articles+ search results

COOPERATIVE binding (Biochemistry), PYRROLES, CHOLINE chloride, DENSITY functional theory, and ULTRAVIOLET-visible spectroscopy

• Synthesis and anion binding studies of meso- one walled cyanophenyl extended C4P have been described. • BindFit and DFT studies have revealed 1:1 anion binding stoichiometry. • Maximum anion binding affinity was observed in case of fluoride ion. • Conformational change from 1,3-alternate to cone in the presence of anion has been confirmed by 1H-NMR. • NH-hydrogen bonding and anion-π interactions cooperatively govern anion binding. A novel one-walled meso -cyanophenyl functionalized calix[4]pyrrole (4) was synthesized from cyanophenyl appended dipyrromethane (3) through conventional strategy and also by utilizing deep eutectic solvent of N,N' -dimethyl urea (DMU) & L -(+)-tartaric acid (TA) in a ratio of 7:3. The structural confirmation of 4 was done through 1H-NMR, 13C-NMR, FT-IR, and HRMS spectral data. Anion binding studies of the receptor 4 with several anions (halides, trigonal oxoanions, tetragonal oxoanions, etc.) used as tetrabutylammonium (TBA) salts, were successfully investigated by virtue of UV–Vis spectroscopy and time dependent density functional theory (TD-DFT). Notably, the UV–Vis absorbance titrations performed in CH 3 CN solvent, revealed significantly higher anion binding of receptor 4 with F¯, Cl¯, Br¯, and SCN¯ in comparison to the simple C4P. This can be ascribed to the fact that the cyanophenyl moiety is π-acidic in nature which participates in anion complexation through weak anion-π interactions (observed through 1H-NMR spectroscopy) and hence modulates anion binding through cooperative effect of preliminary NH-hydrogen bonding due to C4P scaffold and anion-π contacts due to cyanophenyl moiety. [Display omitted] [ABSTRACT FROM AUTHOR]

PHOSPHINE oxides, ARYL iodides, ARYLATION, ALKOXY group, ASYMMETRIC synthesis, ACID derivatives, METHOXY group, CLINICAL chemistry, and SONOGASHIRA reaction

Keywords: phosphinates; P-stereogenic centers; nickel catalysis; cross-coupling; asymmetric catalysis EN phosphinates P-stereogenic centers nickel catalysis cross-coupling asymmetric catalysis 1819 1823 5 08/29/23 20230915 NES 230915 Graph P-Stereogenic organic phosphorus compounds, especially chiral phosphinic acid derivatives, are useful in medicinal chemistry, pesticide chemistry, organic materials science, and biochemistry. Moreover, when we employed aryl iodides with a free amino ( B 26 b ) or hydroxy group ( B 27 b ) at the I para i -position of the aryl ring, P-chiral phosphinates were obtained in moderate yields (71 and 68%) and high ee values (88 and 81% ee). [41] However, we found aryl iodides with different electronic properties all gave the corresponding P-chiral phosphinates with moderate to high ee values (62-82% ee); in other words, the enantioselectivity was only slightly affected by the electronic properties of the aryl iodides. During the preparation of our manuscript, Duan and our group separately reported Ni(0)-catalyzed intermolecular reactions of nonactivated aryl halides [39] and Ni(II)-catalyzed intermolecular reactions of heterocyclic halides, [40] respectively. [Extracted from the article]

HYDROXYLATION, TITANIUM, HYDROGEN peroxide, EPOXIDATION, and KETONES

The titanium complex of the cis‐1,2‐diaminocyclohexane (cis‐DACH) derived Berkessel‐salalen ligand is a highly efficient and enantioselective catalyst for the asymmetric epoxidation of terminal olefins with hydrogen peroxide ("Berkessel‐Katsuki catalyst"). We herein report that this epoxidation catalyst also effects the highly enantioselective hydroxylation of benzylic C−H bonds with hydrogen peroxide. Mechanism‐based ligand optimization identified a novel nitro‐salalen Ti‐catalyst of the highest efficiency ever reported for asymmetric catalytic benzylic hydroxylation, with enantioselectivities of up to 98 % ee, while overoxidation to ketone is marginal. The novel nitro‐salalen Ti‐catalyst also shows enhanced epoxidation efficiency, as evidenced by e.g. the conversion of 1‐decene to its epoxide in 90 % yield with 94 % ee, at a catalyst loading of 0.1 mol‐% only. [ABSTRACT FROM AUTHOR]

LIGNIN structure, LIGNINS, COVALENT bonds, MOLECULAR weights, SUSTAINABLE development, PETROLEUM, and DEPOLYMERIZATION

Lignin holds tremendous and versatile possibilities to produce value-added chemicals and high performing polymeric materials. Over the years, different cutting-edge lignin depolymerization methodologies have been developed, mainly focusing on achieving excellent yields of mono-phenolic products, some even approaching the theoretical maximum. However, due to lignin's inherent heterogeneity and recalcitrance, its depolymerization leads to relatively complex product streams, also containing dimers, and higher molecular weight fragments in substantial quantities. The subsequent chemo-catalytic valorization of these higher molecular weight streams, containing difficult-to-break, mainly C–C covalent bonds, is tremendously challenging, and has consequently received much less attention. In this minireview, we present an overview of recent advances on the development of sustainable biorefinery strategies aimed at the production of well-defined chemicals and polymeric materials, the prime focus being on depolymerized lignin oils, containing high molecular weight fractions. The key central unit operation to achieve this is (bio)catalytic funneling, which holds great potential to overcome separation and purification challenges. [ABSTRACT FROM AUTHOR]

MOLECULAR structure, CHEMICAL properties, COORDINATE covalent bond, COORDINATION polymers, HYDROGENATION, POLYMERS, ORGANIC synthesis, and ELECTRONIC structure

• Molecular properties, i.e. physical and chemical properties, are affected by the functional groups attached to them. • Phosphinidines have been demonstrated to be highly effective in a variety of cases such as polymer chemistry, organic synthesis for the preparation of polyphosphanes, coordination chemistry, and more recently in catalysis as ligands in cross-coupling reactions. • Various types of metal ions and the ancillary ligands existing in the reaction determine the nature of the created products. ligands have crucial impact on the region-, chemo-, and, of course, stereoselectivity in metal- catalytic processes. [ABSTRACT FROM AUTHOR]

