Alternative Synthesis Research Articles

Advances in Novel Animal Vitamin C Biosynthesis Pathways and the Role of Prokaryote-Based Inferences to Understand Their Origin.

Vitamin C (VC) is an essential nutrient required for the optimal function and development of many organisms. VC has been studied for many decades, and still today, the characterization of its functions is a dynamic scientific field, mainly because of its commercial and therapeutic applications. In this review, we discuss, in a comparative way, the increasing evidence for alternative VC synthesis pathways in insects and nematodes, and the potential of myo-inositol as a possible substrate for this metabolic process in metazoans. Methodological approaches that may be useful for the future characterization of the VC synthesis pathways of Caenorhabditis elegans and Drosophila melanogaster are here discussed. We also summarize the current distribution of the eukaryote aldonolactone oxidoreductases gene lineages, while highlighting the added value of studies on prokaryote species that are likely able to synthesize VC for both the characterization of novel VC synthesis pathways and inferences on the complex evolutionary history of such pathways. Such work may help improve the industrial production of VC.

Improving Fmoc Solid Phase Synthesis of Human Beta Defensin 3.

Human β-defensin 3, HBD-3, is a 45-residue antimicrobial and immunomodulatory peptide that plays multiple roles in the host defense system. In addition to interacting with cell membranes, HBD-3 is also a ligand for melanocortin receptors, cytokine receptors and voltage-gated potassium channels. Structural and functional studies of HBD-3 have been hampered by inefficient synthetic and recombinant expression methods. Herein, we report an optimized Fmoc solid-phase synthesis of this peptide using an orthogonal disulfide bonds formation strategy. Our results suggest that utilization of an optimized resin, coupling reagents and pseudoproline dipeptide building blocks decrease chain aggregation and largely improve the amount of the target peptide in the final crude material, making the synthesis more efficient. We also present an alternative synthesis of HBD-3 in which a replacement of a native disulfide bridge with a diselenide bond improved the oxidative folding. Our work enables further biological and pharmacological characterization of HBD-3, hence advancing our understanding of its therapeutic potential.

Selective Oxidation of Biomass Molecules via ZnO Nanoparticles Modified Using Charge Mismatch of the Doped Co ions.

A charge mismatch between transition-metal-ion dopants and metal oxide nanoparticles (MO NPs) within an engineered complex engenders a significant number of oxygen vacancies (VO) on the surface of the MO NP construct. To elucidate in-depth the mechanism of this tendency, Co ions with different charge states (Co3+ and Co2+) were doped into ZnO NPs, and their atomic structural changes were correlated with their photocatalytic efficiency. We ascertained that the increase of the Zn-O bond distances was distinctly affected by Co3+-ion doping, and, subsequently, the number of VO was noticeably increased. We further investigated the mechanistic pathways of the photocatalytic oxidation of 2,5-hydroxymethylfurfural (HMF), which have been widely investigated as biomass derivatives because of their potential use as precursors for the synthesis of sustainable alternatives to petrochemical substances. To identify the reaction products in each oxidation step, selective oxidation products obtained from HMF in the presence of pristine ZnO NPs, Co3+- and Co2+-ion-doped ZnO NPs were evaluated. We confirmed that Co3+-ion-doped ZnO NPs can efficiently and selectively oxidize HMF with a good conversion rate (∼40%) by converting HMF to 2,5-furandicarboxylic acid (FDCA). The present study demonstrates the feasibility of improving the production efficiency of FDCA (an alternative energy material) by using enhanced photocatalytic MO NPs with the help of the charge mismatch between MO and metal-ion dopants.

