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Background: It is generally accepted that methylation status of CpG sites spaced up to 50 bp apart is correlated, and accumulation of locally disordered methylation at adjacent CpG sites is involved in neoplastic transformation, acting in similar way as stochastic accumulation of mutations. Results: We used EPIC microarray data from 596 samples, representing 12 healthy tissue and cell types, as well as 572 blood cancer specimens to analyze methylation status of adjacent CpG sites across human genome, and subsequently validated our findings with NGS and Sanger sequencing. Our analysis showed that there is a subset of the adjacent CpG sites in human genome, with cytosine at one CpG site methylated and the other devoid of methyl group. These loci map to enhancers that are targeted by families of transcription factors involved in cell differentiation. Moreover, our results suggest that the methylation at these loci differ between alleles within a cell, what allows for remarkable level of heterogeneity of methylation patterns. However, different types of specialized cells acquire only one specific and stable pattern of methylation at each of these loci and that pattern is to a large extent lost during neoplastic transformation. Conclusions: We identified a substantial number of adjacent CpG loci in human genome that display remarkably stable and cell type specific methylation pattern. The methylation pattern at these loci appears to reflect different methylation of alleles in cells. Furthermore, we showed that changes of methylation status at those loci are likely to be involved in regulation of the activity of enhancers and contribute to neoplastic transformation. [ABSTRACT FROM AUTHOR]

It has been found out that Pd-Co-based catalyst, supported on anodized aluminum, possesses very high activity in combustion reactions of C1–C6 alkanes and toluene. The catalyst characterization has been made by N2-pysisorption, XRD, SEM, XPS, FTIR, TEM, and EPR methods. In view of the great interest, methane combustion was investigated in detail. It is ascertained that the complete oxidation of methane proceeds by dissociative adsorption on PdO and formation of hydroxyl and methyl groups, the former being highly reactive, and it undergoes further reaction to oxygen-containing intermediates, whereupon HCHO is one of them. The presence of Co2+ cations promotes greatly oxygen adsorption. The dissociative adsorption is favored on neighboring Co2+ cations, leading to the formation of bridging peroxides. Further, the oxygen dissociates on the nearest Pd2+ cations. According to the results from the experimental data, instrumental methods, and the observed kinetics and DFT model calculations, it can be concluded that the reaction pathway over Pd+Co/anodic alumina support (AAS) catalyst proceeds most probably through Mars–van Krevelen. The obtained data on the kinetics were used for simulation of the methane combustion in a full-scale adiabatic reactor. [ABSTRACT FROM AUTHOR]

DNMT1 is an essential DNA methyltransferase that catalyzes the transfer of methyl groups to CpG islands in DNA and generates a prominent epigenetic mark. The catalytic activity of DNMT1 relies on its conformational plasticity and ability to change conformation from an auto-inhibited to an activated state. Here, we present four cryo-EM reconstructions of apo DNMT1 and DNTM1: non-productive DNA, DNTM1: H3Ub2-peptide, DNTM1: productive DNA complexes. Our structures demonstrate the flexibility of DNMT1's N-terminal regulatory domains during the transition from an apo 'auto-inhibited' to a DNA-bound 'non-productive' and finally a DNA-bound 'productive' state of DNMT1. Furthermore, we address the regulation of DNMT1's methyltransferase activity by a DNMT1-selective small-molecule inhibitor and ubiquitinated histone H3. We observe that DNMT1 binds DNA in a 'non-productive' state despite the presence of the inhibitor and present the cryo-EM reconstruction of full-length DNMT1 in complex with a di-ubiquitinated H3 peptide analogue. Taken together, our results provide structural insights into the reaction cycle of DNMT1. [ABSTRACT FROM AUTHOR]

A new azo dye ligand namely ((E)-1-(4-hydroxy-3-(pyridin-3-yldiazenyl)phenyl)ethan-1-one) (HPPE) was synthesized by the coupling reaction of diazoinium salt of 3-aminopyridine and 4-hydroxyacetophenone. The palladium complex was prepared by reacting palladium chloride with the HPPE ligand. These compounds were characterized by different techniques such as mass, 1H-NMR, infrared, UV-Vis spectroscopies. The infrared data reveal that azo ligand reacting as bidentate via oxygen and nitrogen atom of azo group and it reveals the important functions as carbonyl group, methyl group, and azo group in the ligand and the complex such. The palladium complex is square planer. The ligand showed a visible colorimetric pH sensitive chemosensor, fast response time and is fully reversible and exhibited a large wavelength shift more than170 nm accompanied by excellent sensitivity of pH in the range of 3-9. The HPPE ligand and palladium complex showed potential antioxidant activity especially the ligand showed activity so close to the ascorbic acid. [ABSTRACT FROM AUTHOR]

A series of new aromatic substituted indanone and indanol building blocks have been prepared and are anticipated to aid future drug discovery studies. In total, seven compounds (7, 12–17) are expounded on, and all have been fully characterized. In doing so, we have shown multiple examples of highly chemoselective reactions. One example employed an adaptation of Fujioka's chemoselective reduction methodology, allowing an ester to be reduced in the presence of a ketone. In another example, an uncommon benzylic methyl group to aldehyde oxidation was demonstrated for two different compounds. These and other chemoselective interconversions allowed us to identify compound (12) as a remarkably flexible springboard for accessing a diverse array of indan-based building blocks (13–17). [ABSTRACT FROM AUTHOR]

Recent metagenomic studies have identified numerous lineages of hydrogen-dependent, obligately methyl-reducing methanogens. Yet, only a few representatives have been isolated in pure culture. Here, we describe six new species with this capability in the family Methanosarcinaceae (order Methanosarcinales), which makes up a substantial fraction of the methanogenic community in arthropod guts. Phylogenomic analysis placed the isolates from cockroach hindguts into the genus Methanimicrococcus (M. hacksteinii, M. hongohii , and M. stummii) and the isolates from millipede hindguts into a new genus, Methanolapillus (M. africanus, M. millepedarum , and M. ohkumae). Members of this intestinal clade, which includes also uncultured representatives from termites and vertebrates, have substantially smaller genomes (1.6–2.2 Mbp) than other Methanosarcinales. Genome reduction was accompanied by the loss of the upper part of the Wood–Ljungdahl pathway, several energy-converting membrane complexes (Fpo, Ech, and Rnf), and various biosynthetic pathways. However, genes involved in the protection against reactive oxygen species (catalase and superoxide reductase) were conserved in all genomes, including cytochrome bd (CydAB), a high-affinity terminal oxidase that may confer the capacity for microaerobic respiration. Since host-associated Methanosarcinales are nested within omnivorous lineages, we conclude that the specialization on methyl groups is an adaptation to the intestinal environment. [ABSTRACT FROM AUTHOR]