RING-opening polymerization, ACETAL resins, COPOLYMERS, BLOCK copolymers, POLYMERIZATION, MONOMERS, and POLYMERS

Radical Ring‐opening polymerization (RROP) of cyclic ketene acetals (CKAs) emerges to be a valuable polymerization technique. In attracting more attention, RROP has seen a new spike in publications, which the authors will put into perspective. This review will hence address the progress made on the number of available CKAs and the synthetic strategies to get them. In grouping, the available monomers into distinct categories, the enormous variety of available CKAs will be highlighted. Polymerizations of CKAs without vinylenes have the potential to yield fully biodegradable polymers, which is why this kind of polymerization is the focus of this review. Detailing the current understanding of the mechanism, the various side reactions will be noted and also their effect on the overall properties of the final polymers. Current attempts to control the ring‐retaining and branching reactions will be discussed as well. In addition to the polymerization itself, the available materials will be discussed as well as homopolymers, copolymers of CKAs, and block‐copolymers with pure CKA‐blocks have significantly widened the range of possible applications of materials from RROP. Altogether this review highlights the progress in the entire field of RROP just of CKAs to give a holistic overview of the field. [ABSTRACT FROM AUTHOR]

MOLECULAR size, MICROFLUIDICS, POLYDIMETHYLSILOXANE, OVERHAUSER effect (Nuclear physics), SUPRAMOLECULAR chemistry, NUCLEAR magnetic resonance spectroscopy, HYDROGELS, and POLYACRYLAMIDE

The integration of microscopic hydrogels with high specific surface area and physically reactive groups into microfluidic systems for selective molecular interactions is attracting increasing attention. Herein, the reversible capture and release of molecules through host–guest interactions of hydrogel dots in a microfluidic device is reported, which translates the supramolecular chemistry to the microscale conditions under continuous flow. Polyacrylamide (PAAm) hydrogel arrays with grafted β‐cyclodextrin (β‐CD) modified poly(2‐methyl‐2‐oxazoline) (CD‐PMOXA) chains are fabricated by photopolymerization and integrated into a polydimethylsiloxane (PDMS)‐on‐glass chip. The β‐CD/adamantane (β‐CD/Ada) host–guest complex is confirmed by two dimensional Nuclear Overhauser Effect Spectroscopy NMR (2D NOESY NMR) prior to transfer to microfluidics. Ada‐modified molecules are successfully captured by host–guest interaction formed between the CD‐PMOXA grafted chains in the hydrogel network and the guest molecule in the solution. Furthermore, the captured molecules are released by perfusing free β‐CD with higher binding affinity than those grafted in the hydrogel array. A small guest molecule adamantane‐fluorescein‐isothiocyanate (Ada‐FITC) and a macromolecular guest molecule (Ada‐PMOXA‐Cyanine 5 (Cy5)) are separately captured and released for three times with a release ratio up to 46% and 92%, respectively. The reproducible capture and release of functional molecules with different sizes demonstrates the stability of this hydrogel system in microfluidics and will provide an opportunity for future applications. [ABSTRACT FROM AUTHOR]

GENTIAN violet, SCHIFF bases, BASIC dyes, AQUEOUS solutions, COMPUTATIONAL chemistry, EXOTHERMIC reactions, ADSORPTION kinetics, PORE size distribution, and COLOR removal in water purification

• New bis(pyrano[3,2- c ]quinolinone) based on Schiff base was prepared. • The synthesized adsorbent was characterized using several techniques. • The batch adsorption technique toward cationic dye was applied. • The adsorption kinetics, isotherms, recyclability and Thermodynamic parameters were calculated. • The primary adsorption mechanism was confirmed by computational chemistry. Organic compound water pollution is one of the difficult environmental issues facing the advancement of human civilization. So, New bis(pyrano[3,2- c ]quinolinone) based on Schiff base adsorbent was prepared to participate in solving this problem. The synthesized adsorbent was characterized using FT-IR, 1H NMR, XRD, SEM, elemental analysis, N 2 - adsorption-desorption isotherm, S BET , and Pore size distribution studies. The obtained results revealed a significant improvement in the new schiff base surface texture and crystallinity. Further, pH zpc of the new adsorbent has been examined to be 3.7. Its decolorization efficiency toward methylene blue (MB) dye from an aqueous solution was examined. Also, the factors of pH, contact time, reaction temperature, and initial dye concentration were optimized. Overall, this study emphasized that the newly synthesized Schiff base act as an effective adsorbent (99%) at a very short time (5 min., 10 ppm dye concentration, pH = 9 and temperature = 25 °C) and can be regenerated for five cycles for the removal of MB dye from aqueous solutions. Freundlich isotherm model and pseudo-second order kinetic model were fit effectively for the MB dye adsorption experimental data. Also, the calculated thermodynamic parameters revealed a spontaneous and exothermic adsorption reaction. FT- IR study and computational chemistry study proved that the decolorization interaction mechanism between the positive (- N +) sites of MB dye and the negative (- OH) active sites of the new Schiff base adsorbent at the optimum conditions occurred as a physisorption process. [Display omitted] [ABSTRACT FROM AUTHOR]

CELL imaging, PROTISTA, DRUG target, LUMINOPHORES, QUANTUM wells, and PLASMODIOPHORA brassicae

A library of eight different cationic emitters with emission properties in solution and in solid‐state (solution and solid‐state emitters – SSSE) is presented. These compounds, bearing either ammonium or pyridinium groups, have been investigated regarding their photophysical properties as well as their potential application in biological imaging. Besides high quantum yields as well as a high degree of stability during the imaging process, it was additionally revealed that a broad range of biological targets can be addressed, such as different bacterial strains, human cells as well as protists. The reported SSSE approach employing the mentioned robust emitters for biological imaging, will contribute to a rapid and facile way to design and apply affordable emitters with outstanding properties. Additionally, these emitters will overcome the drawbacks of classical luminophores and agents featuring well‐known aggregation‐induced emission (AIE) or aggregation‐caused quenching (ACQ) properties. [ABSTRACT FROM AUTHOR]

