microscopy has revolutionized our understanding of nanomaterial dynamics by allowing for direct observation of their electrochemical production. This technique, primarily applied to inorganic materials, is now being used to explore the self-assembly dynamics of active molecular materials. Our study examines these dynamics across various scales, from the nanoscale behavior of individual fibers to the micrometer-scale hierarchical evolution of fiber clusters. To isolate the influences of the electron beam and electrical potential on material behavior, we conducted thorough beam-sample interaction analyses. Our findings reveal that the dynamics of these active materials at the nanoscale are shaped by their proximity to the electrode and the applied electrical current. By integrating electron microscopy observations with reaction-diffusion simulations, we uncover that local structures and their formation history play a crucial role in determining assembly rates. This suggests that the emergence of nonequilibrium structures can locally accelerate further structural development, offering insights into the behavior of active materials under electrochemical conditions.

DNA digestion and formation of DNA-network structures with Holliday junction-resolving enzyme Hjc_15-6 in conjunction with polymerase reactions.

The recently identified novel Holliday junction-resolving enzyme, termed Hjc_15-6, activity investigation results imply DNA cleavage by Hjc_15-6 in a manner that potentially enhances the molecular self-assembly that may be exploited for creating DNA-networks and nanostructures. The study also demonstrates Pwo DNA polymerase acting in combination with Hjc_15-6 capability to produce large amounts of DNA that transforms into large DNA-network structures even without DNA template and primers. Furthermore, it is demonstrated that Hjc_15-6 prefers Holliday junction oligonucleotides as compared to Y-shaped oligonucleotides as well as efficiently cleaves typical branched products from isothermal DNA amplification of both linear and circular DNA templates amplified by phi29-like DNA polymerase. The assembly of large DNA network structures was observed in real time, by transmission electron microscopy, on negative stained grids that were freshly prepared, and also on the same grids after incubation for 4 days under constant cooling. Hence, Hjc_15-6 is a promising molecular tool for efficient production of various DNA origamis that may be implemented for a wide range of applications such as within medical biomaterials, catalytic materials, molecular devices and biosensors.

Stimuli-Responsive Nanostructured Viologen-Siloxane Materials for Controllable Conductivity.

Spontaneous phase separation is a promising strategy for the development of novel electronic materials, as the resulting well-defined morphologies generally exhibit enhanced conductivity. Making these structures adaptive to external stimuli is challenging, yet crucial as multistate reconfigurable switching is essential for neuromorphic materials. Here, a modular and scalable approach is presented to obtain switchable phase-separated viologen-siloxane nanostructures with sub-5 nm features. The domain spacing, morphology, and conductivity of these materials can be tuned by ion exchange, repeated pulsed photoirradiation and electric stimulation. Counterion exchange triggers a postsynthetic modification in domain spacing of up to 10%. Additionally, in some cases, 2D to 1D order-order transitions are observed with the latter exhibiting a sevenfold decrease in conductivity with respect to their 2D lamellar counterparts. Moreover, the combination of the viologen core with tetraphenylborate counterions enables reversible and in situ reduction upon light irradiation. This light-driven reduction provides access to a continuum of conducting states, reminiscent of long-term potentiation. The repeated voltage sweeps improve the nanostructures alignment, leading to increased conductivity in a learning effect. Overall, these results highlight the adaptivity of phase-separated nanostructures for the next generation of organic electronics, with exciting applications in smart sensors and neuromorphic devices.

Dynamics of Molecular Self-Assembly of Short Peptides at Liquid-Solid Interfaces - Effect of Charged Amino Acid Point Mutations.

Self-organizing solid-binding peptides on atomically flat solid surfaces offer a unique bio/nano hybrid platform, useful for understanding the basic nature of biology/solid coupling and their practical applications. The surface behavior of peptides is determined by their molecular folding, which is influenced by various factors and is challenging to study. Here, the effect of charged amino acids is studied on the self-assembly behavior of a directed evolution selected graphite-binding dodecapeptide on graphite surface. Two mutations, M6 and M8, are designed to introduce negatively and positively charged moieties, respectively, at the anchoring domain of the wild-type (WT) peptide, affecting both binding and assembly. The questions addressed here are whether mutant peptides exhibit molecular crystal formation and demonstrate molecular recognition on the solid surface based on the specific mutations. Frequency-modulated atomic force microscopy is used for observations of the surface processes dynamically in water at molecular resolution over several hours at the ambient. The results indicate that while the mutants display distinct folding and surface behavior, each homogeneously nucleates and forms 2D self-organized patterns, akin to the WT peptide. However, their growth dynamics, domain formation, and crystalline lattice structures differ significantly. The results represent a significant step toward the rational design of bio/solid interfaces, potent facilitators of a variety of future implementations.