Among polymer wastes, poly(ethylene terephthalate) (PET) is the most important commercial thermoplastic polyester. Less than 30% of total PET production is recycled into new products. Therefore, large amounts of waste PET need to be recycled. We describe a feasible approach for the direct application of the glycolysis products of PET (GP-PET), without further purification, for the synthesis of value-added products. It was established that GP-PET is valorized via phosphorylation with phenylphosphonic dichloride (PPD), as well as with trimethyl phosphate (TMP). When PPD is used, a condensation reaction takes place with the evolution of hydrogen chloride. During the interaction between GP-PET and TMP, the following reactions take place simultaneously: a transesterification with the participation of the hydroxyl group of GP-PET and the methoxy group of TMP and an exchange reaction between the ester group of GP-PET and the methyl ester group of TMP. The occurrence of the exchange reaction was confirmed by 1H, 31P, 13C NMR, and GPC analysis. Thermogravimetric analysis (TGA) revealed that the percentage of a carbon residual (CR) implies the possibility of using the end products as flame retardant (FR) additives, especially for polyurethanes as well as thermal stabilizers of polymer materials or Li-ion cells. [ABSTRACT FROM AUTHOR]

A streamlined one-day protocol is described to produce isotopically methyl-labeled protein with high levels of deuterium for NMR studies. Using this protocol, the D2O and 2H-glucose content of the media and protonation level of ILV labeling precursors (ketobutyrate and ketovalerate) were varied. The relaxation rate of the multiple-quantum (MQ) state that is present during the HMQC-TROSY pulse sequence was measured for different labeling schemes and this rate was used to predict upper limits of molecular weights for various labeling schemes. The use of deuterated solvents (D2O) or deuterated glucose is not required to obtain 1H–13C correlated NMR spectra of a 50 kDa homodimeric protein that are suitable for assignment by mutagenesis. High quality spectra of 100–150 kDa proteins, suitable for most applications, can be obtained without the use of deuterated glucose. The proton on the β-position of ketovalerate appears to undergo partial exchange with deuterium under the growth conditions used in this study. [ABSTRACT FROM AUTHOR]

The response of the brain to radiation is important for cancer patients receiving whole or partial brain irradiation or total body irradiation, those exposed to irradiation as part of a nuclear accident or a nuclear war or terrorism event, and for astronauts during and following space missions. The mechanisms mediating the effects of irradiation on the hippocampus might be associated with alterations in hippocampal DNA methylation. Changes in cytosine methylation involving the addition of a methyl group to cytosine (5 mC) and especially those involving the addition of a hydroxy group to 5 mC (hydroxymethylcytosine or 5 hmC) play a key role in regulating the expression of genes required for hippocampal function. In this review article, we will discuss the effects of radiation on hippocampal DNA methylation and whether these effects are associated with hippocampus-dependent cognitive measures and molecular measures in the hippocampus involved in cognitive measures. We will also discuss whether the radiation-induced changes in hippocampal DNA methylation show an overlap across different doses of heavy ion irradiation and across irradiation with different ions. We will also discuss whether the DNA methylation changes show a tissue-dependent response. [ABSTRACT FROM AUTHOR]

Associating molecular structure and mechanical properties is important for silicone rubber design. Although silicone rubbers are widely used due to their odourless, non-toxic, and high- and low-temperature resistance advantages, their application and development are still limited by their poor mechanical properties. The mechanical properties of silicone rubbers can be regulated by designing the cross-link density and cross-linking structure, and altering the molar contents of vinyl in the side groups of methyl vinyl silicone rubber (MVQ) leads to different cross-linking structures and cross-linking densities in the vulcanized rubber. Therefore, this study investigated the differences in molecular parameters and molecular chain structures of unprocessed MVQ rubbers with different vinyl contents. The results showed that MVQ rubbers with high vinyl contents were branched polymers, better facilitating the cross-linking reaction than MVQ rubbers with low vinyl contents. In addition, silicone rubbers with different vinyl contents were co-cross-linked to introduce an inhomogeneous cross-linked network in the silicone rubber to improve its mechanical properties. The cross-linked network properties were analysed by the Flory–Rehner model and Mooney–Rivlin plots, and it was found that the long chains in the sparsely cross-linked domains of the network favoured high elongation at break and the short chains in the densely cross-linked domains contributed to high modulus, which could satisfy the functions of reinforcing and toughening the rubber materials at the same time. It was also found by analysing the filler network and aggregate morphology that the inhomogeneous cross-linked network led to an improvement in the dispersion of silica in the rubber and a significant improvement in the mechanical properties of silicone rubber. [ABSTRACT FROM AUTHOR]

The aryl diester compound, 2-methyl-1,4-phenyl­ene bis­(3,5-di­bromo­benzoate), C21H12Br4O4, was synthesized by esterification of methyl hydroquinone with 3,5-dibromo­benzoic acid. A crystalline sample was obtained by cooling a sample of the melt (m.p. = 502 K/DSC) to room temperature. The molecular structure consists of a central benzene ring with anti-3,5-di­bromo­benzoate groups symmetrically attached at the 1 and 4 positions and a methyl group attached at the 2 position of the central ring. In the crystal structure (space group P1̅), molecules of the title aryl diester are located on inversion centers imposing disorder of the methyl group and H atom across the central benzene ring. The crystal structure is consolidated by a network of C—H⋯Br hydrogen bonds in addition to weaker and offset π–π inter­actions involving the central benzene rings as well as the rings of the attached 3,5-di­bromobenzoate groups. [ABSTRACT FROM AUTHOR]

Pure SnO2 and 1 at.% PdO–SnO2 materials were prepared using a simple hydrothermal method. The micromorphology and element valence state of the material were characterized using XRD, SEM, TEM, and XPS methods. The SEM results showed that the prepared material had a two-dimensional nanosheet morphology, and the formation of PdO and SnO2 heterostructures was validated through TEM. Due to the influence of the heterojunction, in the XPS test, the energy spectrum peaks of Sn and O in PdO–SnO2 were shifted by 0.2 eV compared with SnO2. The PdO–SnO2 sensor showed improved ethanol sensing performance compared to the pure SnO2 sensor, since it benefited from the large specific surface area of the nanosheet structure, the modulation effect of the PdO–SnO2 heterojunction on resistance, and the catalyst effect of PdO on the adsorption of oxygen. A DFT calculation study of the ethanol adsorption characteristics of the PdO–SnO2 surface was conducted to provide a detailed explanation of the gas-sensing mechanism. PdO was found to improve the reducibility of ethanol, enhance the adsorption of ethanol's methyl group, and increase the number of adsorption sites. A synergistic effect based on the continuous adsorption sites was also deduced. [ABSTRACT FROM AUTHOR]