HETEROGENEOUS catalysts, FERRIC oxide, CATALYST synthesis, HEMATITE, FOURIER transform infrared spectroscopy, FIELD emission electron microscopy, AROMATIC aldehydes, and CATALYSTS recycling

• First time report on the synthesis of Fe 2 O 3 nanorods (NRs) by a green process via a mixture of Eucalyptus citriodora and Murraya koenigii leaf extracts. • XRD, FESEM, EDX, FTIR, UV-DRS, BET, and VSM analysis confirmed the biosynthesis of Fe 2 O 3 NRs. • Fe 2 O 3 NRs exhibited excellent catalytic performance for the Biginelli reaction. • The synthesized catalyst exhibited high stability, reusability, an excellent yield of Biginelli products, and easy workup. For the first time, mixed-phase (Hematite and Maghemite) magnetic Fe 2 O 3 nanorods were successfully biosynthesis by sol-gel auto-combustion method using the 1:1 mixture of Eucalyptus citriodora and Murraya koenigii leaf extract as a capping agent, and its catalytic effect on synthesis of 6-(chloromethyl)-1,2,3,4-tetrahydro-2-pyrimidinone (THPMs) derivatives were investigated. Further, the phase formation, surface topography, and crystallinity of biosynthesized Fe 2 O 3 nanorods (NRs) were explored using powder XRD (X-Ray Diffraction), UVDRS (UV–Visible Reflectance Spectroscopy), FTIR (Fourier Transform Infrared Spectroscopy), FESEM (Field Emission Scanning Electron Microscopy), EDX (Energy Dispersive X-Ray), and VSM (Vibrating Sample Magnetometry). Furthermore, the catalytic activity of biosynthesized Fe 2 O 3 NRs (C1, C2, and C3) was examined for one-pot synthesis of ethyl 6-(chloromethyl)-1,2,3,4-tetrahydro-2-oxo-4-arylpyrimidine-5-carboxylate via Biginelli reaction. To achieve high yields (93–99 %) of 6-(chloromethyl)-1,2,3,4-tetrahydro-2-pyrimidinone derivatives, this heterogeneous catalytic method is used with a wide range of aromatic aldehydes within a minimum reaction time, simple reaction work-up, and easily recoverable catalyst by an external magnet. The recovered catalyst is then employed for five successive cycles without non-noticeable loss of catalytic activity. We believe that this protocol presents a broad scope for Biginelli reaction through greenly produced and magnetically separable heterogeneous catalysts. [Display omitted] [ABSTRACT FROM AUTHOR]

INDOLE compounds, INDOLE derivatives, INDOLE, AMINATION, LSD (Drug), PHENYLENEDIAMINES, TRANSITION metal catalysts, ORGANIC chemistry, and ORGANIC acids

B. Acid-catalyzed indole synthesis An efficient one-pot synthesis of I N i SB 1 sb -substituted indole derivatives ( B 15 b ) was reported by Kutznetsov and colleagues[45]. I. Important methods for indole synthesis Numerous methods for the synthesis of indoles are cited in the literature (Figure 2).[7],[8],[25]Table 2 highlights a few important classical methods for the synthesis of indoles. Recently, there has been increased interest in metal-free indole synthesis as compared to classical metal-assisted indole syntheses. Transition metal-free indole synthesis The synthesis of indoles can be accomplished through special reaction types and routes. [Extracted from the article]

TERPENES, ALKENES, METHYLATION, DITERPENES, PROTON transfer reactions, METHYLTRANSFERASES, and CARBOCATIONS

Terpenoids are built from isoprene building blocks and have numerous biological functions. Selective late‐stage modification of their carbon scaffold has the potential to optimize or transform their biological activities. However, the synthesis of terpenoids with a non‐natural carbon scaffold is often a challenging endeavor because of the complexity of these molecules. Herein we report the identification and engineering of (S)‐adenosyl‐l‐methionine‐dependent sterol methyltransferases for selective C‐methylation of linear terpenoids. The engineered enzyme catalyzes selective methylation of unactivated alkenes in mono‐, sesqui‐ and diterpenoids to produce C11, C16 and C21 derivatives. Preparative conversion and product isolation reveals that this biocatalyst performs C−C bond formation with high chemo‐ and regioselectivity. The alkene methylation most likely proceeds via a carbocation intermediate and regioselective deprotonation. This method opens new avenues for modifying the carbon scaffold of alkenes in general and terpenoids in particular. [ABSTRACT FROM AUTHOR]

ALKENES, METHYLATION, and AMINO acid sequence

A variant with three changes in the amino acid sequence was able to produce methylated derivatives of linear terpenoids with high selectivity by C-methylation of an unactivated alkene. Cover Picture: Methylation of Unactivated Alkenes with Engineered Methyltransferases To Generate Non-natural Terpenoids (Angew. Keywords: Alkene Methylation; Biocatalysis; Late-Stage Modification; Methyltransferase; Terpenoids EN Alkene Methylation Biocatalysis Late-Stage Modification Methyltransferase Terpenoids 1 1 1 06/20/23 20230626 NES 230626 B A methyltransferase b from the green alga I Chlamydomonas reinhardtii i was identified and engineered for late-stage modifications of the carbon skeleton of terpenes. [Extracted from the article]

SOLID phase extraction, PULMONARY surfactant, ANALYTICAL chemistry, SURFACE active agents, PREMATURE infants, and DENSITY functional theory