Molecular self-assembled cellulose enabling durable, scalable, high-power osmotic energy harvesting.

In recent years, renewable cellulose-based ion exchange membranes have emerged as promising candidates for capturing green, abundant osmotic energy. However, the low power density and structural/performance instability are challenging for such cellulose membranes. Herein, cellulose-molecule self-assembly engineering (CMA) is developed to construct environmentally friendly, durable, scalable cellulose membranes (CMA membranes). Such a strategy enables CMA membranes with ideal nanochannels (∼7 nm) and tailored channel lengths, which support excellent ion selectivity and ion fluxes toward high-performance osmotic energy harvesting. Finite element simulations also verified the function of tailored nanochannel length on osmotic energy conversion. Correspondingly, our CMA membrane shows a high-power density of 2.27 W/m2 at a 50-fold KCl gradient and super high voltage of 1.32 V with 30-pair CMA membranes (testing area of 22.2 cm2). In addition, the CMA membrane demonstrates long-term structural and dimensional integrity in saline solution, due to their high wet strength (4.2 MPa for N-CMA membrane and 0.5 MPa for P-CMA membrane), and correspondingly generates ultrastable yet high power density more than 100 days. The self-assembly engineering of cellulose molecules constructs high-performance ion-selective membranes with environmentally friendly, scalable, high wet strength and stability advantages, which guide sustainable nanofluidic applications beyond the blue energy.

Unveiling Liquid-Phase Exfoliation of Graphite and Boron Nitride Using Fluorescent Dyes Through Combined Experiments and Simulations.

Liquid-phase exfoliation (LPE) in aqueous solutions provides a simple, scalable, and green approach to produce 2D materials. By combining atomistic simulations with exfoliation experiments, the interaction between a surfactant and a 2D layer at the molecular scale can be better understood. In this work, two different dyes, corresponding to rhodamine B base (Rbb) and to a phenylboronic acid BODIPY (PBA-BODIPY) derivative, are employed as dispersants to exfoliate graphene and hexagonal boron nitride (hBN) through sonication-assisted LPE. The exfoliated 2D sheets, mostly as few-layers, exhibit good quality and high loading of dyes. Using molecular dynamics (MD) simulations, the binding free energies are calculated and the arrangement of both dyes on the layers are predicted. It has been found that the dyes show a higher affinity toward hBN than graphene, which is consistent with the higher yields of exfoliated hBN. Furthermore, it is demonstrated that the adsorption behavior of Rbb molecules on graphene and hBN is quite different compared to PBA-BODIPY.

Ligand-Mediated Mechanical Enhancement in Protein Complexes at Nano- and Macro-Scale.

Protein self-assembly plays a vital role in a myriad of biological functions and in the construction of biomaterials. Although the physical association underlying these assemblies offers high specificity, the advantage often compromises the overall durability of protein complexes. To address this challenge, we propose a novel strategy that reinforces the molecular self-assembly of protein complexes mediated by their ligand. Known for their robust noncovalent interactions with biotin, streptavidin (SAv) tetramers are examined to understand how the ligand influences the mechanical strength of protein complexes at the nanoscale and macroscale, employing atomic force microscopy-based single-molecule force spectroscopy, rheology, and bioerosion analysis. Our study reveals that biotin binding enhances the mechanical strength of individual SAv tetramers at the nanoscale. This enhancement translates into improved shear elasticity and reduced bioerosion rates when SAv tetramers are utilized as cross-linking junctions within hydrogel. This approach, which enhances the mechanical strength of protein-based materials without compromising specificity, is expected to open new avenues for advanced biotechnological applications, including self-assembled, robust biomimetic scaffolds and soft robotics.

Precise Synthesis of Organic Cocrystal Alloys with Full-Spectrum Emission Characteristics for the Stepless Color Changing Display.

Organic luminescent materials are indispensable in optoelectronic displays and solid-state luminescence applications. Compared with single-component, multi-component crystalline materials can improve optoelectronic characteristics. This work forms a series of full-spectrum tunable luminescent charge-transfer (CT) cocrystals ranging from 400 to 800 nm through intermolecular collaborative self-assembly. What is even more interesting is that o-TCP-Cor(x)-Pe(1-x), p-TCP-Cor(x)-Pe(1-x), and o-TCP-AN(x)-TP(1-x) alloys are prepared based on cocrystals by doping strategies, which correspondingly achieve the stepless color change from blue (CIE [0.22, 0.44]) to green (CIE [0.16, 0.14]), from green (CIE [0.27, 0.56]) to orange (CIE [0.58, 0.42]), from yellow (CIE [0.40, 0.57]) to red (CIE [0.65, 0.35]). The work provides an efficient method for precisely synthesizing new luminescent organic semiconductor materials and lays a solid foundation for developing advanced organic solid-state displays.

Self-assembling biomolecules for biosensor applications.