DFT calculations were performed for the methyl group transfer reaction between CH3Co (dmgBF2)py and PPh3Ni(Triphos). The reaction mechanism and its energetics were investigated. This reaction is relevant to the catalytic mechanism of the enzyme acetyl coenzyme A synthase. BP86 and PBE functionals and dispersion corrections were used. It was found that intermolecular interactions are very important for this reaction. The influence of the solvent on the reaction was studied. [ABSTRACT FROM AUTHOR]

Tetroxane derivatives are interesting drugs for antileishmaniasis and antimalaric treatments. The gas-phase thermal decomposition of 3,6,-dimethyl-1,2,4,5-tetroxane (DMT) and 3,3,6,6,-tetramethyl-1,2,4,5-tetroxane (acetone diperoxide (ACDP)) was studied at 493–543 K by direct gas chromatography by means of a flow reactor. The reaction is produced in the injector chamber at different temperatures. The resulting kinetics Arrhenius equations were calculated for both tetroxanes. Including the parent compound of the series 1,2,4,5-tetroxane (formaldehyde diperoxide (FDP)), the activation energy and frequency factors decrease linearly with the number of methyl groups. The reaction mechanisms of ACDP and 3,6,6-trimethyl-1,2,4,5-tetroxane (TMT) decomposition have been studied by means of the DFT method with the BHANDHLYP functional. Our calculations confirm that the concerted mechanism should be discarded and that only the stepwise mechanism occurs. The critical points of the singlet and triplet state potential energy surfaces (S- and T-PES) of the thermolysis reaction of both compounds have been determined. The calculated activation energies of the different steps vary linearly with the number of methyl groups of the methyl-tetroxanes series. The mechanism for the S-PES leads to a diradical O···O open structure, which leads to a C···O dissociation in the second step and the production of the first acetaldehyde/acetone molecule. This last one yields a second C···O dissociation, producing O2 and another acetone/acetaldehyde molecule. The O2 molecule is in the singlet state. A quasi-parallel mechanism for the T-PES from the open diradical to products is also found. Most of the critical points of both PES are linear with the number of methyl groups. Reaction in the triplet state is much more exothermic than the singlet state mechanism. Transitions from the singlet ground state, S0 and low-lying singlet states S1–3, to the low-lying triplet excited states, T1–4, (chemical excitation) in the family of methyl tetroxanes are also studied at the CASSCF/CASPT2 level. Two possible mechanisms are possible here: (i) from S0 to T3 by strong spin orbit coupling (SOC) and subsequent fast internal conversion to the excited T1 state and (ii) from S0 to S2 from internal conversion and subsequent S2 to T1 by SOC. From these experimental and theoretical results, the additivity effect of the methyl groups in the thermolysis reaction of the methyl tetroxane derivatives is clearly highlighted. This information will have a great impact for controlling these processes in the laboratory and chemical industries. [ABSTRACT FROM AUTHOR]

Ten isatin-based hydrazone derivatives were synthesized using two subseries, IA (isatin + acetophenone) and IB (isatin + benzaldehyde), and evaluated for their monoamine oxidases (MAOs) inhibitory activity. All the compounds showed stronger MAO-A inhibition than MAO-B, and the IB series showed more effective MAO-A inhibitory activity than IA series. Compound IB4 most potently inhibited MAO-A (half maximal inhibitory concentration IC50 = 0.015 µM), followed by IB3 (IC50 = 0.019 µM). On the contrary, compound IB3 showed the highest MAO-B inhibition (IC50 = 0.068 µM), followed by IB4 (IC50 = 1.87 µM). Compound IB3 and IB4 had low selectivity indices of 3.68 and 8.50, respectively. Structurally, the methyl group of IA series decreased the inhibition of both MAO-A and MAO-B. Among them, IB3 and IB4 (4-Cl and 4-Br in B-ring, respectively) showed higher MAO-A and MAO-B inhibition than the other substitutions. Inhibition constant Ki values of IB3 and IB4 for MAO-A were 0.0088 and 0.0063 µM, respectively, and those for MAO-B were 0.048 and 0.060 µM, respectively. IB3 and IB4 were competitive, reversible inhibitors of MAO-A and MAO-B. Molecular docking analysis predicted that IB3 and IB4 formed stable hydrogen bonds between Asn181 and the NH atom of isatin in the ligand-protein complex. Dynamic analysis revealed that IB3 and IB4 are stable with both MAO isoforms. These observations suggest IB3 and IB4 are potent and reversible MAO-A and MAO-B inhibitors and both compounds can be used as therapeutic agents for neurological disorders. [ABSTRACT FROM AUTHOR]

Two 3-(p-substituted phenyl)-3a,8a-dihydro-4H-cyclohepta[d]isoxazoles were synthesized by 1,3-dipolar cycloaddition of the corresponding nitrile oxides with cycloheptatriene. Two endoperoxides were synthesized as facially selective and single products in high yields (93%--95%) from the reactions of isoxazole derivatives with singlet oxygen. The exact configurations of the endoperoxide with a methyl group in the phenyl ring and the diol synthesized from it were confirmed by X-ray analysis. To elucidate the mechanism, the formation energy of the endoperoxide was investigated by simulations using the software package Gaussian 09 and density functional theory calculations via the M06-2X/6-311+G(d,p) level method in dichloromethane. The results were consistent with experimental findings showing the formation of isoxazole products. [ABSTRACT FROM AUTHOR]

The aryl diester compound, 2-methyl-1,4-phenylene bis(3,5-dibromobenzoate), C21H12Br4O4, was synthesized by esterification of methyl hydroquinone with 3,5-dibromobenzoic acid. A crystalline sample was obtained by cooling a sample of the melt (m.p. = 502 K/DSC) to room temperature. The molecular structure consists of a central benzene ring with anti-3,5-dibromobenzoate groups symmetrically attached at the 1 and 4 positions and a methyl group attached at the 2 position of the central ring. In the crystal structure (space group P1), molecules of the title aryl diester are located on inversion centers imposing disorder of the methyl group and H atom across the central benzene ring. The crystal structure is consolidated by a network of C--H...Br hydrogen bonds in addition to weaker and offset interactions involving the central benzene rings as well as the rings of the attached 3,5-dibromobenzoate groups. [ABSTRACT FROM AUTHOR]