• A mixed mode DSPE approach was developed using organic polymers. • The method was used to lung surfactants determination in EBC samples. • Density functional theory calculations were used to show the nature of the chemical interactions. • Simplex centroid experimental design was used for optimization of the sorbent composition. A mixed mode dispersive solid phase extraction method was introduced for the extraction of three lung surfactants from exhaled breath condensate samples. Considering the trends to green analytical chemistry, organic polymers including polystyrene (PS), polymethylmethacrylate (PMMA-15 K), and polymethylmethacrylate (PMMA-45 K) were utilized as the sorbent for extraction of the analytes. The extraction capability for each polymer toward the studied analytes was evaluated using simplex centroid design. Based on the results, a mixture of sorbents consisting of PS, PMMA-15 K, and PMMA-45 K mixture with the mass ratio of 1:2:1: w/w/w was selected as the suitable sorbent. The effective parameters influencing the method's efficiency were investigated and optimized. Based on the figure of merit for the developed method, the calibration curves were linear in the concentration range of 0.76–1000 ng mL–1 and limits of detection were from 0.09 to 0.19 ng mL–1. The method repeatability was investigated at three concentrations as inter- and intra-day precisions and the obtained data showed that they were in the ranges of 5.2–9.1 and 4.2–8.9%, respectively. The enrichment factors were in the range of 88–100. The developed method was successfully employed in the analysis of the surfactants in the exhaled breath samples of three premature infants collected from the expiratory circuits of the mechanical ventilators. The nature of the chemical interactions with PMMA-PS complex system of the surfactants was investigated through Density Functional Theory calculations. Calculated binding energies showed that PMMA-PS complex system exhibit high performance in the extraction of lung surfactants. The most powerful interaction is between PMMA-PS complex system and 1-palmitoyl-2-oleoylsn‑glycero-3-phosphocholine. [ABSTRACT FROM AUTHOR]

SCHIFF bases, ESCHERICHIA coli, NUCLEAR magnetic resonance spectroscopy, METAL complexes, MYCOBACTERIUM tuberculosis, DENSITY functional theory, SILVER, and PEPTIDE antibiotics

This article describes the in vitro antibacterial and β-lactamase inhibition of a novel silver(I) complex with the sulfonamide probenecid (Ag-PROB). The formula Ag 2 C 26 H 36 N2O 8 S 2 ·2H 2 O for the Ag-PROB complex was proposed based on elemental analysis. High-resolution mass spectrometric studies revealed the existence of the complex in its dimeric form. Infrared, nuclear magnetic resonance spectroscopies and Density Functional Theory calculations indicated a bidentate coordination of probenecid to the silver ions by the oxygen atoms of the carboxylate. In vitro antibacterial activities of Ag-PROB showed significant growth inhibitory activity over Mycobacterium tuberculosis , S. aureus , and P. aeruginosa PA01biofilm-producers, B. cereus , and E. coli. The Ag-PROB complex was active over multi-drug resistant of uropathogenic E. coli extended spectrum β-lactamases (ESBL) producing (EC958 and BR43), enterohemorrhagic E. coli (O157:H7) and enteroaggregative E. coli (O104:H4). Ag-PROB was able to inhibit CTX-M-15 and TEM-1B ESBL classes, at concentrations below the minimum inhibitory concentration for Ag-PROB, in the presence of ampicillin (AMP) concentration in which EC958 and BR43 bacteria were resistant in the absence of Ag-PROB. These results indicate that, in addition to ESBL inhibition, there is a synergistic antibacterial effect between AMP and the Ag-PROB. Molecular docking results revealed potential key residues involved in interactions between Ag-PROB, CTX-M-15 and TEM 1B, suggesting the molecular mechanism of the ESBL inhibition. The obtained results added to the absence of mutagenic activity and low cytotoxic activity over non-tumor cell of the Ag-PROB complex open a new perspective for future in vivo tests demonstrating its potential of use as an antibacterial agent. Ag-Probenecid complex was active on biofilm-producing multidrug-resistant bacteria and Mycobacterium tuberculosis and was capable to inhibit extended spectral β-lactamase classes produced by Escherichia coli EC958 and BR43 with synergistic antibacterial effect with ampicillin. Ag-PROB was active on biofilm-producing MDR bacteria and Mycobacterium tuberculosis and was capable to inhibit extended spectral β-lactamase classes produced by E. coli EC958 and BR43 with synergistic antibacterial effect with ampicillin. [Display omitted] • Broad spectrum of Ag-Probenecid complex antibacterial activity. • Extend spectrum β-lactamase inhibition. • Mycobacterium tuberculosis growth inhibition. • Absence of mutagenic activity. [ABSTRACT FROM AUTHOR]

REGIOSELECTIVITY (Chemistry), METHYLTRANSFERASES, SUPPLY & demand, BIOMOLECULES, and METHIONINE

Methyltransferases provide excellent specificity in late-stage alkylation of biomolecules. Their dependence on S-adenosyl- L -methionine (SAM) mandates efficient access to SAM analogues for biocatalytic applications. We directly compared halide methyltransferase (HMT) and methionine adenosyltransferase (MAT) to access SAM analogues and explored their utility in cascade reactions with NovO for regioselective, late-stage Friedel-Crafts alkylation of a coumarin. The HMT cascade efficiently provided SAM for methylation, while the MAT cascade also supplied high levels of SAM analogues for alkylation reactions. [ABSTRACT FROM AUTHOR]

DRUG resistance, APOPTOSIS, LEUKEMIA, GOLD compounds, REACTIVE oxygen species, and MITOCHONDRIAL pathology

Gold complexes could be promising for tumor therapy because of their cytotoxic and cytostatic properties. We present novel gold(I) complexes and clarify whether they also show antitumor activity by studying apoptosis induction in different tumor cell lines in vitro, comparing the compounds on resistant cells and analyzing the mechanism of action. We particularly highlight one gold complex that shows cytostatic and cytotoxic effects on leukemia and lymphoma cells already in the nanomolar range, induces apoptosis via the intrinsic signaling pathway, and plays a role in the production of reactive oxygen species. Furthermore, not only did we demonstrate a large number of resistance overcomes on resistant cell lines, but some of these cell lines were significantly more sensitive to the new gold compound. Our results show promising properties for the gold compound as anti-tumor drug and suggest that it can subvert resistance mechanisms and thus targets resistant cells for killing. [Display omitted] • Novel Au(I)-complexes show cytostatic and cytotoxic activity on tumor cells in vitro. • Apoptosis induction studied functions via the intrinsic apoptosis pathway. • Effect reduction by antioxidants indirectly indicates ROS formation. • Au-compound overcomes a variety of multidrug resistances and sensitizes to apoptosis. [ABSTRACT FROM AUTHOR]

