Synthesized Research Articles

Redox-Induced Aromatic Substitution: A Study on Guanidino-Functionalized Aromatics.

Aromatic substitution of redox-active aromatic compounds could be initiated by a preceding redox step. We report on the different reaction pathways of such redox-induced substitution (RIAS) reactions between a redox-active guanidino-functionalized aromatic molecule (GFA) and an amine or guanidine. Oxidation of the GFA leads to an umpolung of the guanidine from a nucleophile to an electrophile and thereby enables addition of the amine or guanidine. Several examples are given, demonstrating the use of redox substitution in synthetic chemistry, e.g. for the convenient synthesis of novel N-heteropolycyclic molecules and unsymmetrically-substituted aromatics.

Copper-catalyzed perfluoroalkylation of propargyl gem-dichlorides.

Herein, we present a highly efficient copper-catalyzed protocol for transforming propargyl gem-dichlorides into the corresponding chloro-substituted fluoroalkylated allenes. This protocol demonstrates a broad substrate scope and excellent tolerance towards various functional groups. Moreover, the strategy of utilizing the chloro-substituted pentafluoroethylation allenes for multiple transformations has shown significant value in synthetic chemistry.

Building Ultrastrong, Tough and Biodegradable Thermoplastic Elastomers from Multiblock Copolyesters via a "Reserve-Release" Crystallization Strategy.

Simultaneously attaining high strength and toughness has been a significant challenge in designing thermoplastic elastomers, especially biodegradable ones. In this context, we present a class of biodegradable elastomers based on multiblock copolyesters that afford extraordinary strength, toughness, and low-strain resilience despite expedient chemical synthesis and sample processing. With the incorporation of the semi-crystalline soft block and the judicious selection of block periodicity, the thermoplastic materials feature low quiescent crystallinity ("reserve") albeit with vast potential for strain-induced crystallization ("release"), resulting in their significantly enhanced ultimate strength and energy-dissipating capabilities. Moreover, a breadth of mechanical responses of the materials - from reinforced elastomers to shape-memory materials to toughened thermoplastics - can be achieved by orthogonal variation of segment lengths and ratios. This work and the "reserve-release" crystallization strategy herein highlight the double crystalline multiblock chain architecture as a potential avenue towards reconciling the strength-toughness trade-off in thermoplastic elastomers and can possibly be extended to other biodegradable building blocks to deliver functional materials with diverse mechanical performances.

Chemical synthesis of NiO nanoparticles from Solanum trilobatum leaf extract for antibacterial and cytotoxic properties

The chemical precipitation approach was employed to synthesize Nickel oxide nanoparticles (NiONPs) using Solanum trilobatum leaf extract as the stimulant and Nickel nitrate as the precursor. The Nickel oxide is examined using a range of characterization methods including X-ray diffraction, Fourier Transform Infrared spectroscopy, High-Resolution Transmission Electron Microscopy, High-Resolution Scanning Electron Microscopy, X-ray photoelectron spectroscopy, Thermo gravimetric Analysis/Derivative Thermo gravimetric Analysis, Diffuse Reflectance Spectroscopy, cytotoxicity and antimicrobial investigations The X-ray diffraction examination determined that the average size of the crystals increases as the quantities of leaf extract in the NiO2 composites rise. The decrease in line broadening (β) value and the increase in leaf extract concentrations may be the cause of this phenomenon. The FTIR spectrum confirms that the as-synthesized NiO-NPs are of great purity and match well with the XRD pattern. The thermal stability of the synthesized samples was determined using TGA/DTG analysis. The analysis was conducted in an air atmosphere, with the temperature increasing at a rate of 10°C per minute. The temperature range for the analysis was from room temperature to 750°C. The optical properties are determined by the use of Diffuse Reflectance Spectroscopy, which examines the coordinated movement of electrons in the conduction band when exposed to electromagnetic waves. Rat skeletal muscle cell line and SKMEL cancer cells were cultured on 96-well plates and incubated at 37°C and 5 % CO2 for 24 hours to allow them to adapt to the culture conditions. An investigation was conducted to assess the antibacterial properties of synthesized nanocomposites against two types of bacteria: gram-positive Staphylococcus aureus (MTCC No: 87) and gram-negative Escherichia coli (MTCC No: 443), in order to explore their potential for biological applications.

