Red Fluorescence from Organic Microdots: Leveraging Foldamer-Linked Azobenzene for Enhanced Stability and Intensity in Bioimaging Applications.

Azobenzene, while relevant, has faced constraints in biological system applications due to its suboptimal quantum yield and short-wavelength emission. This study presents a pioneering strategy for fabricating organic microdots by coupling foldamer-linked azobenzene, resulting in robust fluorescence intensity and stability, especially in aggregated states, thereby showing promise for bioimaging applications. Comprehensive experimental and computational examinations elucidate the mechanisms underpinning enhanced photostability and fluorescence efficacy. In vitro and in vivo evaluations disclose that the external layer of cis-azo-foldamer microdots performs a self-sacrificial function during photo-bleaching. Consequently, these red-fluorescent microdots demonstrate extraordinary structural and photochemical stabilities over extended periods. The conjugation of a ß-peptide foldamer to the azobenzene chromophore through a glycine linker instigates a blue-shifted and amplified π*-n transition. Molecular dynamics simulations reveal that the aggregated state of cis-azo-foldamers fortifies the stability of cis isomers, thereby augmenting fluorescence efficiency. This investigation furnishes crucial insights into conceptualizing novel, biologically inspired materials, promising stable and enduring imaging applications, and carries implications for diverse arenas such as medical diagnostics, drug delivery, and sensing technologies.

Brightening deep-blue perovskite light-emitting diodes: A path to Rec. 2020.

Deep-blue perovskite light-emitting diodes (PeLEDs) of high purity are highly sought after for next-generation displays complying with the Rec. 2020 standard. However, mixed-halide perovskite materials designed for deep-blue emitters are prone to halide vacancies, which readily occur because of the low formation energy of chloride vacancies. This degrades bandgap instability and performance. Here, we propose a chloride vacancy-targeting passivation strategy using sulfonate ligands with different chain lengths. The sulfonate groups have a strong affinity for lead(II) ions, effectively neutralizing vacancies. Our strategy successfully suppressed phase segregation, yielding color-stable deep-blue PeLEDs with an emission peak at 461 nanometers and a maximum luminance (Lmax) of 2707 candela per square meter with external quantum efficiency (EQE) of 3.05%, one of the highest for Rec. 2020 standard-compliant deep-blue PeLEDs. We also observed a notable increase in EQE up to 5.68% at Lmax of 1978 candela per square meter with an emission peak at 461 nanometers by changing the carbon chain length.

Glycocalyx-Mimicking Nanoparticles with Differential Organ Selectivity for Drug Delivery and Therapy.

Organ-selective drug delivery is expected to maximize the efficacy of various therapeutic modalities while minimizing their systemic toxicity. Lipid nanoparticles and polymersomes can direct the organ-selective delivery of mRNAs or gene editing machineries, but their delivery is limited to mostly liver, spleen, and lung. A platform that enables delivery to these and other target organs is urgently needed. Here, a library of glycocalyx-mimicking nanoparticles (GlyNPs) comprising five randomly combined sugar moieties is generated, and direct in vivo library screening is used to identify GlyNPs with preferential biodistribution in liver, spleen, lung, kidneys, heart, and brain. Each organ-targeting GlyNP hit show cellular tropism within the organ. Liver, kidney, and spleen-targeting GlyNP hits equipped with therapeutics effectively can alleviate the symptoms of acetaminophen-induced liver injury, cisplatin-induced kidney injury, and immune thrombocytopenia in mice, respectively. Furthermore, the differential organ targeting of GlyNP hits is influenced not by the protein corona but by the sugar moieties displayed on their surface. It is envisioned that the GlyNP-based platform may enable the organ- and cell-targeted delivery of therapeutic cargoes.

Transformation of (allo)securinine to (allo)norsecurinine via a molecular editing strategy.

