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The reduction of oximes was recently identified as a promiscuous activity of Old Yellow Enzymes (OYEs). This reaction involves a two‐step reduction of α‐oxime‐ß‐ketoesters to the corresponding amines, which spontaneously dimerise to yield pyrazine derivatives. This biotransformation is currently limited to substrates with small substituents like methyl/ethyl on the keto moiety. We used a structure‐based approach to engineer 12‐oxophytodienoate reductase 3 (OPR3) from Solanum lycopersicum as a prototypical OYE to accept oximes with bulkier substituents. To this end, three single and two double variants were prepared and tested on six oxime substrates. The engineered variants indeed showed activity on some of the bulkier substrates, which had not been converted at all by the wild‐type enzyme, including the diester compound diethyl‐2‐(hydroximino) malonate. While we were unable to identify variants capable of converting substrates with branched and aromatic substituents, the results demonstrate the validity of our engineering approach, suggesting potential pathways for expanding the substrate scope of OYEs. [ABSTRACT FROM AUTHOR]

Detailed experimental and computational studies of the nitrone 3,3‐dimethyl‐6‐phenyl‐2,3‐dihydro‐1,2,4‐triazin‐4‐oxide (2), which is a cyclized product of an open‐chain isomer 2‐phenyl‐2‐(propan‐2‐ylidenehydrazono)acetaldehyde oxime (1), are reported. The isolated compound 2 was characterized by elemental analysis, powder X‐ray diffraction, IR and UV‐vis spectroscopy, and spectrofluorometry. Electronic properties of 1 and 2 were elucidated by the DFT‐based calculations in water, which revealed that both compounds are pronounced electrophiles. The ADMET properties of the oxime 1 and nitrone 2 were predicted using the SwissADME, which includes the BOILED‐Egg method, and ProTox‐II online tools. Using a molecular docking approach, the discussed compounds were also predicted to actively interact with all the studied herein SARS‐CoV‐2 proteins. The most pronounced activity for both discussed compounds was established with Nonstructural protein 14 (Nsp14_N7‐MTase). Complex Nsp14_N7‐MTase‐1 is characterized by the calculated ligand efficiency scores being close for a Hit. [ABSTRACT FROM AUTHOR]

Six novel brominated bis-pyridinium oximes were designed and synthesized to increase their nucleophilicity and reactivation ability of phosphorylated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Their pKa was valuably found lower to parent non-halogenated oximes. Stability tests showed that novel brominated oximes were stable in water, but the stability of di-brominated oximes was decreased in buffer solution and their degradation products were prepared and characterized. The reactivation screening of brominated oximes was tested on AChE and BChE inhibited by organophosphorus surrogates. Two mono-brominated oximes reactivated AChE comparably to non-halogenated analogues, which was further confirmed by reactivation kinetics. The acute toxicity of two selected brominated oximes was similar to commercially available oxime reactivators and the most promising brominated oxime was tested in vivo on sarin- and VX-poisoned rats. This brominated oxime showed interesting CNS distribution and significant reactivation effectiveness in blood. The same oxime resulted with the best protective index for VX-poisoned rats. [ABSTRACT FROM AUTHOR]

An overview is given on the significance of the oxime moiety in crop protection chemistry. This review focuses on the two most important aspects of agrochemical oximes, which are the occurrence and role of oxime groups in compounds with herbicidal, fungicidal and insecticidal activity, as well as the application of oxime derivatives as intermediates in the synthesis of crop protection agents not bearing any oxime function. Especially noteworthy is the fact, that in the synthesis of agrochemicals, oximes can be cyclized to isooxazoline, isoxazole, oxadiazole, oxazine, pyrrole, isothiazole and imidazole rings. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is the most common primary malignant tumor of the liver, and its incidence is increasing worldwide. There is a need to develop new therapeutic strategies to treat the disease. In this study, we synthesised the oxime derivative of thymoquinone and investigated cytotoxicity, genotoxicity, and apoptosis in hepatocellular cancer cells. The synthesised thymoquinone-oxime structure was confirmed by NMR. After incubating the hepatocellular cancer cell line for 24 h, the cytotoxicity ATP by luminometric, intracellular reactive oxygen species, and intracellular calcium by fluorometric. The mitochondrial membrane potential was determined by flow cytometry. DNA damage by alkaline single-cell gel electrophoresis, and apoptosis damage by acridine orange/ethidium bromide double dye method. Concentrations of thymoquinone-oxime statistically increased cytotoxicity, intracellular reactive oxygen species, intracellular calcium, apoptosis, and DNA damage in a concentration-dependent manner. Mitochondrial membrane potential and glutathione levels are also decreased. These findings show that thymoquinone-oxime has an anti-tumor effect on hepatocellular carcinoma cells. Among many herbs, Black seed (Nigella sativa) belonging to the Ranunculaceae family has been recognised worldwide as one of the most valuable nutrient-rich herbs There is no relevant data on the effect of the newly synthesised oxime derivative of TQ (TQ-ox) in cancer cells HEP-G2 A new TQ derivative has a higher anti-tumor effect on hepatocellular carcinoma [ABSTRACT FROM AUTHOR]

This study involved the synthesis and investigation of the anticancer and antioxidant capabilities of six newly developed ligands generated from 1,3,4‐thiadiazole and diphenyl ether keto oxime which has never been synthesized before, together with their transition metal complexes. The obtained ligands were characterized using elemental analysis, FTIR, 1H NMR, 13C NMR, and mass spectroscopy. Polymeric complexes of the obtained ligands were synthesized by reacting all ligands with MCl2.nH2O (M: Mn2+/Co2+)/Ni2+/Cu2+)) salts. The polymeric complexes′ structures were determined using elemental analysis, ICP‐AES, FTIR spectroscopy, UV‐vis spectroscopy, magnetic susceptibility analysis, and thermogravimetric analysis. Subsequently, the ligands were examined for their anticancer properties. To achieve this objective, the HT‐22 cell line, which consists of healthy mouse hippocampus neuronal cells, is utilized as the control group. Additionally, the MCF7 (breast cancer), MDA‐MB‐231 (breast cancer), C6 (rat glioma), HT‐29 (colon cancer), and A549 (lung carcinoma) cell lines are employed in cell culture research as representatives of cancerous cell lines. Based on the cell culture investigations, some of the synthesized ligands showed moderate to good anti‐cancer activity, especially for both colon cancer and brain tumors. Finally, a molecular docking analysis was conducted utilizing MOE software to ascertain the binding affinity between the synthesized ligands and the specific proteins of interest. [ABSTRACT FROM AUTHOR]

