Production Of Small Molecules Research Articles

De Novo Drug Design Using Transformer-Based Machine Translation and Reinforcement Learning of an Adaptive Monte Carlo Tree Search.

The discovery of novel therapeutic compounds through de novo drug design represents a critical challenge in the field of pharmaceutical research. Traditional drug discovery approaches are often resource intensive and time consuming, leading researchers to explore innovative methods that harness the power of deep learning and reinforcement learning techniques. Here, we introduce a novel drug design approach called drugAI that leverages the Encoder-Decoder Transformer architecture in tandem with Reinforcement Learning via a Monte Carlo Tree Search (RL-MCTS) to expedite the process of drug discovery while ensuring the production of valid small molecules with drug-like characteristics and strong binding affinities towards their targets. We successfully integrated the Encoder-Decoder Transformer architecture, which generates molecular structures (drugs) from scratch with the RL-MCTS, serving as a reinforcement learning framework. The RL-MCTS combines the exploitation and exploration capabilities of a Monte Carlo Tree Search with the machine translation of a transformer-based Encoder-Decoder model. This dynamic approach allows the model to iteratively refine its drug candidate generation process, ensuring that the generated molecules adhere to essential physicochemical and biological constraints and effectively bind to their targets. The results from drugAI showcase the effectiveness of the proposed approach across various benchmark datasets, demonstrating a significant improvement in both the validity and drug-likeness of the generated compounds, compared to two existing benchmark methods. Moreover, drugAI ensures that the generated molecules exhibit strong binding affinities to their respective targets. In summary, this research highlights the real-world applications of drugAI in drug discovery pipelines, potentially accelerating the identification of promising drug candidates for a wide range of diseases.

Enhanced protein secretion in reduced genome strains of Streptomyces lividans

BackgroundS. lividans TK24 is a popular host for the production of small molecules and the secretion of heterologous protein. Within its large genome, twenty-nine non-essential clusters direct the biosynthesis of secondary metabolites. We had previously constructed ten chassis strains, carrying deletions in various combinations of specialized metabolites biosynthetic clusters, such as those of the blue actinorhodin (act), the calcium-dependent antibiotic (cda), the undecylprodigiosin (red), the coelimycin A (cpk) and the melanin (mel) clusters, as well as the genes hrdD, encoding a non-essential sigma factor, and matAB, a locus affecting mycelial aggregation. Genome reduction was aimed at reducing carbon flow toward specialized metabolite biosynthesis to optimize the production of secreted heterologous protein.ResultsTwo of these S. lividans TK24 derived chassis strains showed ~ 15% reduction in biomass yield, 2-fold increase of their total native secretome mass yield and enhanced abundance of several secreted proteins compared to the parental strain. RNAseq and proteomic analysis of the secretome suggested that genome reduction led to cell wall and oxidative stresses and was accompanied by the up-regulation of secretory chaperones and of secDF, a Sec-pathway component. Interestingly, the amount of the secreted heterologous proteins mRFP and mTNFα, by one of these strains, was 12 and 70% higher, respectively, than that secreted by the parental strain.ConclusionThe current study described a strategy to construct chassis strains with enhanced secretory abilities and proposed a model linking the deletion of specialized metabolite biosynthetic clusters to improved production of secreted heterologous proteins.

In-situ catalytic pyrolysis of cellulose with lithium-ion battery ternary cathodes and ex-situ upgrading over Ru/HZSM-5 for bio-aromatics

