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The development of efficient charge transport layers is crucial for realizing high-performance and stable quantum dot light-emitting diodes (QD-LEDs). The use of a ZnO/ZnMgO bilayer as an electron transporting layer (ETL) has garnered considerable attention. This configuration leverages the high electron mobility of ZnO and the favorable surface state of ZnMgO. Furthermore, the versatility of this configuration extends to its wide range of thickness tunability, rendering it suitable for the construction of thick devices for top-emitting structures with microcavities. However, despite the promising attributes of this bilayer configuration, the impact of the ZnO/ZnMgO bilayer ETL interface on QD-LEDs performance remains largely unexplored. Thus, this study investigated the effect of ultraviolet ozone (UVO) treatment on the stabilization of the ZnO/ZnMgO interface. UVO treatment was found to significantly enhance luminance uniformity across the QD-LEDs emission area while improving operational stability by over 4-fold. Comprehensive analyses employing X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy confirmed that UVO treatment significantly reduced the defect states of the hydroxyl groups and removed the insulating native ethanolamine ligands, thereby facilitating improved and uniform electron transport. Moreover, the effectiveness of UVO treatment in enhancing electron transport was supported by impedance analyses. Therefore, this paper presents an effective approach for enhancing the interface of a highly potent ZnO/ZnMgO bilayer ETL, which can ultimately improve the luminance uniformity and stability of QD-LEDs.

This study reports the formation of self-assembled nanostructures with homo-oligopeptides consisting of amino acids (i.e., alanine, threonine, valine, and tyrosine), the resulting morphologies (i.e., spherical shape, layered structure, and wire structure) in aqueous solution, and their potential as ice growth inhibitors. Among the homo-oligopeptides investigated, an alanine homo-oligopeptide ( n = 5) with a spherical nanostructure showed the highest ice recrystallization inhibition (IRI) activity without showing a burst ice growth property and with low ice nucleation activity. The presence of nanoscale self-assembled structures in the solution showed superior IRI activity compared to an amino acid monomer because of the higher binding affinity of structures on the growing ice crystal plane. Simulation results revealed that the presence of nanostructures induced a significant inhibition of ice growth and increased lifetime of hydrogen bonding compared with unassembled homo-oligopeptide. These results envision extraordinary performance for self-assembled nanostructures as a desirable and potent ice growth inhibitor.

The green organic semiconductor, tris-(8-hydroxyquinoline)aluminum (Alq 3 ), was hybridized with DNA growing in the shape of hexagonal prismatic crystals. In this study, we applied hydrodynamic flow to the fabrication of Alq 3 crystals doped with DNA molecules. The hydrodynamic flow in the Taylor-Couette reactor induced nanoscale pores in the Alq 3 crystals, especially at the side part of the particles. The particles exhibited distinctly different photoluminescence emissions divided into three parts compared to common Alq 3 -DNA hybrid crystals. We named this particle a "three-photonic-unit". After treatment with complementary target DNA, the three-photonic-unit Alq 3 particles doped with DNAs were found to emit depressed luminescence from side parts of the particles. This novel phenomenon would expand the technological value of these hybrid crystals with divided photoluminescence emissions toward a wider range of bio-photonic applications.

Ring-opening alternating copolymerization (ROAC) of cyclic anhydrides and epoxides has emerged as a powerful strategy to produce degradable polyesters with a diverse array of structures from the combination of two distinct building blocks. In this work, we exploited the organocatalytic ROAC of cyclic anhydrides and a functional epoxide, t -butyl glycidoxy acetate, followed by acidic deprotection to access degradable polyesters with carboxylic acid pendants. To study the interplay between monomers, diglycolic anhydride and glutaric anhydride were used as cyclic anhydrides to prepare two polyesters. In particular, the effects of the oxygen heteroatom in the cyclic anhydrides on the properties of the carboxylic acid-containing polyesters were investigated. The introduction of the oxygen heteroatom into the cyclic anhydrides significantly influenced their thermal properties and pH-dependent self-association behavior in an aqueous solution. Furthermore, molecular dynamics simulations elucidate that the number and type of hydrogen bonds play a crucial role in the self-association behavior between the polymers both in the solution and bulk states. The findings of this study highlight the importance of the interplay between monomers in the design of functional polyesters with tunable properties.

