Efficient Strategy For Synthesis Research Articles

Inside-Out Rational Design of Ornithine Cyclodeaminase RlOCD from Rhizobium leguminosarum by a Multiregion Synergy Strategy for Efficient Synthesis of l-Pipecolic Acid.

Lysine cyclodeaminase (LCD)-mediated synthesis of l-pipecolic acid (l-PA) from l-lysine (l-Lys) is a promising approach. However, only one LCD has been reported, and its inadequate activity limits industrial applications. To address this problem, a substrate analogue-guided enzyme mining strategy was employed. A novel ornithine cyclodeaminase (OCD) from Rhizobium leguminosarum (RlOCD) was identified in combination with directed macrogenomic approaches. RlOCD displayed a conversion rate of 28% at a substrate loading as high as 1000 mM. A multiregion synergy strategy consisting of pocket reshaping, dynamical cross-correlation matrix-guided coevolutionary design, and surface modification was used to design RlOCD from the inside-out. A quadruple mutant (V93C/L119C/I170T/R90L) designated Mu4 with significantly increased activity was obtained, which showed a 28.46-fold increase in the catalytic efficiency. The conversion of Mu4 was 91% within 10 h at 1000 mM (146.19 g L-1) loading. The space-time yield of 282.1 g L-1 d-1 is the highest level ever reported. Molecular dynamics simulations and interaction analyses revealed that efficient pocket expansion and unique conformational rearrangements increased the affinity for the substrate, resulting in a more catalytically active conformation. This study expands the toolbox for the production of l-PA and demonstrates the effectiveness and potential of Mu4 for its production.

Efficient Strategy for Synthesizing Vector-Free and Oncolytic Herpes Simplex Type 1 Viruses.

Synthesizing viral genomes plays an important role in fundamental virology research and in the development of vaccines and antiviral drugs. Herpes simplex virus type 1 (HSV-1) is a large DNA virus widely used in oncolytic virotherapy. Although de novo synthesis of the HSV-1 genome has been previously reported, the synthetic procedure is still far from efficient, and the synthesized genome contains a vector sequence that may affect its replication and application. In the present study, we developed an efficient vector-free strategy for synthesis and rescue of synthetic HSV-1. In contrast to the conventional method of transfecting mammalian cells with a completely synthesized genome containing a vector, overlapping HSV-1 fragments synthesized by transformation-associated recombination (TAR) in yeast were linearized and cotransfected into mammalian cells to rescue the synthetic virus. Using this strategy, a synthetic virus, F-Syn, comprising the complete genome of the HSV-1 F strain, was generated. The growth curve and electron microscopy of F-Syn confirmed that its replication dynamics and morphogenesis are similar to those of the parental virus. In addition, by combining TAR with in vitro CRISPR/Cas9 editing, an oncolytic virus, F-Syn-O, with deleted viral genes ICP6, ICP34.5, and ICP47 was generated. The antitumor effect of F-Syn-O was tested in vitro. F-Syn-O established a successful infection and induced dose-dependent cytotoxic effects in various human tumor cell lines. These strategies will facilitate convenient and systemic manipulation of HSV-1 genomes and could be further applied to the design and construction of oncolytic herpesviruses.

Intraphase Switching of Hollow CoCuFe Nanocubes for Efficient Electrochemical Nitrite Reduction to Ammonia.

This study addresses the urgent need to focus on the nitrite reduction reaction (NO2-RR) to ammonia (NH3). A ternary-metal Prussian blue analogue (CoCuFe-PBA) was utilized as the template material, leveraging its tunable electronic properties to synthesize CoCuFe oxide (CoCuFe-O) through controlled calcination. Subsequently, a CoCuFe alloy (CoCuFe-A) was obtained via pulsed laser irradiation in liquids. The electrochemical properties of CoCuFe-O, derived from the PBA crystal structure, demonstrated a high yield of NH4+ at a rate of 555.84 μmol h-1 cm-2, with the highest Faradaic efficiency of 91.8% and a selectivity of 97.3% during a 1-h NO2-RR under an optimized potential of -1.0 V vs. Ag/AgCl. In situ Raman spectroscopy revealed the collaborative role of redox pairs (Co3+/Co2+ and Fe3+/Fe2+) as proton (H+) suppliers, with Cu centers serving as NO2- binders, thereby enhancing the reaction rate. Additionally, theoretical studies confirmed that Fe and Co atoms are more reactive than Cu toward intermediates playing crucial roles in hydrogenation, while Cu primarily activates NO owing to hydrogenation by the Fe and Co atoms and a high kinetic barrier in H2O* adsorption. This comprehensive investigation provides valuable insights into the electrochemical NO2-RR, establishing a foundation for efficient and sustainable NH3 synthesis strategies.