Bio-aromatics preparation via in-situ catalytic pyrolysis of cellulose with lithium-ion battery ternary cathodes and ex-situ upgrading over Ru/HZSM-5 was studied. Three ternary cathodes with different ratios of Ni, Co, and Mn (NCM111, NCM532 and NCM811) were selected, and the effects of ternary cathodes and bifunctional Ru/HZSM-5 on the cellulose conversion were investigated from the perspectives of thermogravimetric kinetics and fixed-bed upgrading. The results indicated that cellulose pyrolyzed with cathodes reduced the solid residue content from 13.07% to 7.78%, 7.11%, and 6.63%, and decreased the weightlessness peak temperature from 358 ℃ to 348 ℃, 347 ℃, and 341 ℃; herein, the reaction order gradually elevated from 1.34 to 1.67 with the increased cathode Ni ratio, but the activation energy and pre-exponential factor obviously reduced. In-situ catalytic pyrolysis of ternary cathodes combined with ex-situ upgrading of Ru/HZSM-5 resulted in more cellulose-derived products being converted, increasing bio-oil yield from 22.47% to 25.08%, 24.75%, and 25.42%. Furfural was largely deoxygenated and dehydrated to become the precursor of aromatics, so NCM111, NCM532 and NCM811 usage increased the MAHs selectivity from 28.42% to 78.69%, 85.98%, and 87.27%, and high Ni ratio had higher deoxygenation capability and aromatic selectivity, simultaneously, it prone to creating material basis and spatiotemporal conditions for alkylation side reaction to increase C9 and above hydrocarbons. However, 1H NMR analysis confirmed that the main reaction of aromatization was still stronger than the side reaction even under high Ni ratio condition. Aromatics and coke production from acidic zeolite catalyzed reforming of oxygenates were competing reactions. In-situ catalysis of ternary cathodes produced more small molecule products to enter the inner pores of Ru/HZSM-5, forming more difficult to remove microporous coke, and the effect of increased Ni ratio was more obvious, but coke content reduced from 4.51% to 4.11%, 4.13%, and 3.05%, respectively.

Recent advances in carrier-free natural small molecule self-assembly for drug delivery.

Natural small-molecule drugs have been used for thousands of years for the prevention and treatment of human diseases. Most of the natural products available on the market have been modified into various polymer materials for improving the solubility, stability, and targeted delivery of drugs. However, these nanomedicines formed based on polymer carriers would produce severe problems such as systemic toxicity and kidney metabolic stress. In contrast, the carrier-free nanomedicines formed by their self-assembly in water have inherent advantages such as low toxicity, good biocompatibility, and biodegradability. This review summarizes the assembly process and application of natural small-molecule products, which are mainly driven by multiple non-covalent interactions, and includes single-molecule assembly, bimolecular assembly, drug-modified assembly, and organogels. Meanwhile, the molecular mechanism involved in different self-assembly processes is also discussed. Self-assembly simulation and structural modification of natural small-molecule products or traditional Chinese medicine molecules using molecular dynamics simulation and computer-assisted methods are proposed, which will lead to the discovery of more carrier-free nanomedicine drug delivery systems. Overall, this review provides an important understanding and strategy to study single-molecule and multi-molecule carrier-free nanomedicines.

Anode Catalysts for Electrocatalytic Alcohol Oxidation Coupled to CO2 Reduction in Continuous-Flow Electrolyzers