A safe alternative synthesis of primary carbamates from alcohols; in vitro and in silico assessments as an alternative acetylcholinesterase inhibitors

Carbamates are important molecules because they are used in various biochemical processes. In this study, effective alternative method for the synthesis of primary carbamates from alcohols was developed in the presence of chlorosulfonyl isocyanate (CSI) in pyridine at room temperature in mild conditions. The primary carbamates were synthesized excellent yield. This method is easy, practical, and inexpensive without any additive, metal, or catalyst. Alzheimer’s disease (AD) is a neurodegenerative disease and has been reported to affect approximately 50 million people worldwide in 2020. Drugs that reversibly inhibit the acetylcholinesterase (AChE) activity are used for the treatment of AD. For this reason, there is a growing interest in developing alternative AChE inhibitors. Concordantly, Anti-anticholinesterase activity of synthesized carbamate derivatives was investigated as an alternative AChE inhibitors. In order to determine the inhibitory effect of these molecules, IC50, and Ki values and inhibition types were determined. According to the Ki results, the most effective inhibitors were 3 b and 3e with the Ki values of 22 and 38 µM, respectively. It was found that all molecules showed competitive inhibition type. For clarify the inhibitors-enzyme interactions, molecular docking studies were performed and possible binding interactions between the synthesized molecules and AChE were determined. Additionally, the pharmacokinetic and properties of the synthesized molecules were evaluated in silico. Communicated by Ramaswamy H. Sarma.

Cobalt and Nickel Free Disorder Rock Salt Cathodes – Recent Developments

Disordered Li-excess rock salt (DRX) cathodes are a promising class of high capacity (and voltage) cathodes for next-generation Li-ion batteries. Compared to conventional Li-ion cathodes which are generally restricted to Co/Ni-based compositions with specific cation ordering, DRX materials have a wide compositional design space based on earth abundant metals such as Mn, Ti, Mo, Al, Zr, V, and Nb. Furthermore, Li-rich oxyfluoride DRX cathodes have demonstrated specific energies up to 1,000 Wh/kg which exceeds that of state-of-the-art layered LiNixMnyCo1-x-yO2 (NMC) cathodes (~700 Wh/kg). Despite such scientific advancements, widespread adoption of DRX cathodes has been hindered by several technical challenges. First, most of the high fluorine content DRX compositions are synthesized using mechano-chemical synthesis that has inherent limitation in scalability and maintaining a uniform particle-size and morphology. Further, DRX compositions have about 3-4 order lower electronic conductivity compared to layered cathodes requiring a high carbon loading in the electrode (up to 25%) compromising energy density. The focus of this talk will be on developing alternate synthesis method for Li-Mn rich DRX compositions. Specifically solid-state and sol-gel synthesis methods to produce DRX cathodes with the nominal composition Li1.2Mn0.4+xTi0.4-xO2-xFx (x = 0-0.3). Detailed advanced characterization (i.e., neutron total scattering and electron microscopy) and modelling efforts (i.e., Reverse Monte Carlo simulations) to understand how SRO impacts cathode performance will be presented. Different choice of precursors based on thermodynamic and kinetic consideration that minimizes formation of LiF impurity phases will be proposed.AcknowledgmentThis work was supported by the Assistant Secretary for Energy Efficiency and Renewable Energy, Vehicle Technologies Office, under the Applied Battery Materials Program, of the U.S. Department of Energy under Contract No. DE-AC05-00OR22725

Removing roadblocks and opening new opportunities for MXenes

The 2D carbides and nitrides, known as MXenes, are among the most recent, and quickly expanding, material families. The field is experiencing very fast growth with the number of papers on MXenes roughly doubling every year since their discovery in 2011. Great progress in synthesis and control of MXene properties has since been achieved. Synthesis of numerous theoretically predicted MXenes, including ordered solid solutions and high-entropy structures, led to the exploration of numerous applications. MXenes are not only promising candidates for energy storage and related electrochemical applications, such as electrocatalysis, but also applications in optoelectronics, plasmonics, electromagnetic interference shielding, medicine, sensing, catalysis and water desalination. We particularly focus on key material manufacturing and stability issues. We describe the scalable synthesis of MXenes by selective etching in aqueous acidic solutions; alternative synthesis methods, particularly fluorine-free synthesis; delamination without the use of organic intercalants; and improving the environmentally stability and shelf life of MXenes in colloidal suspensions. Finally, we discuss the current understanding of electronic transport in MXene films, which is of critical importance for many MXene applications.