Interfacially crystallized Enzyme@MOFs biocatalytic membranes for highly efficient synthesis of D-amino acids via continuously recirculating stereoinversion

D-Amino acids (D-AAs) constitute essential building blocks found in many pharmaceuticals and fine chemicals. We herein presented the coating of polyvinylidene fluoride (PVDF) hollow fiber membrane with L-amino acid oxidase (LAAO) embedded zeolitic imidazolate framework-8 (ZIF-8) layer by a single-step interfacial biomineralization strategy for efficient synthesis of D-AAs. The ZIF-8 skeleton and PVDF membrane structure not only guaranteed free enzyme activity and stability, but also reinforced the applicability of this bioreactor for continuous enzymatic reactions. By placing the prepared biocatalytic membrane in the constructed circulation device, only the L-AAs can be specifically oxidized. The D-AAs are accumulated and synthesized after multiple rounds of continuously recirculating stereoinversion. Impressively, using tryptophan (Trp) as the model molecule, the thus-designed bioreactor exhibited an excellent conversion rate (92.10%) and ee% (99.41%) of D-Trp with a shorter time under constant flow conditions. This study provides an unprecedented protocol for highly efficient synthesis of D-AAs, and immensely advances the promising application field of membrane bioreactors.

Membraneless Electrochemical Synthesis Strategy toward Nitrate-to-Ammonia Conversion.

Electroreduction of nitrate (NO3RR) to ammonia in membraneless electrolyzers is of great significance for reducing the cost and saving energy consumption. However, severe chemical crossover with side reactions makes it challenging to achieve ideal electrolysis. Herein, we propose a general strategy for efficient membraneless ammonia synthesis by screening NO3RR catalysts with inferior oxygen reduction activity and matching the counter electrode (CE) with good oxygen evolution activity while blocking anodic ammonia oxidation. Consequently, screening the available Co-Co system, the membraneless NO3--to-NH3 conversion performance was significantly higher than H-type cells using costly proton-exchange membranes. At 200 mA cm-2, the full-cell voltage of the membraneless system (∼2.5 V) is 4 V lower than that of the membrane system (∼6.5 V), and the savings are 61.4 kW h (or 56.9%) per 1 kg NH3 produced. A well-designed pulse process, inducing reversible surface reconstruction that in situ generates and restores the active Co(III) species at the working electrode and forms favorable Co3O4/CoOOH at the CE, further significantly improves NO3--to-NH3 conversion and blocks side reactions. A maximum NH3 yield rate of 1500.9 μmol cm-2 h-1 was achieved at -0.9 V (Faraday efficiency 92.6%). This pulse-coupled membraneless strategy provides new insights into design complex electrochemical synthesis.

Cu‐Catalyzed Reaction of Trifluoromethylated β‐Keto Diazos and Nitriles Proceeding via H2O Addition to Nitrile Ylides

AbstractA Cu‐catalyzed multi‐component reaction of trifluoromethylated β‐amino ketones and nitriles using tert‐butyl nitrite as a diazotization reagent has been developed. Under the optimized conditions, N‐trifluoroalkyl amides were obtained with yields up to 87%. Control experiments and computational studies reveal that the reaction proceeds through the generation of diazo, in situ formation of nitrile ylide, water addition and final enol tautomerism. This approach features mild reaction conditions, wide substrate tolerance, and scale‐up applicability, which provides an efficient and practical strategy for amide synthesis.