A new application involving a water–stable amido–functionalized allylboronate has been developed for 1,2‐addition to carbon–nitrogen double bonds. The process achieves highly enantioselective allylation of aldoxime derivatives in water, by employing O‐Boc oximes as substrates under Zn(OH)2–chiral aminophenol catalysis. This process affords the corresponding homoallylic amines with 91–96 % ee. The products could be transformed into N‐hydroxy‐γ‐lactam or 1,2‐oxazinan‐6‐one, through an acidic or a protection‐acidic treatment sequence, respectively, almost without enantiopurity loss. [ABSTRACT FROM AUTHOR]

The Beckmann rearrangement of ketoximes to their corresponding amides, using a Brønsted acid-mediated fragmentation and migration sequence, has found wide-spread industrial application. We postulated that the development of a methodology to access ylideneamino sulfates using tributylsulfoammonium betaine (TBSAB) would afford isolable Beckmann-type intermediates and competent partners for subsequent rearrangement cascades. The ylideneamino sulfates generated, isolated as their tributylammonium salts, are sufficiently activated to undergo Beckmann rearrangement without additional reagent activation. The generation of sulfuric acid in situ from the ylideneamino sulfate giving rise to a routine Beckmann rearrangement and additional amide bond cleavage to the corresponding aniline was detrimental to reaction success. The screening of bases revealed inexpensive sodium bicarbonate to be an effective additive to prevent classic Brønsted acid-mediated fragmentation and achieve optimal conversions of up to 99%. [ABSTRACT FROM AUTHOR]

Water is not a good solvent for most organic compounds, yet water can offer many benefits to some organic reactions, hence enriching organic chemistry. Herein, the unique divergent reactivity of 2‐substituted indoles with ⋅NO sources is presented. The amount of water solvent was harnessed for a scalable, benign, and expedient synthesis of indolenine oximes, albeit with water's inability to dissolve the reactants. 2‐Methoxyethyl nitrite, which has been tailored for reactions in water, empowered this protocol by enhancing the product selectivity. We further report on chemoselective transformations of the products that rely on their structural features. Our findings are expected to offer access to an underexplored chemical space. The platform is also applicable to oximinomalonate synthesis. Mechanistic studies revealed the important role of water in the reversal of stability between oxime and nitroso compounds, promoting the proton transfer. [ABSTRACT FROM AUTHOR]

During recrystallization from benzene or toluene of the products of interaction of triarylantimony or triarylbismuth with carboxylic acids, phenol, or oxime in the presence of tert-butyl hydroperoxide (molar ratio 1 : 2 : 1, diethyl ether, 24°C, 24 h), minor products, adducts of aryl compounds of antimony or bismuth of the Ar3MX2 type with carboxylic acids, phenol, and oxime are isolated. According to X-ray structural analysis conducted at 293 K using an automatic D8 Quest Bruker four-circle diffractometer (two-coordinate CCD detector, Mo Kα radiation, λ = 0.71073 Å, graphite monochromator), the metal atoms in the crystals of m-Tol3Sb[OC(O)C6H3F2-2,5]2 ⋅ HOC(O)C6H3F2-2,5 (1) [C42H31O6F6Sb, M 867.42; triclinic system, symmetry group P ; cell parameters a = 8.78(5) Å, b = 13.10(6) Å, c = 16.64(8) Å; α = 102.86(19)°, β = 99.3(2)°, γ = 98.0(3)°; V = 1813(16) Å3; Z 2; reflection index intervals –7 ≤ h ≤ 7, –11 ≤ k ≤ 11, –14 ≤ l ≤ 14; total reflections 14 149; independent reflections 2603; Rint 0.0284; GOOF 1.049; R1 = 0.0348, wR2 = 0.0938; residual electron density 0.55/–0.42 e/Å3], p‑Tol3Bi[OC(O)C6HF4-3,4,5,6]2 ⋅ HOC(O)C6HF4-3,4,5,6 (2) [C42H25O6F12Bi, M 1062.60; triclinic system, symmetry group P ; cell parameters a = 12.246(11) Å, b = 12.976(18) Å, c = 14.391(13) Å; α = 68.27(4)°, β = 69.89(3)°, γ = 86.11(5)°; V = 1990(4) Å3; Z 2; reflection index intervals –15 ≤ h ≤ 15, ‒16 ≤ k ≤ 16, –18 ≤ l ≤ 18; total reflections 48 542; independent reflections 9207; Rint 0.0321; GOOF 1.136; R1 = 0.0322, wR2 = 0.0648; residual electron density 1.81/–1.08 e/Å3], [(2-MeO-5-BrC6H3)3SbOC6H4Br-4]2O ⋅ 2HOC6H4Br-4 (3) [C66H54Br10O11Sb2, M 2065.69; monoclinic system, symmetry group C21/c; cell parameters a = 12.017(14) Å, b = 25.54(3) Å, c = 13.181(18) Å; β = 116.71(5)°; V = 3613(8) Å3; Z 2; reflection index intervals –13 ≤ h ≤ 13, –27 ≤ k ≤ 27, –12 ≤ l ≤ 12; total reflections 29 461; independent reflections 4545; Rint 0.0656; GOOF 1.062; R1 = 0.0565, wR2 = 0.1200; residual electron density 1.59/–1.31 e/Å3], and [(2-MeO)C6H4]3Sb[ON=CHC4H2(NO2-2)]2 ∙ 2HON=CHC4H2(NO2-2) ∙ 1/2PhH (4) [C44H38N8O19Sb, M 1104.57; triclinic system, symmetry group P ; cell parameters a = 10.240(5) Å, b = 14.480(8) Å, c = 18.093(11) Å; α = 103.43(3)°, β = 104.50(2)°, γ = 98.876(17)°; V = 2461(2) Å3; Z 2; reflection index intervals –13 ≤ h ≤ 13, –18 ≤ k ≤ 18, –23 ≤ l ≤ 23; total reflections 58 643; independent reflections 10 886; Rint 0.0558; GOOF 1.061; R1 = 0.0429, wR2 = 0.1095; residual electron density 1.91/–0.51 e/Å3] show distorted trigonal-bipyramidal coordination with oxygen atoms in axial positions. Full tables of atom coordinates, bond lengths, and valence angles for the structures are deposited in the Cambridge Structural Database (no. 2050322 for 1, no. 2045173 for 2, no. 2070387 for 3, and no. 2119790 for 4; deposit@ccdc.cam.ac.uk; https://www.ccdc.cam.ac.uk). [ABSTRACT FROM AUTHOR]