Microwave-Assisted Synthesis of Sulfide Solid Electrolytes for All-Solid-State Sodium Batteries

Sulfide-based solid electrolytes are one of the potential candidates for all-solid-state batteries due to their high ionic conductivity and low synthesis temperature compared to their oxide counterparts. However, the preparation methods involve the requirement of an inert atmosphere for ball milling, heating, and quenching facilities that severely limit their implementation, which necessitates a resurgence of interest in alternate synthesis approaches. Herein, a simple, accelerated, and energy-efficient method for the synthesis of highly crystalline cubic sodium thiophosphate solid electrolyte (Na3PS4) is developed using the microwave-assisted irradiation technique. Along with impedance studies, 23Na solid-state NMR spin-lattice relaxation experiments are performed to obtain insights into Na-ion mobility in Na3PS4 solid electrolytes. The electrochemical properties and the interfacial stability of the electrolyte with the metallic sodium anode are thoroughly investigated and presented in this work. Further, a prototype full-cell constructed using a Na3V2(PO4)3 cathode, a Na3PS4 solid electrolyte, and a modified sodium anode showed promising electrochemical properties. Although numerous studies focus on solid electrolyte interface modification and design, the simple and energy-efficient approach for sodium-ion solid electrolyte synthesis presented here will provide a meaningful advance to the accelerated synthesis of sulfide electrolyte-based all-solid-state batteries.

A Review of the Green Synthesis of ZnO Nanoparticles Utilising Southern African Indigenous Medicinal Plants.

Metal oxide nanoparticles (NPs), such as zinc oxide (ZnO), have been researched extensively for applications in biotechnology, photovoltaics, photocatalysis, sensors, cosmetics, and pharmaceuticals due to their unique properties at the nanoscale. ZnO NPs have been fabricated using conventional physical and chemical processes, but these techniques are limited due to the use of hazardous chemicals that are bad for the environment and high energy consumption. Plant-mediated synthesis of ZnO NPs has piqued the interest of researchers owing to secondary metabolites found in plants that can reduce Zn precursors and stabilise ZnO NPs. Thus, plant-mediated synthesis of ZnO NPs has become one of the alternative green synthesis routes for the fabrication of ZnO NPs. This is attributable to its environmental friendliness, simplicity, and the potential for industrial-scale expansion. Southern Africa is home to a large and diverse indigenous medicinal plant population. However, the use of these indigenous medicinal plants for the preparation of ZnO NPs is understudied. This review looks at the indigenous medicinal plants of southern Africa that have been used to synthesise ZnO NPs for a variety of applications. In conclusion, there is a need for more exploration of southern African indigenous plants for green synthesis of ZnO NPs.

Synthesis of MAX phase-based ceramics from early transition metal hydride powders

MAX phase ceramics are typically prepared by the reactive sintering of elemental powders that are often coarse, expensive, and prone to oxidation. The temperature-driven dehydrogenation of metal hydride powders offers an alternative synthesis approach, as the hydrides decompose into phase-pure, dimensionally fine elemental powder particles. The increased reactivity of these in situ formed, fine powder particles drastically reduces the formation temperature of the antecedent intermetallic phases, without forming excess binary carbides or facilitating powder oxidation in the Ti-Al-C and Zr-Al-C systems. This work elucidates the effect of metal hydrides on the sequence of formation reactions in MAX phase ceramics. In the Zr-Al-C system, the use of coarse, oxidation-prone elemental Zr powders prevented MAX phase formation, whereas spark plasma sintering of ZrH2 powders at 1500 °C produced ceramics containing 60 wt% Zr3AlC2. Similarly, in the Ti-Al-C system, spark plasma sintering of TiH2 powders at 1200 °C produced phase-pure Ti3AlC2 ceramics.