Thanks to the intense scientific interest, the field of CO2 electrolysis witnessed remarkable progress (industrially relevant partial current densities, selective electrocatalysts towards small molecule products, multi-cell stacks, etc.) in the past decade. However, despite all these efforts, the energy efficiency of CO2 electrolyzers is still relatively low, which is rooted in the large cell voltages. A reason behind this is that the kinetically sluggish water oxidation (OER) is performed at the anode in parallel with CO2 reduction (CO2RR) at the cathode. This issue can be circumvented by coupling CO2RR with alternative anode processes, resulting in smaller cell voltage (better energy efficiency) along with the possible generation of products at the anode with high market value. Thus, maximizing the potential of utilizing waste carbon sources to generate value-added products. Such alternative reactions include, for example, the electrocatalytic oxidation of chloride ions, aliphatic and aromatic alcohols, amines, urea, hydrazine, and numerous biomass-derived substances such as 5-(hydroxymethyl)furfural, sorbitol, etc.In this study, CO2RR to CO was driven at the cathode, and the electrocatalytic oxidation of glycerol (GOR) was performed at the anode of a small (1 cm2 active surface area) microfluidic electrolyzer cell. Ir black was replaced by carbon-supported Pt nanoparticles, while Ag nanoparticles were used as the cathode catalyst. During our experiments, we identified four main factors influencing the GOR activity and selectivity: i) the quality and quantity of the used ionomer, ii) the electrolyte flow rate, iii) glycerol concentration, and iv) the applied anode potential. The latter was particularly important since Pt showed the highest activity toward GOR in a potential window where its surface starts to oxidize. The formation of a continuous oxide layer has to be avoided since it inhibits the alcohol oxidation reaction. By setting optimal conditions, a close to 100% Faradic efficiency (FE) toward CO formation on the cathode and between 70-80% FE toward GOR was achieved above 200 mA cm-2 total current density. The amount of the formed products were tracked by mass spectrometry, gas-, and high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy. Dihydroxyacetone, glycerate, glycolate, oxalate, tartronate, formate, and lactate were identified as GOR products. The missing charge was attributed to the formation and a small amount of CO2. To improve the stability and selectivity of Pt in GOR, semipermeable metal oxide layers were introduced to the top of the catalyst layer. The thin films were synthesized by electrodeposition in different thicknesses. Based on our measurements, a set of criteria were defined regarding the composition of the anode catalyst layer (ionomer, co-catalyst overlayer, etc.), the composition of the electrolyte solution, and the applied electrochemical protocol to allow stable and selective GOR at high achievable current densities.

(Invited) Stabilization and Activation of Copper(I)-Oxide-Semiconducting Interfaces for Photoelectrochemical Reduction of Carbon Dioxide

Electroreduction of carbon dioxide to simple organic fuels and chemicals is a topic of growing scientific and technological interest. The reaction provides means for both reducing emissions of CO2 into atmosphere and storing renewable energy. The presentation will address low-temperature CO2-conversion processes based on electrocatalytic and photoelectrochemical approaches. Among important issues are choice of the catalytic or semiconducting materials, their morphology and operating conditions including temperature, solvent, electrolyte, pH etc. There is a need to improve the reaction dynamics and selectivity toward specific products. In practical electrolysis cells, the CO2-reduction (at cathode) is accompanied by water oxidation (at anode or photoanode).Recently, we have concentrated on the development of hybrid materials by utilizing combination of metal oxide semiconductors thus capable of effective photoelectrochemical reduction of carbon dioxide. For example, the combination of conducting polymers, or titanium (IV) oxide, and copper (I) oxide has been considered before and after sunlight illumination. Application of the hybrid system composed of both above-mentioned oxides resulted in high current densities originating from photoelectrochemical reduction of carbon dioxide mostly to methanol (CH3OH) as demonstrated upon identification of final products. Among important issue is intentional stabilization, activation, and functionalization of the mixed-metal-oxide-based photoelectrochemcal interface toward better long-term performance and selectivity production of small organic molecules (C1-C4) and other chemicals. In this respect, ultra-thin films of conducting polymers (simple or polyoxometallate-derivatized) and supramolecular complexes (with nitrogen containing ligands and certain transition metal sites), sub-monolayers of metals (Cu, Au), networks of noble metal (Au, Ag) nanoparticles or layers of robust bacterial biofilms have been considered. The photobiocathode utilizing robust biofilms have also been demonstrated to stabilize copper(I) oxide surfaces and to induce the system’s activity toward reduction of carbon dioxide under illuminations with visible light.In the presentation, special attention will be paid to the mechanistic aspects of electroreduction of carbon dioxide, fabrication and characterization of highly selective and durable semiconductor photoelectrode materials and to the importance of the reaction conditions.