Securinega alkaloids have intrigued chemists since the isolation of securinine in 1956. This family of natural products comprises a securinane subfamily with a piperidine substructure and norsecurinane alkaloids featuring a pyrrolidine core. From a biosynthetic perspective, the piperidine moiety in securinane alkaloids derives from lysine, whereas the pyrrolidine moiety in norsecurinane natural products originates from ornithine, marking an early biogenetic divergence. Herein, we introduce a single-atom deletion strategy that enables the late-stage conversion of securinane to norsecurinane alkaloids. Notably, for the first time, this method enabled the transformation of piperidine-based (allo)securinine into pyrrolidine-based (allo)norsecurinine. Straightforward access to norsecurinine from securinine, which can be readily extracted from the plant Flueggea suffruticosa, abundant across the Korean peninsula, holds promise for synthetic studies of norsecurinine-based oligomeric securinega alkaloids.

A molecular dynamics study of cell-penetrating peptide transportan-10 (TP10): Binding, folding and insertion to transmembrane state in zwitterionic membrane.

Transportan 10 (TP10) is a 21-residue, cationic, α-helical cell-penetrating peptide that can be used as a delivery vector for various bioactive molecules. Based on recent confocal microscopy studies, it is believed that TP10 can translocate across neutral lipid membrane passively, possibly as a monomer, without the formation of permanent pore. Here, we performed extensive molecular dynamics (MD) simulations of TP10W (Y3W variant of TP10) to find the microscopic details of binding, folding and insertion of TP10W to transmembrane state in POPC bilayer. Binding study with CHARMM36 force field showed that TP10W initially binds to the membrane surface in unstructured configuration, but it spontaneously folds into α-helical conformation under the lipid head groups. Further insertion of TP10W, changing from a surface bound state to a vertically oriented transmembrane state, was investigated via umbrella simulations. The resulting free energy profile shows a relatively small barrier between two states, suggesting a possible translocation pathway as a monomer. In fact, unbiased simulation of transmembrane TP10W revealed how a charged Lys side chain can move from one leaflet to the other without a significant free energy cost. Finally, we compared the results of TP10W simulations with those of point mutated variants (TP10W-K12A18 and TP10W-K19L) to understand the effect of charge distribution on the peptide. It was observed that such a conservative mutation can cause noticeable changes in the conformations of both surface bound and transmembrane states. The results of present study will be discussed in relation to the experimentally observed activities of TP10W against neutral membrane.

Cu(I)-thioether coordination complexes based on a chiral cyclic ß-amino acid ligand.

Coordination complexes, particularly metalloproteins, highlight the significance of metal-sulfur bonds in biological processes. Their unique attributes inspire efforts to synthetically reproduce these intricate metal-sulfur motifs. Here, we investigate the synthesis and characterization of copper(I)-thioether coordination complexes derived from copper(I) halides and the chiral cyclic ß-amino acid trans-4-aminotetrahydrothiophene-3-carboxylic acid (ATTC), which present distinctive structural properties and ligand-to-metal ratios. By incorporating ATTC as the ligand, we generated complexes that feature a unique chiral conformation and the capacity for hydrogen bonding, facilitating the formation of distinct geometric structures. Through spectroscopic analyses and density functional theory (DFT) calculations, we studied the complexes' optical properties, including their emission bands and variable second-harmonic generation (SHG) efficiencies, which vary based on the halide used. Our findings underscore the potential of the ATTC ligand in creating unusual coordination complexes and pave the way for further investigations into their potential applications, particularly within materials science.

Corrective feedback guides human perceptual decision-making by informing about the world state rather than rewarding its choice.