Hydroxylation of aryl sulfonium salts could be realized by utilizing acetohydroxamic acid and oxime as hydroxylative agents in the presence of cesium carbonate as a base, leading to a variety of structurally diverse hydroxylated arenes in 47–95% yields. In addition, the reaction exhibited broad functionality tolerance, and a range of important functional groups (e.g., cyano, nitro, sulfonyl, formyl, keto, and ester) could be well amenable to the mild reaction conditions. [ABSTRACT FROM AUTHOR]

Abstract Introduction: In the last two decades, nanoparticles obtained from graphene oxide (GO) have been of great interest to researchers in various sciences, including chemistry. Also, the functionalization of graphene oxide can improve its functional properties. In industrial chemistry, one of the most important applications of functionalized graphene oxide is its use as a catalyst. Methods: In this project, after preparing graphene oxide nanoparticles, they were grafted by functionalized polyamine (GO-NH2), and then by Preissler's heteropolyacid (Pr@GO-NH2). Preysler is one of the types of polyoxometalate clusters, which has unique characteristics and is used as a Lewis acid catalyst due to having a large number of acidic protons. The structure of these new nanoparticles was investigated by spectral methods such as XRD, FTIR, SEM, TEM, EDX and TGA. Also, after preparing Pr@GO-NH2, its catalytic activity was measured in the reaction of producing oxime from aldehyde and hydroxylamine. Findings: By using the mentioned spectral methods and comparing some spectra of Pr@GO-NH2 with GO-NH2 and GO, the structure of Pr@GO-NH2 nanoparticles was identified and confirmed. Also, the preparation of oxime in the presence of these nanoparticles confirmed its high catalytic activity. Based on the obtained results, this reaction was carried out in the presence of 0.03 grams of catalyst at 50°C for 30 minutes and in the presence of water as an environmentally friendly solvent.

The high annual mortality rate of organophosphorus (OP) poisoning indicates that the treatment is mostly ineffective in this regard. It has been suggested to add calcium channel blocking (CCB) drugs or magnesium sulfate (MgSO4) to normal care to decrease the release of acetylcholine (ACh) at the cholinergic synapse. Moreover, the diagnosis of OP poisoning is chiefly based on clinical evidence. Oximes and atropine are the recognized antidotes of OP. However, low-priced medications such as MgSO4 and sodium bicarbonate (NaHCO3), as well as novel adjunct therapies, have been introduced recently. Furthermore, antioxidants are recommended for managing OP poisoning. In addition, hemoperfusion, fresh frozen plasma (FFP), and K-oximes are a number of innovative management modalities that deserve further evaluation. However, prevention seems to be the most effective management modality in this respect. Therefore, this study aimed to briefly discuss the controversies in OP poisoning management and present recent advances in its management and prognosis. The results of this study revealed that multiple factors including type of exposure, acetylcholinesterase (AChE) plasma level, time of hospitalization, and severity confirming OP poisoning should be considered to provide the best treatment strategy.

Beckmann rearrangement has been quite successful in the preparation of many medicinally potent scaffolds. In synthetic organic chemistry, the Beckmann rearrangement is quite popular, caprolactam is synthesized from cyclohexanone oxime on a large scale for Nylon‐6 production. The function of numerous catalysts and media in the Beckmann rearrangement has been discussed in depth in this review. In the last 20 years, Beckmann rearrangement catalysis has evolved from a potentially hazardous to a more environmentally friendly catalyst, as a result of greater usage. Catalytic performance and synthetic performance of various catalytic systems have been re‐evaluated in the present review article. [ABSTRACT FROM AUTHOR]

Naphtho[1,8-de][1,2]oxazin-4-ol and its acyl or benzyl derivatives ring open to various 2,8-dihydroxy-1-naphthonitriles, which, through (de)protection protocols and reduction, afford the target (E)-2-hydroxy-8-methoxy-1-naphthaldehyde. This was converted to its corresponding oxime, which was oxidatively o-cyclized with phenyliodine(III) diacetate (PIDA) to 9-methoxynaphtho[1,2-d]isoxazole 2-oxide. The latter, in deuterated DMSO at room temperature, was rearranged to its isomer 2-hydroxy-8-methoxy(naphthalen-1-yl)nitrile oxide. The isomerization was detected by time-course plot 1H NMR spectroscopy and further identified from its 13C NMR and HRMS spectra. The nitrile oxide was stable in (non)deuterated DMSO for at least 18 h. A 3,4-bis(2-hydroxy-8-methoxynaphthalen-1-yl)-1,2,5-oxadiazole 2-oxide, as a dimerization product or an isocyanate as a rearrangement isomer, was ruled out, the former by its HRMS spectrum and the latter by its 1,3-dipolar cycloaddition reactions to substituted isoxazoles. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is an essential reactive oxygen species and a signal molecule in plants. Although several studies have proposed the occurrence of oxidative NO production, only reductive routes for NO production, such as the nitrate (NO-3) -upper-reductase pathway, have been evidenced to date in land plants. However, plants grown axenically with ammonium as the sole source of nitrogen exhibit contents of nitrite and NO 3 −, evidencing the existence of a metabolic pathway for oxidative production of NO. We hypothesized that oximes, such as indole-3-acetaldoxime (IAOx), a precursor to indole-3-acetic acid, are intermediate oxidation products in NO synthesis. We detected the production of NO from IAOx and other oximes catalyzed by peroxidase (POD) enzyme using both 4-amino-5-methylamino-2′,7′-difluorescein fluorescence and chemiluminescence. Flavins stimulated the reaction, while superoxide dismutase inhibited it. Interestingly, mouse NO synthase can also use IAOx to produce NO at a lower rate than POD. We provided a full mechanism for POD-dependent NO production from IAOx consistent with the experimental data and supported by density functional theory calculations. We showed that the addition of IAOx to extracts from Medicago truncatula increased the in vitro production of NO, while in vivo supplementation of IAOx and other oximes increased the number of lateral roots, as shown for NO donors, and a more than 10-fold increase in IAOx dehydratase expression. Furthermore, we found that in vivo supplementation of IAOx increased NO production in Arabidopsis thaliana wild-type plants, while prx33-34 mutant plants, defective in POD33-34, had reduced production. Our data show that the release of NO by IAOx, as well as its auxinic effect, explain the superroot phenotype. Collectively, our study reveals that plants produce NO utilizing diverse molecules such as oximes, POD, and flavins, which are widely distributed in the plant kingdom, thus introducing a long-awaited oxidative pathway to NO production in plants. This knowledge has essential implications for understanding signaling in biological systems. This study reveals a new metabolic pathway for oxidative production of NO in plants. It is found that plant POD hemoproteins are capable of catalyzing in vitro production of NO from oximes, most efficiently from the IAA precursor indole-3-acetaldoxime (IAOx), that in vivo production of NO is higher in IAOx-supplemented A. thaliana and M. truncatula plants but is lost in A. thaliana mutant plants defective in POD33 and POD34. Through density functional theory-based calculations, a modeled mechanism for POD reaction is developed, which is correlated with the experimental results obtained. [ABSTRACT FROM AUTHOR]