Hydration behaviour of cement in polymer cement waterproof coating and its effect on the macroscopic performance

In polymer-cement waterproof coating systems, the polymer emulsion influences the hydration behaviour of the cement component, which in turn affects the macroscopic performance of the coating. In this study, the effects of styrene–acrylate (SA), vinyl acetate copolymer emulsion (VAE), and styrene–butadiene (SB) emulsions on the hydration behaviour of cement and macroscopic properties of waterproofing coatings were investigated through chemical binding water testing; thermogravimetric, X-ray diffraction X-ray photoelectron spectroscopy, and Fourier transform infrared microscopic analyses; and macroscopic property characterisation. Moreover, the mechanism of the chemical reaction between the emulsion and cement was clarified. The degree of cement hydration is the least and most affected by the SB and VAE emulsions, respectively. When the cement proportion in the inorganic phase is 50%, the hydration degree of cement in cases involving SA, VAE, and SB emulsions is 24.87%, 19.57%, and 28.61%, respectively. As the cement proportion in the powder phase increases, the tensile strength and bond strength of the polymer cement waterproof coating increase and the elongation at break decreases. The rate of increase of the tensile strength and rate of decrease of the elongation at break both decrease after the cement content becomes 50%. The SA emulsion complexes with the calcium ions in the hydrated environment, which enhances the interfacial bonding between the organic and inorganic phases and results in excellent macroscopic performance of SA waterproof coatings. The SB emulsion waterproof coating has the best mechanical properties and highest water resistance owing to the highest degree of hydration of cement under the action of SB emulsion and hydrophobicity of the emulsion. The VAE emulsion generates hydrophilic polyvinyl-vinyl alcohol and small molecule products that easily dissolve in alkaline hydration environments, leading to low water resistance of the corresponding waterproof coating.

Living Alternating Ring-Opening Metathesis Copolymerization of 2,3-Dihydrofuran to Provide Completely Degradable Polymers.

2,3-Dihydrofuran (DHF) has recently been gaining significant attention as a comonomer in metathesis polymerization, thanks to its ability to provide the resultant polymer backbones with stimuli-responsive degradability. In this report, we present living alternating copolymerization of DHF with less reactive endo-tricyclo[4.2.2.02,5 ]deca-3,9-dienes (TDs) and endo-oxonorbornenes (oxoNBs). By carefully controlling the reactivity of both the Ru initiators and the monomers, we have achieved outstanding A, B-alternation (up to 98 %) under near stoichiometric DHF loading conditions. Notably, we have also found that the use of a more sterically hindered Ru initiator helps to attain polymer backbones with higher DHF incorporation and superior A, B-alternation. While preserving the living characteristics of DHF copolymerization, as evidenced by controlled molecular weights (up to 73.9 kDa), narrow dispersities (down to 1.05), and block copolymer formation, our DHF copolymers could be broken down to a single repeat unit level under acidic conditions. 1 H NMR analysis of the model copolymer revealed that after 24 hours of degradation, up to 80 % of the initial polymer was transformed into a single small molecule product, and after purification, up to 66 % of the degradation product was retrieved. This study provides a versatile approach to improve the alternation and degradability of DHF copolymers.

Living Alternating Ring‐Opening Metathesis Copolymerization of 2,3‐Dihydrofuran to Provide Completely Degradable Polymers

Abstract2,3‐Dihydrofuran (DHF) has recently been gaining significant attention as a comonomer in metathesis polymerization, thanks to its ability to provide the resultant polymer backbones with stimuli‐responsive degradability. In this report, we present living alternating copolymerization of DHF with less reactive endo‐tricyclo[4.2.2.02,5]deca‐3,9‐dienes (TDs) and endo‐oxonorbornenes (oxoNBs). By carefully controlling the reactivity of both the Ru initiators and the monomers, we have achieved outstanding A, B‐alternation (up to 98 %) under near stoichiometric DHF loading conditions. Notably, we have also found that the use of a more sterically hindered Ru initiator helps to attain polymer backbones with higher DHF incorporation and superior A, B‐alternation. While preserving the living characteristics of DHF copolymerization, as evidenced by controlled molecular weights (up to 73.9 kDa), narrow dispersities (down to 1.05), and block copolymer formation, our DHF copolymers could be broken down to a single repeat unit level under acidic conditions. 1H NMR analysis of the model copolymer revealed that after 24 hours of degradation, up to 80 % of the initial polymer was transformed into a single small molecule product, and after purification, up to 66 % of the degradation product was retrieved. This study provides a versatile approach to improve the alternation and degradability of DHF copolymers.