Corrective feedback received on perceptual decisions is crucial for adjusting decision-making strategies to improve future choices. However, its complex interaction with other decision components, such as previous stimuli and choices, challenges a principled account of how it shapes subsequent decisions. One popular approach, based on animal behavior and extended to human perceptual decision-making, employs "reinforcement learning," a principle proven successful in reward-based decision-making. The core idea behind this approach is that decision-makers, although engaged in a perceptual task, treat corrective feedback as rewards from which they learn choice values. Here, we explore an alternative idea, which is that humans consider corrective feedback on perceptual decisions as evidence of the actual state of the world rather than as rewards for their choices. By implementing these "feedback-as-reward" and "feedback-as-evidence" hypotheses on a shared learning platform, we show that the latter outperforms the former in explaining how corrective feedback adjusts the decision-making strategy along with past stimuli and choices. Our work suggests that humans learn about what has happened in their environment rather than the values of their own choices through corrective feedback during perceptual decision-making.

Boundary updating as a source of history effect on decision uncertainty.

When sorting a sequence of stimuli into binary classes, current choices are often negatively correlated with recent stimulus history. This phenomenon-dubbed the repulsive bias-can be explained by boundary updating, a process of shifting the class boundary to previous stimuli. This explanation implies that recent stimulus history can also influence "decision uncertainty," the probability of making incorrect decisions, because it depends on the location of the boundary. However, there have been no previous efforts to elucidate the impact of previous stimulus history on decision uncertainty. Here, from the boundary-updating process that accounts for the repulsive bias, we derived a prediction that decision uncertainty increases as current choices become more congruent with previous stimuli. We confirmed this prediction in behavioral, physiological, and neural correlates of decision uncertainty. Our work demonstrates that boundary updating offers a principled account of how previous stimulus history concurrently relates to choice bias and decision uncertainty.

The Effect of Dexmedetomidine on the Mini-Cog Score and High-Mobility Group Box 1 Levels in Elderly Patients with Postoperative Neurocognitive Disorders Undergoing Orthopedic Surgery.

Dexmedetomidine prevents postoperative cognitive dysfunction by inhibiting high-mobility group box 1 (HMGB1), which acts as an inflammatory marker. This study investigated the HMGB1 levels and the cognitive function using a Mini-Cog© score in elderly patients undergoing orthopedic surgery with dexmedetomidine infusion. In total, 128 patients aged ≥ 65 years were analyzed. The patients received saline in the control group and dexmedetomidine in the dexmedetomidine group until the end of surgery. Blood sampling and the Mini-Cog© test were performed before the surgery and on postoperative days 1 and 3. The primary outcomes were the effect of dexmedetomidine on the HMGB1 levels and the Mini-Cog© score in terms of postoperative cognitive function. The Mini-Cog© score over time differed significantly between the groups (p = 0.008), with an increase in the dexmedetomidine group. The postoperative HMGB1 levels increased over time in both groups; however, there was no significant difference between the groups (p = 0.969). The probability of perioperative neurocognitive disorders decreased by 0.48 times as the Mini-Cog© score on postoperative day 3 increased by 1 point. Intraoperative dexmedetomidine has shown an increase in the postoperative Mini-Cog© score. Thus, the Mini-Cog© score is a potential tool for evaluating cognitive function in elderly patients.

Tailoring Enantiomeric Chiral Channels in Metal-Peptide Networks: A Novel Foldamer-Based Approach for Host-Guest Interactions.

Designing chiral channels in organic frameworks presents an ongoing challenge due to the intricate control of size, shape, and functionality required. A novel approach is presented, which crafts enantiomeric chiral channels in metal-peptide networks (MPNs) by integrating short foldamer ligands with CuI clusters. The MPN structure serves as a 3D blueprint for host-guest chemistry, fostering modular substitution to refine chiral channel properties at the atomic scale. Incorporating hydrogen bond networks augments guest molecule interactions with the channel surface. This approach expedites enantiomer discrimination in racemic mixtures and incites adaptable guest molecules to take on specific axially chiral conformations. Distinct from traditional metal-organic frameworks (MOFs) and conventional reticular architectures, this foldamer-based methodology provides a predictable and customizable host-guest interaction system within a 3D topology. This innovation sets the stage for multifunctional materials that merge host-guest interaction systems with metal-complex properties, opening up potential applications in catalysis, sensing, and drug delivery.