Adsorption-dissociation-association mechanism for enhancing electrochemical nitrate to ammonia conversion

The electrocatalytic nitrate reduction to ammonia is a promising strategy for efficient NH3 synthesis. In this study, we introduce an electrocatalyst comprising a Fe-Nx layer and porous carbon-dispersed Fe nanoparticles. This configuration achieves an exceptionally high ammonia yield rate and Faradaic efficiency of 30,151.4 ± 1060.6 µg‧h−1‧mgcat−1 and 98.4 %, respectively, via the nitrate reduction reaction. Our findings indicate that the porosity and electrical properties of the catalyst play a crucial role in NO3− adsorption, surpassing the importance of specific surface area. The abundant metal-nitrogen active sites preferentially adsorb NO3− over H2O, facilitating increased production of adsorbed hydrogen. Additionally, the elevated energy barrier from H to H2 reduces the formation of hydrogen evolution byproducts, thus favoring ammonia synthesis. This study offers valuable insights into designing highly selective catalysts for adsorption-dissociation-association mechanism and has implications for a wide range of applications.

Stable Mn(II) metal–organic framework for efficient visible light initiated trifluoromethylation reaction

A 2D Mn-based MOF ([Mn4(PDI)2(DMF)7(H2O)]n (MOF 1)) (H4PDI = 5,5′-(1,3,6,8-tetraoxo-1,3,6,8-tetrahydrobenzo[lmn][3,8]phenanthroline-2,7-diyl)diisophthalic acid) was synthesized. Visible light excited Mn-PDI unit in MOF 1 oxidizes NaSO2CF3 to generate CF3 radical and enables MOF 1 to exhibit activity for trifluoromethylation of (hetero)arenes under visible light. The unusual stability of MOF 1 in the trifluoromethylation reactions can be attributed to its unique structure, which prevents it from corrosion by acid byproduct. The peeling of MOF 1 to ultrathin nanosheets or partial oxidation of Mn(II) to Mn(III) in MOF 1 led to MOL 1 and NB 1 with significant improved activity for trifluoromethylation reactions, demonstrating the important role of composition and morphology of a catalyst on its performance. The light initiated trifluoromethylation reactions over these Mn-based MOFs was applied to a variety of substrates. This study provides an efficient strategy for synthesis of trifluoromethylated compounds and highlights the potential of MOFs in light initiated organic syntheses.

Efficient synthesis strategy and synergistic effect of Ni-Fe-Ru electrode for boosting alkaline water electrolysis

Hydrogen production from alkaline water electrolysis (AWE) has promising potential in energy storage due to the advantages of low cost and large scale, but its bottleneck is the low current density and poor durability of non-precious metal electrodes. Although numerous electrode designs with superior activity have been reported, the complicated synthesis process and refined microstructure have not changed the high preparation cost, high resistance, and poor durability of conventional AWE electrodes. Here, we report an efficient synthesis strategy of high-density Ni-Fe-Ru electrode (particle size < 5 nm) and explore the synergistic effect between Ni-Fe-Ru elements at different potentials. The electrode exhibits excellent OER activity (264 mV@100 mA cm−2, Tafel slope = 49 mV dec−1) and AWE performance (400 mA cm−2@1.89 V), it can work stably for 300 h at 500 mA cm−2, with potential for industrial applications.

Combinatorial Metabolic Engineering for Improving Betulinic Acid Biosynthesis in Saccharomyces cerevisiae.

