Intramolecular Interactions Research Articles

Arylazopyrazole Photoconversion Enables Tunable Morphology and Mechanical Properties.

A red-light switchable fast, near-quantitative two-way photoswitching of an azoheteroarene, arylazo-N-phenyl-3,5-diphenyl pyrazole (AAP1), with a high thermal half-life of the cis-isomer is reported here. The photochromic molecule switches in the solution phase and even in thin films. The design of AAP1 incorporates structural features that enable cis → trans reversal under red light quantitatively. Solid-state photoswitching in pristine thin films has been demonstrated using AAP1. Various photo patterns on paper with AAP1 as the photochromic ink are generated and their switching displaying the change in color is investigated. Single-crystal XRD structures of the trans-isomer as well as, the more exciting and rarely observed form, the cis-isomer of AAP1 is obtained. The SCXRD analysis reveals that the phenyl groups in the pyrazole ring engage in an intramolecular π-stacking interaction only in the cis-isomer which significantly enhances its thermal stability. The needle-shaped crystals of the thermodynamically stable trans-AAP1 display exceptional elastic mechanical flexibility, whilst the plate-like cis-isomers are brittle. The quantitative difference of the mechanical properties of both the isomers is exhibited by nanoindentation experiments. The trans crystals are significantly softer than the cis ones and a roughly three-fold difference inmechanical characteristics is identified.

Incorporation of kiwifruit peel improved the property of carboxymethyl cellulose-gum Arabic active film and its effects on the quality of beef sausages

In the present study, different doses of lyophilized kiwifruit peel powder extract (KPE) were incorporated into carboxymethyl cellulose (CMC) and gum Arabic (GA) based polymer matrices to fabricate films CG-CT (control film), CG-KPE1 (1% KPE), CG-KPE2 (2% KPE), and CG-KPE3 (3% KPE) to investigate their effects on active packaging functionality and sliced-beef sausage quality. Consequently, CG-KPE films demonstrated a superior antimicrobial effect on Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative (Escherichia coli) bacteria and antioxidant efficacy compared to CG-CT films. The scanning electronic microscopy (SEM) of CG-KPE films revealed an enhanced micrograph. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) evidenced the intramolecular interaction between KPE and CG and the improved thermal stability of film matrix. Film X-ray diffraction (XRD) peaks revealed a good crystallinity. CG-KPE films exhibited better physical and mechanical properties, increased opacity, and better ultraviolet (UV) emission barrier due to KPE addition and pigmentation compared to CG-CT films. The quick biodegradability of CG-KPE film suggested potential for KPE as a biopolymer. Subsequently, sliced-beef sausages were packaged with CG-CT, CG-KPE1, CG-KPE2, and CG-KPE3 (respective to CT, TI, T2, and T3) and stored for 12 d (4 ± 1 °C). The product’s pH and moisture content were controlled due to KPE addition in CG-KPE films. The products revealed that during storage CG-KPE treatments had a positive impact on the textural property, the color stability, and the sensory quality compared to CG-CT treatments. CG-KPE treatments showed antimicrobial effectiveness and lesser TBARS values than CG-CT treatments during storage.Graphical

Engineering Protein-Based Lipid-Binding Nanovesicles via Catechol-Amine-Derived Coacervation with Their Underlying Interfacial Mechanisms.

The development of nonphospholipid nanovesicles has garnered tremendous attention as a viable alternative to traditional liposomal nanovesicles. Protein/peptide-based nanovesicles have demonstrated their potential to reduce immunogenicity while enhancing bioactivity. However, a fundamental understanding of how proteinaceous vesicles interact with lipids and cell membranes remains elusive. In this study, we engineered a series of protamine-based nonphospholipid nanovesicles by modulating intramolecular catechol-amine interactions. By grafting trihydroxybenzene (GA) and catechol (CA) groups onto the protamine (Prot), a salt-triggered coacervation was observed in an alkaline environment with the size of as-prepared vesicles ranging from 200 to 1200 nm. The bonding affinity to lipid interfaces followed the order of Prot-CA-Fe3+(25 μM) > Prot-CA-Fe3+(10 μM) > Prot-CA > original Prot with the underlying nanomechanics investigated by the lipid bubble force measurement. Direct quantification of interactions between the nanovesicles and living human gingival fibroblasts was performed by using surface charge difference mapping. Introducing trace amounts of Fe3+ (at 10 and 25 μM) enhanced vesicle-lipid interactions via the synergy of catechol-amine interactions and Fe3+-induced complexation. This work provides improved valuable insights into the interactions between nanovesicles and cell membranes, offering an energetic paradigm for modulating cell-target delivery processes via intramolecular short-range interactions.