Owing to their potential to cause serious adverse health effects, significant efforts have been made to develop antidotes for organophosphate (OP) anticholinesterases, such as nerve agents. To be optimally effective, antidotes must not only reactivate inhibited target enzymes, but also have the ability to cross the blood–brain barrier (BBB). Progress has been made toward brain-penetrating acetylcholinesterase reactivators through the development of a new group of substituted phenoxyalkyl pyridinium oximes. To help in the selection and prioritization of compounds for future synthesis and testing within this class of chemicals, and to identify candidate broad-spectrum molecules, an in silico framework was developed to systematically generate structures and screen them for reactivation efficacy and BBB penetration potential. [ABSTRACT FROM AUTHOR]

Enantiomerically pure acyclic O,O‐acetal compounds (up to 97 % ee) have been accessed through chemo‐, regio‐ and enantioselective palladium‐catalyzed addition of oximes to alkoxyallenes. DFT calculations support that a protonative hydropalladation pathway is favourable, in which the hydrogen bonding interaction between the amide group of the diphosphine ligand and the alkoxyallene is critical for the highly stereoselective formation of the dioxygenated stereogenic center. [ABSTRACT FROM AUTHOR]

Using computational methods and chemical intuition, the proposed structure of janthinolide A is shown to be incorrect. It is further shown that the material described as janthinolide A is highly likely to be janthinolide C. [ABSTRACT FROM AUTHOR]

Pyridine oximes produced from aldehyde or ketone with hydroxylamine (NH2OH) have been widely applied in pharmaceutics, enzymatic and sterilization. However, the important raw material NH2OH exhibits corrosive and unstable properties, leading to substantial energy consumption during storage and transportation. Herein, this work presents a novel method for directly synthesizing highly valuable pyridine oximes using in situ generated NH2OH from electrocatalytic NO reduction with well‐design nanofiber membranes (Al‐NFM) derived from NH2‐MIL‐53(Al). Particularly, 2‐pyridinealdoxime, the precursor of antidote pralidoxime (2‐PAM) for nerve agents suffering from scarcity and high cost, was achieved with a Faraday efficiency up to 49.8 % and a yield of 92.1 %, attributing to the high selectivity of NH2OH production on Al‐NFM, further easily reacted with iodomethane to produce 2‐PAM. This study proposes a creative approach, having wide universality for synthesizing pyridine and other oximes with a range of functional groups, which not only facilitates the conversion of exhaust gas (NO) and waste water (NO2−) into valuable chemicals especially NH2OH production and in situ utilization through electrochemistry, but also holds significant potential for synthesis of neuro detoxifying drugs to humanity security. [ABSTRACT FROM AUTHOR]

Oxime reactivators of acetylcholinesterase are commonly used to treat highly toxic organophosphate poisoning. They are effective nucleophiles that can restore the catalytic activity of acetylcholinesterase; however, their main limitation is the difficulty in crossing the blood–brain barrier (BBB) because of their strongly hydrophilic nature. Various approaches to overcome this limitation and enhance the bioavailability of oxime reactivators in the CNS have been evaluated; these include structural modifications, conjugation with molecules that have transporters in the BBB, bypassing the BBB through intranasal delivery, and inhibition of BBB efflux transporters. A promising approach is the use of nanoparticles (NPs) as the delivery systems. Studies using mesoporous silica nanomaterials, poly (l-lysine)-graft-poly(ethylene oxide) NPs, metallic organic frameworks, poly(lactic-co-glycolic acid) NPs, human serum albumin NPs, liposomes, solid lipid NPs, and cucurbiturils, have shown promising results. Some NPs are considered as nanoreactors for organophosphate detoxification; these combine bioscavengers with encapsulated oximes. This study provides an overview and critical discussion of the strategies used to enhance the bioavailability of oxime reactivators in the central nervous system. [ABSTRACT FROM AUTHOR]

The asymmetric unit of the title molecule, C8H7NO3, consists of two molecules differing slightly in conformation and in their intermolecular interactions in the solid. The dihedral angle between the benzene and dioxolane rings is 0.20 (7)° in one molecule and 0.31 (7)° in the other. In the crystal, the two molecules are linked into dimers through pairwise O—H...N hydrogen bonds, with these units being formed into stacks by two different sets of aromatic π-stacking interactions. The stacks are connected by C—H...O hydrogen bonds. A Hirshfeld surface analysis indicates that the most significant contacts in the crystal packing are H...O/O...H (36.7%), H...H (32.2%) and C...H/H...C (12.7%).