Passive water penetration across the cell membrane by osmotic diffusion is essential for the homeostasis of cell volume, in addition to the protein-assisted active transportation of water. Since membrane components can regulate water permeability, controlling compositional variation during the volume regulatory process is a prerequisite for investigating the underlying mechanisms of water permeation and related membrane dynamics. However, the lack of a viable in vitro membrane platform in hypertonic solutions impedes advanced knowledge of cell volume regulation processes, especially cholesterol-enriched lipid domains called lipid rafts. By reconstituting the liquid-ordered (L o ) domain as a likeness of lipid rafts, we verified suppressed water permeation across the L o domains, which had yet to be confirmed with experimental demonstrations despite a simulation approach. With the help of direct transfer of the L o domains from vesicles to supported lipid membranes, the biological roles of lipid composition in suppressed water translocation were experimentally confirmed. Additionally, the improvement in membrane stability under hypertonic conditions was demonstrated based on molecular dynamics simulations.

Despite their high potency, the widespread implementation of natural antimicrobial peptides is still challenging due to their low scalability and high hemolytic activities. Herein, we address these issues by employing a modular approach to mimic the key amino acid residues present in antimicrobial peptides, such as lysine, leucine, and serine, but on the highly biocompatible poly(ethylene glycol) (PEG) backbone. A series of these PEG-based peptides (PEGtides) were developed using functional epoxide monomers, corresponding to each key amino acid, with several possessing highly potent bactericidal activities and controlled selectivities, with respect to their hemolytic behavior. The critical role of the composition and the structure of the PEGtides in their selectivities was further supported by coarse-grained molecular dynamic simulations. This modular approach is anticipated to provide the design principles necessary for the future development of antimicrobial polymers.

The general practice of photodynamic therapy (PDT) comprises repeated multiple sessions, where photosensitizers are repeatedly administered prior to each operation of light irradiation. To address potential problems arising from the total overdose of photosensitizer by such repeated injections, we here introduce an internalizing RGD peptide (iRGD) derivative (Ppa-iRGDC-BK01) that self-aggregates into an injectable single-component supramolecular depot. Ppa-iRGDC-BK01 is designed as an in situ self-implantable photosensitizer so that it forms a depot by itself upon injection, and its molecular functions (cancer cell internalization and photosensitization) are activated by sustained release, tumor targeting, and tumor-selective proteolytic/reductive cleavage of the iRGD segment. The experimental and theoretical studies revealed that when exposed to body temperature, Ppa-iRGDC-BK01 undergoes thermally accelerated self-assembly to form a supramolecular depot through the hydrophobic interaction of the Ppa pendants and the reorganization of the interpeptide hydrogen bonding. It turned out that the self-aggregation of Ppa-iRGDC-BK01 into a depot exerts a multiple-quenching effect on the photosensitivity to effectively prevent nonspecific phototoxicity and protect it from photobleaching outside the tumor, while enabling autonomous tumor rephotosensitization by long sustained release, tumor accumulation, and intratumoral activation over time. We demonstrate that depot formation through a single peritumoral injection and subsequent quintuple laser irradiations at intervals resulted in complete eradication of the tumor. During the repeated PDT, depot-implanted normal tissues around the tumor exhibited no phototoxic damage under laser exposure. Our approach of single-component photosensitizing supramolecular depot, combined with a strategy of tumor-targeted therapeutic activation, would be a safer and more precise operation of PDT through a nonconventional protocol composed of one-time photosensitizer injection and multiple laser irradiations.

A new series of cyclic sulfamide derivatives were synthesized and evaluated for their ability to inhibit 11β-HSD1. Among this series, 18e showed good in vitro activity toward human 11β-HSD1, selectivity against 11β-HSD2, microsomal stability, and pharmacokinetic and safety profiles (hERG, CYP, and acute toxicity). Additionally, 18e exhibited good in vivo efficacy in rat and monkey models.

Dictyostatin (DCT, 1) is a complex, flexible polyketide macrolide that demonstrates potent microtubule-polymerization activity. Both a solution structure (2a) and a possible binding mode for DCT (Conf-1) have been proposed by earlier NMR experiments. In the present study, the conformational landscape of DCT in DMSO-d(6) and methanol-d(4) was explored using extensive force-field-based conformational searches combined with geometric parameters derived from solution NMR data. The results portray a diversity of conformations for dictyostatin that illustrates the molecule's flexibility and excludes the previously suggested dominant solution conformation 2a. One conformation present in DMSO-d(6) with a 7% population (Conf-2, 0.6 kcal/mol above the global minimum at 298°) also satisfies the TR-NOESY NMR parameters of Canales et al. that characterize the taxane binding-site interaction between DCT and assembled microtubules in water. Application of several docking methods (Glide, Autodock, and RosettaLigand) has identified a low-energy binding model of the DCT/β-tubulin complex (Pose-2/Conf-2) that is gratifyingly compatible with the emerging DCT structure-activity data.