QUINAZOLINONES, CHEMICAL stability, ANTI-infective agents, CHEMICAL structure, CHEMICAL processes, DNA topoisomerase I, and VAN der Waals forces

The review characterizes the role of the basic targets of antibacterial agents: efflux pumps, enzymes (DNA gyrases as a subclass of topoisomerases, homoserine transacetylase, various classes of sortases, aromatase, lipoteichoic synthase, polyketide synthase, pantothenate synthetase, acetyl-CoA carboxylase, sensory histidine kinase, kinase, cyclooxygenase, etc.), penicillin-binding protein, quorum sensing systems, and adhesins in significant biochemical processes of pathogen maintenance and virulence manifestation. It has been demonstrated that a chemical can exhibit the antimicrobial effect when it binds to protein molecules responsible for pathogenicity of a microorganism. The role of quinazolinone derivatives exhibiting high reactivity and stability in chemical processes and characterized by a wide spectrum of pharmacological activity, including antimicrobial activity with respect to various Gram-positive and Gram-negative bacteria, has been determined. It has been shown that structural changes induced by introducing various substituents contribute to a change in the degree of hydrophilicity and, as a result, determine a different degree of penetration of the drug through the cell membrane, the ability to form intermediate complex compounds stabilized by a system of hydrogen bonds, as well as by van der Waals and stacking interactions, with enzymatic targets, receptor regulatory proteins, and signaling systems of pathogen cells. The results of mathematical modeling of the mechanism of action of the compounds synthesized by the authors of the article are discussed. The possibility of creating a pharmaceutical with a pronounced antimicrobial activity by combining the quinazolinone core with various heterocyclic derivatives is assessed. The considered regularities are of practical importance for the researchers in the field of medicinal chemistry, organic synthesis, biotechnology, clinical pharmacology, and pharmaceutical chemistry and technology, whose efforts are aimed at designing a new drug. [ABSTRACT FROM AUTHOR]

PYRIMIDINES, ANAPLASTIC lymphoma kinase, GLIOBLASTOMA multiforme, and EPIDERMAL growth factor receptors

Glioblastoma multiforme (GBM) is a highly‐aggressive, dreadful disease with poor prognosis and disappointing clinical success. There is an unmet medical need of molecularly‐targeted therapeutics for GBM treatment. In the present work, a series of novel 2‐phenyl‐substituted 4‐amino–6,7‐dihydro‐5H‐cyclopenta[d]pyrimidines was designed, synthesized, purified, characterized, and evaluated for cytotoxicity against glioblastoma cell line U87‐MG. The design process (virtual library enumeration around the core, physicochemical and molecular property prediction/calculation of the designs, filtering the undesirable ones, and the diversity analyses of the lead‐like designs), was carefully curated so as to obtain a set of structurally‐diverse, novel molecules (total 20), with a particular focus on the relatively unexplored core structure, 6,7‐dihydro‐5H‐cyclopenta[d]pyrimidine. The preliminary screening was done using MTT assay at 10 and 100 μM concentrations of the title compounds F1−F20 and positive control cisplatin, which yielded six hits (% inhibition at 10 μM: ~50%)—F2, F3, F5, F7, F15, and F20, which were taken up for IC50 determination. The top hits F2 and F7 (IC50 < 10 μM) were further used for computational studies such as target prediction, followed by their molecular docking in the binding sites of the top‐3 predicted targets (epidermal growth factor receptor kinase domain, cyclin‐dependent kinase 2 [CDK2]) /cyclin E, and anaplastic lymphoma kinase [ALK]). The docking pose analyses revealed interesting trends. The relatively planar core structure, presence of favorable hinge‐binding substructures, basic groups, all added up, and culminated in appreciable cytotoxicity against GBM cell line. [ABSTRACT FROM AUTHOR]

ENDOPHYTIC fungi, ARTEMIA, ASPERGILLUS, ETHYL acetate, CELL lines, FLAVONOIDS, and ANTI-inflammatory agents

A new unsaturated aliphatic anhydride derivative (Z)-(12Z)-heptadec-12-enoic-2′-hydroxypropanoic anhydride (1) and ten known compounds, three flavonoids (2–4), two terphenyllins (5-6), four triterpenoids (7-8, 10-11), and one n-fatty acid (9), were isolated from the EtOAc extract of Aspergillus candidus T1219W1, an endophytic fungus, inhabiting Pittosporum mannii. All the isolated compounds were characterized using 1D- and 2D-NMR and HR-EI experiments together with the reported literature. p-terphenyls are suggested to be the chemophenetic marker of the genus Aspergillus. The ethyl acetate crude extract as well as some isolated compounds of A. candidus was assayed for antibiofilm activity, anti-inflammatory (ROS) activity, and cytotoxicity on brine shrimps and the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity assay on 3T3 cell lines. The tested sample showed good antibiofilm activity with the lowest MBEC50 obtained at 64 μg/mL. Compounds showed low anti-inflammatory activity even at high concentration (250 μg·mL−1 with an IC50 of 59.6 ± 0.1 μg·mL−1) with moderate cytotoxicity on brine shrimps at high concentration (1000 μg·mL−1, with 46.67% mortality). However, no cytotoxic activity was observed against 3T3 cell lines. [ABSTRACT FROM AUTHOR]

MOLYBDATES, CATALYSTS, LAYERED double hydroxides, CATALYTIC activity, GRAPHENE oxide, OXIDATION, and KEGGIN anions