Pharmaceutical Forced Degradation (Stress Testing) Endpoints: A Scientific Rationale and Industry Perspective

Forced degradation (i.e., stress testing) of small molecule drug substances and products is a critical part of the drug development process, providing insight into the intrinsic stability of a drug that is foundational to the development and validation of stability-indicating analytical methods. There is a lack of clarity in the scientific literature and regulatory guidance as to what constitutes an “appropriate” endpoint to a set of stress experiments. That is, there is no clear agreement regarding how to determine if a sample has been sufficiently stressed. Notably, it is unclear what represents a suitable justification for declaring a drug substance (DS) or drug product (DP) “stable” to a specific forced degradation condition. To address these concerns and to ensure all pharmaceutically-relevant, potential degradation pathways have been suitably evaluated, we introduce a two-endpoint classification designation supported by experimental data. These two endpoints are 1) a % total degradation target outcome (e.g., for “reactive” drugs) or, 2) a specified amount of stress, even in the absence of any degradation (e.g., for “stable” drugs). These recommended endpoints are based on a review of the scientific literature, regulatory guidance, and a forced degradation data set from ten global pharmaceutical companies. The experimental data set, derived from the Campbell et al. (2022) benchmarking study,1 provides justification for the recommendations. Herein we provide a single source reference for small molecule DS and DP forced degradation stress conditions and endpoint best practices to support regulatory submissions (e.g., marketing applications). Application of these forced degradation conditions and endpoints, as part of a well-designed, comprehensive and a sufficiently rigorous study plan that includes both the DS and DP, provides comprehensive coverage of pharmaceutically-relevant degradation and avoids unreasonably extreme stress conditions and drastic endpoint recommendations sometimes found in the literature.

Chemical upcycling of polyethylene, polypropylene, and mixtures to high-value surfactants.

Conversion of plastic wastes to fatty acids is an attractive means to supplement the sourcing of these high-value, high-volume chemicals. We report a method for transforming polyethylene (PE) and polypropylene (PP) at ~80% conversion to fatty acids with number-average molar masses of up to ~700 and 670 daltons, respectively. The process is applicable to municipal PE and PP wastes and their mixtures. Temperature-gradient thermolysis is the key to controllably degrading PE and PP into waxes and inhibiting the production of small molecules. The waxes are upcycled to fatty acids by oxidation over manganese stearate and subsequent processing. PP ꞵ-scission produces more olefin wax and yields higher acid-number fatty acids than does PE ꞵ-scission. We further convert the fatty acids to high-value, large-market-volume surfactants. Industrial-scale technoeconomic analysis suggests economic viability without the need for subsidies.

Reactive molecular dynamics insight into the thermal decomposition mechanism of 2,6-Bis(picrylamino)-3,5-dinitropyridine