The dictyostatins are a promising class of potential anti-cancer drugs because they are powerful microtubule-stabilizing agents, but the complexity of their chemical structures is a severe impediment to their further development. On the basis of both synthetic and medicinal chemistry analyses, 16-desmethyl-25,26-dihydrodictyostatin and its C6 epimer were chosen as potentially potent yet accessible dictyostatin analogues, and three new syntheses were developed. A relatively classical synthesis involving vinyllithium addition and macrocyclization gave way to a newer and more practical approach based on esterification and ring-closing metathesis reaction. Finally, aspects of these two approaches were combined to provide a third new synthesis based on esterification and Nozaki-Hiyama-Kishi reaction. This was used to prepare the target dihydro analogues and the natural product. All of the syntheses are streamlined because of their high convergency. The work provided several new analogues of dictyostatin, including a truncated macrolactone and a C10 E-alkene, which were 400- and 50-fold less active than (-)-dictyostatin, respectively. In contrast, the targeted 16-desmethyl-25,26-dihydrodictyostatin analogues retained almost complete activity in preliminary biological assays.

Cellular phone housings were ground to make original particulates using a knife mill. Foams and adhesives with a lighter density than water were removed from ground mixtures using a sink-float process in water; ground metals, button rubbers, and wires were separated from desired materials by using a sink float process in salt All housing materials, consisting of seven thermoplastics included in cellular phone housings, showed better tensile properties than pure housing materials made of polycarbonate/acrylonitrile butadiene styrene, but they only had about half of the impact strength. In contrast, the low impact strength for all housing materials was improved by adding 25 wt % polyethylene elastomer and/or 2.4 wt % ground epoxy circuit boards for batch mixing. Impact strengths, tensile strengths, and the energy absorption ability of all housing materials were improved by adding 5.4wt% glycidyl methacrylate for twin screw extrusion.

Structure-activity studies centered on the naturally occurring antitumor agent dictyostatin have recently identified several highly active epimers and analogues. From these compounds, 6- epi-dictyostatin was selected for scaleup preparation and evaluation in animals. Here we describe a new total synthesis that produced more than 30 mg of 6- epi-dictyostatin. The compound was found to have potent antitumor activity in SCID mice bearing MDA-MB231 human breast cancer xenografts.

The structure-activity relationship of the crucial C16 region of (-)-dictyostatin was established through total synthesis of analogs followed by detailed biological characterization. A versatile synthetic strategy was used to prepare milligram quantities of 16-normethyldictyostatin, 16-epi-dictyostatin, and the C16-normethyl-C15Z isomer. Along the way, a number of other E/Z isomers and epimers were prepared, and a novel lactone ring contraction to make iso-dictyostatins with 20-membered macrolactones (instead of 22-membered macrolactones) was discovered. The synthesis of 16-normethyl-15,16-dehydrodictyostatin is the first of any dictyostatin by a maximally convergent route in which three main fragments are assembled, coupled in back-to-back steps, and then processed through refunctionalization and macrolactonization. Cell-based and biochemical evaluations showed 16-normethyl-15,16-dehydrodictyostatin and 16-normethyldictyostatin to be the most potent of the new agents, only 2- and 5-fold less active than (-)-dictyostatin itself. This data and that from previously generated dictyostatin analogs are combined to produce a picture of the structure-activity relationships in this series of anticancer agents.

Agonists of peroxisome proliferator-activated receptor gamma (PPAR gamma) are of interest as a treatment for diabetes, which prompted the identification of a new class of non-TZD PPAR gamma agonist. Moreover, compound 14c has displayed the most active agonistic activity with an EC50 value of 50 nM, in addition to exhibiting a new binding mode in the X-ray cocrystal structure.

Thrombin, a crucial enzyme in the blood coagulation, has been a target for antithrombotic therapy. Orally active thrombin inhibitors would provide effective and safe prophylaxis for venous and arterial thrombosis. We conducted optimization of a highly efficacious benzamidine-based thrombin inhibitor LB30812 (3, K(i) = 3 pM) to improve oral bioavailability. Of a variety of arylamidines investigated at the P1 position, 2,5-thienylamidine effectively replaced the benzamidine without compromising the thrombin inhibitory potency and oral absorption. The sulfamide and sulfonamide derivatization at the N-terminal position in general afforded highly potent thrombin inhibitors but with moderate oral absorption, while the well-absorbable N-carbamate derivatives exhibited limited metabolic stability in S9 fractions. The present work culminated in the discovery of the N-carboxymethyl- and 2,5-thienylamidine-containing compound 22 that exhibits the most favorable profiles of anticoagulant and antithrombotic activities as well as oral bioavilability (K(i) = 15 pM; F = 43%, 42%, and 15% in rats, dogs, and monkeys, respectively). This compound on a gravimetric basis was shown to be more effective than a low molecular weight heparin, enoxaparin, in the venous thrombosis models of rat and rabbit. Compound 22 (LB30870) was therefore selected for further preclinical and clinical development.