Molecular glue-mediated targeted protein degradation: A novel strategy in small-molecule drug development.

Small-molecule drugs are effective and thus most widely used. However, their applications are limited by their reliance on active high-affinity binding sites, restricting their target options. A breakthrough approach involves molecular glues, a novel class of small-molecule compounds capable of inducing protein-protein interactions (PPIs). This opens avenues to target conventionally undruggable proteins, overcoming limitations seen in conventional small-molecule drugs. Molecular glues play a key role in targeted protein degradation (TPD) techniques, including ubiquitin-proteasome system-based approaches such as proteolysis targeting chimeras (PROTACs) and molecular glue degraders and recently emergent lysosome system-based techniques like molecular degraders of extracellular proteins through the asialoglycoprotein receptors (MoDE-As) and macroautophagy degradation targeting chimeras (MADTACs). These techniques enable an innovative targeted degradation strategy for prolonged inhibition of pathology-associated proteins. This review provides an overview of them, emphasizing the clinical potential of molecular glues and guiding the development of molecular-glue-mediated TPD techniques.

The pivotal role of bromine in FeMnKBr/YNa catalyst for CO2 hydrogenation to light olefins.

Light olefins are key intermediates in the synthesis of petrochemicals, and the conversion of stabilized carbon dioxide to light olefins using catalysts containing halogenated elements such as chlorine is a major challenge. Building on previous reports emphasizing the toxic effects of halogen elements on catalysts, we present the synthesis of FeMnKBr/YNa catalysts. This involved the synthesis of the catalyst by melt permeation using Br-containing potassium salts, other metal nitrates and YNa zeolites. The catalyst performed well in converting syngas (H2/CO2 = 3) to light olefins with a selectivity of 56.2%, CO2 conversion of 34.4%, and CO selectivity of 13.6%. Adding Br aids in reducing the Fe phase, boosts catalyst carburization, and produces more iron carbide species. It also moderately deposits carbon on the active center's surface, enhancing active phase dispersion. Br's electronegativity mitigates the influence of K, reducing catalyst's carbon-carbon coupling ability, leading to more low-carbon olefins generation.

Satisfactory degradation of tetracycline by a pH-universal CoFe-LDH/MoS2 heterojunction catalyst in Fenton process.

Fenton or Fenton-like reactions have been widely used in various fields, including solar energy conversion to generate hydroxyl radicals, environmental remediation, biology, and life science. However, the slow Fe3+/Fe2+ cycle and narrow applicable pH range still present significant challenges. Here, a heterostructured CoFe-layered double hydroxide/MoS2 nanocomposite (CoFe-LDH/MoS2) was prepared via simple electrostatic interactions. The heterostructure establishes a robust interfacial contact, leading to an abundance of exposed Mo6+ sites. Consequently, the developed CoFe-LDH/MoS2+H2O2 system exhibited superior performance in the degradation of tetracycline (>85%) within 60 min across a wide pH range from acidic to basic. Moreover, the CoFe-LDH/MoS2 heterojunction catalysts exhibited exceptional resistance to common anions and efficiently degraded various organic pollutants. The mechanism study verified that the CoFe-LDH/MoS2 had high efficiency in producing 1O2 and ‧OH to degrade various organic pollutants. The present study will serve as a foundation for creating efficient catalyst systems for related environmental remediation.

Exploring terahertz spectral characteristics of L-sorbose and D-melibiose in solid and liquid states.

Saccharides are essential organic compounds that perform critical functions in sustaining life processes. As biomolecules, their vibrational frequencies predominantly fall in the terahertz (THz) range, making them amenable to analysis using THz techniques. In this study, L-sorbose and D-melibiose were measured using a THz time-domain spectroscopy system covering a frequency range of 0.1-2.0 THz, and their crystal structures were simulated using density functional theory. The experimental results demonstrated significant agreement with the simulation findings. In addition, the spectral properties of the two saccharides in solution were determined using microfluidic chip technology, thereby facilitating a comparison between the solid and aqueous states. The results demonstrate that the intramolecular and intermolecular interactions of the saccharides were weakened by the presence of water molecules, and the THz absorption spectrum of the same substance solution was found to be correlated with its concentration and temperature.