Molecular self-assembly has received considerable attention in biomedical fields as a simple and effective method for developing biomolecular nanostructures. Self-assembled nanostructures can exhibit high binding affinity and selectivity by displaying multiple ligands/receptors on their surface. In addition, the use of supramolecular structure change upon binding is an intriguing approach to generate binding signal. Therefore, many self-assembled nanostructure-based biosensors have been developed over the past decades, using various biomolecules (e.g., peptides, DNA, RNA, lipids) and their combinations with non-biological substances. In this review, we provide an overview of recent developments in the design and fabrication of self-assembling biomolecules for biosensing. Furthermore, we discuss representative electrochemical biosensing platforms which convert the biochemical reactions of those biomolecules into electrical signals (e.g., voltage, ampere, potential difference, impedance) to contribute to detect targets. This paper also highlights the successful outcomes of self-assembling biomolecules in biosensor applications and discusses the challenges that this promising technology needs to overcome for more widespread use.

Oriented Self-assembly of Flexible MOFs Nanocrystals into Anisotropic Superstructures with Homogeneous Hydrogels Behaviors.

Building of metal-organic frameworks (MOFs) homogeneous hydrogels made by spontaneous crystallization remains a significant challenge. Inspired by anisotropically structured materials in nature, an oriented super-assembly strategy to construct micro-scale MOFs superstructure is reported, in which the strong intermolecular interactions between zirconium-oxygen (Zr─O) cluster and glutamic acid are utilized to drive the self-assembly of flexible nanoribbons into pumpkin-like microspheres. The confined effect between water-flexible building blocks and crosslinked hydrogen networks of superstructures achieved a mismatch transformation of MOFs powders into homogeneous hydrogels. Importantly, the elastic and rigid properties of hydrogels can be simply controlled by precise modulation of coordination and self-assembly for anisotropic superstructure. Experimental results and theoretical calculations demonstrates that MOFs anisotropic superstructure exhibits dynamic double networks with a superior water harvesting capacity (119.73 g g-1 ) accompanied with heavy metal removal (1331.67 mg g-1 ) and strong mechanical strength (Young's modulus of 0.3 GPa). The study highlights the unique possibility of tailoring MOFs superstructure with homogeneous hydrogel behavior for application in diverse fields.

Predicting Molecular Self-Assembly on Metal Surfaces Using Graph Neural Networks Based on Experimental Data Sets.

The application of supramolecular chemistry on solid surfaces has received extensive attention in the past few decades. To date, combining experiments with quantum mechanical or molecular dynamic methods represents the key strategy to explore the molecular self-assembled structures, which is, however, often laborious. Recently, machine learning (ML) has become one of the most exciting tools in material research, allowing for both efficiency and accuracy in predicting molecular properties. In this work, we constructed a graph neural network to predict the self-assembly of functional polycyclic aromatic hydrocarbons (PAHs) on metal surfaces. Using scanning tunneling microscopy (STM), we characterized the self-assembled nanostructures of a homologous series of PAH molecules on different metal surfaces to construct an experimental data set for model training. Compared with traditional ML algorithms, our model exhibits better predictive performance. Finally, the generalization of the model is further verified by comparing the ML predictions and experimental results of different functionalized molecule. Our results demonstrate training experimental data sets to produce a predictive ML model of molecular self-assembly with generalization performance, which allows for the predictive design of nanostructures with functional molecules.

Near-Infrared Self-Assembled Hydroxyl Radical Generator Based on Photoinduced Cascade Electron Transfer for Hypoxic Tumor Phototherapy.

The hydroxyl radical (•OH) is an extremely potent reactive oxygen species that plays a crucial role in photooxidations within the realm of hypoxic tumor therapy. However, the current methods for •OH photogeneration typically rely on inorganic materials that require UV/vis light excitation. Consequently, photogenerators based on organic molecules, especially those utilizing near-infrared (NIR) light excitation, are rare. In this study, the concept of photoinduced cascade charge transfer (PICET), which utilizes NIR heavy-atom-free photosensitizers (ANOR-Cy5) to generate •OH is introduced. The ANOR-Cy5 photosensitizer, with its flexible hydrophobic structure, enables the formation of nanoparticles in aqueous solutions through molecular assembly. PICET involves a symmetry-breaking charge separation-induced localized charge-separated state, transitioning to a delocalized charge-separated state, which governs the efficiency of •OH generation. Thanks to the oxygen-independent nature of •OH generation and its robust oxidative properties, the ANOR-Cy5-based photosensitizer demonstrates highly effective photoinduced anti-cancer effects, even under severely hypoxic conditions. This discovery emphasizes the potential for achieving •OH photogeneration using a single organic molecule through the engineering of molecular self-assembly, thereby opening up new possibilities for phototherapy and beyond.