Thermal atomic layer etching (ALE) is one promising method to achieve atomic level precision and high conformality over three-dimensional structures that can further enable the manufacturing of gate-all-around devices. Initially, an ALE process using CF4/NH3/Ar remote plasma exposure followed by infrared (IR) annealing was studied on SiCO films. The process showed self-limiting behavior and achieved an etch per cycle (EPC) of 0.2 nm/cycle. To increase the EPC, an O2 remote plasma exposure step was added before the CF4/NH3/Ar plasma exposure step in the ALE cycle. The process achieved an EPC of 1.0 nm/cycle. Measurements of the EPC of the SiCO film showed self-limiting behavior in both the O2 and CF4/NH3/Ar steps. X-ray photoelectron spectroscopy results showed an increase in atomic concentration (AC) of oxygen while the AC of carbon decreased following the exposure of the film to an O2 remote plasma. The results indicate that methyl groups (-CH3) in the top layers of the film are being replaced by hydroxyl (-OH) groups and Si-O-Si bonding. The N1s spectrum showed the formation of an ammonium fluorosilicate (NH4)2SiF6-based surface-modified layer following exposure to a CF4/NH3/Ar remote plasma. IR annealing of the film showed desorption of the ammonium fluorosilicate surface-modified layer and the return to an as grown SiCO film surface composition. [ABSTRACT FROM AUTHOR]

The molecular structure of a crystalline monolayer of hydrocarbon chains was modeled and studied via computer simulation using the Metropolis Monte Carlo algorithm at a temperature T = 300 K. The only interactions in this system occur through Lennard‐Jones dispersion forces and short‐range atom‐atom repulsion. The intent was to establish whether the chains were either rigidly extended or twisted via the thermal formation of gauche bonds and apply the results to understand observations made on two possible oleogelators: triacontane and stearic acid. Specifically, we aimed to understand if their observed crystalline monolayer thicknesses are due to gauche‐bond‐shortened hydrocarbon chains oriented perpendicular to the monolayer surface, or to fully extended rigid chains oriented at a tilt angle with respect to the surface. The results showed that crystals of hydrocarbon chains did not include significant gauche bonds, so that all molecules were rigidly extended, thus explaining the experimental data previously reported. Accordingly, TC and SA dimer molecules are packed in crystalline multilayers with tilt angles in relation to the methyl group plane. [ABSTRACT FROM AUTHOR]

The aim of this study was to obtain new halolactones with a gem-dimethyl group in the cyclohexane ring (at the C-3 or C-5 carbon) and a methyl group in the lactone ring and then subject them to biotransformations using filamentous fungi. Halolactones in the form of mixtures of two diasteroisomers were subjected to screening biotransformations, which showed that only compounds with a gem-dimethyl group located at the C-5 carbon were transformed. Strains from the genus Fusarium carried out hydrolytic dehalogenation, while strains from the genus Absidia carried out hydroxylation of the C-7 carbon. Both substrates and biotransformation products were then tested for antimicrobial activity against multidrug-resistant strains of both bacteria and yeast-like fungi. The highest antifungal activity against C. dubliniensis and C. albicans strains was obtained for compound 5b, while antimicrobial activity against S. aureus MRSA was obtained for compound 4a. [ABSTRACT FROM AUTHOR]

The reaction of lithium hexa­methyl­disilyl­amide, [Li{N(Si(CH3)3)2}] (LiHMDS), with 4,4-dimethyl-2-phenyl-2-oxazoline (Phox, C11H13NO) in hexane produced colourless crystals of bis­(4,4-dimethyl-2-phenyl-2-oxazoline-κN)(hexa­methyl­disilyl­amido-κN)lithium, [Li(C6H18NSi2)(C11H13NO)2] or [Li{N(Si(CH3)3)2}(Phox)2] in high yield (89%). Despite the 1:1 proportion of the starting materials in the reaction mixture, the product formed with a 1:2 amide:oxazoline ratio. In the unit cell of the C2/c space group, the neutral mol­ecules lie on twofold rotation axes coinciding with the Li—N(amide) bonds. The lithium(I) centre adopts a trigonal–planar coordination geometry with three nitro­gen donor atoms, one from the HMDS anion and two from the oxazolines. All ligands are monodentate. In the phenyl­oxazoline units, the dihedral angle defined by the five-membered heterocyclic rings is 35.81 (5)°, while the phenyl substituents are approximately face-to-face, separated by 3.908 (5) Å. In the amide, the methyl groups assume a nearly eclipsed arrangement to minimize steric repulsion with the analogous substituents on the oxazoline rings. The non-covalent inter­actions in the solid-state structure of [Li{N(Si(CH3)3)2}(Phox)2] were assessed by Hirshfeld surface analysis and fingerprint plots. This new compound is attractive for catalysis due to its unique structural features. [ABSTRACT FROM AUTHOR]

The present study is focused on the use of cubic metal-organic frameworks-5 (MOF-5) and its functionalized form in the removal of phenolic pollutants by molecular dynamics (MD) and Well-tempered metadynamics (WTMD) simulation methods. It was found that the adsorption mechanism of MOF-5s/phenolic compounds is mostly due to the van der Waals and π–π interactions. However, electrostatic and hydrogen bond (HB) interactions also play a significant role in removing phenolic pollutants by MOF-5 and its functionalized form. The results show that the fluorine functional group (F-MOF-5) increases the adsorption capacity of phenol compounds on the adsorbent surface. By functionalizing the MOF-5 with a methyl functional group (CH3-MOF-5), the adsorption strength decreases. The WTMD calculation confirmed that at the most stable state, the free energy (FE) value of system II (the most stable system in functionalized systems with –F functional group) is about −289.528 kJ mol−1. This value is ~5.781 and 35.514 kJ mol−1 more negative than the FE of the I and III systems (the most stable systems in the pristine and CH3-MOF-5/pollutant systems, respectively). Altogether, the results indicate that F-MOF-5 can be considered a more suitable adsorbent than MOF-5 and CH3-MOF-5 for phenolic pollutants removal from the environment for more assessment. [ABSTRACT FROM AUTHOR]

The computation of the rotation barriers of the methyl groups (Me) of tribromomesitylene (TBM) crystals has been carried out. Experimentally, the barriers of the three Me groups of TBM are found to be high and different. These groups do not experience the same hindering environment in the crystal state. For an isolated TBM molecule, the three barriers are equal and very low. We found that a cluster of 21 TBM molecules permits the reproduction of the crystal symmetry and structure of the bulk, with a central molecule surrounded by six molecules in the same plane and seven other molecules in two planes above and below. DFT computations including dispersion corrections have been carried out using the ONIOM procedure. The Me groups of the central TBM molecule were rotated step by step to determine the conformations of lowest and highest energy for each Me, thus allowing estimation of the rotation barriers as the difference between these energies. In doing so, we found the following barrier values, namely 105, 173, and 205 cm−1, whereas the experimental values were 111, 180 and 200 cm−1. [ABSTRACT FROM AUTHOR]