Molecular Insights into α-Synuclein Fibrillation: A Raman Spectroscopy and Machine Learning Approach.

The aggregation of α-synuclein is crucial to the development of Lewy body diseases, including Parkinson's disease and dementia with Lewy bodies. The aggregation pathway of α-synuclein typically involves a defined sequence of nucleation, elongation, and secondary nucleation, exhibiting prion-like spreading. This study employed Raman spectroscopy and machine learning analysis, alongside complementary techniques, to characterize the biomolecular changes during the fibrillation of purified recombinant wild-type α-synuclein protein. Monomeric α-synuclein was produced, purified, and subjected to a 7-day fibrillation assay to generate preformed fibrils. Stages of α-synuclein fibrillation were analyzed using Raman spectroscopy, with aggregation confirmed through negative staining transmission electron microscopy, mass spectrometry, and light scattering analyses. A machine learning pipeline incorporating principal component analysis and uniform manifold approximation and projection was used to analyze the Raman spectral data and identify significant peaks, resulting in differentiation between sample groups. Notable spectral shifts in α-synuclein were found in various stages of aggregation. Early changes (D1) included increases in α-helical structures (1303, 1330 cm-1) and β-sheet formation (1045 cm-1), with reductions in COO- and CH2 bond regions (1406, 1445 cm-1). By D4, these structural shifts persist with additional β-sheet features. At D7, a decrease in β-sheet H-bonding (1625 cm-1) and tyrosine ring breathing (830 cm-1) indicates further structural stabilization, suggesting a shift from initial helical structures to stabilized β-sheets and aggregated fibrils. Additionally, alterations in peaks related to tyrosine, alanine, proline, and glutamic acid were identified, emphasizing the role of these amino acids in intramolecular interactions during the transition from α-helical to β-sheet conformational states in α-synuclein fibrillation. This approach offers insight into α-synuclein aggregation, enhancing the understanding of its role in Lewy body disease pathophysiology and potential diagnostic relevance.

A study of alpha-synuclein and poly(N-isopropylacrylamide) complex formation through detailed atomistic simulations.

This work presents an investigation of the influence of poly(N-isopropylacrylamide) (PNIPAM) polymer on the structural dynamics of intrinsically disordered alpha-synuclein (α-syn) protein, exploring the formation and intricate features of the resulting α-syn/PNIPAM complexes. Using atomistic molecular dynamics (MD) simulations, our study analyzes the impact of initial configuration, polymer molecular weight, and protein mutations on the α-syn and the α-syn/PNIPAM complex. Atomistic simulations, of a few μs, of the protein/polymer complex reveal crucial insights into molecular interactions within the complex, emphasizing a delicate balance of forces governing its stability and structural evolution. Our findings indicate that PNIPAM polymer engages in significant non-polar interactions with the non-amyloid component (NAC) region of α-syn, which plays a crucial role in fibril formation, under various conditions such as the mutations in the protein structure and polymer chain length. Especially the PNIPAM polymer with a 40mer monomer exhibits a stabilizing effect on the structural properties of the protein, reducing intramolecular interactions that contribute to misfolding. These findings, which delve into protein/polymer interactions, hold promise as potential guidance for therapeutic strategies in various neurodegenerative disorders.

Local Adaptive Fusion Regression (LAFR) for Local Linear Multivariate Calibration: Application to Large Datasets.

Impeding linear calibration models from accurately predicting target sample analyte amounts are the target sample-wise deviations in measurement profiles (e.g., spectra) relative to calibration samples. Target sample measurement shifts are due to uncontrollable factors, compositely termed matrix effects, such as temperature, instrument drift, and sample composition divergences relative to analyte and other species amounts altering inter and intramolecular interactions. One approach to circumvent the matrix effect matching problem is to use local modeling where a library with thousands of samples and respective reference analyte values is mined for unique calibration sets matched to each target sample, including analyte amounts between calibration and target samples. Current local modeling methods suffer because it is wrongly assumed similar measurements between calibration and target samples translate to a complete locally matched calibration set. Measurements can be similar, but the underlying matrix effects (and analyte amount) can be drastically different. The presented procedure named local adaptive fusion regression (LAFR) solves this matrix effect matching problem with crucial local modeling paradigm shifts. Expertise with LAFR is unnecessary because input hyperparameters are self-optimized. The capabilities of LAFR to form highly dense localized linear calibration sets matched to target samples spectrally and analyte amounts are verified using a well-studied nonlinear benchmark near-infrared (NIR) meat dataset, a NIR sugarcane dataset covering four major process steps with multiple subgroups within, and a NIR soil database of 98 910 samples spanning the contiguous USA. While LAFR is tested on NIR datasets, it is applicable to other measurement systems affected by matrix effects in a broad sense.