The BODIPY-labelled oxime reactivator was prepared and used to study its biodistribution into central nervous system. The newly synthesized oxime was found to be weak inhibitor of acetylcholinesterase and strong inhibitor of butyrylcholinesterase. Its reactivation ability for organophosphate inhibited acetylcholinesterase was found similar to a parent oxime. The BODIPY-labelled oxime was further encapsulated into recombinant human H-ferritin and evaluated in vitro and in vivo. The oxime or encapsulated oxime were found to be bioaccumulated primarily in liver and kidneys of mice, but some amount was distributed also to the brain, where it was detectable even after 24 h. The BODIPY-labelled oxime encapsulated to human H-ferritin showed better CNS bioaccumulation and tissue retention at 8 and 24 h time points compared to free oxime, although the fluorescence results might be biased due to BODIPY metabolites identified in tissue homogenates. Taken together, the study demonstrates the first utilization of recombinant ferritins for changing the unfavourable pharmacokinetics of oxime reactivators and brings promising results for follow-up studies.

Dynamic hydrogels offer the opportunity to meet the expectations of smart materials with adaptable properties such as stimuli responsiveness, self‐healing, shear thinning, stress relaxation, dynamic viscoelasticity, energy dissipation mechanisms, time‐dependent adaptation, etc. In the past decades, reversible C═N bonds including imine, hydrazone, and oxime have received great research interest in the design of dynamic polymer networks (DPNs). Moreover, reversible C═N bonds can be well‐integrated into DPNs in combination with permanent covalent crosslinks and/or other dynamic bonds (supramolecular interactions and dynamic covalent bonds), thus outfitting the hydrogels with enhanced mechanical properties, multiresponsiveness, printability, adhesion, and various other functions. This literature review first describes how reversible C═N bonds can be introduced into hydrogels from the perspective of dynamic bonds and network topologies. The design strategies (building blocks, crosslink type combinations, network topologies) reported in the literature are then discussed, as well as the effects of dynamic crosslinking on the hydrogel properties and the potential applications. [ABSTRACT FROM AUTHOR]

Isocembrol C(3)-ketoxime was synthesized regioselectively and the C—C bond was cleaved under the standard Beckmann fragmentation conditions. Subsequent hydrolysis of nitrile to give ω-hydroxy acid and cyclization on treatment with 2,2′-dipyridyl disulfide finalized the synthesis of 15-membered macrolide. [ABSTRACT FROM AUTHOR]

Modular trans‐acyltransferase polyketide synthases (trans‐AT PKSs) are enzymatic assembly lines that biosynthesize complex polyketide natural products. Relative to their better studied cis‐AT counterparts, the trans‐AT PKSs introduce remarkable chemical diversity into their polyketide products. A notable example is the lobatamide A PKS, which incorporates a methylated oxime. Here we demonstrate biochemically that this functionality is installed on‐line by an unusual oxygenase‐containing bimodule. Furthermore, analysis of the oxygenase crystal structure coupled with site‐directed mutagenesis allows us to propose a model for catalysis, as well as identifying key protein‐protein interactions that support this chemistry. Overall, our work adds oxime‐forming machinery to the biomolecular toolbox available for trans‐AT PKS engineering, opening the way to introducing such masked aldehyde functionalities into diverse polyketides. [ABSTRACT FROM AUTHOR]

Alzheimer Disease (AD) is a neurological disorder that causes the brain to shrink and brain cells to eventually die. Main symptom of AD is dementia. Today, approximately 50 million people worldwide are estimated to have AD. However, there is not a determined cure known against AD today. There are just four drugs against AD on the market. Unfortunately, none of them can totally destroy AD. Thus, discovering new molecules having capability to treat AD is required and significant. Benzofurans and oximes demonstrate a number of biological effects including anti‐inflammatory and brain‐barrier penetrating. For this reason, a number of novel compounds bearing oxime and benzofuran skeletons were designed and synthesized, and their anticholinesterase activities were investigated. Based on the results, several molecules demonstrated very strong anticholinesterase activities against both AChE and BChE enzymes, even much better than the reference drug molecule, Galantamine. Besides, structure‐activity relationship (SAR) studies belonging to these chemical cores were revealed through this study for the first time. Various derivatives with different types of selective activities were obtained, which brightens the detailed SAR tendency of these molecules. This study can contribute to discover a novel lead drug molecule against AD, which is an urgent need. [ABSTRACT FROM AUTHOR]

Epoxy, a typical thermosetting resin, exhibits excellent mechanical properties, thermal stability, and chemical resistance. However, it can cause environmental pollution when discarded prior to decomposition. In this study, a novel oxime epoxy based on 1,4‐benzoquinone dioxime was developed. It decomposes quickly under mild conditions and without requiring organic solvents, thus is environmentally friendly. The optimal curing temperature for benzoquinone oxime epoxy (BOE) with a curing agent was 85°C as determined by differential scanning calorimetry. In addition, the tensile strength and Young's modulus of the BOE/1,6‐hexanediamine (HMDA) resin are 20 and 400 MPa, respectively, and Tg is 76°C. Furthermore, thermogravimetric analysis revealed that the BOE resin was thermally stable. Interestingly, BOE/HMDA degraded in 8 h under mild conditions. This rapid degradation will facilitate the development of new chemically degradable epoxy molecules with embedded oximes and provide insights into solving the environmental problems caused by discarded epoxy resin. [ABSTRACT FROM AUTHOR]