The enzymes performing protein post-translational modifications (PTMs) form a critical post-translational regulatory circuitry that orchestrates literally all cellular processes in the organism. In particular, the balance between cellular stemness and differentiation is crucial for the development of multicellular organisms. Importantly, the fine-tuning of this balance on the genetic level is largely mediated by specific PTMs of histones including lysine methylation. Lysine methylation is carried out by special enzymes (lysine methyltransferases) that transfer the methyl group from S-adenosyl-L-methionine to the lysine residues of protein substrates. Set7/9 is one of the exemplary protein methyltransferases that however, has not been fully studied yet. It was originally discovered as histone H3 lysine 4-specific methyltransferase, which later was shown to methylate a number of non-histone proteins that are crucial regulators of stemness and differentiation, including p53, pRb, YAP, DNMT1, SOX2, FOXO3, and others. In this review we summarize the information available to date on the role of Set7/9 in cellular differentiation and tissue development during embryogenesis and in adult organisms. Finally, we highlight and discuss the role of Set7/9 in pathological processes associated with aberrant cellular differentiation and self-renewal, including the formation of cancer stem cells. [ABSTRACT FROM AUTHOR]

Luminescent materials with narrowband emission show great potential for diverse applications in optoelectronics. Purely organic phosphors with room-temperature phosphorescence (RTP) have made significant success in rationally manipulating quantum efficiency, lifetimes, and colour gamut in the past years, but there is limited attention on the purity of the RTP colours. Herein we report a series of closed-loop molecules with narrowband phosphorescence by multiple resonance effect, which significantly improves the colour purity of RTP. Phosphors show narrowband phosphorescence with full width at half maxima (FWHM) of 30 nm after doping into a rigid benzophenone matrix under ambient conditions, of which the RTP efficiency reaches 51.8%. At 77 K, the FWHM of phosphorescence is only 11 nm. Meanwhile, the colour of narrowband RTP can be tuned from sky blue to green with the modification of methyl groups. Additionally, the potential applications in X-ray imaging and display are demonstrated. This work not only outlines a design principle for developing narrowband RTP materials but also makes a major step forward extending the potential applications of narrowband luminescent materials in optoelectronics. Luminescent materials with narrowband emissions are vital for optoelectronic applications. Here, the authors achieve room temperature phosphorescence with a FWHM of 30 nm through the multiple resonance effect and showcase its practical application in X-ray imaging. [ABSTRACT FROM AUTHOR]

To further extend the structure-activity relationships (SARs) of 5-aminopyrazoles (5APs) and identify novel compounds able to interfere with inflammation, oxidative stress, and tumorigenesis, 5APs 1–4 have been designed and prepared. Some chemical modifications have been inserted on cathecol function or in aminopyrazole central core; in detail: (i) smaller, bigger, and more lipophilic substituents were introduced in meta and para positions of catechol portion (5APs 1); (ii) a methyl group was inserted on C3 of the pyrazole scaffold (5APs 2); (iii) a more flexible alkyl chain was inserted on N1 position (5APs 3); (iv) the acylhydrazonic linker was moved from position 4 to position 3 of the pyrazole scaffold (5APs 4). All new derivatives 1–4 have been tested for radical scavenging (DPPH assay), anti-aggregating/antioxidant (in human platelets) and cell growth inhibitory activity (MTT assay) properties. In addition, in silico pharmacokinetics, drug-likeness properties, and toxicity have been calculated. 5APs 1 emerged to be promising anti-proliferative agents, able to suppress the growth of specific cancer cell lines. Furthermore, derivatives 3 remarkably inhibited ROS production in platelets and 5APs 4 showed interesting in vitro radical scavenging properties. Overall, the collected results further confirm the pharmaceutical potentials of this class of compounds and support future studies for the development of novel anti-proliferative and antioxidant agents. [ABSTRACT FROM AUTHOR]

In this work, five phenanthroline derivatives substituted with different methyl groups have been selected to synthesize β‐diketonate‐based europium complexes to check the influence of the substitutions on the degradation effect of those complexes in poly(methyl methacrylate) (PMMA) films. The photophysical properties of Eu(III) complexes, including absorbance, excitation, and emission have been carefully investigated in solution, solid‐state, and doped in PMMA film. In all these states, the complexes exhibit an impressive red emission at 614 nm with a high photoluminescence quantum yield of up to 85 %. The films have been exposed under outdoor, indoor, and dark storage stability lifetime conditions for 1200 hours. The photoluminescence measurements recorded every 400, 800, and 1200 hours demonstrated that the film containing europium complex with phenanthroline ligand substituted by a high number of methyl groups (Eu(TTA)3L5) showed good photoluminescent stability in indoor and dark conditions, and exhibited better resistance to degradation in outdoor conditions compared to other complexes. This study has proved that phenanthroline ligands could be tuned chemically leading to better stability of those types of complexes in films which can be end‐used for future stable optoelectronic devices such as luminescent solar concentrators. [ABSTRACT FROM AUTHOR]

Ramalina sp. (Ramalinaceae) is a type of lichen known to contain many active secondary metabolite compounds that have the potential to be used as medicine or medicinal raw materials. One of the biological activities possessed by Ramalina sp. lichen is its anticancer activity. This research aims to isolate and identify active secondary metabolite compounds from the methanol extract of the Ramalina sp. lichen and to find out the cytotoxic activity of the isolated compound against MCF7 breast cancer cells. Compound 1 (usnic acid) was successfully isolated from fraction A. The isolation and purification process was carried out starting with a maceration process using acetone solvent, followed by silica gel column chromatography using a gradient solvent system consisting of n-hexane, n-hexane:EtOAc, EtOAc, EtOAc:MeOH, and MeOH with 5% increment of polarity to obtain 17 fractions (F- 1 to F-17). From the 17 fractions obtained, fraction 3 (F-3) and fraction 4 (F-4) (eluted with n-hexane:EtOAc 30%), which had the same TLC profile, were combined and named as fraction A. Compound 1 (50 mg) is a yellow needle crystal that was formed in a bottle of fraction A, which was obtained after the process of combining fractions F-3 and F-4 and solvent evaporation process. The crystals were then separated and purified with CHCl3 and MeOH. Compound 1 was then characterized based on spectroscopic data. Various spectroscopic analysis data, including FTIR, 1D- and 2D-NMR, and LC-ESI-MS, show that Compound 1 is a dibenzofuran derivative compound with 18 carbons (3 from carbonyl groups (C=O) and 3 from methyl groups) and 2 hydroxyl (-OH). Cytotoxicity assay showed that at a low concentration of 18.75 ug/mL, Compound 1 caused a 67.06% decrease in MCF7 viability [ABSTRACT FROM AUTHOR]