H2SO4 assisted hydrothermal conversion of biomass with solid acid catalysis to produce aviation fuel precursors.

With hydrothermal reaction, lignocellulosic biomass can be efficiently converted into furfural (FF) and levulinic acid (LA), both of which are key platform compounds that can be used for the subsequent preparation of aviation fuels. In order to reduce the acid concentration in traditional hydrolysis and provide a reaction system with good catalytic activity, we propose a biomass conversion route as dilute acid hydrolysis coupled with solid acid catalysis. Firstly, at different temperatures, the hemicellulose and cellulose in corn stover were step-hydrolyzed by sulfuric acid solution with a concentration of 0.9 wt. % to produce xylose and glucose, with conversion reaching 100% and 97.3%, respectively. Subsequently, a new resin-derived carbon-based solid acid catalyst was used to catalyze the aforementioned saccharide solutions to obtain FF with yield of 68.7 mol % and LA of 70.3 mol %, respectively. This work provides a promising approach for the efficient production of bio-aviation fuel precursors.

Nb-doped NiO nanoflowers for nitrite electroreduction to ammonia.

Electrocatalytic reduction of nitrite to ammonia (NO2RR) is considered as an appealing route to simultaneously achieve sustainable ammonia production and abate hazardous nitrite pollution. Herein, atomically Nb-doped NiO nanoflowers are designed as a high-performance NO2RR catalyst, which exhibits the highest NH3-Faradaic efficiency of 92.4% with an NH3 yield rate of 200.5 µmol h-1 cm-2 at -0.6 V RHE. Theoretical calculations unravel that Nb dopants can act as Lewis acid sites to render effective NO2- activation, decreased protonation energy barriers, and restricted hydrogen evolution, ultimately leading to a high NO2RR selectivity and activity.

Catalytic conversion of cellulosic biomass to harvest high-valued organic acids.

Catalytic conversion of biomass provides an alternative way for the production of organic acids from renewable feedstocks. The emerging process contains complex reactions and strategies to cut down those complex biogenic materials into target molecules. Here, we review the catalytic conversion of cellulosic biomass toward high-valued organic acids. This work has summarized the key controlling reactions which lead toward formic acid, glycolic acid, or sugar acids in oxidative conditions and the main pathways for lactic acid or levulinic acid in the anaerobic environment from cellulosic biomass and its derivatives. We evaluate and compare different strategies and methods such as one-pot and two-step conversion. Additionally, the optimization of catalytic reactions has been discussed to realize the design of C-C coupling reactions, the development of multifunctional materials, and new efficient system. In all, this article gives an insight guide to precisely convert cellulosic biomass into target organic acids.

Selective electrocatalytic hydrogenation of lignocellulose-derived 5-hydroxymethylfurfural with superior productivities.

Recently, valorization of biomass to value-added chemicals has drawn increasing attention due to carbon neutrality and sustainability. 5-Hydroxymethylfurfural is an important lignocellulose-derived biomass molecule. Herein, we have demonstrated the efficient electrocatalytic hydrogenation of 5-hydroxymethylfurfural to value-added 2,5-bis(hydroxymethyl)furan. An optimized electrolyzer with a highly electrolyte-permeable Pd cathode well balanced the selectivity, faradaic efficiency, and productivity. We have achieved high selectivity (97%) and faradaic efficiency (72%) at 50 mA cm-2 current density, and a record high productivity of 0.923 mmol cm-2·h-1 at 100 mA cm-2 current density, ∼2 times advanced compared with the best productivity in prior reports. We applied in situ infrared reflection-absorption spectroscopy to investigate the electrode-potential-dependent reaction pathways and mechanism, confirming that the highly selective hydrogenation of HMF is due to the tilted adsorption geometry through carbonyl group bonding to the surface of electrode. This work offers an opportunity for the sustainable electrocatalytic valorization of renewable lignocellulose-derived biomass with superior productivities approaching industrial level.

Neutron-activated, plasmonically excitable Fe-Pt-Yb2O3 nanoparticles delivering anti-cancer radiation against human glioblastoma cells.