This paper is focused on the utilization of hybrid catalysts obtained from layered double hydroxides containing molybdate as the compensation anion (Mo-LDH) and graphene oxide (GO) in advanced oxidation using environmentally friendly H2O2 as the oxidation agent for the removal of indigo carmine dye (IC) from wastewaters at 25 °C using 1 wt.% catalyst in the reaction mixture. Five samples of Mo-LDH-GO composites containing 5, 10, 15, 20, and 25 wt% GO labeled as HTMo-xGO (where HT is the abbreviation used for Mg/Al in the brucite type layer of the LDH and x stands for the concentration of GO) have been synthesized by coprecipitation at pH 10 and characterized by XRD, SEM, Raman, and ATR-FTIR spectroscopy, determination of the acid and base sites, and textural analysis by nitrogen adsorption/desorption. The XRD analysis confirmed the layered structure of the HTMo-xGO composites and GO incorporation in all samples has been proved by Raman spectroscopy. The most efficient catalyst was found to be the catalyst that contained 20%wt. GO, which allowed the removal of IC to reach 96.6%. The results of the catalytic tests indicated a strong correlation between catalytic activity and textural properties as well as the basicity of the catalysts. [ABSTRACT FROM AUTHOR]

SPECTROMETRY, INFRARED spectra, and BIOMACROMOLECULES

Carbohydrates constitute one of the four key classes of biomacromolecules but have not been studied by 2D-IR spectroscopy so far. Similarly as for proteins, a lack of native vibrational reporter groups, combined with their huge structural diversity, leads to spectrally congested infrared spectra already for single carbohydrates. Biophysical studies are further impeded by the strong overlap between water modes and carbohydrate modes. Here, we demonstrate the application of the known vibrational reporter group thiocyanate (SCN) as a label in glucose. In this first study, we are able to perform IR and 2D-IR spectroscopy of β-glucose with SCN at the C2 position in chloroform. Upon improved synthesis and the removal of all protecting groups, we successfully performed 2D-IR spectroscopy of β-glucose in H2O. All experimental results are compared to those of methyl-thiocyanate as a reference sample. Overall, we show that the concept of using site-specific vibrational reporter groups can be transferred to carbohydrates. Thus, biophysical studies with 2D-IR spectroscopy can now expand to glycoscience. [ABSTRACT FROM AUTHOR]

ORGANIC chemistry, COMPUTATIONAL chemistry, SUPRAMOLECULAR chemistry, COLLECTIONS, and PERIODICAL editors

Organic chemistry, computational chemistry, supramolecular chemistry, synthetic methods, young researchers Keywords: computational chemistry; organic chemistry; supramolecular chemistry; synthetic methods; young researchers EN computational chemistry organic chemistry supramolecular chemistry synthetic methods young researchers 1 1 1 04/11/23 20230406 NES 230406 Guest Editor Prof. Stefano Protti introduces the #NextGenOrgChem special collection, which includes original research papers, reviews and concept articles by young organic chemists (post-doctoral and early-career researchers) nominated by the EurJOC advisory and editorial board members. [Extracted from the article]

MOLECULAR docking, ELECTRIC potential, DENSITY of states, AZEPINES, and CANCER cells

In this strategy, we attempt to design various novel nitrogen-rich heterocycles in one molecule. Green, simple, and efficient aza-annulations of an active, versatile building block, 1-amino-4-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (1), with different bifunctional reagents were developed under solvent-free conditions, resulting in the bridgehead tetrazines and azepines (triazepine and tetrazepines). Pyrido[1,2,4,5]tetrazines have been synthesized through two pathways; [3 + 3]- and [5 + 1]-annulations. In addition, pyrido-azepines have been developed by applying [4 + 3]-and [5 + 2]-annulations. This protocol establishes an efficient technique for synthesizing essential biological derivatives of 1,2,4,5-tetrazines, 1,2,4-triazepines, and 1,2,4,5-tetrazepine, tolerating a diverse variety of functionalities without the need for catalysis and fast reaction rates in high yields. The National Cancer Institute (NCI, Bethesda, USA) examined twelve compounds produced at a single high dosage (10−5 M). Compounds 4, 8, and 9 were discovered to have potent anticancer action against certain cancer cell types. To explain NCI results, the density of states was calculated to conduct a better description of the FMOs. The molecular electrostatic potential maps were created to explain a molecule's chemical reactivity. In silico ADME experiments were performed to better understand their pharmacokinetic characteristics. Finally, the molecular docking investigations on Janus Kinase-2 (PDB ID: 4P7E) were carried out to study the binding mechanism, binding affinity, and non-bonding contacts. [ABSTRACT FROM AUTHOR]

INDUCTIVELY coupled plasma mass spectrometry, PORITES, X-ray spectroscopy, CORALS, INDUCTIVELY coupled plasma atomic emission spectrometry, and BIOGEOCHEMICAL cycles

Coral skeletal P/Ca ratio has been developed as an indicator of temporal seawater dissolved inorganic phosphorus (DIP). The use of coral P/Ca proxy helps to assess oceanographic and climatic impacts such as upwelling, circulation, and continent runoffs on marine biogeochemical cycles. However, factors controlling skeletal P incorporation and elemental partitioning between seawater and coral skeletons remain elusive. We conducted temperature-controlled (∼21 to 29 °C) aquaria culture experiments using two colonies of Porites australiensis corals (here refer to B and C) with the only difference in zooxanthellae density (B > C). The coral growth rate ranges from 9.4 to 19.4 mg/day (B) and 0.7 to 14.1 mg/day (C). Only the growth rate of colony C significantly correlates to temperature, potentially reflecting physiological controls on the two colonies given the difference in the zooxanthellae density. We measured coral P/Ca ratios by Inductively coupled plasma mass spectrometry and determined skeletal P speciation through a synchrotron-based spectroscopic approach. Coral P/Ca ratio ranges from 6.5 to 18.6 μmol/mol (B) and 7.2 to 19.8 μmol/mol (C). The dominance of organic-P is confirmed, and the presence of inorganic-P cannot be excluded. Only colony C has a strong P/Ca dependence on temperature and both colonies show strong correlations between P/Ca and growth rate. Although growth rate and temperature are intercorrelated, the growth rate is more likely the direct controlling factor on coral P/Ca in our experiments. Combined laboratory data with field observations, we suggest that the validity of the Porites P/Ca proxy may be influenced by seawater DIP, coral species, and growth rate. • Cultured coral P/Ca ratio can be variable with relatively constant seawater chemistry. • Organic phosphorus is widely present in coral skeletons despite oxidative cleaning. • The validity of the P/Ca proxy could be influenced by seawater DIP, coral species, and growth rate. [ABSTRACT FROM AUTHOR]