The main focus of this review is to introduce readers to the fascinating class of lipid molecules known as norsteroids, exploring their distribution across various biotopes and their biological activities. The review provides an in-depth analysis of various modified steroids, including A, B, C, and D-norsteroids, each characterized by distinct structural alterations. These modifications, which range from the removal of specific methyl groups to changes in the steroid core, result in unique molecular architectures that significantly impact their biological activity and therapeutic potential. The discussion on A, B, C, and D-norsteroids sheds light on their unique configurations and how these structural modifications influence their pharmacological properties. The review also presents examples from natural sources that produce a diverse array of steroids with distinct structures, including the aforementioned A, B, C, and D-nor variants. These compounds are sourced from marine organisms like sponges, soft corals, and starfish, as well as terrestrial entities such as plants, fungi, and bacteria. The exploration of these steroids encompasses their biosynthesis, ecological significance, and potential medical applications, highlighting a crucial area of interest in pharmacology and natural product chemistry. The review emphasizes the importance of researching these steroids for drug development, particularly in addressing diseases where conventional medications are inadequate or for conditions lacking sufficient therapeutic options. Examples of norsteroid synthesis are provided to illustrate the practical applications of this research. [ABSTRACT FROM AUTHOR]

The complexity of crude oil composition, combined with the fluctuating oxygen level in contaminated environments, poses challenges for the bioremediation of oil pollutants, because of compound-specific microbial degradation of petroleum hydrocarbons under certain conditions. As a result, facultative bacteria capable of breaking down petroleum hydrocarbons under both aerobic and anaerobic conditions are presumably effective, however, this hypothesis has not been directly tested. In the current investigation, Shewanella putrefaciens CN32, a facultative anaerobic bacterium, was used to degrade petroleum hydrocarbons aerobically (using O2 as an electron acceptor) and anaerobically (using Fe(III) as an electron acceptor). Under aerobic conditions, CN32 degraded more saturates (65.65 ± 0.01%) than aromatics (43.86 ± 0.03%), with the following order of degradation: dibenzofurans > n-alkanes > biphenyls > fluorenes > naphthalenes > alkylcyclohexanes > dibenzothiophenes > phenanthrenes. In contrast, under anaerobic conditions, CN32 exhibited a higher degradation of aromatics (53.94 ± 0.02%) than saturates (23.36 ± 0.01%), with the following order of degradation: dibenzofurans > fluorenes > biphenyls > naphthalenes > dibenzothiophenes > phenanthrenes > n-alkanes > alkylcyclohexanes. The upregulation of 4-hydroxy-3-polyprenylbenzoate decarboxylase (ubiD), which plays a crucial role in breaking down resistant aromatic compounds, was correlated with the anaerobic degradation of aromatics. At the molecular level, CN32 exhibited a higher efficiency in degrading n-alkanes with low and high carbon numbers relative to those with medium carbon chain lengths. In addition, the degradation of polycyclic aromatic hydrocarbons (PAHs) under both aerobic and anaerobic conditions became increasingly difficult with increased numbers of benzene rings and methyl groups. This study offers a potential solution for the development of targeted remediation of pollutants under oscillating redox conditions. [ABSTRACT FROM AUTHOR]

In this study, we provide a theoretical explanation for the experimentally observed decrease in the organocatalytic activity of N-aryl imidazolylidenes methylated at the C4/5-H positions in the benzoin condensation of aromatic aldehydes. A comparative quantum chemical study of energy profiles for the NHC-mediated benzoin condensation of furfural has revealed a high energy barrier to the formation of the IPrMe-based furanic Breslow intermediate that can be attributed to the negative steric interactions between the imidazole backbone methyl groups and N-aryl substituents. [ABSTRACT FROM AUTHOR]

It is important to search for cytostatic compounds in order to fight cancer. One of them could be 2′-methylthiamine, which is a thiamine antimetabolite with an additional methyl group at the C-2 carbon of thiazole. So far, the cytostatic potential of 2′-methylthiamine has not been studied. We have come forward with a simplified method of synthesis using commercially available substrates and presented a comparison of its effects, as boosted by oxythiamine, on normal skin fibroblasts and HeLa cancer cells, having adopted in vitro culture techniques. Oxythiamine has been found to inhibit the growth and metabolism of cancer cells significantly better than 2′-methylthiamine (GI50 36 and 107 µM, respectively), while 2′-methylthiamine is more selective for cancer cells than oxythiamine (SI = 180 and 153, respectively). Docking analyses have revealed that 2′-methylthiamine (ΔG −8.2 kcal/mol) demonstrates a better affinity with thiamine pyrophosphokinase than thiamine (ΔG −7.5 kcal/mol) and oxythiamine (ΔG −7.0 kcal/mol), which includes 2′-methylthiamine as a potential cytostatic. Our results suggest that the limited effect of 2′-methylthiamine on HeLa arises from the related arduous transport as compared to oxythiamine. Given that 2′-methylthiamine may possibly inhibit thiamine pyrophosphokinase, it could once again be considered a potential cytostatic. Thus, research should be carried out in order to find the best way to improve the transport of 2′-methylthiamine into cells, which may trigger its cytostatic properties. [ABSTRACT FROM AUTHOR]

Trichlorido(4-methylpiperidine)gold(III), [AuCl3(C6H13N)], 1, crystallizes in Pbca with Z = 8. Tribromido(4-methylpiperidine)gold(III), [AuBr3(C6H13N)], 2, crystallizes as two polymorphs, 2a in Pnma with Z = 4 (imposed mirror symmetry) and 2b, which is isotypic to 1. The Au--N bonds trans to Cl are somewhat shorter than those trans to Br, and the Au--Cl bonds trans to N are longer than those cis to N, whereas the Au--Br bonds trans to N are slightly shorter than the cis bonds. The methyl and AuX3 groups (X = halogen) occupy equatorial positions at the six-membered ring. The packing of all three structures involves chains of molecules with offset stacking of the AuX3 moieties associated with short Au...X contacts; for 1 and 2b these are reinforced by N--H...X hydrogen bonds, whereas for 2a there are no classical hydrogen bonds and the chains are interconnected by Br...Br contacts. [ABSTRACT FROM AUTHOR]

The asymmetric unit of the title compound, C25H18N6.H2O, comproses two molecules (I and II), together with a water molecule. The terminal phenyl groups attached to the methyl groups of the molecules I and II do not overlap completely, but are approximately perpendicular. In the crystal, the molecules are connected by N--H...N, C--H...N, O--H...N and N--H...O hydrogen bonds with each other directly and through water molecules, forming layers parallel to the (001) plane. C--H...π interactions between these layers ensure the cohesion of the crystal structure. A Hirshfeld surface analysis indicates that H...H (39.1% for molecule I; 40.0% for molecule II), C...H/H...C (26.6% for molecule I and 25.8% for molecule II) and N...H/H...N (24.3% for molecules I and II) interactions are the most important contributors to the crystal packing. [ABSTRACT FROM AUTHOR]