On-Resin Selenopeptide Catalysts: Synthesis and Applications of Enzyme-Mimetic Reactions and Cyclization of Unsaturated Carboxylic Acids

Selenium reagents are useful for selenoenzyme-mimicking reactions, as well as for organic synthesis. However, the reaction waste containing selenium frequently smells unpleasant and exhibits serious toxicity. Herein, we have developed new-type on-resin selenium reagents, H-UXX···-PAM (5) and Ac-(X)U*XX···-PAM (6), where U and U* represent selenocysteine (U) and p-methoxybenzyl (PMB)-protected U, respectively, as recyclable catalysts, in which U-containing peptide chains are linked to the polystyrene resin PAM. Synthesized on-resin selenopeptides 5a–g with a variable amino acid sequence were evaluated for their glutathione peroxidase (GPx)-like activity using the UV and 1H NMR methods, using the reaction between dithiothreitol (DTTred) and H2O2 in methanol. It was found that the intramolecular interaction between U and a basic amino acid residue, such as histidine (H) and lysine (K), enhances peroxidase activity through the formation of an NH···Se hydrogen bond. On the other hand, the catalytic activity of 6a–d was evaluated in the oxidative cyclization of β,γ-unsaturated acids (7) into α,β-unsaturated lactones (8). Although the yield of 8 was significantly decreased after second- or third-round reaction, due to detachment of the selenium moiety from the resin, the results demonstrated reusability, as well as a substrate scope of 6 as a catalyst. Since U is a natural amino acid, on-resin selenopeptides are potential targets as novel-type green redox catalysts.

Physical properties of chlorophyll–quinone conjugates prepared via Friedel–Crafts reaction

Pheophytin-a derivatives possessing plastoquinone and phylloquinone analogs in the peripheral 3-substituent were prepared by Friedel–Crafts reactions of a 3-hydroxymethyl-chlorin as one of the chlorophyll-a derivatives with benzo- and naphthohydroquinones, respectively, and successive oxidation of the 1,4-dihydroxy-aryl groups in the resulting dehydration products. The 3-quinonylmethyl-chlorins exhibited ultraviolet–visible absorption and circular dichroism spectra in acetonitrile, which were composed of those of the starting 3-hydroxymethyl-chlorin and the corresponding methylated benzo- and naphthoquinones. No intramolecular interaction between the chlorin and quinone π-systems was observed in the solution owing to the methylene spacer. The first reduction potentials of the quinone moieties in the synthetic conjugates were determined by cyclic voltammetry and shifted positively from those of the reference quinones. The former quinonyl groups were reduced more readily by approximately 0.1 V than the latter quinones, which was ascribable to the stabilization of the quinonyl anion radical by the nearby macrocyclic chlorin π-chromophore. This observation implied that the reduction potentials of quinones were regulated by the close pheophytin-a derivative by through-space interaction. Considering the charge shift from pheophytin-a anion radical to plastoquinone and phylloquinone in reaction centers of photosystems II and I, respectively, the reduction potentials of these quinones as a determinant factor of the rapid electron transfer process would be dependent on the pheophytin-a in the photosynthetic reaction centers of oxygenic phototrophs as well as on the neighboring peptides.

β-Diketonate Coordination: Vibrational Properties, Electronic Structure, Molecular Topology, and Intramolecular Interactions. Beryllium(II), Copper(II), and Lead(II) as Study Cases.

