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ORAL drug administration, NANOSTRUCTURED materials, MAGNETIC nanoparticles, TRANSMISSION electron microscopy, NANOPARTICLE toxicity, RIETVELD refinement, and TRANSCRANIAL magnetic stimulation

Assessing the biocompatibility of magnetic nanoparticles for biomedical applications is highly demanded and attracted an increasing interest in the last years. We, herein report the synthesis, physical characterization, and biocompatibility of CoFe (2-x-y-z) Gd x Sm y Ho z O 4 (x = y = z = 0, 0.01) nanoparticles (NPs) synthesized by the auto-combustion method for the first time. The physicochemical and magnetic properties of the synthesized nanoparticles were fully characterized using various techniques including X-ray diffraction (XRD), Fourier transforms infrared spectra (FTIR), scanning electron microscopy (SEM), Transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM). A single-phase with a space group Fd-3m and mixed spinel structure were confirmed by XRD, Rietveld analysis, and the cation distribution study. FTIR confirms the formation of the crystallographic sites of the spinel structure, namely the octahedral site and the tetrahedral site. The nanoparticles exhibited a quasi-spherical shape with size distribution (24–51 nm). VSM measurements reveal that magnetic properties can be tuned by doping for biomedical applications. To evaluate the safety of our nanoparticle sub-chronic toxicity was highlighted in Wistar rats by oral administration at doses of 500, 250,125, and 50 mg/kg and by intraperitoneal injection at doses of 40,20,10, and 5 mg/kg. Results showed no significant changes in the hematological parameters, serum biochemical system, organ weight, and histopathological examination (p > 0,05) for doses below 250 mg/kg and 40 mg/kg administered orally or by intraperitoneal injection respectively. The results of the current study suggesting that treatment with the nanoparticle for 28 days does not produce any significant toxicity in the male and female rats for the either using voices (oral, intraperitoneal) except at high doses. These findings reported here strongly suggest that the as-prepared nanoparticles can be used in several biomedical applications, including separation and purification, drug delivery, imaging (MRI contrast), and therapy (hyperthermia). [ABSTRACT FROM AUTHOR]

BRONSTED acids, PHOSPHORIC acid, PHASE-transfer catalysis, COVALENT bonds, QUINOLINE, ACIDS, FLUORINATION, and CATALYSIS

The linking of phosphoric acids via covalent or mechanical bonds has proven to be a successful strategy for the design of novel organocatalysts. Here, we present the first systematic investigation of singly‐linked and macrocyclic bisphosphoric acids, including their synthesis and their application in phase‐transfer and Brønsted acid catalysis. We found that the novel bisphosphoric acids show dramatically increased enantioselectivities in comparison to their monophosphoric acid analogues. However, the nature, length and number of linkers has a profound influence on the enantioselectivities. In the asymmetric dearomative fluorination via phase‐transfer catalysis, bisphosphoric acids with a single, rigid bisalkyne‐linker give the best results with moderate to good enantiomeric excesses. In contrast, bisphosphoric acids with flexible linkers give excellent enantioselectivities in the transfer‐hydrogenation of quinolines via cooperative Brønsted acid catalysis. In the latter case, sufficiently long linkers are needed for high stereoselectivities, as found experimentally and supported by DFT calculations. [ABSTRACT FROM AUTHOR]

POLYMERIZATION, RENEWABLE natural resources, MONOMERS, DEPOLYMERIZATION, PETROLEUM, LIGNINS, and AMMONIA