2,6-bis(picrylamino)-3,5-dinitropyridine (PYX) has excellent thermostability, which makes its thermal decomposition mechanism receive much attention. In this paper, the mechanism of PYX thermal decomposition was investigated thoroughly by the ReaxFF-lg force field combined with DFT-B3LYP(6–311++G) method. The detailed decomposition mechanism, small-molecule product evolution, and cluster evolution of PYX were mainly analyzed. In the initial stage of decomposition, the intramolecular hydrogen transfer reaction and the formation of dimerized clusters are earlier than the denitration reaction. With the progress of the reaction, one side of the bitter amino group is removed from the pyridine ring, and then the pyridine ring is cleaved. The final products produced in the thermal decomposition process are CO2, H2O, N2, and H2. Among them, H2O has the earliest generation time, and the reaction rate constant (k3) is the largest. Many clusters are formed during the decomposition of PYX, and the formation, aggregation, and decomposition of these clusters are strongly affected by temperature. At low temperatures (2500 K–2750 K), many clusters are formed. At high temperatures (2750 K–3250 K), the clusters aggregate to form larger clusters. At 3500 K, the large clusters decompose and become small. In the late stage of the reaction, H and N in the clusters escaped almost entirely, but more O was trapped in the clusters, which affected the auto-oxidation process of PYX. PYX’s initial decomposition activation energy (Ea) was calculated to be 126.58 kJ/mol. This work contributes to a theoretical understanding of PYX’s entire thermal decomposition process.

Investigating the pyrolysis mechanisms of three archetypal ablative resins through pyrolysis experiments and ReaxFF MD simulations

Boron (B-PF), high carbon (HC-PF), and silicone phenolic resins (Si-PF) are typical structures of high-temperature resistant resins with exceptional ablation resistance. Nevertheless, the mechanism of their pyrolytic behavior under ultra-high temperatures remains unclear. Herein, the pyrolysis processes and mechanisms of the three resins are investigated in-depth through experiments and ReaxFF molecular dynamics simulations. According to the experimental results, the final residual carbon rate of the resin shows B-PF > HC-PF > Si-PF. The main products of resin pyrolysis are H2, CH4, CO, small molecular hydrocarbons, and phenolic compounds. The simulation results show that the different types of phenolic resins have consistent pyrolysis products. The main small molecule products are H2, H2O, CO and C2H2. Moreover, these reaction paths are monitored and analyzed. The hydroxyl groups on the naphthalene ring in the high-carbon phenolic make the ring more active and susceptible to decarbonization processes, releasing more carbon monoxide (CO). When silicone resins undergo pyrolysis at high temperatures, the resulting H2O reacts with fragments of silicon-containing molecules to form new silicon oxides upon cooling. The B-O bond in boron phenolic undergoes reorganization upon breakage to form a B-containing five-membered ring, a factor that affects its thermal stability. This research reveals the pyrolytic properties of various phenolic resins and provides a theoretical basis for further research into the pyrolytic behavior of different resins.

Engineering cellular communication between light-activated synthetic cells and bacteria

Gene-expressing compartments assembled from simple, modular parts, are a versatile platform for creating minimal synthetic cells with life-like functions. By incorporating gene regulatory motifs into their encapsulated DNA templates, in situ gene expression and, thereby, synthetic cell function can be controlled according to specific stimuli. In this work, cell-free protein synthesis within synthetic cells was controlled using light by encoding genes of interest on light-activated DNA templates. Light-activated DNA contained a photocleavable blockade within the T7 promoter region that tightly repressed transcription until the blocking groups were removed with ultraviolet light. In this way, synthetic cells were activated remotely, in a spatiotemporally controlled manner. By applying this strategy to the expression of an acyl homoserine lactone synthase, BjaI, quorum-sensing-based communication between synthetic cells and bacteria was controlled with light. This work provides a framework for the remote-controlled production and delivery of small molecules from nonliving matter to living matter, with applications in biology and medicine.