Nine metal complexes formed by three symmetric β-diketonates (viz., acetylacetonate (acac), 1,1,1,3,3,3-hexafluoro-acetylacetonate (hfac), and 2,2,6,6-tetramethylheptane-3,5-dionate (tmhd)) and three metal ions (with three different coordination geometries, viz., BeII - tetrahedral, CuII - square planar, and PbII - "swing" square pyramidal) were investigated. The study combines structural analyses, vibrational spectroscopic techniques, and quantum chemical calculations with the aim of bridging crystal structure, electronic structure, molecular topology, and far-infrared (FIR) spectroscopic characteristics. The effect of intramolecular interactions on the structural, electronic, and spectroscopic features is the center of this study. The crystal structure of Be(tmhd)2 is also reported and discussed for the first time. A complete review of the experimental IR spectra is offered; discrepancies in the assignments of some peaks are revealed among the published works. Anharmonic effects were considered for acac complexes; however, they were negligible for the FIR modes. A systematic comparison between computed and experimentally measured data allowed us to design an inexpensive, yet efficient computational protocol to investigate large polynuclear complexes.

Synthesis of Nonplanar Push-Pull Chromophores with Various Heterocyclic Moieties via [2 + 2] Cycloaddition-Retroelectrocyclization Reaction.

A series of 1,1,4,4-tetracyanobuta-1,3-diene (TCBD) derivatives with various heterocyclic moieties, including pyridine, carbazole, indole, and benzothiadiazole, was newly synthesized through a [2 + 2] cycloaddition-retroelectrocyclization reaction. Symmetric electron-rich 1,3-butadiynes with end-capped heterocyclic substituents were reacted with tetracyanoethylene (TCNE), yielding the target TCBD products in 60-80% yields under ambient or mild heating conditions. The thermal stability and optical and electrochemical properties of both 1,3-butadiyne precursors and the corresponding TCBD derivatives were investigated by using thermogravimetric analysis (TGA), UV-vis spectroscopy, and cyclic voltammetry (CV). The TCBD derivatives featured narrow bandgaps due to the intramolecular charge transfer interactions of push-pull chromophores. In addition, the optimized structures and frontier molecular orbitals with their energy levels were determined by density functional theory (DFT) calculations.

Mechanistic Insights into the Anticancer Potential of Methoxyflavones Analogs: A Review.

2-phenylchromen-4-one, commonly known as flavone, plays multifaceted roles in biological response that can be abundantly present in natural sources. The methoxy group in naturally occurring flavones promotes cytotoxic activity in various cancer cell lines by targeting protein markers, in facilitating ligand-protein binding mechanisms and activating cascading downstream signaling pathways leading to cell death. However, the lipophilic nature of these analogs is a key concern as it impacts drug membrane transfer. While lipophilicity is crucial for drug efficacy, the excessive lipophilic effects in flavonoids can reduce water solubility and hinder drug transport to target sites. Recent in vitro studies suggest that the incorporation of polar hydroxyl groups which can form hydrogen bonds and stabilize free radicals may help overcome the challenges associated with methoxy groups while maintaining their essential lipophilic properties. Naturally coexisting with methoxyflavones, this review explores the synergistic role of hydroxy and methoxy moieties through hydrogen bonding capacity in maximizing cytotoxicity against cancer cell lines. The physicochemical analysis revealed the potential intramolecular interaction and favorable electron delocalization region between both moieties to improve cytotoxicity levels. Together, the analysis provides a useful strategy for the structure-activity relationship (SAR) of flavonoid analogs in distinct protein markers, suggesting optimal functional group positioning to achieve balanced lipophilicity, effective hydrogen bonding, and simultaneously minimized steric hindrance in targeting specific cancer cell types.

Intramolecular Agostic Interactions and Dynamics of a Methyl Group at a Preorganized Dinickel(II) Site.

Alkyl nickel intermediates relevant to catalytic processes often feature agostic stabilization, but relatively little is known about the situation in oligonickel systems. The dinickel(I) complex K[LNiI2], which is based on a compartmental pyrazolato-bridged ligand L3- with two β-diketiminato chelate arms, or its masked version, the dihydride complex [KL(NiII-H)2] that readily releases H2, oxidatively add methyl tosylate to give diamagnetic [LNiII2(CH3)] (1) with d(Ni···Ni) ≈ 3.7 Å. Structural characterization shows that the methyl group in 1 is bound to one NiII and exhibits an intramolecular agostic interaction with the more distant NiII. This is supported spectroscopically (viz., a ν(C-H) stretch at 2658 cm-1 and lowered 1JC-H of 114 Hz) and by DFT calculations, including topological analysis of the computed electron density for 1. NMR spectroscopy reveals very fast hopping of the CH3 group between the two NiII ions, which according to DFT has a minute barrier of 4 kcal mol-1 and proceeds via a planar CH3 moiety in the transition state (Walden-like inversion). The alkylidene group in K[LNi2(μ-CHSi(Me3)3)], obtained from the reaction of [KL(Ni-H)2] with N2CHSiMe3, is symmetrically bridging. This work provides new insight into the stabilization and dynamics of alkyl ligands at dinickel sites with a constrained metal···metal distance.