The complete utilization of all lignin depolymerization streams obtained from the reductive catalytic fractionation (RCF) of woody biomass into high-value-added compounds is a timely and challenging objective. Here, we present a catalytic methodology to transform beech lignin-derived dimers and oligomers (DO) into well-defined 1,4-cyclohexanediol and 1,4-cyclohexanediamine. The latter two compounds have vast industrial relevance as monomers for polymer synthesis as well as pharmaceutical building blocks. The proposed two-step catalytic sequence involves the use of the commercially available RANEY® Ni catalyst. Therefore, the first step involves the efficient defunctionalization of lignin-derived 2,6-dimethoxybenzoquinone (DMBQ) into 1,4-cyclohexanediol (14CHDO) in 86.5% molar yield, representing a 10.7 wt% yield calculated on a DO weight basis. The second step concerns the highly selective amination of 1,4-cyclohexanediol with ammonia to give 1,4-cyclohexanediamine (14CHDA) in near quantitative yield. The ability to use RANEY® Ni and ammonia in this process holds great potential for future industrial synthesis of 1,4-cyclohexanediamine from renewable resources. [ABSTRACT FROM AUTHOR]

In this contribution, we describe a set of three chlorinated bridged ethers with varying numbers of sulfur and oxygen atoms. The substitution leads to highly emissive compounds with tunable photophysical properties in relationship to their state of aggregation, i. e. in solution, as aggregates and in the solid state. Additionally, an in‐depth X‐ray diffractometric analysis supported by a Hirshfeld study of non‐covalent interactions and quantum chemical simulations was carried out. As the outcome, it was found that the content of sulfur in the compounds regulates the tuning of emission in solution as well as in the aggregated states as a consequence of their variation of planarity. [ABSTRACT FROM AUTHOR]

ANTIFUNGAL agents, CHITIN, MOLECULAR docking, AMINES, TACROLIMUS, and ASPERGILLUS nidulans

Agents with antifungal activity play a vital role as therapeutics in health care, as do fungicides in agriculture. Effectiveness, toxicological profile, and eco-friendliness are among the properties used to select suitable substances. Furthermore, a steady supply of new agents with different modes of action is required to counter the well-known potential of human and phyto-pathogenic fungi to develop resistance against established antifungals. Here, we use an in vitro growth assay to investigate the activity of the calcineurin inhibitor tacrolimus in combination with the commercial fungicides cyproconazole and hymexazol, as well as with two earlier reported novel {2-(3-R-1H-1,2,4-triazol-5-yl)phenyl}amines, against the fungi Aspergillus niger, Colletotrichum higginsianum, Fusarium oxysporum and the oomycete Phytophthora infestans, which are notoriously harmful in agriculture. When tacrolimus was added in a concentration range from 0.25 to 25 mg/L to the tested antifungals (at a fixed concentration of 25 or 50 mg/L), the inhibitory activities were distinctly enhanced. Molecular docking calculations revealed triazole derivative 5, (2-(3-adamantan-1-yl)-1H-1,2,4-triazol-5-yl)-4-chloroaniline), as a potent inhibitor of chitin deacetylases (CDA) of Aspergillus nidulans and A. niger (AnCDA and AngCDA, respectively), which was stronger than the previously reported polyoxorin D, J075-4187, and chitotriose. The results are discussed in the context of potential synergism and molecular mode of action. [ABSTRACT FROM AUTHOR]

ACID derivatives, ELLAGIC acid, COLUMN chromatography, METABOLITES, ANTI-infective agents, ETHYL acetate, and FLAVONOIDS