CONFERENCES & conventions, ANTIVIRAL agents, CAREER development, VACCINE development, SCIENTIFIC community, and INFORMATION sharing

The 35th International Conference on Antiviral Research (ICAR), sponsored by the International Society for Antiviral Research (ISAR), was held in Seattle, Washington, USA, on March 21–25, 2022 and concurrently through an interactive remote meeting platform. This report gives an overview of the conference on behalf of the society. It provides a general review of the meeting and awardees, summarizing the presentations and their main conclusions from the perspective of researchers active in many different areas of antiviral research and development. Through ICAR, leaders in the field of antiviral research were able to showcase their efforts, as participants learned about key advances in the field. The impact of these efforts was exemplified by many presentations on SARS-CoV-2 demonstrating the remarkable response to the ongoing pandemic, as well as future pandemic preparedness, by members of the antiviral research community. As we address ongoing outbreaks and seek to mitigate those in the future, this meeting continues to support outstanding opportunities for the exchange of knowledge and expertise while fostering cross-disciplinary collaborations in therapeutic and vaccine development. The 36th ICAR will be held in Lyon, France, March 13–17, 2023. • This report summarizes presentations at the 35th International Conference on Antiviral Research. • This meeting used a hybrid model with in-person sessions in Seattle, WA, USA, and concurrent live virtual sessions. • Meeting sessions covered the treatment of a wide variety of viruses, pandemic preparedness, and other topics. • Plenary lectures focused on the role of foundations in antiviral development, pandemic preparedness and other key concepts. • The meeting also featured special sessions and events, late-breaking oral presentations, and a career development workshop. [ABSTRACT FROM AUTHOR]

HETEROGENEOUS catalysts, UNSATURATED compounds, DECOMPOSITION method, ETHANOL, AROMATIC aldehydes, CALCITE, and OXINDOLES

[Display omitted] • CaCO 3 nanoflowers (NFs) were synthesized by the thermal decomposition method. • Knoevenagel condensation of 2-oxindole has been investigated using Calcite NFs first time. • The higher catalytic activity of NFs is due to the size, surface area, and hollow, sheet-like structures of flower petals. • According to the findings, the technique is far more cost-effective and has a lower environmental toxicity impact. • The catalyst could be recycled without significantly decreasing reactivity until five cycles. α-β unsaturated heterocyclic compounds such as C3-arylidene-oxindoles, with five-member rings containing nitrogen, have an important role in the realm of medicine. This study aims to synthesize the C3-arylindene-oxindoles derivative compounds using calcite nanoflowers (CaCO 3 NFs) as a heterogeneous catalyst for the first time. These CaCO 3 NFs prepared by the thermal decomposition method, which is an active and reusable catalyst for stereospecific Knoevenagel condensation reaction between 2-oxindole and aromatic aldehyde under different solvent conditions like water, ethyl alcohol, and 50 % aqueous ethyl alcohol. This catalytic method is employed with a wide range of aromatic aldehydes to produce high yields of C3-arylidene-oxindoles (93–99 %), with stereo-specifically E -isomers (100 %) for 50 % alcohol and alcohol as a solvent. [ABSTRACT FROM AUTHOR]

SMALL molecules, STYRENE, ALKENES, FATTY acids, and ALCOHOL

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]

ENZYME stability, THERAPEUTIC immobilization, AMINOTRANSFERASES, KINETIC resolution, BIOCATALYSIS, ENZYMES, and AMINE oxidase

Biocatalytic syntheses often require unfavorable conditions, which can adversely affect enzyme stability. Consequently, improving the stability of biocatalysts is needed, and this is often achieved by immobilization. In this study, we aimed to compare the stability of soluble and immobilized transaminases from different species. A cysteine in a consensus sequence was converted to a single aldehyde by the formylglycine-generating enzyme for directed single-point attachment to amine beads. This immobilization was compared to cross-linked enzyme aggregates (CLEAs) and multipoint attachments to glutaraldehyde-functionalized amine- and epoxy-beads. Subsequently, the reactivity and stability (i.e., thermal, storage, and solvent stability) of all soluble and immobilized transaminases were analyzed and compared under different conditions. The effect of immobilization was highly dependent on the type of enzyme, the immobilization strategy, and the application itself, with no superior immobilization technique identified. Immobilization of HAGA-beads often resulted in the highest activities of up to 62 U/g beads, and amine beads were best for the hexameric transaminase from Luminiphilus syltensis. Furthermore, the immobilization of transaminases enabled its reusability for at least 10 cycles, while maintaining full or high activity. Upscaled kinetic resolutions (partially performed in a SpinChemTM reactor) resulted in a high conversion, maintained enantioselectivity, and high product yields, demonstrating their applicability. [ABSTRACT FROM AUTHOR]

HYDROGELS, ELASTICITY, INCLUSION compounds, CHEMICAL structure, POLYMER networks, DOUBLE bonds, MACROMONOMERS, and POLYACRYLAMIDE

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]

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]

SULFUR compounds, SOLIDS, DIPYRRINS, SULFUR, COMPUTATIONAL chemistry, and ETHERS

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]

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]

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]

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, 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]

DIAMINES, MOLECULAR docking, CYTOCHROME c, SCHIFF bases, PEROXIDASE, ESCHERICHIA coli, and DENSITY functional theory