Photo‐Mediated Reduction of Carbon Dioxide to Formic and Other Carboxylic Acids by Ni‐Catalysis with Chelating Ligand

In this minireview, photo-mediated reductions of CO2 to formic and other carboxylic acids by Ni-chelate catalysts were discussed with mechanistic details. Formic and other carboxylic acid products are formed exclusively over CO by insertion of CO2 in Ni−H/Ni−C bonds in these Ni-catalysed light-mediated CO2 reductions. Role of chelating ligands in modulating the catalytic efficiency and product selectivity of such catalysis has also been encompassed in the minireview.

Green methodologies for the synthesis of 2-aminothiophene.

Pollution and the rising energy demand have prompted the design of new synthetic reactions that meet the principles of green chemistry. In particular, alternative synthesis of 2-aminothiophene have recently focused interest because 2-aminothiophene is a unique 5-membered S-heterocycle and a pharmacophore providing antiprotozoal, antiproliferative, antiviral, antibacterial or antifungal properties. Here, we review new synthetic routes to 2-aminothiophenes, including multicomponent reactions, homogeneously- or heterogeneously-catalyzed reactions, with focus on green pathways.

Reductive SN 2' Reaction of Epoxydienoate with Borane and its Application to the Synthesis and Structural Revision of an Antitumor Active Torrubiellutin Analogue.

A reductive SN 2' reaction of epoxydienoates and epoxyenoates with borane was developed to afford skipped dienoates and unconjugated enoates with trisubstituted Z-alkene linked to asymmetric centers on one side or both sides. This reaction was successfully applied to the alternative synthesis of an antitumor active artificial analogue of torrubiellutin C. A geometric isomer for α,β-unsaturated amide of the artificial analogue was also synthesized. These syntheses clarified the true structure of the antitumor active artificial analogue of torrubiellutin C.

Synthesis, and Cytotoxic Activity of Novel Pyrazoline-Thiazolidinone Derivatives with Molecular Docking Studies

1-(4-substitutesd)-2-(5-phenyl-3-(1H-pyrrol-2-yl)-4,5-dihydropyrazol-1-yl)thiazol-5-yl)-2-aryldiazene 9a-f were prepared through reactions of 5-phenyl-3-(1H-pyrrol-2-yl)-4, 5-dihydropyrazole-1-carbothioamide 5 with hydrazonoyl halides. Furthermore, thioamide 5 was utilized as starting materials for thiazolidone synthesis 10 and arylidene thiazoles 15a–c. Also pyran derivatives 12a-b, 13a-b,14a-b and thioanilide derivaives 16 were obtained from the reaction of thiazilidone 10 with arylidenemalononitrile and phenyl isothiocyanat, respectively. When possible, the structures of experimentally synthesized compounds were identified by elemental analysis, spectral analysis, and alternative synthesis routes. Some of the synthesized compounds as 9f, 10, 12b, and 16 were screened for their cytotoxicity against MCF-7 and HCT-116 cells using the MTT assay. They exhibited remarkable cytotoxic activities with promising IC50 values. Interestingly, compound 16 exhibited potent cytotoxicity against MCF-7 and HCT-116 with IC50 values of 5.05 and 3.08 μM, compared to doxorubicin with IC50 values of 7.27 and 8.92 μM, respectively show interesting biological activities as anticancer activities. Additionally, the tested compounds were nontoxic against WISH cells with higher IC50 values. Hence, these compounds may serve as potent and selective cytotoxic agents.