Medicinal plants are known as sources of potential antimicrobial compounds belonging to different classes. The aim of the present work was to evaluate the antimicrobial potential of the crude extract, fractions, and some isolated secondary metabolites from the leaves of Macaranga occidentalis, a Cameroonian medicinal plant traditionally used for the treatment of microbial infections. Repeated column chromatography of the ethyl acetate and n-butanol fractions led to the isolation of seventeen previously known compounds (1−17), among which three steroids (1−3), one triterpene (4), four flavonoids (5−8), two stilbenoids (9 and 10) four ellagic acid derivatives (11−14), one geraniinic acid derivative (15), one coumarine (16), and one glyceride (17). Their structures were elucidated mainly by means of extensive spectroscopic and spectrometric (1D and 2D NMR and, MS) analysis and comparison with the published data. The crude extract, fractions, and isolated compounds were all screened for their antimicrobial activity. None of the natural compounds was active against Candida strains. However, the crude extract, fractions, and compounds showed varying levels of antibacterial properties against at least one of the tested bacterial strains, with minimal inhibitory concentrations (MICs) ranging from 250 to 1000 μg/mL. The n-butanol (n-BuOH) fraction was the most active against Escherichia coli ATCC 25922, with an MIC value of 250 μg/mL. Among the isolated compounds, schweinfurthin B (10) exhibited the best activity against Staphylococcus aureus NR 46003 with a MIC value of 62.5 μg/mL. In addition, schweinfurthin O (9) and isomacarangin (6) also exhibited moderate activity against the same strain with a MIC value of 125 μg/mL. Therefore, pharmacomodulation was performed on compound 6 and three new semisynthetic derivatives (6a–c) were prepared by allylation and acetylation reactions and screened for their in vitro antimicrobial activity. None of the semisynthetic derivatives showed antimicrobial activity against the same tested strains. The chemophenetic significance of the isolated compounds is also discussed in this paper. [ABSTRACT FROM AUTHOR]

Enantioselective synthesis of chiral alcohols through asymmetric addition of water across an unactivated alkene is a highly sought‐after transformation and a big challenge in catalysis. Herein we report the identification and directed evolution of a fatty acid hydratase from Marinitoga hydrogenitolerans for the highly enantioselective hydration of styrenes to yield chiral 1‐arylethanols. While directed evolution for styrene hydration was performed in the presence of heptanoic acid to mimic fatty acid binding, the engineered enzyme displayed remarkable asymmetric styrene hydration activity in the absence of the small molecule activator. The evolved styrene hydratase provided access to chiral alcohols from simple alkenes and water with high enantioselectivity (>99 : 1 e.r.) and could be applied on a preparative scale. [ABSTRACT FROM AUTHOR]

Abstract An ultrasound-assisted simple, easy and straightforward method for the synthesis of α-aminophosphonates has been developed via Kornblum/Kabachnik-fields reaction. The method involves in situ generation of an aldehyde intermediate from benzyl halides via oxidative dehalogenation followed by coupling with aryl amine and trialkyl phosphite in a one-pot three component manner under ultrasonic irradiations. The developed method is compatible with various functionalities and the desired products are obtained in good to excellent yield under mild conditions. [ABSTRACT FROM AUTHOR]

Smart hydrogels are interesting materials as they can change their dimensions upon an external trigger. Herein, a photoresponsive double cross‐linked hydrogel system based on polyacrylamide (AAm) with grafted poly(2‐methyl‐2‐oxazoline) (PMOXA) chains with a α‐cyclodextrin/azobenzene host–guest complex is present. Switching azobenzene from the trans to the cis‐conformation through irradiation with UV light breaks the complex reversibly. Well‐defined PMOXA macromonomers have been synthesized and functionalized with the respective host and guest functionalities as well as double bonds for the incorporation into the polymer network as grafted side chains. The chemical structure of the macromonomers and the complex is confirmed by 1H NMR, 2D NOESY NMR, GPC, and UV–VIS measurements. Hydrogels with different ratios of permanent and photoresponsive cross‐linkers as well as different chain lengths of the PMOXA macromonomers are analyzed toward differences in their swelling/deswelling and elastic properties. Successive irradiation of supramolecular hydrogels with UV and VIS light allowed for a repeated swelling and de‐swelling of the hydrogels. This system is studied at both macro and micro scales, showing similar swelling tendencies. The tuned properties of photoresponsive double cross‐linked hydrogel makes this system a promising tool for various applications, for example, as in situ controllable valves in microfluidic flow cells. [ABSTRACT FROM AUTHOR]