Biosynthesis of novel non-proteinogenic amino acids β-hydroxyenduracididine and β-methylphenylalanine in Escherichia coli

Non-proteinogenic amino acids (npAAs) are valuable building blocks for the development of advanced pharmaceuticals and agrochemicals. The surge in interest in their synthesis is primarily due to the potential to enhance and diversify existing bioactive molecules. This can be achieved by altering these bioactive molecules to improve their effectiveness, reducing resistance compared to their natural counterparts or generating molecules with novel functions. Traditional production of npAAs in native hosts requires specialized conditions and complex cultivation media. Furthermore, these compounds are often found in organisms that challenge genetic manipulation. Thus, the recombinant production of these npAAs in a model organism like Escherichia coli paves the way for groundbreaking advancements in synthetic biology. Two synthetic operons, comprising of five heterologous proteins were genomically integrated into E. coli for the synthesis of npAAs β-methylphenylalanine (BmePhe), β-hydroxyenduracididine (BhEnd), and enduracididine (End). Proteomic and metabolomic analysis confirmed production of these compounds in E. coli for the first time. Interestingly, we discovered that the exogenous addition of pathway precursors to the E. coli system enhanced the yield of BmePhe by 2.5 times, whereas it concurrently attenuated the production of BhEnd and End, signifying a selective precursor-dependent yield enhancement. The synthetic biology landscape is broadened in this study by expanding the repertoire of amino acids beyond the conventional set of 22 standard proteinogenic amino acids. The biosynthesized npAAs, End, BhEnd, and BmePhe hold promise for engineering proteins with modified functions, integrating into novel metabolites and/or enhancing biological stability and activity. Additionally, these amino acids’ biological production and subsequent purification present an alternative to traditional chemical synthesis methods, paving a direct pathway for pharmacological evaluation.

Chemical Design of Spin Frustration to Realize Topological Spin Glasses.

Patterning spins to generate collective behavior is at the core of condensed matter physics. Physicists develop techniques, including the fabrication of magnetic nanostructures and precision layering of materials specifically to engender frustrated lattices. As chemists, we can access such exotic materials through targeted chemical synthesis and create new lattice types by chemical design. Here, we introduce a new approach to induce magnetic frustration on a modified honeycomb lattice through a competition of alternating antiferromagnetic (AFM) and ferromagnetic (FM) nearest-neighbor interactions. By subtly modulating these two types of interactions through facile synthetic modifications, we created two systems: (1) a topological spin glass and (2) a frustrated spin-canted magnet with low-temperature exchange bias. To design this unconventional magnetic lattice, we used a metal-organic framework (MOF) platform, Ni3(pymca)3X3 (NipymcaX where pymca = pyrimidine-2-carboxylato and X = Cl, Br). We isolated two MOFs, NipymcaCl and NipymcaBr, featuring canted Ni2+-based moments. Despite this similarity, differences in the single-ion anisotropies of the Ni2+ spins result in distinct magnetic properties for each material. NipymcaCl is a topological spin glass, while NipymcaBr is a rare frustrated magnet with low-temperature exchange bias. Density functional theory calculations and Monte Carlo simulations on the NipymcaX lattice support the presence of magnetic frustration as a result of alternating AFM and FM interactions. Our calculations enabled us to determine the ground-state spin configuration and the distribution of spin-spin correlations relative to paradigmatic kagomé and triangular lattices. This modified honeycomb lattice is similar to the electronic Kekulé-O phase in graphene and provides a highly tunable platform to realize unconventional spin physics.

Terpyridine Ni(II) Complex Grafted CdS Nanorods for Cooperative Selective Benzyl Alcohol Oxidation and Hydrogen Production.

Efficient utilization of photogenerated charge carriers to realize photocatalytic solar fuel production and oxidative chemical synthesis is a challenging task. Herein, a conventional amidation reaction route is adopted to successfully construct a novel composite photocatalyst composed of a Ni(II)-terpyridine complex with carboxyl groups grafted on CdS nanorods (labeled as CdS@Ni(terpyC)2). Experimental results have unequivocally revealed that the as-fabricated composite catalyst exhibited a remarkable enhancement in photocatalytic activity for the dehydrogenation of benzyl alcohol under visible light, demonstrating superior hydrogen evolution efficiency and benzaldehyde selectivity, surpassing both pristine CdS and the blend of CdS and Ni(terpyC)2. The carrier dynamics study demonstrated that the Ni(terpyC)2 on the surface of CdS could quickly extract the photogenerated electrons of CdS, which reduced the carrier recombination efficiency, further improving the photocatalytic activity of the catalyst. This work illustrates the effect of surface active site engineering on photocatalysis and is expected to shed substantial inspiration on future surface modulation and design of semiconductor photocatalysts.