Microbial communities and biosynthetic pathways for the production of sulfated polysaccharides in the activated sludge system

Sulfated polysaccharides (SP) are widely used as industrial additives and pharmaceutical intermediates. As SP can only be extracted from sea algae, making them scarce raw materials. Recently, SP have been detected and extracted from the waste activated sludge of a saline secondary wastewater treatment plant, suggesting that there are alternative primary producers and synthesis pathways of the SP within the biological activated sludge. This study aimed to identify the primary SP producers, the SP biosynthesis pathways as well as the SP production rates in different types of activated sludges cultivated anoxically and/or anaerobically, with and without the presence of sufficient sulfate. The results showed that alternating anaerobic/anoxic conditions in sludge effectively produced the SP by the ordinary heterotrophic organisms (OHOs). The synthesis pathways for the three most common bioactive SP viz. fucoidan, carrageen, and heparin, were identified and elucidated at both the substrate and enzymatic levels. The Western Blot analyses revealed key enzymes for the SP synthesis (e.g., GDP-L-fucose-synthetase, GDP-fucose-pyrophosphorylase, β-1,4-galactosyltransferase), when sulfate was sufficient (>170 mg S/L) under an alternating anaerobic/anoxic conditions. In contrast, the absence of sulfate suppressed the SP production during the initial step of the SP generation. The synthesis of the SP in the sulfate-reducing (anaerobic) sludge was suppressed by the enzymatic inhibition, when sulfide exceeded 160 mg S/L, due to the competition for energy between the SP synthesis and sulfide detoxification. However, in the case of the sulfide-oxidizing sludge both the organic carbon and metabolism energy deficiencies inhibited the SP production. The findings of this study expand the understandings of the SP synthesis in the activated sludge under different operating conditions, including different sulfate levels.

Trinuclear Magnesium Imidazolate Borohydride Complex.

A new type of hybrid compound, combining properties of MOFs and borohydrides, was synthesized solvothermally using Mg(BH4)2 and imidazole as precursors. Material in the form of acetonitrile solvate with formula [Mg3{(Im)BH2(Im)}6(ImH)6]·CH3CN crystallizes in the space group R3̅, having the unit cell parameters a = 15.1942(2) Å and c = 28.3157(3) Å as determined by single crystal X-ray diffraction. The structure was further investigated by solid-state NMR and DFT quantum chemical calculations. The main feature of the structure, reported here for the first time, is a linear trinuclear complex, where octahedrally nitrogen-coordinated Mg2+ ions are bridged with {(Im)BH2(Im)}− units, forming inside voids of 4.6 Å in diameter between the magnesium ions. Polar intermolecular interactions hold the molecules in a dense rhombohedral stacking, where a disordered acetonitrile molecule plays a cohesive role. The compound is stable in air and upon heating to about 160 °C. Using an alternative synthesis method from an imidazole melt, an imidazole solvate with the formula [Mg3{(Im)BH2(Im)}6(ImH)6]·ImH and a very similar crystal structure to acetonitrile solvate was prepared. It is stable up to 220 °C. Upon further heating, it transformed into a layered structure with the formula Mg(Im3BH)2, space group P3̅1c, and unit cell parameters a = 8.7338(9) Å and c = 17.621(2) Å determined by synchrotron powder diffraction. Besides its structural novelty, two types of potentially reactive hydrogens, bonded to boron and nitrogen in the same molecule, make the material highly interesting for future investigations in the fields of energy storage applications.

(Digital Presentation) Sol-Gel Based Synthesis Route for High Capacity Disordered Rocksalt (DRX) Oxyfluoride Cathodes

The cost and energy density of commercial Li-ion batteries (LIBs) are largely limited by the cathode. Currently, the LIB cathode market is dominated by intercalation type layered transition metal oxides of the general form LiNixMnyCo1-x-yO2 (NMC). As the LIB market continues to grow, there is an increasing risk of over-reliance on cobalt and nickel, which not only leads to increased cost and resource depletion, but also raises ethical concerns related to the cobalt mining industry. Hence, there is an urgent need to develop new cathodes based on earth abundant materials. Disordered rocksalt (DRX) oxides and oxyfluorides have emerged as a promising candidate for next generation LIB cathodes due to their high energy density and ability to utilize low-cost, earth abundant elements such as Mn and Ti. Studies have shown that anionic substitution of oxygen with fluorine enhances electrochemical performance and cycling stability of DRX cathodes. DRX cathodes are traditionally synthesized using high temperature solid-state and high energy mechanochemical routes. While these methods have yielded promising cathodes, they face challenges with fluorine substitution and process scalability. Keeping this in mind, the goal of this research is to develop alternate synthesis routes to prepare DRX oxyfluoride cathodes and identify key structure – property correlations to optimize cathode performance. Our team recently developed a sol-gel based approach to synthesize Li1.2MnxTi0.8-xO2-yFy (y=0-0.2; x=0.4-0.6) DRX oxides and oxyfluorides. This presentation will discuss recent development related to the synthesis, structure, and performance of these cathodes Acknowledgements This research was conducted at Oak Ridge National Laboratory, managed by UT Battelle, LLC, for the U.S. Department of Energy (DOE) and is sponsored by the Office of Energy Efficiency and Renewable Energy (EERE) through the Vehicle Technologies Office (VTO).