Nano-fibrous biopolymers as building blocks for gel networks: Interactions, characterization, and applications.

Biopolymers derived from natural resources are highly abundant, biodegradable, and biocompatible, making them promising candidates to replace non-renewable fossil fuels and mitigate environmental and health impacts. Nano-fibrous biopolymers possessing advantages of biopolymers entangle with each other through inter-/intra-molecular interactions, serving as ideal building blocks for gel construction. These biopolymer nanofibers often synergize with other nano-building blocks to enhance gels with desirable functions and eco-friendliness across various applications in biomedical, environmental, and energy sectors. The inter-/intra-molecular interactions directly affect the assembly of nano-building blocks, which determines the structure of gels, and the integrity of connected nano-building blocks, influencing the mechanical properties and the performance of gels in specific applications. This review focuses on four biopolymer nanofibers (cellulose, chitin, silk, collagen), commonly used in gel preparations, as representatives for polysaccharides and polypeptides. The covalent and non-covalent interactions between biopolymers and other materials have been categorized and discussed in relation to the resulting gel network structures and properties. Nanomechanical characterization techniques, such as surface forces apparatus (SFA) and atomic force microscopy (AFM), have been employed to precisely quantify the intermolecular interactions between biopolymers and other building blocks. The applications of these gels are classified and correlated to the functions of their building blocks. The inter-/intra-molecular interactions act as "sewing threads", connecting all nano-building blocks to establish suitable network structures and functions. This review aims to provide a comprehensive understanding of the interactions involved in gel preparation and the design principles needed to achieve targeted functional gels.

Accurate Enthalpies of Formation for Bioactive Compounds from High-Level Ab Initio Calculations with Detailed Conformational Treatment: A Case of Cannabinoids.

Our recently developed approach based on the local coupled-cluster with single, double, and perturbative triple excitation [LCCSD(T)] model gives very efficient means to compute the ideal-gas enthalpies of formation. The expanded uncertainty (95% confidence) of the method is about 3 kJ·mol-1 for medium-sized compounds, comparable to typical experimental measurements. Larger compounds of interest often exhibit many conformations that can significantly differ in intramolecular interactions. Although the present capabilities allow processing even a few hundred distinct conformer structures for a given compound, many systems of interest exhibit numbers well in excess of 1000. In this study, we investigate how to reduce the number of expensive LCCSD(T) calculations for large conformer ensembles while controlling the error of the approximation. The best strategy found was to correct the results of the lower-level, surrogate model (density functional theory, DFT) in a systematic manner. It was also found that the error in the conformational contribution introduced by a surrogate model is mainly driven by a systematic (bias) rather than a random component of the DFT energy deviation from the LCCSD(T) target. This distinction is usually overlooked in DFT benchmarking studies. As a result of this work, the enthalpies of formation for 20 cannabinoid and cannabinoid-related compounds were obtained. Comprehensive uncertainty analysis suggests that the expanded uncertainties of the obtained values are below 4 kJ·mol-1.

Isolation of Inner-Sphere Aquo Complexes of Samarium(II).