Magnetic nanoparticles can be functionalized in many ways for biomedical applications. Here, we combine four advantageous features in a novel Fe-Pt-Yb2O3 core-shell nanoparticle. (a) The nanoparticles have a size of 10 nm allowing them to diffuse through neuronal tissue. (b) The particles are superparamagnetic after synthesis and ferromagnetic after annealing, enabling directional control by magnetic fields, enhance NMRI contrast, and hyperthermia treatment. (c) After neutron-activation of the shell, they carry low-energetic, short half-life ß-radiation from 175Yb, 177Yb, and 177Lu. (d) Additionally, the particles can be optically visualized by plasmonic excitation and luminescence. To demonstrate the potential of the particles for cancer treatment, we exposed cultured human glioblastoma cells (LN-18) to non-activated and activated particles to confirm that the particles are internalized, and that the ß-radiation of the radioisotopes incorporated in the neutron-activated shell of the nanoparticles kills more than 98% of the LN-18 cancer cells, promising for future anti-cancer applications.

Lignin-derived carbon nanosheets boost electrochemical reductive amination of pyruvate to alanine.

Efficient and sustainable amino acid synthesis is essential for industrial applications. Electrocatalytic reductive amination has emerged as a promising method, but challenges such as undesired side reactions and low efficiency persist. Herein, we demonstrated a lignin-derived catalyst for alanine synthesis. Carbon nanosheets (CNSs) were synthesized from lignin via a template-assisted method and doped with nitrogen and sulfur to boost reductive amination and suppress side reactions. The resulting N,S-co-doped carbon nanosheets (NS-CNSs) exhibited outstanding electrochemical performance. It achieved a maximum alanine Faradaic efficiency of 79.5%, and a yield exceeding 1,199 µmol h-1 cm-2 on NS-CNS, with a selectivity above 99.9%. NS-CNS showed excellent durability during long-term electrolysis. Kinetic studies including control experiments and theoretical calculations provided further insights into the reaction pathway. Moreover, NS-CNS catalysts demonstrated potential in upgrading real-world polylactic acid plastic waste, yielding value-added alanine with a selectivity over 75%.

Molecular oxygen-assisted in defect-rich ZnO for catalytic depolymerization of polyethylene terephthalate.

Polyethylene terephthalate (PET) is the most produced polyester plastic; its waste has a disruptive impact on the environment and ecosystem. Here, we report a catalytic depolymerization of PET into bis(2-hydroxyethyl) terephthalate (BHET) using molecule oxygen (O2)-assisted in defect-rich ZnO. At air, the PET conversion rate, the BHET yield, and the space-time yield are 3.5, 10.6, and 10.6 times higher than those in nitrogen, respectively. Combining structural characterization with the results of DFT calculations, we conclude that the (100) facet of defect-rich ZnO nanosheets conducive to the formation of reactive oxygen species (∗O2-) and Zn defect, promotes the PET breakage of the ester bond and thus complete the depolymerization processed. This approach demonstrates a sustainable route for PET depolymerization by molecule-assisted defect engineering.

Imidazo[1,2-a]pyridine derivatives synthesis from lignin ß-O-4 segments via a one-pot multicomponent reaction.

The catalytic conversion of lignin into N-containing chemicals is of great significance for the realization of value-added biorefinery concept. In this article, a one-pot strategy was designed for the transformation of lignin ß-O-4 model compounds to imidazo[1,2-a]pyridines in yields up to 95% using 2-aminopyridine as a nitrogen source. This transformation involves highly coupled cleavage of C-O bonds, sp3C-H bond oxidative activation, and intramolecular dehydrative coupling reaction to construction of N-heterobicyclic ring. With this protocol, a wide range of functionalized imidazo[1,2-a]pyridines sharing the same structure skeleton as those commercial drug molecules, such as Zolimidine, Alpidem, Saripidem, etc., were synthesized from different lignin ß-O-4 model compounds and one ß-O-4 polymer, emphasizing the application feasibility of lignin derivatives in N-heterobicyclic pharmaceutical synthesis.

Efficient photodegradation of polystyrene microplastics integrated with hydrogen evolution: Uncovering degradation pathways.