• Synthesis of symmetrical bis-benzoxazines. • Density Functional Theory (DFT) estimation was disclosed for compound 5e. • A Molecular docking study was carried out against Cytochrome c Peroxidase (2 × 08). • Compounds 3 g, 4 g, 5c, and 5 g showed remarkable antimicrobial activity. • Compounds 3b, 3c, 3 g, 4c, 5b, & 5f displayed good antioxidant activity. We herein report the efficient synthesis of symmetrical bis-benzoxazines by substituted salicylaldehydes and alkyl diamines. The substituted salicylaldehydes (1a-d) and alkyl diamines (2a-b) on reaction synthesize Schiff's bases 3a-h. These compounds on reduction with NaBH4 in dry methanol yielded 2,2′-((alkyl-1,2-diylbis (azanediyl)) bis(methylene))disubstituted phenol, 4a-h in good yield. The preferable 1,2-bis(6-substituted-2 H -benzo[ e ][1,3]oxazin-3(4 H)-yl)ethanes, 5a-h formed when the compounds 4a-h undergo an internal Mannich reaction with formaldehyde. Different spectroscopic methods prove the formation of all the compounds. The compounds 3 g, 4 g, 5c, and 5 g showed excellent antibacterial activity against S. aureus, E. coli, S. Typhi, and B. subtilis , antifungal activity against A. flavus, C. Albicans, A. niger, and C. oxysporum with MIC values of 6.25 µg/ml and anti-TB activity against M. tuberculosis for which is equivalent to the standard drug. Furthermore, studies on the antioxidant activity of the compounds 3b, 3c, 3 g, 4c, 5b, and 5f revealed that they have excellent antioxidant activity. To comprehend the electronic behavior of compound 5e, Density Functional Theory estimations at the DFT/B3LYP level via 6–31G++ (d, p) replicate the structure and geometry. The first-order hyperpolarizability calculation finds the non-linear visual feature of compound 5e. Finally, HOMO and LUMO analysis were used for the charge transfer interface between the structures. Against Cytochrome c Peroxidase (2 × 08), the compounds 3c and 4c exhibited good docking properties in Molecular docking studies. [Display omitted] [ABSTRACT FROM AUTHOR]

ALBIZIA, NORMAL-phase chromatography, ANTI-infective agents, LEGUMES, FRUIT, and COLUMN chromatography

Twenty-two compounds were isolated from the fruit of Albizia lebbeck including one unprecedented, rare amino acid-derived zwitterionic and one new flavone derivative. The isolation was performed on repeated column chromatography over silica gel and their structures were determined by 1D-, 2D-NMR and HR-ESI-MS spectra together with reported data in the literature. The chemophenetic significance is also discussed. Some isolated compounds were reported for the first time to be found in the species. Additionally, compound 2 showed antibacterial activity and compounds 1 and 2 revealed moderate cytotoxic activity against the Raw 264.7 cancer cell line with IC50 values of 37.19 µM and 29.36 µM, respectively. Furthermore, a proposed biosynthetic pathway of compound 1 is described. [ABSTRACT FROM AUTHOR]

AMINO acids, COLLOIDAL gels, CATALYST supports, LIGHT beating spectroscopy, and TRANSMISSION electron microscopy

Polyacrylamide-based waterborne microgels were prepared with copolymerized carboxylic acid and tertiary amine moieties. The colloidal gels were loaded with palladium nanoparticles and utilized for the Suzuki–Miyaura cross-coupling of amino acids and peptides. The thermoresponsive properties of the prepared microgels were characterized by means of photon correlation spectroscopy (PCS) at solvent conditions of the catalytic reaction. The localization and morphology of the incorporated nanoparticles were characterized with transmission electron microscopy (TEM). Palladium-catalyzed Suzuki–Miyaura cross-coupling of N α-Boc-4-iodophenylalanine and N α-Boc-7-bromotryptophan with phenylboronic acid was carried out under ambient atmosphere in water at 20, 37, and 60 °C, respectively. The properties of the thermoresponsive microgel showed a strong influence on the reactivity and selectivity towards the respective substrate. For the amine containing microgels, a recyclability for up to four cycles without loss in activity could be realized. Furthermore, the systems showed good catalytic activity regarding Suzuki–Miyaura cross-coupling of halogenated amino acids in selected tri- and tetrapeptides. [ABSTRACT FROM AUTHOR]

IODINE, CHEMICAL synthesis, HYDRAZONES, POTASSIUM carbonate, HETEROCYCLIC compounds, OXIDATION, and HYDRAZONE derivatives

An oxidative cyclization of 2‐arenoxybenzaldehyde N‐acyl hydrazones 3 a–o was employed to synthesize new 2,5‐disubstituted 1,3,4‐oxadiazole compounds 4 a–d, 4 f–i, 4 k–n. This method involves oxidative cyclization of 2‐arenoxybenzaldehyde N‐acyl hydrazones 3 a–o with molecular iodine mediated catalysis in which potassium carbonate served as a base. Characterization of all the synthesized novel compounds involved, proton and carbon NMR, mass spectrometry, and CHN elemental analysis. The synthesis of novel 2,5‐disubstituted 1,3,4‐oxadiazoles may display potential to provide pharmacologically important heterocyclic compounds. [ABSTRACT FROM AUTHOR]

CHEMICAL processes, ORGANIC acids, AMIDES, ENANTIOMERIC purity, ENZYMES, AMIDATION, ACYL chlorides, and ORGANIC solvents

Efficient amide formation is of high importance for the chemical and pharmaceutical industry. The direct biocatalytic one-pot transformation of acids into amides without substrate activation is a highly desirable but highly challenging reaction; this is why in general the acid is activated using additional reagents before amide formation occurs. In particular, amidation of α-amino acids is challenging and in general requires protection strategies for the amino functionality. A further challenge is the low solubility of the unprotected amino acids in organic solvents. Furthermore, the amidation process is prone to racemisation as observed for the acyl chloride derivative. These three challenges may be addressed using biocatalysis. Here the enzyme catalyzed, racemization-free amidation of unprotected L-proline with ammonia in an organic solvent is described. Comprehensive reaction, solvent and enzyme engineering allowed obtaining high L-prolinamide concentrations. For instance at 145 mM substrate concentration, 80% conversion was achieved employing an immobilized CalB variant and ammonia in 2-methyl-2-butanol at 70 °C. A twofold increase in L-prolinamide formation was achieved employing the immobilized and engineered enzyme variant CalBopt-24 T245S compared to wild type CalB. In contrast to chemical processes, racemization, halogenated solvents and waste are avoided/minimized and atom efficiency is significantly improved from 45.5% to 86.4%. The excellent optical purity of the obtained product (ee >99%) and the stability of immobilized CalB pave the way for an innovative industrial process to produce L-prolinamide, a key intermediate in drug synthesis. [ABSTRACT FROM AUTHOR]