The cis-anti-cis and cis-syn-cis isomers of [Sm(dicyclohexano-18-crown-6)(H2O)2]I2 exhibiting trans water molecules bound to the Sm2+ ion have been isolated and characterized. Sm2+ possesses an electrochemical potential sufficient for water reduction, and thus these complexes add to the recent body of evidence that the oxidation of Sm2+ by water can operate by a mechanism that is not straightforward. These complexes are obtained by the direct addition of stoichiometric amounts of water to solutions of the respective Sm(dicyclohexano-18-crown-6)I2 isomers under an inert atmosphere. The parent complex, Sm(dicyclohexano-18-crown-6)I2, lacking coordinating water molecules can be obtained through rigorous exclusion of water. It was determined that the bulky cyclohexano-substituents deter intramolecular interactions between [Sm(dicyclohexano-18-crown-6)(H2O)2]I2 complexes and slow the oxidization of the metal centers. The extent of the stability of these complexes to the presence of water has been further probed through cyclic voltammetry, where it was found that the redox potential of both isomers of [Sm(dicyclohexano-18-crown-6)(H2O)2]I2 maintains quasi-reversible behavior with a 50,000-fold excess of water to Sm2+ in solution with the cis-syn-cis complex being quasi-reversible at even higher concentrations of water. Solution-phase spectroscopy of these complexes in acetonitrile shows a corresponding hypsochromic shift of the Sm2+ 4f → 5d transition typically observed in the visible region from Sm2+ complexes. The crystalline compounds obtained in this study support solid-state spectroscopic trends observed from other Sm2+ crown-ether complexes containing iodide counterions, wherein the proximity of the iodide ions to the metal center determines whether the complex can exhibit 4f → 4f photoluminescence.

Evaluation of Machine Learning/Molecular Mechanics End-State Corrections with Mechanical Embedding to Calculate Relative Protein-Ligand Binding Free Energies.

The development of machine-learning (ML) potentials offers significant accuracy improvements compared to molecular mechanics (MM) because of the inclusion of quantum-mechanical effects in molecular interactions. However, ML simulations are several times more computationally demanding than MM simulations, so there is a trade-off between speed and accuracy. One possible compromise are hybrid machine learning/molecular mechanics (ML/MM) approaches with mechanical embedding that treat the intramolecular interactions of the ligand at the ML level and the protein-ligand interactions at the MM level. Recent studies have reported improved protein-ligand binding free energy results based on ML/MM using ANI-2x with mechanical embedding, arguing that intramolecular interactions like torsion potentials of the ligand are often the limiting factor for accuracy. This claim is evaluated based on 108 relative binding free energy calculations for four different benchmark systems. As an alternative strategy, we also tested a tool that fits the MM dihedral potentials to the ML level of theory. Fitting was performed with the ML potentials ANI-2x and AIMNet2, and, for the benchmark system TYK2, also with quantum-mechanical calculations using ωB97M-D3(BJ)/def2-TZVPPD. Overall, the relative binding free energy results from MM with Open Force Field 2.2.0, MM with ML-fitted torsion potentials, and the corresponding ML/MM end-state corrected simulations show no statistically significant differences in the mean absolute errors (between 0.8 and 0.9 kcal mol-1). This can probably be explained by the usage of the same MM parameters to calculate the protein-ligand interactions. Therefore, a well-parametrized force field is on a par with simple mechanical embedding ML/MM simulations for protein-ligand binding. In terms of computational costs, the reparametrization of poor torsional potentials is preferable over employing computationally intensive ML/MM simulations of protein-ligand complexes with mechanical embedding. Also, the refitting strategy leads to lower variances of the protein-ligand binding free energy results than the ML/MM end-state corrections. For free energy corrections with ML/MM, the results indicate that better convergence and more advanced ML/MM schemes will be required for applications in computer-guided drug discovery.

Intramolecular Repulsive Interactions Enable High Efficiency of NIR-II Aggregation-Induced Emission Luminogens for High-Contrast Glioblastoma Imaging.

Strategies to acquire high-efficiency luminogens that emit in the second near-infrared (NIR-II, 1000-1700 nm) range are still rare due to the impediment of the energy gap law. Herein, a feasible strategy is pioneered by installing large-volume encumbrances in a confined space to intensify the repulsive interactions arising from overlapping electron densities. The experimental results, including smaller coordinate displacement, reduced reorganization energy, and suppressed internal conversion, demonstrate that the repulsive interactions assist in the inhibition of radiationless deactivation. Meanwhile, the configuration and hybridization form of the donor units are transformed along with the repulsive interactions, bringing about improved oscillator strength. A 3.8-fold higher luminescence efficiency is realized via the synergistic effect. Furthermore, the repulsive interactions endow the NIR-II fluorophores with a highly twisted conformation, superior AIE activity, and cascaded improvement of fluorescence emission from isolated molecules to aggregates. By utilizing a brain-targeting peptide to functionalize the NIR-II nanoparticles, accurate detection and high-contrast imaging of orthotopic glioblastoma are realized. This work not only explores a fundamental principle to handle the intractable energy gap law but also provides potential applications of NIR-II luminogens in high-contrast bioimaging and glioblastoma detection.