Photocatalytic microplastics (MPs) conversion into valuable products is a promising approach to alleviate MPs pollution in aquatic environments. Herein, we developed an amorphous alloy/photocatalyst composite (FeB/TiO2) that can successfully convert polystyrene (PS) MPs to clean H2 fuel and valuable organic compounds (92.3% particle size reduction of PS-MPs and 103.5 µmol H2 production in 12 h). FeB effectively enhanced the light-absorption and carrier separation of TiO2, thereby promoting more reactive oxygen species generation (especially ‧OH) and combination of photoelectrons with protons. The main products (e.g., benzaldehyde, benzoic acid, etc.) were identified. Additionally, the dominant PS-MPs photoconversion pathway was elucidated based on density functional theory calculations, by which the significant role of ‧OH was demonstrated in combination with radical quenching data. This study provides a prospective approach to mitigate MPs pollution in aquatic environments and reveals the synergistic mechanism governing the photocatalytic conversion of MPs and generation of H2 fuel.

Resourcelized conversion of livestock manure to porous cage microsphere for eliminating emerging contaminants under peroxymonosulfate trigger.

Pollution and resource waste caused by the improper disposal of livestock manure, and the threat from the release of emerging contaminants (ECs), are global challenges. Herein, we address the both problems simultaneously by the resourcelized conversion of chicken manure into porous Co@CM cage microspheres (CCM-CMSs) for ECs degradation through the graphitization process and Co-doping modification step. CCM-CMSs exhibit excellent performance for ECs degradation and actual wastewater purification under peroxymonosulfate (PMS) initiation, and show adaptability to complex water environments. The ultra-high activity can maintain after continuous operation over 2160 cycles. The formation of C-O-Co bond bridge structure on the catalyst surface caused an unbalanced electron distribution, which allows PMS to trigger the sustainable electron donation of ECs and electron gain of dissolved oxygen processes, becoming the key to the excellent performance of CCM-CMSs. This process significantly reduces the resource and energy consumption of the catalyst throughout the life cycle of production and application.

Estimating thermodynamic equilibrium solubility and solute-solvent interactions of niclosamide in eight mono-solvents at different temperatures.

Niclosamide is an FDA-approved oral anthelmintic drug currently being repurposed for COVID-19 infection. Its interesting applicability in multiple therapeutic indications has sparked interest in this drug/ scaffold. Despite its therapeutic use for several years, its detailed solubility information from Chemistry Manufacturing & Controls perspective is unavailable. Thus, the present study is intended to determine the mole fraction solubility of niclosamide in commonly used solvents and cosolvents at a temperature range of 298.15-323.15 K. The polymorphic changes from crystalline to monohydrate forms post-equilibration in various solvents were observed. The maximum mole fraction solubility of niclosamide at 323.15 K is 1.103 × 10-3 in PEG400, followed by PEG200 (5.272 × 10-4), 1-butanol (3.047 × 10-4), 2-propanol (2.42 × 10-4), ethanol (1.66 × 10-4), DMSO (1.52 × 10-4), methanol (7.78 × 10-5) and water (3.27 × 10-7). The molecular electrostatic potential showed a linear correlation with the solubility. PEG400 has higher electrostatic potential, and H-bond acceptor count, which forms a hydrogen bond with phenolic -OH of niclosamide and thus enhances its solubility. This data is valuable for the drug discovery and development teams working on the medicinal chemistry and process chemistry of this scaffold.

Predictive energetic tuning of C-Nucleophiles for the electrochemical capture of carbon dioxide.

This work maps the thermodynamics of electrochemically generated C-nucleophiles for reactive capture of CO2. We identify a linear relationship between the pKa, the reduction potential of a protonated nucleophile (E red ), and the nucleophile's free energy of CO2 binding ( Δ G b i n d ). Through synergistic experiments and computations, this study establishes a three-parameter correlation described by the equation Δ G b i n d = - 0.78 p K a + 4.28 E r e d + 20.95 for a series of twelve imidazol(in)ium/N-heterocyclic carbene pairs with an R 2 of 0.92. The correlation allows us to predict the Δ G b i n d of C-nucleophiles to CO2 using reduction potentials or pKas of imidazol(in)ium cations. The carbenes in this study were found to exhibit a wide range CO2 binding strengths, from strongly CO2 binding to nonspontaneous. This observation suggests that the Δ G b i n d of imidazol(in)ium-based carbenes is tunable to a desired strength by appropriate structural changes. This work sets the stage for systematic energetic tuning of electrochemically enabled reactive separations.