Study on the Aging Mechanism of Aerospace Plexiglass by Ultraviolet

As the main material of aircraft windshield glass, the safety and reliability of aviation plexiglass are very important. YB-3 aviation Plexiglass was used as aircraft windshield material for a four-seater electric aircraft developed in China to explore the mechanism of ultraviolet aging. The artificially accelerated aging test of YB-3 aviation plexiglass was carried out, and the mechanical and thermodynamic system of YB-3 aviation Plexiglass after aging was studied. Through the thermogravimetric dynamic analysis, it is to explore the internal aging mechanism of PMMA photolysis materials, and combined with the mechanical test data to quantitatively and qualitatively reveal the aging law of YB-3 aviation plexiglass under ultraviolet radiation. The results show that the tensile ultimate stress decreases from 72.74 MPa to 45.63 MPa when the aging time reaches 1440 h. During the aging process, the elastic modulus decreased from 4.45 GPa to 3.68 GPa and then increased to 4.12 GPa. The results show that the photolysis of YB-3 aero-plexiglass under ultraviolet radiation first results in the fracture of the polymer and then the production of small molecules, which leads to the decrease of tensile resistance and the improvement of thermal stability of the material.

Selective production of p-hydroxybenzaldehyde in the oxidative depolymerization of alkali lignin catalyzed by copper-containing imidazolium-based ionic liquids

The oxidative depolymerization of alkali lignin (AL) catalyzed by copper-containing imidazolium-based ionic liquids ([C4C1im]CuCl3) was investigated with CH3OH-H2O (9/1, v/v) as solvent under an initial oxygen pressure of 1.5 MPa at 150 °C for 3 h. Compared with other transition-metal chlorides and metal-containing ionic liquids (ILs), [C4C1im]CuCl3 presented a relatively remarkable catalytic capacity for AL oxidative depolymerization due to the cooperative effects of [C4C1im]+ and CuCl3−. [C4C1im]CuCl3 molar concentration (xMcIL) greatly influenced AL conversion and product selectivity. The highest AL conversion of 70.4% was achieved at xMcIL = 0.18 mol.%. For the obtained small-molecule products, the highest selectivity of p-hydroxybenzaldehyde reached 51.3% at xMcIL = 0.72mol.% (corresponding yield of 103.6 mg·g−1). The inter-unit linkages of lignin were effectively cleaved in the oxidative depolymerization catalyzed by [C4C1im]CuCl3, and the H unit in lignin was preferentially destroyed. The molecular interactions and microenvironment of [C4C1im]CuCl3–solvent (CH3OH-H2O) system were investigated with xMcIL varied from 0.05 mol.% to 5.12 mol.% by using attenuated total reflectance-infrared spectroscopy and molecular-dynamics method, respectively. The catalytic properties of [C4C1im]CuCl3 strongly depended on the interactions of [C4C1im]CuCl3 and solvent molecules with changes in microstructure organization. The optimum catalytic capacity of [C4C1im]CuCl3 was obtained when the ion pair formed through hydrogen bonding at xMcIL = 0.18–0.36 mol.%. The solvation of solvent molecules on CuCl3− and the formation of ionic cluster with the hydrogen-bonding self-association of [C4C1im]CuCl3 were unfavorable for the oxidative depolymerization of lignin.

The Upper Nasal Space: Option for Systemic Drug Delivery, Mucosal Vaccines and "Nose-to-Brain".

Sino-nasal disease is appropriately treated with topical treatment, where the nasal mucosa acts as a barrier to systemic absorption. Non-invasive nasal delivery of drugs has produced some small molecule products with good bioavailability. With the recent COVID pandemic and the need for nasal mucosal immunity becoming more appreciated, more interest has become focused on the nasal cavity for vaccine delivery. In parallel, it has been recognized that drug delivery to different parts of the nose can have different results and for "nose-to-brain" delivery, deposition on the olfactory epithelium of the upper nasal space is desirable. Here the non-motile cilia and reduced mucociliary clearance lead to longer residence time that permits enhanced absorption, either into the systemic circulation or directly into the CNS. Many of the developments in nasal delivery have been to add bioadhesives and absorption/permeation enhancers, creating more complicated formulations and development pathways, but other projects have shown that the delivery device itself may allow more differential targeting of the upper nasal space without these additions and that could allow faster and more efficient programs to bring a wider range of drugs-and vaccines-to market.