Protein–Polymer Conjugates: Advancing Enzyme Catalysis in Synthetic Chemistry

AbstractEnzyme catalysis is prominent in chemical synthesis due to its specificity, selectivity, and efficiency. However, enzymes often face challenges, such as inactivation and inhibition in practical applications, and they are also limited by narrow reaction scopes in complex catalytic scenarios like cascade reactions. These persistent issues have driven the development of chemical modifications of enzymes, aiming to enhance enzyme catalysis with external chemical entities. Polymers are particularly notable among these entities for their functional moieties and protective effects on biomolecules, enhancing enzyme properties, and even creating new‐to‐nature catalysis by harnessing catalytic promiscuity. This concept aims to introduce the field of protein–polymer conjugates for diverse emerging applications across emulsion biocatalysis, artificial enzymes, and supramolecular enzyme catalysis.

Emergence of a distinct mechanism of C-N bond formation in photoenzymes.

C-N bond formation is integral to modern chemical synthesis due to the ubiquity of nitrogen heterocycles in small-molecule pharmaceuticals and agrochemicals. Alkene hydroamination with unactivated alkenes is an atom economical strategy for constructing these bonds. However, these reactions are challenging to render asymmetric when preparing fully substituted carbon stereocenters. Here, we report a photoenzymatic alkene hydroamination to prepare 2,2-disubstituted pyrrolidines by a Baeyer-Villiger Monooxygenase. Five rounds of protein engineering afforded a mutant, providing excellent product yield and stereoselectivity. Unlike related photochemical hydroaminations, which rely on the oxidation of the amine or alkene for C-N bond formation, this work exploits a through-space interaction of a reductively generated benzylic radical and the nitrogen lone pair. This antibonding interaction lowers the oxidation potential of the radical, enabling electron transfer to the flavin cofactor. Experiments indicate that the enzyme microenvironment is essential in enabling a novel C-N bond formation mechanism with no parallel in small molecule catalysis. Molecular dynamics simulations were performed to investigate the substrate in the enzyme active site which further support this hypothesis. This work is a rare example of an emerging mechanism in non-natural biocatalysis, where an enzyme has access to a mechanism that its individual components do not. Our study showcases the potential of enhancing emergent mechanisms using protein engineering to provide unique mechanistic solutions to unanswered challenges in chemical synthesis.

Expanding the “Terpenome”: Applications of Unspecific Peroxygenases (UPOs) in Oxidations of Unnatural Terpenoids

AbstractAn unnatural tricyclic oxaterpenoid, obtained by treatment of the sesquiterpene synthase presilphiperfolan‐8β‐ol synthase (BcBOT2) with an unnatural farnesyl pyrophosphate ether derivative, itself obtained by chemical synthesis, was converted in oxidation studies as part of a broad screening program by selected unspecific peroxygenases (UPOs). Product analysis revealed that Agrocybe aegerita UPO, its mutant PaDa‐I, and two commercial ones, UPO54 and UPO49, provided new oxidation products with sufficient efficiency for subsequent upscaling that allowed product isolation and structure elucidation. As such new terpene‐based oxiranes and hemiacetals were formed by UPO‐mediated epoxidations and CH‐activation. The structure elucidation was further supported by comparison with products generated by chemical oxidation.

Isoniazid Hybrids As Potential Antitubercular Agents

AbstractThe rapid emergence of various forms of drug‐resistant tuberculosis (TB) has massively impacted people's health globally. According to the WHO, TB care and facilities have been downgraded by 21% since the COVID‐19 pandemic, which has further slowed down the progress toward the “End TB Strategy.” Multiple studies have shown drug‐resistant tuberculosis to be resilient to front‐line antituberculosis drugs, including isoniazid (INH), thus constantly prompting researchers worldwide to probe new potent chemical entities to replace/supplement the current artillery of anti‐TB therapeutics. The molecular hybridization (MH) technique has recently been adopted by many synthetic and medicinal chemists to combine different pharmacophoric units into a single molecular architecture which in most cases has been reported to exhibit a better pharmacological profile as compared to its precursors. The present review provides a concise account of the MH hybridization strategies directed at the structural manipulations of isoniazid to develop new anti‐TB agents and their structure‐activity relationships. Furthermore, their toxicity profiles and docking studies with relevant receptors are also briefly discussed.