Caferana seeds (Bunchosia glandulifera) as a new source of nutrients: Evaluation of the proximal composition, solvent extraction, bioactive compounds, and δ-lactam isolation.

The proximal composition, amino acid, carbohydrate, and volatile profiles of caferana (Bunchosia glandulifera) seeds flour were here assessed. Seeds were also subjected to the following extraction processes: one with pressurized ethanol (PLE) and two with ethanol + supercritical CO2 mixture at different temperatures and pressures (SC1 and SC2). Extracts were characterized in terms of caffeine, total phenolic, and δ-lactam. The characterization of caferana seed and its extracts is unprecedented in terms of carbohydrate and volatiles profiles, besides the δ-lactam identification/isolation. SC2 extract exhibited a higher caffeine (9.3 mg/g) and δ-lactam (29.4 mg/g) content, whereas the PLE extract contained a higher total phenolic amount (3.0 mgGAE/g). Caferana is regionally associated to protective effects on mental health. Its byproduct (seed) revealed to be a promising source of bioactive compounds, and a potential raw material of nutritive extracts and flours that can be incorporated into pharmaceutical, nutraceutical, cosmetic, and food products.

MCDB: A comprehensive curated mitotic catastrophe database for retrieval, protein sequence alignment, and target prediction.

Mitotic catastrophe (MC) is a form of programmed cell death induced by mitotic process disorders, which is very important in tumor prevention, development, and drug resistance. Because rapidly increased data for MC is vigorously promoting the tumor-related biomedical and clinical study, it is urgent for us to develop a professional and comprehensive database to curate MC-related data. Mitotic Catastrophe Database (MCDB) consists of 1214 genes/proteins and 5014 compounds collected and organized from more than 8000 research articles. Also, MCDB defines the confidence level, classification criteria, and uniform naming rules for MC-related data, which greatly improves data reliability and retrieval convenience. Moreover, MCDB develops protein sequence alignment and target prediction functions. The former can be used to predict new potential MC-related genes and proteins, and the latter can facilitate the identification of potential target proteins of unknown MC-related compounds. In short, MCDB is such a proprietary, standard, and comprehensive database for MC-relate data that will facilitate the exploration of MC from chemists to biologists in the fields of medicinal chemistry, molecular biology, bioinformatics, oncology and so on. The MCDB is distributed on http://www.combio-lezhang.online/MCDB/index_html/.

Preparation, Characterization and Application of Nano-Graphene-Based Energetic Materials.

Nano-graphene-based energetic materials, as a new type of composite energetic materials such as desensitizer and combustion catalyst, have attracted extensive attention from energetic researchers. In this paper, the preparation of nano-graphene-based energetic materials, the desensitization effect of nano-graphene-based on energetic compounds, the thermal decomposition and combustion behavior of the materials are reviewed. Meanwhile, the existing problems and future development of nano-graphene-based energetic compounds are discussed.

Iridium-catalyzed C-H methylation and d 3-methylation of benzoic acids with application to late-stage functionalizations.

Late-stage functionalization (LSF) has over the past years emerged as a powerful approach in the drug discovery process. At its best, it allows for rapid access to new analogues from a single drug-like molecule, bypassing the need for de novo synthesis. To be successful, methods able to tolerate the diverse functional groups present in drug-like molecules that perform under mild conditions are required. C-H methylation is of particular interest due to the magic methyl effect in medicinal chemistry. Herein we report an iridium-catalyzed carboxylate-directed ortho C-H methylation and d 3-methylation of benzoic acids. The method uses commercially available reagents and precatalyst and requires no inert atmosphere or exclusion of moisture. Substrates bearing electron-rich and electron-poor groups were successfully methylated, including compounds with competing directing/coordinating groups. The method was also applied to the LSF of several marketed drugs, forming analogues with increased metabolic stability compared with the parent drug.