Effect of biomass components’ interaction on the pyrolysis reaction kinetics and small-molecule product release characteristics

The first step in uncovering pyrolysis interaction is to understand the pyrolysis reaction kinetics and small-molecule product release mechanisms of biomass components. Therefore, the cross-coupled thermal decomposition properties, gaseous product release characteristics, and functional group evolution of cellulose, hemicellulose, and lignin were investigated. The reaction activation energy is shown to be lower in co-pyrolysis, and there exist optimal mixing ratios where they favor each other's thermal breakdown. When the cellulose ratio was low, dehydration reactions, as well as the cyclization and condensation processes of open-chain hexoses and pentoses, were stimulated, but these processes were hindered when the cellulose level was high. Mixing with lignin aids in the opening of cellulose rings. However, at lower lignin levels, the dehydration, demethylation, decarboxylation, and decarbonylation processes were largely hindered, and these reactions were only stimulated at greater lignin content. The pyrolysis reaction kinetics, as well as product composition and distribution, may be altered by adjusting the composition ratio of biomass. This research helps to better understand the biomass pyrolysis interaction.

The efficient degradation of organic pollutants by Z-scheme MIL-88A@TiO2 heterojunction photo-Fenton catalyst: The synergistic effect of photocatalysis and Fenton catalysis

The combination of photocatalysis technology and Fenton technology to realize photo-Fenton degradation of organic pollutants is an effective way to improve the catalytic performance of materials. In this paper, a novel heterojunction photo-Fenton catalyst MIL-88A@TiO2 (MT-X) has been prepared using MIL-88A and TiO2 as substrate by one-pot hydrothermal method. The formation of MT-X heterogeneous structure not only improves the electron-hole separation performance of the composites, but also accelerates the regeneration of Fe2+. Under the synergistic action of photocatalysis and Fenton catalysis, MT-2 with the best performance can completely degrade methylene blue (MB, 100 mL, 20 mg/L) within 16 min and can mineralize 76.23 % MB into small molecule products. Meanwhile, MT-2 also has excellent adsorption and degradation properties for tetracycline (TC), which can degrade 99 % TC (100 mL, 50 mg/L) within 20 min, the reaction kinetic constant k = 0.27938 min‐1 is higher than most reported photocatalysts. Hydroxyl radical is identified as the main active species in the degradation process by quenching and hydroxyl radical capture experiments, and a possible degradation mechanism is proposed (Z-scheme electron transfer mechanism). Therefore, this study provides an efficient and feasible photo-Fenton catalyst for pollutant treatment, which is helpful to further understand the synergistic effect of photocatalysis and Fenton catalysis.

Recovery of homogeneous photocatalysts by covalent organic framework membranes

Transition metal-based homogeneous photocatalysts offer a wealth of opportunities for organic synthesis. The most versatile ruthenium(II) and iridium(III) polypyridyl complexes, however, are among the rarest metal complexes. Moreover, immobilizing these precious catalysts for recycling is challenging as their opacity may obstruct light transmission. Recovery of homogeneous catalysts by conventional polymeric membranes is promising but limited, as the modulation of their pore structure and tolerance of polar organic solvents are challenging. Here, we report the effective recovery of homogeneous photocatalysts using covalent organic framework (COF) membranes. An array of COF membranes with tunable pore sizes and superior organic solvent resistance were prepared. Ruthenium and iridium photoredox catalysts were recycled for 10 cycles in various types of photochemical reactions, constantly achieving high catalytical performance, high recovery rates, and high permeance. We successfully recovered the photocatalysts at gram-scale. Furthermore, we demonstrated a cascade isolation of an iridium photocatalyst and purification of a small organic molecule product with COF membranes possessing different pore sizes. Our results indicate an intriguing potential to shift the paradigm of the pharmaceutical and fine chemical synthesis campaign.