Background: Vegetable viruses are difficult to prevent and control in the field, causing massive economic losses of agricultural production in the world. A new natural product‐based antiviral agent would be an effective means to control viral diseases. As a class of natural products, 1‐indanones present various pharmacologically actives, while their application in agriculture remains to be found. Results: A series of novel 1‐indanone derivatives were designed and synthesized and the antiviral activities were systematically evaluated. Bioassays showed that most compounds exhibited good protective activities against cucumber mosaic virus (CMV), tomato spotted wilt virus (TSWV), and pepper mild mottle virus (PMMoV). Notably, compound 27 exhibited the best protective effects against PMMoV with EC50 values of 140.5 mg L−1, superior to ninanmycin (245.6 mg L−1). Compound 27 induced immunity responses through multilayered regulation on mitogen‐activated protein kinase, plant hormone signal transduction and phenylpropanoid biosynthesis pathways. Conclusion: These 1‐indanone derivatives especially compound 27 can be considered as potential immune activators to resist plant virus. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The Beckmann rearrangement of ketoximes to their corresponding amides, using a Brønsted acid-mediated fragmentation and migration sequence, has found wide-spread industrial application. We postulated that the development of a methodology to access ylideneamino sulfates using tributylsulfoammonium betaine (TBSAB) would afford isolable Beckmann-type intermediates and competent partners for subsequent rearrangement cascades. The ylideneamino sulfates generated, isolated as their tributylammonium salts, are sufficiently activated to undergo Beckmann rearrangement without additional reagent activation. The generation of sulfuric acid in situ from the ylideneamino sulfate giving rise to a routine Beckmann rearrangement and additional amide bond cleavage to the corresponding aniline was detrimental to reaction success. The screening of bases revealed inexpensive sodium bicarbonate to be an effective additive to prevent classic Brønsted acid-mediated fragmentation and achieve optimal conversions of up to 99%.

Hydroxylation of aryl sulfonium salts could be realized by utilizing acetohydroxamic acid and oxime as hydroxylative agents in the presence of cesium carbonate as a base, leading to a variety of structurally diverse hydroxylated arenes in 47–95% yields. In addition, the reaction exhibited broad functionality tolerance, and a range of important functional groups (e.g., cyano, nitro, sulfonyl, formyl, keto, and ester) could be well amenable to the mild reaction conditions.

11H-Indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) and tryptanthrin-6-oxime are potent c-Jun N-terminal kinase 3 (JNK-3) inhibitors demonstrating neuroprotective, anti-inflammatory and anti-arthritic activity. However, the stereochemical configuration of the oxime carbon–nitrogen double bond (E- or Z-) in these compounds was so far unknown. In this contribution, we report the results of the determination of the double bond configuration in the solid state by single crystal X-ray diffraction and in solution by 1D and 2D NMR techniques and DFT calculations. It was found that both in the solid state and in solution, IQ-1 adopts the E-configuration stabilized by intermolecular hydrogen bonds, in contrast to previously assumed Z-configuration that could be stabilized only by an intramolecular hydrogen bond. [ABSTRACT FROM AUTHOR]

The c-Jun N-terminal kinase (JNK) family includes three proteins (JNK1-3) that regulate many physiological processes, including cell proliferation and differentiation, cell survival, and inflammation. Because of emerging data suggesting that JNK3 may play an important role in neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease, as well as cancer pathogenesis, we sought to identify JNK inhibitors with increased selectivity for JNK3. A panel of 26 novel tryptanthrin-6-oxime analogs was synthesized and evaluated for JNK1-3 binding (Kd) and inhibition of cellular inflammatory responses. Compounds 4d (8-methoxyindolo[2,1-b]quinazolin-6,12-dione oxime) and 4e (8-phenylindolo[2,1-b]quinazolin-6,12-dione oxime) had high selectivity for JNK3 versus JNK1 and JNK2 and inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcriptional activity in THP-1Blue cells and interleukin-6 (IL-6) production by MonoMac-6 monocytic cells in the low micromolar range. Likewise, compounds 4d, 4e, and pan-JNK inhibitor 4h (9-methylindolo[2,1-b]quinazolin-6,12-dione oxime) decreased LPS-induced c-Jun phosphorylation in MonoMac-6 cells, directly confirming JNK inhibition. Molecular modeling suggested modes of binding interaction of these compounds in the JNK3 catalytic site that were in agreement with the experimental data on JNK3 binding. Our results demonstrate the potential for developing anti-inflammatory drugs based on these nitrogen-containing heterocyclic systems with selectivity for JNK3. [ABSTRACT FROM AUTHOR]

The tubulin-microtubule system is a major target for a variety of small molecules which can interfere in cell cycle progression. Therefore, it serves as a prospective to control the incessant division of cancer cells. To identify novel inhibitors of the tubulin-microtubule system, a group of estrogen derivatives has been tested with tubulin as a target since literature surveys portray coveted behaviour from the same. Out of them, β-Estradiol-6-one 6- (O-carboxy methyl Oxime) abbreviated as Oxime, disrupts the cytoskeleton network and induces apoptosis with nuclei fragmentation. It has been revealed from the work that Oxime targets the colchicine binding site and binds tubulin in an entropy-driven manner. This suggests that structural variation might play a key role in modulating the anti-mitotic role of estrogen derivatives. Our work reveals that Oxime might serve as a lead molecule to nurture anti-cancer research, having the potential for recovery of the vast cancer population. [ABSTRACT FROM AUTHOR]

During the last years, the need to create textile materials provided with peculiar properties has grown significantly. In particular, new textiles are studied to be a first protection in the prevention of living organisms from pathogens. In this regard, modifying a textile material with biologically active compounds, such as antibacterial or antiviral peptides would be useful for many applications. Our work shows a study on the possibility of modifying cotton fabrics with peptides using thiazolidine and oxime chemoselective ligations. For this purpose, an enzymatic oxidation of cellulose in a heterogeneous phase and the possibility to reuse the oxidation solution for multiple times was successfully applied. Model peptides have been designed and synthesized in order to set up the conditions for conjugating peptides to cotton via either thiazolidine or oxime bond. A systematic study of the time, pH, and quantities needed for the best reaction conditions has been conducted. The efficiency and stability of the two chemoselective ligation bonds have been studied and compared. [ABSTRACT FROM AUTHOR]

The asymmetric unit of the title molecule, C8H7NO3, consists of two molecules differing slightly in conformation and in their intermolecular interactions in the solid. The dihedral angle between the benzene and dioxolane rings is 0.20 (7)° in one molecule and 0.31 (7)° in the other. In the crystal, the two molecules are linked into dimers through pairwise O--H-- -N hydrogen bonds, with these units being formed into stacks by two different sets of aromatic--stacking interactions. The stacks are connected by C--H-- -O hydrogen bonds. A Hirshfeld surface analysis indicates that the most significant contacts in the crystal packing are H-- -O/O-- -H (36.7%), H-- -H (32.2%) and C-- -H/H-- -C (12.7%). [ABSTRACT FROM AUTHOR]