NICOTINIC acetylcholine receptors, NICOTINIC receptors, LIGAND-gated ion channels, CHOLINERGIC receptors, LIGANDS, CONOTOXINS, PROTEIN-ligand interactions, ALZHEIMER'S disease, and DRUG design

The neuronal nicotinic acetylcholine receptors (nAChRs) belong to the ligand-gated ion channel (GLIC) group, presenting a crucial role in several biological processes and neuronal disorders. The α4β2 and α7 nAChRs are the most abundant in the central nervous system (CNS), being involved in challenging diseases such as epilepsy, Alzheimer's disease, schizophrenia, and anxiety disorder, as well as alcohol and nicotine dependencies. In addition, in silico-based strategies may contribute to revealing new insights into drug design and virtual screening to find new drug candidates to treat CNS disorders. In this context, the pharmacophore maps were constructed and validated for the orthosteric sites of α4β2 and α7 nAChRs, through a docking-based Comparative Intermolecular Contacts Analysis (dbCICA). In this sense, bioactive ligands were retrieved from the literature for each receptor. A molecular docking protocol was developed for all ligands in both receptors by using GOLD software, considering GoldScore, ChemScore, ASP, and ChemPLP scoring functions. Output GOLD results were post-processed through dbCICA to identify critical contacts involved in protein-ligand interactions. Moreover, Crossminer software was used to construct a pharmacophoric map based on the most well-behaved ligands and negative contacts from the dbCICA model for each receptor. Both pharmacophore maps were validated by using a ROC curve. The results revealed important features for the ligands, such as the presence of hydrophobic regions, a planar ring, and hydrogen bond donor and acceptor atoms for α4β2. Parallelly, a non-planar ring region was identified for α7. These results can enable fragment-based drug design (FBDD) strategies, such as fragment growing, linking, and merging, allowing an increase in the activity of known fragments. Thus, our results can contribute to a further understanding of structural subunits presenting the potential for key ligand-receptor interactions, favoring the search in molecular databases and the design of novel ligands. [ABSTRACT FROM AUTHOR]

SUSTAINABILITY, COVID-19 pandemic, SUSTAINABLE chemistry, UNDERGRADUATES, PHYSICAL constants, and CHEMICAL laboratories

In this section of Resonance, we invite readers to pose questions likely to be raised in a classroom situation. We may suggest strategies for dealing with them, or invite responses, or both. "Classroom" is equally a forum for raising broader issues and sharing personal experiences and viewpoints on matters related to teaching and learning science. Amidst the Covid-19 pandemic, we have planned a strategy for our institution which aims towards reuse and reduce principles of Green Chemistry. Organic preparations in the undergraduate curriculum can be utilized for other sister laboratory experiments such as recrystallization, determination of physical constants (m.pt) and detection of extra elements, detection of functional group and in qualitative analysis. The product of preparation can also be subjected to a second synthesis. This approach will reduce the amount of chemicals needed for carrying out experiments other than organic preparations. This paper illustrates a few organic preparations which can be reused for other companion laboratory exercises. This approach may set a model towards sustainability for other undergraduate laboratories. [ABSTRACT FROM AUTHOR]

HETEROCYCLIC compounds, INDAZOLES, ETHYLATION, METHYLTRANSFERASES, BIOCATALYSIS, and IMIDAZOLES

Methods for regioselective N‐methylation and ‐alkylation of unsaturated heterocycles with "off the shelf" reagents are highly sought‐after. This reaction could drastically simplify synthesis of privileged bioactive molecules. Here we report engineered and natural methyltransferases for challenging N‐(m)ethylation of heterocycles, including benzimidazoles, benzotriazoles, imidazoles and indazoles. The reactions are performed through a cyclic enzyme cascade that consists of two methyltransferases using only iodoalkanes or methyl tosylate as simple reagents. This method enables the selective synthesis of important molecules that are otherwise difficult to access, proceeds with high regioselectivity (r.r. up to >99 %), yield (up to 99 %), on a preparative scale, and with nearly equimolar concentrations of simple starting materials. [ABSTRACT FROM AUTHOR]