Versatile Post-synthetic Modifications of Helical ß-Peptide Foldamers Derived from a Thioether-Containing Cyclic ß-Amino Acid.

We introduce a novel cyclic ß-amino acid, trans-(3S,4R)-4-aminotetrahydrothiophene-3-carboxylic acid (ATTC), as a versatile building block for designing peptide foldamers with controlled secondary structures. We synthesized and characterized a series of ß-peptide hexamers containing ATTC using various techniques, including X-ray crystallography, circular dichroism, and NMR spectroscopy. Our findings reveal that ATTC-containing foldamers can adopt 12-helical conformations similar to their isosteres and offer the possibility of fine-tuning their properties via post-synthetic modifications. In particular, chemoselective conjugation strategies demonstrate that ATTC provides unique post-synthetic modification opportunities, which expand their potential applications across diverse research areas. Collectively, our study highlights the versatility and utility of ATTC as an alternative to previously reported cyclic ß-amino acid building blocks in both structural and functional aspects, paving the way for future research in the realm of peptide foldamers and beyond.

Anti-inflammatory Glycocalyx-Mimicking Nanoparticles for Colitis Treatment: Construction and In Vivo Evaluation.

Common medications for treating inflammatory bowel disease (IBD) have limited therapeutic efficacy and severe adverse effects. This underscores the urgent need for novel therapeutic approaches that can effectively target inflamed sites in the gastrointestinal tract upon oral administration, exerting potent therapeutic efficacy while minimizing systemic effects. Here, we report the construction and in vivo therapeutic evaluation of a library of anti-inflammatory glycocalyx-mimicking nanoparticles (designated GlyNPs) in a mouse model of IBD. The anti-inflammatory GlyNP library was created by attaching bilirubin (BR) to a library of glycopolymers composed of random combinations of the five most naturally abundant sugars. Direct in vivo screening of 31 BR-attached anti-inflammatory GlyNPs via oral administration into mice with acute colitis led to identification of a candidate GlyNP capable of targeting macrophages in the inflamed colon and effectively alleviating colitis symptoms. These findings suggest that the BR-attached GlyNP library can be used as a platform to identify anti-inflammatory nanomedicines for various inflammatory diseases.

Neural Evidence for Boundary Updating as the Source of the Repulsive Bias in Classification.

Binary classification, an act of sorting items into two classes by setting a boundary, is biased by recent history. One common form of such bias is repulsive bias, a tendency to sort an item into the class opposite to its preceding items. Sensory-adaptation and boundary-updating are considered as two contending sources of the repulsive bias, yet no neural support has been provided for either source. Here, we explored human brains of both men and women, using functional magnetic resonance imaging (fMRI), to find such support by relating the brain signals of sensory-adaptation and boundary-updating to human classification behavior. We found that the stimulus-encoding signal in the early visual cortex adapted to previous stimuli, yet its adaptation-related changes were dissociated from current choices. Contrastingly, the boundary-representing signals in the inferior-parietal and superior-temporal cortices shifted to previous stimuli and covaried with current choices. Our exploration points to boundary-updating, rather than sensory-adaptation, as the origin of the repulsive bias in binary classification.SIGNIFICANCE STATEMENT Many animal and human studies on perceptual decision-making have reported an intriguing history effect called "repulsive bias," a tendency to classify an item as the opposite class of its previous item. Regarding the origin of repulsive bias, two contending ideas have been proposed: "bias in stimulus representation because of sensory adaptation" versus "bias in class-boundary setting because of belief updating." By conducting model-based neuroimaging experiments, we verified their predictions about which brain signal should contribute to the trial-to-trial variability in choice behavior. We found that the brain signal of class boundary, but not stimulus representation, contributed to the choice variability associated with repulsive bias. Our study provides the first neural evidence supporting the boundary-based hypothesis of repulsive bias.