The organophosphorus antidotes, so-called oximes, are able to restore the enzymatic function of acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) via cleavage of organophosphate from the active site of the phosphylated enzyme. In this work, the charged pyridinium oximes containing thiocarboxamide moiety were designed, prepared and tested. Their stability and pKa properties were found to be analogous to parent carboxamides (K027, K048 and K203). The inhibitory ability of thiocarboxamides was found in low µM levels for AChE and high µM levels for BChE. Their reactivation properties were screened on human recombinant AChE and BChE inhibited by nerve agent surrogates and paraoxon. One thiocarboxamide was able to effectively restore function of NEMP- and NEDPA-AChE, whereas two thiocarboxamides were able to reactivate BChE inhibited by all tested organophosphates. These results were confirmed by reactivation kinetics, where thiocarboxamides were proved to be effective, but less potent reactivators if compared to carboxamides.

In the molecule of the title compound, C9H11N5O2, the oxime and hydrazide groups are situated in a cis-position in relation to the C—C bond linking the two functional groups. The CH3C(=NOH)C(O)NH fragment deviates from planarity because of a twist between the oxime and amide groups. In the crystal, molecules are linked by O—H...O hydrogen bonds, forming zigzag chains in the [013] and [0\overline{1}3] directions.

The development of corrosion inhibitors with outstanding performance is a never-ending and complex process engaged in by researchers, engineers and practitioners. The computational assessment of organic corrosion inhibitors' performance is a crucial step towards the design of new task-specific materials. Herein, the electronic features, adsorption characteristics and bonding mechanisms of two pyridine oximes, namely 2-pyridylaldoxime (2POH) and 3-pyridylaldoxime (3POH), with the iron surface were investigated using molecular dynamics (MD), and self-consistent-charge density-functional tight-binding (SCC-DFTB) simulations. SCC-DFTB simulations revealed that the 3POH molecule can form covalent bonds with iron atoms in its neutral and protonated states, while the 2POH molecule can only bond with iron through its protonated form, resulting in interaction energies of −2.534, −2.007, −1.897, and −0.007 eV for 3POH, 3POH+, 2POH+, and 2POH, respectively. Projected density of states (PDOSs) analysis of pyridines–Fe(110) interactions indicated that pyridine molecules were chemically adsorbed on the iron surface. Quantum chemical calculations (QCCs) revealed that the energy gap and Hard and Soft Acids and Bases (HSAB) principles were efficient in predicting the bonding trend of the molecules investigated with an iron surface. 3POH had the lowest energy gap of 1.706 eV, followed by 3POH+ (2.806 eV), 2POH+ (3.121 eV), and 2POH (3.431 eV). In the presence of a simulated solution, MD simulation showed that the neutral and protonated forms of molecules exhibited a parallel adsorption mode on an iron surface. The excellent adsorption properties and corrosion inhibition performance of 3POH may be attributed to its low stability compared to 2POH molecules. [ABSTRACT FROM AUTHOR]

New N-substituted oxime derivatives (5b, 5d-g, 5i-k, and 5m) and known compounds (5a, 5c, 5h, 5g, 5l, and 5n-q) were obtained by reacting phenyl and butyl oxime chloride analogs with aniline, piperazine derivatives, piperidine, and diethylamine. Structures of all new compounds were determined by 1H NMR, 13C NMR, HRMS, and FTIR methods. All compounds were evaluated in vitro for their antiradical activity and hydrogen peroxide scavenging activity. Compounds 5g, 5h, 5i, 5j, 5k, 5l, 5m, and 5p have shown good antiradical activities with EC50 values < 1 (conc. antiradical (µM)/conc. DPPH (µM)). Similar results were obtained in the peroxide scavenging activity tests. These results have shown that piperidine and butyl substitution greatly increases the antiradical activity of the oximes. Compounds 5l and 5m were found to be the best radical scavengers. In addition, molecular docking studies were performed for compounds (5a-q) against CP450 (CYP1A2), NADPH oxidase, and Xanthine oxidase to predict their antioxidant capabilities through ROS-producing enzyme inhibitions. [ABSTRACT FROM AUTHOR]

In this study, a total of 13 compounds (5–17) were synthesized starting from oleanolic acid (OA), a natural triterpenoid. Five new compounds (10, 11, 12, 15 and 17), are the main targets of the study, which were synthesized for the first time in this work as oxime, imine and hydrazone derivatives of OA. Other compounds were previously obtained as natural or semi-synthetically. NMR and HRMS analyses were carried out to determine of structures of all the synthesized molecules. The inhibitory effects of the synthesized compounds on acetylcholinesterase (AChE), human carbonic anhydrase I (hCA I) and II (hCA II) were evaluated. Compounds 13 and 15 showed better inhibitory activity than the other compounds against both hCA I and hCA II isoenzymes, which are competing with AZA. In addition, compound 15 showed the strongest AChE inhibitory activity among all the tested compounds, with an IC50 value of 34.46 µM. [ABSTRACT FROM AUTHOR]

New hydrazone derivate, (1Z,2E)-2-(2-(1-(1,3-dimethyl-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)ethyl)hydrazineylidene)-2-(p-tolyl)acetaldehyde oxime (H2L) was synthesized by 5-acetyl-1,3-dimethyl-barbituric acid and p-methyl isonitrosophenylhydrazine. Its molecular and crystal structures were determined by single crystal X-ray analysis. It belongs to triclinic system P-1 space group with a = 7.1722 (3) Å, b = 10.5362 (4) Å, c = 11.7675 (5) Å, α = 98.844 (4)°, β = 98.882 (4)°, γ = 104.330 (4)°, Z = 2 and V = 833.95 (6) Å3. In the molecular structure, the intramolecular N–H···O and N–H···N hydrogen bonds enclose S(6) ring motifs. In the crystal structure, the intermolecular C–H···O and O–H···O hydrogen bonds link the molecules into centrosymmetric dimers, enclosing R22(10) and R44(10) ring motifs, in which they may be effective in stabilization of the structure. The Hirshfeld surface analysis of crystal structure indicates that the most important contributions for crystal packing are from H...H (48.5%), H...O/O...H (23.7%) and H...C/C...H (9.7%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in crystal packing. Computational chemistry indicates that in the crystal, O–H···O and C–H···O hydrogen bond energies are 95.9 and 87.5 kJ mol−1. The evaluation of the electrostatic, dispersion and total energy frameworks indicates that stabilization is dominated via the nearly equal strengths of the electrostatic and dispersion energy contributions. [ABSTRACT FROM AUTHOR]