CATALYSIS, ORGANIC chemistry, FLOW chemistry, and METAL catalysts

Fine chemical industry, flow chemistry, organic process, single-atom catalysis Keywords: fine chemical industry; flow chemistry; organic process; single-atom catalysis EN fine chemical industry flow chemistry organic process single-atom catalysis 1 1 1 11/11/22 20221108 NES 221108 B The Cover Feature b shows a flow reactor employing a single-atom catalyst schematically represented. Cover Feature: Continuous Flow Single-Atom Catalysis: A Viable Organic Process Technology?. [Extracted from the article]

AROMATIC amines, AMINES, HYDROGEN peroxide, METALS, DEAMINATION, and FUNCTIONAL groups

A new and green strategy to synthesize α‐aminophosphonates has been developed using benzyl amines as carbonyl alternates. The method involves oxidative deamination of benzyl amines to produce in situ aldehyde intermediate which is then directly converted into aminophosphonates by coupling with aryl amines and trialkylphosphite. The synthesis offers a green alternative strategy which involves benzyl amines as useful carbonyl surrogate and their possible application in multicomponent reactions to synthesize value added products like aminophosphonates. The methodology has a wide substrate scope and functional group compatibility. Further, the synthesis uses aqueous hydrogen peroxide (H2O2) as a green oxidant and enables to synthesize these products under mild and metal‐free conditions in water as a medium. [ABSTRACT FROM AUTHOR]

SINGLE molecules, AMMONIA, CATALYSTS, LIGNOCELLULOSE, DIAMINES, and GLYCOLS

Diamines are important industrial chemicals. In this paper we outline the feasibility of lignocellulose as a source of diol‐containing molecules. We also illustrate the possibility of turning these diols into their diamines in good to excellent yields. Central to these transformations is the use of commercially available Raney Ni. For diol formation, the Raney Ni engages in hydrogenation and often also demethoxylation, that way funneling multiple components to one single molecule. For diamine formation, Raney Ni catalyzes hydrogen‐borrowing mediated diamination in the presence of NH3. [ABSTRACT FROM AUTHOR]

CHALCONE, PHARMACEUTICAL chemistry, ANTI-infective agents, CHALCONES, COMPLEMENT activation, and ORGANIC synthesis

Chalcones have been well examined in the extant literature and demonstrated antibacterial, antifungal, anti-inflammatory, and anticancer properties. A detailed evaluation of the purported health benefits of chalcone and its derivatives, including molecular mechanisms of pharmacological activities, can be further explored. Therefore, this review aimed to describe the main characteristics of chalcone and its derivatives, including their method synthesis and pharmacotherapeutics applications with molecular mechanisms. The presence of the reactive α,β-unsaturated system in the chalcone's rings showed different potential pharmacological properties, including inhibitory activity on enzymes, anticancer, anti-inflammatory, antibacterial, antifungal, antimalarial, antiprotozoal, and anti-filarial activity. Changing the structure by adding substituent groups to the aromatic ring can increase potency, reduce toxicity, and broaden pharmacological action. This report also summarized the potential health benefits of chalcone derivatives, particularly antimicrobial activity. We found that several chalcone compounds can inhibit diverse targets of antibiotic-resistance development pathways; therefore, they overcome resistance, and bacteria become susceptible to antibacterial compounds. A few chalcone compounds were more active than conventional antibiotics, like vancomycin and tetracycline. On another note, a series of pyran-fused chalcones and trichalcones can block the NF-B signaling complement system implicated in inflammation, and several compounds demonstrated more potent lipoxygenase inhibition than NSAIDs, such as indomethacin. This report integrated discussion from the domains of medicinal chemistry, organic synthesis, and diverse pharmacological applications, particularly for the development of new anti-infective agents that could be a useful reference for pharmaceutical scientists. [ABSTRACT FROM AUTHOR]