Betulinic acid (BA) is a lupane-type triterpenoid with potent anticancer and anti-HIV activities. Its great potential in clinical applications necessitates the development of an efficient strategy for BA synthesis. This study attempted to achieve efficient BA biosynthesis in Saccharomyces cerevisiae using systematic metabolic engineering strategies. First, a de novo BA biosynthesis pathway in S. cerevisiae was constructed, which yielded a titer of 14.01 ± 0.21 mg/L. Then, by enhancing the BA synthesis pathway and dynamic inhibition of the competitive pathway, a greater proportion of the metabolic flow was directed toward BA synthesis, achieving a titer of 88.07 ± 5.83 mg/L. Next, acetyl-CoA and NADPH supply was enhanced, which increased the BA titer to 166.43 ± 1.83 mg/L. Finally, another BA synthesis pathway in the peroxisome was constructed. Dual regulation of the peroxisome and cytoplasmic metabolism increased the BA titer to 210.88 ± 4.76 mg/L. Following fed-batch fermentation process modification, the BA titer reached 682.29 ± 8.16 mg/L. Overall, this work offers a guide for building microbial cell factories that are capable of producing terpenoids with efficiency.

Convenient construction of electrocatalysts via combustion-assisted corrosion engineering for efficient water oxidation

Developing an efficient strategy for the universal synthesis of electrocatalysts is crucial for advancing the industrialization of water splitting, yet it remains a significant challenge. In this study, we propose combustion-assisted corrosion engineering as a rapid method to fabricate electrocatalysts for the oxygen evolution reaction (OER) within seconds. By utilizing a three-dimensional framework composed of nickel foam and the unique structure of the active species, we enable swift electrolyte diffusion and gas release. Consequently, the optimized S–NiO/NF exhibits remarkable OER catalytic activity, requiring a low overpotential of 236 mV to achieve a current density of 50 mA cm−2 in 1.0 M KOH solution. Notably, the reconfiguration during the OER process leads to the formation of actual catalytic active species, enhancing the number of active centers and thereby improving the catalyst's performance. This research presents a versatile method for industrially fabricating non-noble metal self-supporting electrodes with high efficiency, offering a practical solution for energy conversion and storage.

One‐step Synthesis of Organic Terminal 2D Ti3C2Tx MXene Nanosheets by Etching of Ti3AlC2 in an Organic Lewis Acid Solvent

AbstractThe surface and interface chemistry are critical for controlling the properties of two‐dimensional transition metal carbides and nitrides (MXenes). Numerous efforts have been devoted to the functionalization of MXenes with small inorganic ligands; however, few etching methods have been reported on the direct bonding of organic groups to MXene surfaces. In this work, we demonstrated an efficient and rapid strategy for the direct synthesis of 2D Ti3C2Tx MXene nanosheets with organic terminal groups in an organic Lewis acid (trifluoromethanesulfonic acid) solvent, without introducing additional intercalations. The dissolution of aluminum and the subsequent in situ introduction of trifluoromethanesulfonic acid resulted in the extraction of Ti3C2Tx MXene (T=CF3SO3−) (denoted as CF3SO3H−Ti3C2Tx) flakes with sizes reaching 15 μm and high productivity (over 70 %) of monolayers or few layers. More importantly, the large CF3SO3H−Ti3C2Tx MXene nanosheets had high colloidal stability, making them promising as efficient electrocatalysts for the hydrogen evolution reaction.

One-step Synthesis of Organic Terminal 2D Ti3C2Tx MXene Nanosheets by Etching of Ti3AlC2 in an Organic Lewis Acid Solvent.

The surface and interface chemistry are critical for controlling the properties of two-dimensional transition metal carbides and nitrides (MXenes). Numerous efforts have been devoted to the functionalization of MXenes with small inorganic ligands; however, few etching methods have been reported on the direct bonding of organic groups to MXene surfaces. In this work, we demonstrated an efficient and rapid strategy for the direct synthesis of 2D Ti3C2Tx MXene nanosheets with organic terminal groups in an organic Lewis acid (trifluoromethanesulfonic acid) solvent, without introducing additional intercalations. The dissolution of aluminum and the subsequent in situ introduction of trifluoromethanesulfonic acid resulted in the extraction of Ti3C2Tx MXene (T=CF3SO3 -) (denoted as CF3SO3H-Ti3C2Tx) flakes with sizes reaching 15 μm and high productivity (over 70 %) of monolayers or few layers. More importantly, the large CF3SO3H-Ti3C2Tx MXene nanosheets had high colloidal stability, making them promising as efficient electrocatalysts for the hydrogen evolution reaction.