Microwave‐Assisted, Multicomponent Synthesis of Pyrazolo [3, 4‐b] Pyridines Under Green Conditions

AbstractDeveloping novel and environmentally friendly green methodologies are critical in synthetic organic chemistry. Here, we investigated the one‐pot, efficient green synthesis of pyrazolo[3,4‐b]pyridine derivatives via a multicomponent approach. The reactions were operated in an aqueous medium by using microwave irradiation and conventional protocols. The green protocol offered high yields of desired product in swift reaction time, and good tolerance under reaction conditions.

Retraction Note: Advancing chemical sensors synthesis and classification for the integration of mems optical phased array in polymer nanocomposites

Retraction Note: Advancing chemical sensors synthesis and classification for the integration of mems optical phased array in polymer nanocomposites

Surface Cation Cross‐Locking Enables Non‐Destructive “On‐Demand” Synthesis of Anion‐Exchanged CsPbX3 Perovskite Nanocrystals

AbstractPost‐synthetic halide anion exchange is considered a “double‐edged sword” for perovskite nanocrystals (PNCs), which offer unique access to color tunability while bringing about surface defects. Herein, a novel surface cation cross‐locking (SCCL) strategy is proposed to achieve the anion‐exchanged CsPbX3 PNCs (X is Cl, Br, I) with non‐destructive emissions. This is achieved using a dendritic ligand of Pentaerythritol tetrakis (3‐mercaptopropionate) (PETMP) as a surface cross‐locker, which can form the multiple coordination to the surface Pb cation of octahedral [PbX6]4− during the fast halide anion exchange via four end‐thiolates and four side‐carboxylates. As a result, the red‐ and blue‐emitting anion‐exchanged CsPbX3 PNCs exhibit high photoluminescence quantum yield (PLQY) values of >97%, close to the parent green‐emitting CsPbBr3 PNCs. Moreover, the “on‐demand” synthesis of anion‐exchanged CsPbX3 PNCs is also performed via autonomous robotic in‐flow experimentation. This work provides a new general post‐synthetic way for the full‐color CsPbX3 PNCs with compositions that are inaccessible via direct synthetic routes.

Enzymatic and Bio-Inspired Enantioselective Oxidation of Non-Activated C(sp 3)–H Bonds

AbstractThe enantioselective oxidation of C–H bonds relies on two different approaches: the use of enzymes or bio-inspired transition metal catalysts. Both are powerful tools, as they transform ubiquitous C(sp3)–H bonds into valuable oxygenated building blocks. However, the reaction remains a challenge in synthetic chemistry, continuously demanding efficient catalytic systems to improve substrate scopes. Optimization of site- and enantioselectivities in bio-catalytic systems is underpinned by protein engineering, while ligand design and medium effects play crucial roles in bio-inspired synthetic complexes. In this Short Review, recent advances in the field are described, focusing on reactions that target strong, non-activated C–H bonds.1 Introduction1.1 Enantioselective Catalytic C–H Oxidation in Nature and Bio-Inspired Systems1.2 Biological C–H Oxidation Mechanism and Challenges for the Implementation of Chirality with Synthetic Catalysts1.3 Bio-Catalytic C–H Oxidation Systems: From Microorganism to Engineered Enzymes1.4 Mimicking Nature: The Bio-Inspired C–H Oxidation Approach1.5 Origin of Enantioselectivity2 Enantioselective C–H Oxidation of Non-Activated C–H Bonds2.1 Hydroxylation at Non-Activated C–H Bonds by Bio-Catalytic Systems2.2 Enantioselective C–H Lactonization with Enzymatic Systems2.3 Oxidation at Non-Activated C–H Bonds by Synthetic Catalysts2.4 Enantioselective Lactonization with Small-Molecule Catalysts3 Conclusions

Chemical Synthesis, Herbicidal Activity, Crop Safety, and Molecular Basis of ortho-Fluoroalkoxy Substituted Sulfonylureas as Novel Acetohydroxyacid Synthase Inhibitors.

In the face of increasing resistance to the currently used commercial herbicides and the lack of success in identifying new herbicide targets, alternative herbicides need to be developed to control unwanted monocotyledon grasses in food crops. Here, a panel of 29 novel sulfonylurea-based compounds with ortho-fluoroalkoxy substitutions at the phenyl ring were designed and synthesized. Pot assays demonstrated that two of these compounds, 6d and 6u, have strong herbicidal activities against Echinochloa crus-galli, Eleusine indica, Alopecurus aequalis, and Alopecurus japonicus Steudel at a dosage of 15 g ha-1. Furthermore, these two compounds exhibited <5% inhibition against wheat at a dosage of 30 g ha-1 under post-emergence conditions. 6u also exhibited <5% inhibition against rice at a dosage of 30 g ha-1 under both post-emergence and pre-emergence conditions. A kinetics study demonstrated that 6d and 6u are potent inhibitors of Arabidopsis thaliana acetohydroxyacid synthase (AHAS; EC 2.2.1.6) with potent Ki values of 18 ± 1.1 and 11.9 ± 4.0 nM, respectively. The crystal structure of 6u in complex with A. thaliana (At)AHAS has also been determined at 2.7 Å resolution. These new compounds represent new alternative herbicide choices to protect wheat or rice from invading grasses.