Conformational landscapes of artificial peptides predicted by various force fields: are we ready to simulate ß-amino acids?

With the introduction of artificial peptides as antimicrobial agents and organic catalysts, numerous efforts have been made to design foldamers with desirable structures and functions. Computational tools are a helpful proxy for revealing the dynamic structures at atomic resolution and understanding foldamer's complex structure-function relationships. However, the performance of conventional force fields in predicting the structures of artificial peptides has not been systematically evaluated. In this study, we critically assessed three popular force fields, AMBER ff14SB, CHARMM36m, and OPLS-AA/L, in predicting conformational propensities of a ß-peptide foldamer at monomer and hexamer levels. Simulation results were compared to those obtained from quantum chemistry calculations and experimental data. We also utilised replica exchange molecular dynamics simulations to investigate the energy landscape of each force field and assess the similarities and differences between force fields. We compared different solvent systems in the AMBER ff14SB and CHARMM36m frameworks and confirmed the unanimous role of hydrogen bonds in shaping energy landscapes. We anticipate that our data will pave the way for further improvements to force fields and for understanding the role of solvents in peptide folding, crystallisation, and engineering.

Crystalline Metal-Peptide Networks: Structures, Applications, and Future Outlook.

Metal-peptide networks (MPNs), which are assembled from short peptides and metal ions, are considered one of the most fascinating metal-organic coordinated architectures because of their unique and complicated structures. Although MPNs have considerable potential for development into versatile materials, they have not been developed for practical applications because of several underlying limitations, such as designability, stability, and modifiability. In this review, we summarise several important milestones in the development of crystalline MPNs and thoroughly analyse their structural features, such as peptide sequence designs, coordination geometries, cross-linking types, and network topologies. In addition, potential applications such as gas adsorption, guest encapsulation, and chiral recognition are introduced. We believe that this review is a useful survey that can provide insights into the development of new MPNs with more sophisticated structures and novel functions.

Systematic Screening and Therapeutic Evaluation of Glyconanoparticles with Differential Cancer Affinities for Targeted Cancer Therapy.

Cancer-targeting ligands used for nanomedicines have been limited mostly to antibodies, peptides, aptamers, and small molecules thus far. Here, a library of glycocalyx-mimicking nanoparticles as a platform to enable screening and identification of cancer-targeting nanomedicines is reported. Specifically, a library of 31 artificial glycopolymers composed of either homogeneous or heterogeneous display of five different sugar moieties (ß-glucose, ß-galactose, α-mannose, ß-N-acetyl glucosamine, and ß-N-acetyl galactosamine) is converted to a library of glyconanoparticles (GlyNPs). GlyNPs optimal for targeting CT26, DU145, A549, and PC3 tumors are systematically screened and identified. The cypate-conjugated GlyNP displaying α-mannose and ß-N-acetyl glucosamine show selective targeting and potent photothermal therapeutic efficacy against A549 human lung tumors. The docetaxel-contained GlyNP displaying ß-glucose, ß-galactose, and α-mannose demonstrate targeted chemotherapy against DU145 human prostate tumors. The results presented herein collectively demonstrate that the GlyNP library is a versatile platform enabling the identification of cancer-targeting glyconanoparticles and suggest its potential applicability for targeting various diseased cells beyond cancer.

Evidence for Participation of 4f and 5d Orbitals in Lanthanide Metal-Ligand Bonding and That Y(III) Has Less of This Complex-Stabilizing Ability. A Thermodynamic, Spectroscopic, and DFT Study of Their Complexation by the Nitrogen Donor Ligand TPEN.