Modular synthesis of pentacyclic-fused pyranoquinoliziniums as organelle-selective fluorescent probes

On basis of their unique chemical and photophysical properties, and excellent biological activities, quinoliziniums have been widely used in various research fields. Herein, modular synthetic strategies for efficient synthesis of novel fluorescent quinoliziniums by using one-pot and stepwise rhodium(III)-catalyzed C–H annulations were developed. In the one-pot synthesis, the reaction between 2-aryl-4-quinolones (1) and 1,2-diarylalkynes (2) proceeded in a chemo- and regioselective manner to give quinolinone-fused isoquinolines (3) and pentacyclic-fused pyranoquinoliziniums (4). The structural diversity of pentacyclic-fused pyranoquinoliziniums (4) was expanded by the stepwise synthesis from 3 and 2, allowing the strategic incorporation of electron-donating (OMe and OH) and electron-withdrawing (Cl) substituents on the top and bottom parts of the pyranoquinoliziniums (4). These newly synthesized pyranoquinoliziniums (4) exhibited tunable absorptions (455–532 nm), emissions (520–610 nm), fluorescence lifetime (0.3–5.6 ns), large Stokes shifts (up to 120 nm), and excellent fluorescence quantum yields (up to 0.73) upon adjusting the different substituents. The the unique arrangement of N and O atoms and extended π-conjugation of 4 could cause the relocation of HOMO comparing with our previous quinoliziniums. Importantly, pyranoquinoliziniums (4a-4g and 4i) targeted the mitochondria, while 4h was localized in lysosome. Due to the remarkable photophysical properties and the potential for organelle targeting of the novel class of quinoliziniums, they could be further applied for biological, chemical and material applications.

Copper Phenylacetylide and TiO2 Modification for an Efficient Visible-Light-Driven Oxidative Coupling of Amines.

The selective oxidation of amines to imines under mild conditions has attracted much attention. Our study reveals that copper phenylacetylide (PhC2Cu) could serve as an efficient photocatalyst for imine synthesis under visible-light irradiation (>400 nm). Utilizing benzylamine as a model reactant, PhC2Cu achieves an imine yield of 50.4%, which is 5 times higher than that of P25 under the same conditions and comparable to the yield obtained by the 3 wt % Au/P25 photocatalyst (55.4%). Further loading 3.9 nm TiO2 onto PhC2Cu through tetrabutyl titanate hydrolysis increases the imine yield to 84.7%, with a Ti:Cu atomic ratio of 3.65%. Control experiments, photoluminescence (PL) spectra, optical pump terahertz probe (OPTP) spectra, and electron spin resonance (ESR) tests confirm that the optimized TiO2 modification promotes the separation of excited carriers and electron transfer in PhC2Cu and facilitates the activation of surface oxygen, thereby enhancing the formation of superoxide radicals, a key active oxygen species in the reaction system. This work presents a promising strategy for efficient imine synthesis via amine coupling and expands the application field of PhC2Cu-based photocatalysts.

Stereoselective Synthesis of Acylethenyl Tetrahydropyridino- and Deazepanopyrrolo[1,2-c]imidazolidines via Annulation of Cyclic Imines with Acylethynylpyrroles

AbstractA new and efficient strategy for the stereoselective synthesis of tetrahydropyridino- and deazepanopyrrolo[1,2-c]imidazolidines has been developed. Annulation of acylethynylpyrroles with six- and seven-membered cyclic imines (MeCN/THF, 20–25 °C, 24–72 h) leads to tetrahydropyrrolo[1′,2′:3,4]imidazo[1,2-a]pyridines and hexahydropyrrolo[1′,2′:3,4]imidazo[1,2-a]azepines with (E)-acylethenyl moiety in 28–96% yields.