Chemical synthesis, in vitro testing and in silico Nampt-based molecular docking of novel aniline aromatic ring-substituted 2-Aminothiazole analogues.

The heterocyclic 2-Aminothiazoles scaffolds are used in a wide range of therapeutic applications against various diseases for its antioxidant, anti-inflammatory, antimicrobial and anticancer actions. In the present study, we synthesized novel aniline aromatic ring-substituted 2-Aminothiazole derivatives. Molecular docking was performed using Glide module of the Schrödinger Suite to fit compounds JG-49, JG-62, and KBA-18 against the Nicotinamide phosphoribosyl transferase (Nampt) enzyme, an intracellular regulator of Nicotinamide adenine dinucleotide (NAD) redox cofactor involved in energy metabolism and epigenetics and are implicated in aging and metabolic diseases. The three compounds viz. JG-49, JG-62, and KBA-18 showed an increase in Nampt enzymatic activity in vitro. All three substituted derivatives of 2-Aminothiazole showed no cytotoxicity with the mouse C2C12 myoblasts cultures assessed with the MTT cell viability assay. Moreover, the wound closure of the mouse C2C12 myoblasts in vitro displayed no significant difference between the treatment groups of the 2-Aminothiazole derivatives compared with the control naïve and DMSO treated myoblasts cultures, except for the 2-Aminothiazole substituted derivatives JG-62 and KBA-18, which showed a significant increase in the wound closure compared with the control cells at different concentrations. Taken together, we demonstrated that 2-Aminothiazole substituted derivatives provide enhanced Nampt activity, wound closure, and no cytotoxic effects in vitro. Further studies will allow to improve the substitution of 2-Aminothiazole derivatives and test their potential therapeutic applications.

Lower-Carbon Hydrogen Production from Wastewater: A Comprehensive Review

Hydrogen has the capability of being a potential energy carrier and providing a long-term solution for sustainable, lower-carbon, and ecologically benign fuel supply. Because lower-carbon hydrogen is widely used in chemical synthesis, it is regarded as a fuel with no emissions for transportation. This review paper offers a novel technique for producing hydrogen using wastewater in a sustainable manner. The many techniques for producing hydrogen with reduced carbon emissions from wastewater are recognized and examined in detail, taking into account the available prospects, significant obstacles, and potential future paths. A comparison of the assessment showed that water electrolysis and dark fermentation technologies are the most effective methods for hydrogen generation from wastewater, with microbial electrolysis and photofermentation. Thus, the incorporation of systems that are simultaneously producing lower-carbon hydrogen and meant for wastewater treatment is important for the minimization of emissions from greenhouse gases and recovering the energy utilized in the treatment of wastewater.

Dehydrogenative Coupling Reactions with Guanidino-Functionalized Aromatics.

Dehydrogenative coupling (DC) reactions are of importance for the construction of new carbon-element bonds in synthetic organic chemistry. In this work, we report on the synthesis and characterization of several redox-active guanidino-functionalized aromatic molecules (GFAs) for use in DC (C-C and C-O) reactions. In a systematic approach, we first characterize the new DC reagents in all relevant redox and protonation states, and compare their performance in competitive test proton-coupled electron transfer (PCET) reactions. Then, their use in four different DC reactions with different mechanisms is evaluated.

Xylochemical synthesis of diarylated heterocycles

The production of (hetero)aromatic fine chemicals heavily relies on base chemicals sourced from petroleum. The concept of xylochemistry focuses on using compounds derived from wood and other plant materials as building blocks for chemical synthesis, thereby reducing our dependence on fossil carbon. In this study, we demonstrate that the xylochemical apocynin can be readily converted into several diarylated heterocycles that resemble molecules of interest in medicinal, materials, and natural product chemistry. In all cases, the heteroatoms (O, N, S) can be sourced from biorenewable resources and as a result, every atom in all the products can be considered biogenic.