The formation constants (log K1) of lanthanide(III) (Ln) ions [except for Pm(III)] and the Y(III) cation have been measured with the ligand TPEN (N,N,N',N'-tetra-2-picolylethylenediamine). These log K1 values show a typical variation with ionic radius, with a local maximum at Sm(III) and a local minimum at Gd(III), with an overall increase in log K1 from La(III) to Lu(III) as the ionic radius decreases. The log K1 for the Y(III)/TPEN complex is much lower than expected from its ionic radius, while the literature log K1 for Am(III) is much higher. The latter effect is thought to be due to greater covalence in the M-L (metal-ligand) bond than for Ln(III) ions: the low log K1 for Y(III) is interpreted as being due to lower covalence. The f → f transitions in the Nd(III) and Pr(III) complexes were examined for effects that might indicate the participation of f orbitals in M-L bonding. The intensity of the f → f transitions in the Nd(III)/TPEN complex was greatly increased compared to that of the Nd3+ aqua ion, which appeared to be due to additional sharp peaks, possibly parity forbidden transitions where parity rules were broken by covalence in the M-L bond. The Pr(III)/TPEN complex showed that all of the f → f transitions shifted to longer wavelengths by some 5 nm, with modest increases in intensity. The effects seen in the f → f transitions of Nd(III) and Pr(III) with TPEN with its six nitrogen donors were present to a much smaller extent in the EDTA and other complexes with fewer nitrogen donors. The changes in the f → f transitions of the TPEN complexes of Er(III) and Ho(III) were small, suggesting a smaller contribution of f orbitals to M-L bonding in these heavier Ln(III) ions. The intense Laporte allowed f → d transitions in Ce(III) complexes show large shifts to longer wavelengths as complexes of, for example, EDTA with increasing numbers of nitrogen donors, suggesting the participation of both f and d orbitals, or either, in M-L bonding. The nature of M-L bonding in M(III)/TPEN complexes was further investigated via density functional theory calculations.

Synthesis and Reactivity of 1-Hydroxyherquline A.

Herein, we present the synthesis of 1-hydroxyherquline A and describe its reactivity discovered during its attempted conversion to herquline A, a long-sought natural product target in the synthetic chemical community. The strategic installation of the C1 hydroxyl group enabled the key aza-Michael addition-mediated N10-C2 bond formation and eventually access to 1-hydroxyherquline A, the most advanced herquline A congener reported to date. Our attempted reductive transformation of 1-hydroxyherquline A to herquline A was challenged by the extremely strained bowl-shaped pentacyclic structures of key precursors that prevented either radical formation at C1 or protonation (or hydrogenation) from the desired face. These discoveries regarding the innate chemical reactivities of advanced intermediates toward herquline A may prove useful in efforts toward this formidable target.

Nanoparticle design and assembly for p-type metal oxide gas sensors.

Metal oxide semiconductors have wide band gaps with tailorable electrical properties and high stability, suitable for chemiresistive gas sensors. p-Type oxide semiconductors generally have less sensitivity than their n-type counterparts but provide unique functionality with low humidity dependence. Among various approaches to enhance the p-type characteristics, nanostructuring of active materials is essential to exhibit high sensing performances comparable to n-type materials. Moreover, p-n heterojunction formation can achieve superior sensitivity at low operating temperatures. The representative examples are hollow and urchin-like particles, mesoporous structures, and nanowire networks. These morphologies can generate abundant active surface sites with a high surface area and induce rapid gas diffusion and facile charge transport. For growing interests in environmental and healthcare monitoring, p-type oxide semiconductors and their heterojunctions with well-designed nanostructures gain much attention as advanced gas sensing materials for practical applications. In addition to precise nanostructure design, the combination with other strategies, e.g. light activation and multiple gas sensing analysis using sensor arrays will be able to fabricate the desired gas sensors with exclusive gas detection at ultra-low concentrations operating even at room temperature.

Programmed hierarchical radial association of anisotropic foldamer assemblies.

Herein, we report the first example of a programmed radial assembly of anisotropic microparticles derived from a helical foldamer with a C-terminal cysteine residue. Surface-exposed thiols played a crucial role in facilitating the interparticle hydrogen bonding to form higher-order structures in an aqueous solution.