Naphtho[1,8-de][1,2]oxazin-4-ol and its acyl or benzyl derivatives ring open to various 2,8-dihydroxy-1-naphthonitriles, which, through (de)protection protocols and reduction, afford the target (E)-2-hydroxy-8-methoxy-1-naphthaldehyde. This was converted to its corresponding oxime, which was oxidatively o-cyclized with phenyliodine(III) diacetate (PIDA) to 9-methoxynaphtho[1,2-d]isoxazole 2-oxide. The latter, in deuterated DMSO at room temperature, was rearranged to its isomer 2-hydroxy-8-methoxy(naphthalen-1-yl)nitrile oxide. The isomerization was detected by time-course plot 1H NMR spectroscopy and further identified from its 13C NMR and HRMS spectra. The nitrile oxide was stable in (non)deuterated DMSO for at least 18 h. A 3,4-bis(2-hydroxy-8-methoxynaphthalen-1-yl)-1,2,5-oxadiazole 2-oxide, as a dimerization product or an isocyanate as a rearrangement isomer, was ruled out, the former by its HRMS spectrum and the latter by its 1,3-dipolar cycloaddition reactions to substituted isoxazoles.

Nitrenes and nitrenoids are highly reactive species and the proposed key intermediates in nitrogen‐containing heterocyclic compound synthesis. In this work, we developed a practical method for the synthesis of phenanthridines by the reaction of oximes and Grignard reagents (with or without diethylzinc) via ring‐expansion of magnesium coordinated nitrenoid complex as the key step. The method has been used to synthesize optically active planar chiral ferrocenyl phenanthridines. [ABSTRACT FROM AUTHOR]

The Pd‐catalyzed coupling cyclization of δ,ϵ‐alkenyl oxime with (hetero)aryl and halides is presented, which affords seven membered N,O‐heterocycle, tetrahydro‐1,2‐oxezapines, in moderate to good yields. DFT calculation favors an outer‐sphere anti‐oxypalladation pathway and provides key insights on the reaction mechanism. The reaction represents an unprecedented example of seven‐membered ring formation by heterocyclization. [ABSTRACT FROM AUTHOR]

A facile synthesis of 1,3-difunctionalized 2-sulfonamidopropane derivatives by practical and novel reactions of N-(2,3-dibromopropyl)-aryl(alkyl)sulfonamide with substituted thiourea or oxime derivatives in the presence of MeONa without catalyst is described. [ABSTRACT FROM AUTHOR]

A new strategy for the synthesis of pyrrole through intramolecular cyclization of γ-alkynyl oximes promoted by SmI2 is reported for the first time. In contrast to the prior methods, the selection of oxime instead of oxime ether or ester as substrate makes the synthetic method without accompaniment of organic waste (ArCO2 H, AcOH, or ROH) because the hydroxyl group in oxime acts as the leaving group and is finally removed in the form of water molecule in the reaction. From a synthetic point of view, a series of pyrroles were obtained in this one-pot reaction with a broad scope of substrates and feasible reaction conditions. [ABSTRACT FROM AUTHOR]

A new strategy for the synthesis of pyrrole through intramolecular cyclization of γ-alkynyl oximes promoted by SmI2 is reported for the first time. In contrast to the prior methods, the selection of oxime instead of oxime ether or ester as substrate makes the synthetic method without accompaniment of organic waste (ArCO2 H, AcOH, or ROH) because the hydroxyl group in oxime acts as the leaving group and is finally removed in the form of water molecule in the reaction. From a synthetic point of view, a series of pyrroles were obtained in this one-pot reaction with a broad scope of substrates and feasible reaction conditions. [ABSTRACT FROM AUTHOR]

A series of new Coumarin hydrazone oxime scaffolds were synthesised as potential anti‐TB agents. The structures of the scaffolds were confirmed by spectroscopic and analytical techniques. X‐ray crystallography confirmed the structure of compound 6‐methyl‐4‐((((Z)‐((E)‐3‐(2‐phenylhydrazono)butan‐2‐ylidene)amino)oxy)methyl)‐2H‐chromen‐2‐one (5a). The coumarin hydrazone oxime scaffolds were tested in‐vitro against the Mycobacterium tuberculosis H37Rv strain, and Vero cells were used to assess cytotoxicity. Compound 5b was obtained as the hit candidate, exhibiting MIC 0.78 μg/mL, showing more potent anti‐TB activity than Rifamycin and comparable activity to Isoniazid. There was minimal cytotoxicity observed against Vero cells for the most active compounds, indicating a good safety‐profile.In addition, the most diligent compound 5b demonstrated substantial binding interactions at the PDB:4DQU enzyme's active site and also displayed greater C‐score value than that of 4DQU ligand which validates the observed results. [ABSTRACT FROM AUTHOR]

The organophosphorus antidotes, so-called oximes, are able to restore the enzymatic function of acetyl-cholinesterase (AChE) or butyrylcholinesterase (BChE) via cleavage of organophosphate from the active site of the phosphylated enzyme. In this work, the charged pyridinium oximes containing thiocarboxamide moiety were designed, prepared and tested. Their stability and pKa properties were found to be analogous to parent carboxamides (K027, K048 and K203). The inhibitory ability of thiocarboxamides was found in low µM levels for AChE and high µM levels for BChE. Their reactivation properties were screened on human recombinant AChE and BChE inhibited by nerve agent surrogates and paraoxon. One thiocarboxamide was able to effectively restore function of NEMP- and NEDPA-AChE, whereas two thiocarboxamides were able to reactivate BChE inhibited by all tested organophosphates. These results were confirmed by reactivation kinetics, where thiocarboxamides were proved to be effective, but less potent reactivators if compared to carboxamides. [ABSTRACT FROM AUTHOR]