Enhanced motivated behavior mediated by pharmacological targeting of the FGF14/Nav1.6 complex in nucleus accumbens neurons

Protein/protein interactions (PPI) play crucial roles in neuronal functions. Yet, their potential as drug targets for brain disorders remains underexplored. The fibroblast growth factor 14 (FGF14)/voltage-gated Na+ channel 1.6 (Nav1.6) complex regulates excitability of medium spiny neurons (MSN) of the nucleus accumbens (NAc), a central hub of reward circuitry that controls motivated behaviors. Here, we identified compound 1028 (IUPAC: ethyl 3-(2-(3-(hydroxymethyl)-1H-indol-1-yl)acetamido)benzoate), a brain-permeable small molecule that targets FGF14R117, a critical residue located within a druggable pocket at the FGF14/Nav1.6 PPI interface. We found that 1028 modulates FGF14/Nav1.6 complex assembly and depolarizes the voltage-dependence of Nav1.6 channel inactivation with nanomolar potency by modulating the intramolecular interaction between the III-IV linker and C-terminal domain of the Nav1.6 channel. Consistent with the compound’s effects on Nav1.6 channel inactivation, 1028 enhances MSN excitability ex vivo and accumbal neuron firing rate in vivo in murine models. Systemic administration of 1028 maintains behavioral motivation preferentially during motivationally deficient conditions in murine models. These behavioral effects were abrogated by in vivo gene silencing of Fgf14 in the NAc and were accompanied by a selective reduction in accumbal dopamine levels during reward consumption in murine models. These findings underscore the potential to selectively regulate complex behaviors associated with neuropsychiatric disorders through targeting of PPIs in neurons.

Structural relaxation chirality transfer enhanced circularly polarized luminescence in heteronuclear CeIII-MnII complexes.

Circularly polarized luminescence (CPL) materials have developed rapidly in recent years due to their wide application prospects in fields like 3D displays and anti-counterfeiting. Utilizing energy transfer processes to transfer chirality has been proven as an efficient way to obtain CPL materials. However, the physics behind energy-transfer induced CPL is still not clear. Herein, in a well-designed heteronuclear CeIII-MnII complex system [(Ce((R/S)-L)Br(μ-Br))2]MnBr4 [(R/S)-L = (2R,3R)- or (2S,3S)-2,3-dimethyl-1,4,7,10,13,16-hexaoxacyclooctadecane] with intra energy transfer from CeIII to MnII, the luminescence dissymmetry factor of MnII obtained by excitation of CeIII is around 10 times higher than that obtained by direct excitation of MnII, while the CeIII center itself shows an almost negligible CPL. To address this unusual phenomenon, we proposed a new mechanism named structural relaxation chirality transfer (SRCT) where structural relaxation of the excited chiral donor amplified chirality transfer to the acceptor by intramolecular interactions. As an assistant proof, a mixture of CeIII-ZnII and LaIII-MnII complexes with inter energy transfer showed no CPL amplification. These results will inspire more breakthroughs in the physics nature and development of energy-transfer induced CPL.

Exploring the potential of malononitrile functionalized donor-acceptor systems for non-volatile memory device applications.

A novel series of D-bridge-A type organic small molecules has been designed, synthesized, and evaluated for non-volatile resistive switching write-once read-many (WORM) memory application. This study explores structure-property relationships by coupling electron-deficient malononitrile units with donors such as dibenzofuran, dibenzothiophene, and triphenylamine. Photophysical investigations revealed significant intramolecular charge transfer interaction, while electrochemical analyses demonstrated optimal band gaps ranging from 2.20 to 3.10 eV. All synthesized compounds exhibited robust, non-volatile, resistive switching memory capabilities, with ON/OFF ratios spanning 102 to 103. The lowest recorded threshold voltage was -1.25 V, and devices demonstrated substantial stability with retention times of 103 s. Notably, triphenylamine-based compounds displayed superior memory performance compared to their counterparts. The solubility of the compounds in common organic solvents suggests that they are viable for cheap fabrication techniques. Density functional theory calculations were used to visualize the key molecular orbitals and support the proposed mechanisms for resistive switching. The strategic implementation of equipotential donors and acceptors is highly desirable. This well-rounded approach guarantees optimal performance and fosters broader applicability of these devices.