Silver Ion-Induced Formation of Unprecedented Thorium Nonamer Clusters via Lacuna-Construction Strategy

Silver Ion-Induced Formation of Unprecedented Thorium Nonamer Clusters via Lacuna-Construction Strategy

Green Synthesis via Eucalyptus globulus L. Extract of Ag-TiO2 Catalyst: Antimicrobial Activity Evaluation toward Water Disinfection Process.

The problem of water pollution by persistent substances and microorganisms requires solutions that materials such as silver-modified titanium dioxide can provide due to their excellent photocatalytic and antimicrobial properties. However, the synthesis methods conventionally used to obtain these materials involve toxic chemical reagents such as sodium borohydride (NaBH4). The search for alternative synthesis methods that use environmentally friendly substances, such as the biosynthesis method, was evaluated. Silver-titanium dioxide (Ag-TiO2) was synthesized by a Eucalyptus globulus L. extract as a reductive agent through sol-gel and microwave-assisted sol-gel processes. Four different solvents were tested to extract secondary metabolites to determine their roles in reducing silver nanoparticles. Titanium dioxide nanoparticles with sizes from 11 to 14 nm were obtained in the anatase phase, and no narrowing of the bandgap was observed (3.1–3.2 eV) for the Ag-TiO2 materials compared with the pure TiO2. Interestingly, the bacterial inhibition values were close to 100%, suggesting an effective antimicrobial mechanism related to the properties of silver. Finally, by the physicochemical characterization of the materials and their antimicrobial properties, it was possible to obtain a suitable biosynthesized Ag-TiO2 material as a green option for water disinfection that may be compared to the conventional methods.

Alternative Synthesis of the Alkaloid Guvacine and Its Derivatives

Alternative Synthesis of the Alkaloid Guvacine and Its Derivatives

Alternative Synthesis of Cefamandole with Biocatalytic Acylation Catalyzed by Immobilized Cephalosporin-Acid Synthetase

The processes of the biocatalytic acylation of 1-methyl-5-mercapto-1,2,3,4-tetrazolil-7-amino-cephalosporanic acid (7-TMCA) and 7-aminocephalosporanic acid (7-ACA) by methyl ester of mandelic acid (MEMA) were optimized with an immobilized cephalosporin-acid synthetase as the biocatalyst. Under optimized conditions in water-organic medium containing 43% (vol/vol) of ethylene glycol at 30°С with a spontaneous pH gradient in the range of 8.0–6.0, the following yields of biocatalytic transformations were reached: (80.8 ± 1.9)% for 7‑TMCA acylation (at a concentration of 100–120 mМ) resulted in cefamandole (CFM) production, and (88.6 ± 2.0)% for 7-ACA acylation of (at concentration of 140–170 mМ) resulted in a semiproduct of CFM (S-p CFM) formation. In the second process, the concentration of the target β-lactam product in the final reaction mixture is one and a half times higher than that with the first one. In light of the undoubted environmental benefits of the chemical transformation of S-p CFM to CFM over the process of the chemical production of 7-TMCA from 7-ACA, we conclude that the second pathway of combined chemical and biocatalytic CFM synthesis is preferable.