Construction of diverse hollow MFI zeolites through regulating the micropore filling agents

Constructing hollow structure into microporous zeolites can improve the accessibility of acid sites located at the inner part and the diffusion property. Hence, the development of an efficient synthesis strategy to acquire zeolites with tunable hollow structures and acidity has attracted much attention. In this work, an innovative tandem synthesis route was proposed to prepare MFI zeolites with diverse hollow structure while maintaining solid yields exceeding 90 %. The substitution of ethanol molecules, which previously occupied the micropores, with tetrapropylammonium cations was proved to be the key factor to construct hollow structure. And a crystallization-driven particle dissolution mechanism was proposed. The dimension of the hollow cavity, particle size, and Si/Al ratio can be flexibly regulated. Interestingly, hollow MFI samples featuring the common cavity structure, “eye-like” cavity structure, or double-cavity structure can be directly synthesized by controlling the dissolution of core parts. In the 1-butene catalytic cracking reactions, a much higher conversion of 67.2 % was acquired over hollow ZSM-5 compared with that over conventional ZSM-5 (35.8 %) after 64 h of reaction. This improvement can be attributed to the eightfold increase of diffusivity in hollow ZSM-5. This facile and efficient synthesis method endows accurate regulation of the hollow structure, which is meaningful for both fundamental research and industrial applications of hollow zeolites.

The Biological Activities of Polyether Ionophore Antibiotic Routiennocin is Independent of Absolute Stereochemistry.

Carboxylic polyether ionophores (CPIs) are among the most prevalent agricultural antibiotics (notably in the US) and these compounds have been in use for decades. The potential to reposition CPIs beyond veterinary use, e. g. through chemical modifications to enhance their selectivity window, is an exciting challenge and opportunity, considering their general resilience towards resistance development. Given the very large societal impact of these somewhat controversial compounds, it is surprising that many aspects of their mechanisms and activities in cells remain unclear. Here, we report comparative biological activities of the CPI routiennocin and two stereoisomers, including its enantiomer. We used an efficient convergent synthesis strategy to access the compounds and conducted a broad survey of antibacterial activities against planktonic cells and biofilms as well as the compounds' effects on mammalian cells, the latter assessed both via standard cell viability assays and broad morphological profiling. Interestingly, similar bioactivity of the enantiomeric pair was observed across all assays, strongly suggesting that chiral interactions do not play a decisive role in the mode of action. Overall, our findings are consistent with a mechanistic model involving highly dynamic behaviour of CPIs in biological membranes.

Efficient Synthesis of (2Z,5Z)-3-Benzyl/alkyl-5-(2-oxo-5-aryl-3 (2H)-furanylidene)-2-(phenylimino)-1,3-thiazolidin-4-ones via a One-Pot Three-Component Reaction

AbstractA simple and efficient strategy for the chemoselective synthesis of (2Z,5Z)-3-benzyl/alkyl-5-(2-oxo-5-arylfuran-3(2H)-ylidene)-2-(phenylimino)thiazolidin-4-one derivatives is developed via a sequential three-component reaction of readily available phenacyl bromides, pyridine and methyl 2-(3-benzyl/alkyl-4-oxo-2-(phenylimino)thiazolidin-5-ylidene)acetates in acetonitrile at room temperature. The advantages of this one-pot sequential Michael addition/1,2-H shift/elimination of pyridine/intramolecular cyclization are highlighted by its low energy requirements (short reaction times at room temperature), excellent yields, the absence of a metal catalyst, and mild conditions. The product structures are characterized by spectroscopic techniques and single-crystal X-ray analysis.

Sustainable Synthesis of Heteroaryl‐Ethers: Fe(III)‐Catalyzed C−H Activation under Air Using a Mild Oxidant

AbstractA cost effective protocol has been developed for the synthesis of diverse heterocyclic ethers through the radical cross‐coupling of heteroarenes and cyclic ethers. This reaction is catalyzed by inexpensive iron(III) perchlorate and employs TBHP (tert‐butyl hydroperoxide) as an external oxidant. The protocol demonstrates remarkable versatility in substrate compatibility and can accommodate various functional groups, all under mild reaction conditions. Importantly, this method eliminates the need for costly metals and avoids photo‐redox processes, making it a promising strategy for efficient and sustainable chemical synthesis.