Abstract In the present work, a series of novel oxazolidinone derivatives containing thieno-pyridine ring system (11a–n) were synthesized in six steps. Synthesis of amino oxazolidinone scaffold (10) involved nucleophilic substitution of thienopyridine (4) with P-chloro-nitrobenzene (3) in dimethyl formamide at 65 °C give nitro compound (5) which was further reduced in catalytic hydrogenation condition using Raney-Nickel in isopropyl alcohol afforded amine (6). Reaction of compound (6) with 2-[(2S)-oxiran-2-ylmethyl]-1H-isoindole-1,3(2H)-dione (7) at mild reflux condition in isopropyl alcohol gives compound (8). Hydroxy amine compound (8) further undergo carbonyl insertion reaction with 1, 1’-carbonylbis(1H-imidazole) afforded oxazolidinone compound (9). The de-protection of phthalamide group of compound (9) carried by treating with aqueous solution of hydrazine hydrate in methanol at room temperature give compound (10). Finally, compound (10) reacts with acetyl chloride, carboxylic acid, sulfonyl chloride and chloro format by customary method provided amides, sulfonamide and carbamate derivative of (5S)-5-(aminomethyl)-3-[4-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)phenyl]-1,3-oxazolidin-2-one.The developed synthetic approach was operationally simple and high yielding. The structures of the synthesized compounds were elucidated by IR, MS, 1H and 13C-NMR. Synthesized compounds (11a–n) were tested for antibacterial activity against a panel of Gram-positive bacteria comprising Staphylococcus aureus (ATCC5638), Streptococcus pyogenes (ATCC12344), Bacillus subtilis (ATCC6051), Bacillus pumilus (ATCC27142), and Enterococcus faecalis (NCIM5253). The investigation of antimicrobial screening data revealed that, most of the compounds tested have demonstrated sensible to good bacterial activity. In summary, preliminary results of activity indicate that, acetyl derivative (11a), methane sulfonamide derivative (11c) and p-toluene sulfonamide derivative (11e) found to be good activity and di-(methane sulfonamide) derivative (11d) showed comparable activity to reference drug substances. [ABSTRACT FROM AUTHOR]

CYCLODEXTRINS, ISOTHERMAL titration calorimetry, PHOSPHORESCENCE, COMPLEX compounds, MASS spectrometry, and INCLUSION compounds

We present an in‐depth investigation of cyclodextrin complexes with guest compounds featuring complexation‐induced room temperature phosphorescence (RTP) in aqueous solution. Very interestingly, only the complexed regioisomers bearing lateral substituents on meta‐position show RTP, whereas the stronger host‐guest systems with para‐substituted dyes show no RTP features. The reported systems were investigated regarding their complexation behavior in water using isothermal titration calorimetry and mass spectrometry. In the case of γ‐CD very strong 1 : 1 inclusion complexes (Ka up to 5.13×105 M−1) were unexpectedly observed. It was found that not only a strong binding to the cyclodextrin cavity is needed to restrict motion, inducing the emission, but also the conformation inside the cavity plays a pivotal role – as supported by an extensive NMR study and MD simulations. [ABSTRACT FROM AUTHOR]

ORGANIC solvents, PEPTIDES, POISONS, FIELD research, RESEARCH teams, ORGANIC synthesis, and SOLVENTS

Dihydrolevoclucosenone (Cyrene is its market name) is a biomass-derived solvent that can be produced in only two steps from biomass, while being biodegradable, non-mutagenic and non-toxic. Its "green" profile combined with its physical properties makes Cyrene a plausible substitute for a number of widely used toxic organic solvents. The first attempt to assess Cyrene as a solvent dates back to 2014 and since then, numerous research groups have opted for this promising alternative. Cyrene has successfully been employed as a solvent in materials chemistry, peptide chemistry, organic synthesis and many more research fields, which are going to be discussed in the context of this review. [ABSTRACT FROM AUTHOR]