Reaction of Co(NCS)2 with 4-methylpyridine N-oxide in methanol leads to the formation of crystals of the title compound, [Co2(NCS)4(C6H7NO)4(CH4O)2] or Co2(NCS)4(4-methylpyridine N-oxide)4(methanol)2. The asymmetric unit consist of one CoII cation, two thiocyanate anions, two 4-methylpyridine N-oxide coligands and one methanol molecule in general positions. The H atoms of one of the methyl groups are disordered and were refined using a split model. The CoII cations octahedrally coordinate two terminal N-bonded thiocyanate anions, three 4-methylpyridine N-oxide coligands and one methanol molecule. Each two CoII cations are linked by pairs of μ-1,1(O,O)-bridging 4-methylpyridine N-oxide coligands into dinuclear units that are located on centers of inversion. Powder X-ray diffraction (PXRD) investigations prove that the title compound is contaminated with a small amount of Co(NCS)2(4-methylpyridine N-oxide)3. Thermogravimetric investigations reveal that the methanol molecules are removed in the beginning, leading to a compound with the composition Co(NCS)2(4-methylpyridine N-oxide), which has been reported in the literature and which is of poor crystallinity. [ABSTRACT FROM AUTHOR]

TMC-anti and TMC-syn, the two topological isomers of [FeIV(O)(TMC)(CH3CN)]2+ (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane, or Me4cyclam), differ in the orientations of their FeIV=O units relative to the four methyl groups of the TMC ligand framework. The FeIV=O unit of TMC-anti points away from the four methyl groups, while that of TMC-syn is surrounded by the methyl groups, resulting in differences in their oxidative reactivities. TMC-syn reacts with HAT (hydrogen atom transfer) substrates at 1.3-to 3-fold faster rates than TMC-anti, but the reactivity difference increases dramatically in oxygen-atom transfer reactions. R2S substrates are oxidized into R²S=O products at rates 2-to-3 orders of magnitude faster by TMC-syn than TMC-anti. Even more remarkably, TMC-syn epoxidizes all the olefin substrates in this study, while TMC-anti reacts only with cis-cyclooctene but at a 100-fold slower rate. Comprehensive quantum chemical calculations have uncovered the key factors governing such reactivity differences found between these two topological isomers. [ABSTRACT FROM AUTHOR]

Recently, we identified a novel mechanism of enzyme inhibition in N-myristoyltransferases (NMTs), which we have named 'inhibitor trapping'. Inhibitor trapping occurs when the protein captures the small molecule within its structural confines, thereby preventing its free dissociation and resulting in a dramatic increase in inhibitor affinity and potency. Here, we demonstrate that inhibitor trapping also occurs in the kinases. Remarkably, the drug imatinib, which has revolutionized targeted cancer therapy, is entrapped in the structure of the Abl kinase. This effect is also observed in p38α kinase, where inhibitor trapping was found to depend on a 'magic' methyl group, which stabilizes the protein conformation and increases the affinity of the compound dramatically. Altogether, these results suggest that inhibitor trapping is not exclusive to N-myristoyltransferases, as it also occurs in the kinase family. Inhibitor trapping could enhance the binding affinity of an inhibitor by thousands of times and is as a key mechanism that plays a critical role in determining drug affinity and potency. [ABSTRACT FROM AUTHOR]

In the structure of the title compound, C22H22N4O4⋯C3H7NO⋯H2O, the entire tricyclic system is approximately planar except for the carbon atom bearing the two methyl groups; the methoxyphenyl ring is approximately perpendicular to the tricycle. All seven potential hydrogen-bond donors take part in classical hydrogen bonds. The main molecule and the DMF combine to form broad ribbons parallel to the a axis and roughly parallel to the ab plane; the water molecules connect the residues in the third dimension. [ABSTRACT FROM AUTHOR]

The title compound, C22H18N2O12, was obtained as a by-product during the planned synthesis of 1,2-bis(2-nitro-4,5-dimethyl phthalate)ethane by oxidative dimerization starting from dimethyl-4-methyl-5-nitro phthalate. To identify this compound unambiguously, a single-crystal structure analysis was performed. The asymmetric unit consists of half a molecule that is located at a centre of inversion. As a result of symmetry restrictions, the molecule shows an E configuration around the double bond. Both phenyl rings are coplanar, whereas the nitro and the two methyl ester groups are rotated out of the ring plane by 32.6 (1), 56.5 (2) and 49.5 (2)°, respectively. In the crystal, molecules are connected into chains extending parallel to the a axis by pairs of C--H⋯O hydrogen bonds that are connected into a tri-periodic network by additional C--H⋯O hydrogen-bonding interactions. [ABSTRACT FROM AUTHOR]

Understanding the physical properties of organic–inorganic hybrid [NH(CH3)3]2ZnCl4 is necessary for its potential application in batteries and fuel cells due to its environmentally-friendly, and highly stable character. Here, we determine its overall properties in detail, such as its orthorhombic crystal structure, and phase transition temperatures associated with five different phases. Structural geometry was studied by the chemical shifts caused by the local field around 1H. No changes were observed for the environment around 1H for CH3, whereas the 1H chemical shifts around NH in the cation were shown due to the change in the hydrogen bond N‒H···Cl. This is related to the change in Cl around Zn in the anion. In addition, the coordination geometry of 14N and 1H around 13C exhibited increased symmetry at high temperatures. Finally, we were able to understand its molecular dynamics by the significant change with temperature observed from the spin–lattice relaxation time T1ρ values, which represent the energy transfer for the 1H and 13C atoms of the cation. The activation energies obtained from the T1ρ results were 3–4 times large at phase I (> 348 K) than at phase V and IV (< 286 K). The relaxations show that the energy barriers in phases IV and V are related to the reorientation of methyl groups around the triple symmetry axis, while the reorientation of methyl groups of the cation in phase I is related to as a whole. [ABSTRACT FROM AUTHOR]

Understanding the physical properties of organic–inorganic hybrid [NH(CH3)3]2ZnCl4 is necessary for its potential application in batteries and fuel cells due to its environmentally-friendly, and highly stable character. Here, we determine its overall properties in detail, such as its orthorhombic crystal structure, and phase transition temperatures associated with five different phases. Structural geometry was studied by the chemical shifts caused by the local field around 1H. No changes were observed for the environment around 1H for CH3, whereas the 1H chemical shifts around NH in the cation were shown due to the change in the hydrogen bond N‒H···Cl. This is related to the change in Cl around Zn in the anion. In addition, the coordination geometry of 14N and 1H around 13C exhibited increased symmetry at high temperatures. Finally, we were able to understand its molecular dynamics by the significant change with temperature observed from the spin–lattice relaxation time T1ρ values, which represent the energy transfer for the 1H and 13C atoms of the cation. The activation energies obtained from the T1ρ results were 3–4 times large at phase I (> 348 K) than at phase V and IV (< 286 K). The relaxations show that the energy barriers in phases IV and V are related to the reorientation of methyl groups around the triple symmetry axis, while the reorientation of methyl groups of the cation in phase I is related to as a whole. [ABSTRACT FROM AUTHOR]