Short-chain glucan self-assembly for green synthesis of functional biomaterials: Mechanism, synthesis, and microstructural control.

Short-chain glucan (SCG) is a linear homopolymer containing 10 to 50 glucose units linked with α(1,4) glycosidic bonds. With its abundant, low-cost, nontoxic, biodegradable/biocompatible nature, self-assembled SCG particles (SSC) have emerged as functional biomaterials, which have recently attracted tremendous attentions in various fields. SCG self-assembly occurs through the spontaneous association of molecules under equilibrium conditions into stable and structurally well-defined nanoscale or micrometer-scale aggregates, which is governed by various intermolecular non-covalent interactions, including hydrogen-bonding, electrostatic, hydrophobic, and van der Waals. With precise and effective control of the self-assembly process of SSC, its structural modulation and function integration can be expected. Thus, we convinced that SCG self-assembly could provide an effective means of developing starch-based functional biomaterials with beneficial health properties and wide application in food industries. In this review, we provide an overview of recent advances in the green approach for the self-assembly of SSC, as well as the influence of thermodynamic and kinetic factors on its morphology and physicochemical properties. We highlight recent contributions to developing strategies for the construction of SSC with increasing complexity and functionality that are suitable for a variety of food applications. Finally, we briefly outline our perspectives and discuss the challenges in the field.

Self-assembly of a multimeric genomic hydrogel via multi-primed chain reaction of dual single-stranded circular plasmids for cell-free protein production.

Recent technical advances in cell-free protein synthesis (CFPS) offer several advantages over cell-based expression systems, including the application of cellular machinery, such as transcription and translation, in the test tube. Inspired by the advantages of CFPS, we have fabricated a multimeric genomic DNA hydrogel (mGD-gel) via rolling circle chain amplification (RCCA) using dual single-stranded circular plasmids with multiple primers. The mGD-gel exhibited significantly enhanced protein yield. In addition, mGD-gel can be reused at least five times, and the shape of the mGD-gel can be easily manipulated without losing the feasibility of protein expression. The mGD-gel platform based on the self-assembly of multimeric genomic DNA strands (mGD strands) has the potential to be used in CFPS systems for a variety of biotechnological applications.

Adsorption configurations and electronic properties of self-assembled C60and C70molecules on a semiconductor CuSe monolayer with periodic nanopores.

Two-dimensional (2D) supramolecular self-assembly architectures are considered one of the most significant and challenging topics in nanotechnology and modern organic chemistry. The study of these processes on surfaces is vital to achieving a higher degree of control in the design of supramolecular architecture. Herein, we report on the 2D self-assembly monolayer architectures based on C60and C70molecules on a semiconductor CuSe monolayer with periodic nanopores, which are essential for providing ideas for surface template chemistry. With the aid of low-temperature scanning tunneling microscopy/spectroscopy (LT-STM/STS) and density functional theory (DFT) calculation methods, we systematically investigate the adsorption configurations and electronic properties of C60and C70on CuSe monolayer with periodic nanopores. Our results show that both the C60and C70molecules above the nanopores will fall into the nanopores, while those on the CuSe surface will show well-defined self-assembly with various adsorption configurations. Besides, through STS measurement, the lowest unoccupied molecular orbitals (LUMOs) and characteristic peaks of fullerene molecules will be slightly different due to different adsorption configurations. This work helps us to study the adsorption behavior of the fullerene family on various kinds of semiconductor substrates, and also provides vigorous support for the development of fullerene electrical devices in the future.

Self-Assembling Nanoarchitectonics of Twisted Nanofibers of Fluorescent Amphiphiles as Chemo-Resistive Sensor for Methanol Detection.

The inhalation, ingestion, and body absorption of noxious gases lead to severe tissue damage, ophthalmological issues, and neurodegenerative disorders; death may even occur when recognized too late. In particular, methanol gas present in traces can cause blindness, non-reversible organ failure, and even death. Even though ample materials are available for the detection of methanol in other alcoholic analogs at ppm level, their scope is very limited because of the use of either toxic or expensive raw materials or tedious fabrication procedures. In this paper, we report on a simple synthesis of fluorescent amphiphiles achieved using a starting material derived from renewable resources, this material being methyl ricinoleate in good yields. The newly synthesized bio-based amphiphiles were prone to form a gel in a broad range of solvents. The morphology of the gel and the molecular-level interaction involved in the self-assembly process were thoroughly investigated. Rheological studies were carried out to probe the stability, thermal processability, and thixotropic behavior. In order to evaluate the potential application of the self-assembled gel in the field of sensors, we performed sensor measurements. Interestingly, the twisted fibers derived from the molecular assembly could be able to display a stable and selective response towards methanol. We believe that the bottom-up assembled system holds great promise in the environmental, healthcare, medicine, and biological fields.