5-Deazaflavins are analogs of naturally occurring flavin cofactors. They serve as substitutes for natural flavin cofactors to investigate and modify the reaction pathways of flavoproteins. Demethylated 5-deazaflavins are potential candidates for artificial cofactors, allowing us to fine-tune the reaction kinetics and absorption characteristics of flavoproteins. In this contribution, demethylated 5-deazariboflavin radicals are investigated (1) to assess the influence of the methyl groups on the electronic structure of the 5-deazaflavin radical and (2) to explore their photophysical properties with regard to their potential as artificial cofactors. We determined the proton hyperfine structure of demethylated 5-deazariboflavins using photochemically induced dynamic nuclear polarization (photo-CIDNP) spectroscopy, as well as density functional theory (DFT). To provide context, we compare our findings to a study of flavin mononucleotide (FMN) derivatives. We found a significant influence of the methylation pattern on the absorption properties, as well as on the proton hyperfine coupling ratios of the xylene moiety, which appears to be solvent-dependent. This effect is enhanced by the replacement of N5 by C5-H in 5-deazaflavin derivatives compared to their respective flavin counterparts. [ABSTRACT FROM AUTHOR]

Epitranscriptomic RNA modifications play a crucial role in the posttranscriptional regulation of gene expression. N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic RNA and plays a pivotal role in RNA fate. RNA m6A modification is regulated by a group of cellular proteins, methyltransferases (writers) and demethylases (erasers), which add and remove the methyl group from adenosine, respectively. m6A modification is recognized by a group of cellular RNA-binding proteins (readers) that specifically bind to m6A-modified RNA, mediating effects on RNA stability, splicing, transport, and translation. The functional significance of m6A modification of viral and cellular RNA is an active area of virology research. In this review, we summarize and analyze the current literature on m6A modification of HIV-1 RNA, the multifaceted functions of m6A in regulating HIV-1 replication, and the role of viral RNA m6A modification in evading innate immune responses to infection. Furthermore, we briefly discuss the future directions and therapeutic implications of mechanistic studies of HIV-1 epitranscriptomic modifications. [ABSTRACT FROM AUTHOR]

Secondary metabolites derived from plants are recognized as valuable products with several successful applications in the pharmaceutical, cosmetic, and food industries. The major limitation to the broader implementation of these compounds is their low manufacturing efficiency. Current efforts to overcome unprofitability depend mainly on biotechnological methods, especially through the application of plant in vitro cultures. This concept allows unprecedented bioengineering opportunities for culture system modifications with in situ product removal. The silica-based xerogels can be used as a novel, porous biomaterial characterized by a large surface area and high affinity to lipophilic secondary metabolites produced by plant tissue. This study aimed to investigate the influence of xerogel-based biomaterials functionalized with methyl, hydroxyl, carboxylic, and amine groups on Rindera graeca transgenic root growth and the production of naphthoquinone derivatives. The application of xerogel-based scaffolds functionalized with the methyl group resulted in more than 1.5 times higher biomass proliferation than for reference untreated culture. The naphthoquinone derivatives' production was noted exclusively in culture systems supplemented with xerogel functionalized with methyl and hydroxyl groups. Applying chemically functionalized xerogels as in situ adsorbents allowed for the enhanced growth and productivity of in vitro cultured R. graeca transgenic roots, facilitating product isolation due to their selective and efficient accumulation. [ABSTRACT FROM AUTHOR]

One of the most important steps in the synthesis of 1,4-dihydropyridine (1,4-DHP) amphiphiles is the bromination of methyl groups in positions 2 and 6 of the entire ring. However, up to now, only N-bromosuccinimide was mainly used for bromination 1,4-DHPs. In this work, the synthesis of bis-1,4-DHP derivatives with ethyl and dodecyl ester groups attached to 1,4-DHP ring at positions 3 and 5 was performed by Hantzsch synthesis. The experimental studies were carried out to find out the best conditions and the agent for the tetra bromination of bis-1,4-DHP methyl groups at positions 2 and 6. Four different brominating agents were screened. The use of pyridinium bromide–perbromide in ethyl acetate was found to be optimal for the bromination of methyl groups. The bromination reaction was followed by the synthesis of cationic pyridine moiety containing amphiphilic bis-1,4-DHP derivatives. By nucleophilic substitution of bromine with various substituted pyridines, 12 new amphiphilic bis-1,4-DHP derivatives were obtained. Evaluation of self-assembling properties of tetracationic bis-1,4-dihydropyridine derivatives by dynamic light scattering (DLS) measurements was also performed. [ABSTRACT FROM AUTHOR]

m6A is the most prevalent internal modification of eukaryotic mRNA, and plays a crucial role in tumorigenesis and various other biological processes. Lung cancer is a common primary malignant tumor of the lungs, which involves multiple factors in its occurrence and progression. Currently, only the demethylases FTO and ALKBH5 have been identified as associated with m6A modification. These demethylases play a crucial role in regulating the growth and invasion of lung cancer cells by removing methyl groups, thereby influencing stability and translation efficiency of mRNA. Furthermore, they participate in essential biological signaling pathways, making them potential targets for intervention in lung cancer treatment. Here we provides an overview of the involvement of m6A demethylase in lung cancer, as well as their potential application in the diagnosis, prognosis and treatment of the disease. [ABSTRACT FROM AUTHOR]

The reaction between the (R,S)-fixolide 4-methyl­thio­semicarbazone and PdII chloride yielded the title compound, [Pd(C20H30N3S)2]·C2H6O {common name: trans-bis­[(R,S)-fixolide 4-methyl­thio­semicarbazonato-κ²N²S]palladium(II) ethanol monosolvate}. The asymmetric unit of the title compound consists of one bis-thio­semicarbazonato PdII complex and one ethanol solvent mol­ecule. The thio­semicarbazononato ligands act as metal chelators with a trans configuration in a distorted square-planar geometry. A C—HS intra­molecular inter­action, with graph-set motif S(6), is observed and the coordination sphere resembles a hydrogen-bonded macrocyclic environment. Additionally, one C—HPd anagostic inter­action can be suggested. Each ligand is disordered over the aliphatic ring, which adopts a half-chair conformation, and two methyl groups [s.o.f. = 0.624 (2):0.376 (2)]. The disorder includes the chiral carbon atoms and, remarkably, one ligand has the (R)-isomer with the highest s.o.f. value atoms, while the other one shows the opposite, the atoms with the highest s.o.f. value are associated with the (S)-isomer. The N—N—C(=S)—N fragments of the ligands are approximately planar, with the maximum deviations from the mean plane through the selected atoms being 0.0567 (1) and −0.0307 (8) Å (r.m.s.d. = 0.0403 and 0.0269 Å) and the dihedral angle with the respective aromatic rings amount to 46.68 (5) and 50.66 (4)°. In the crystal, the complexes are linked via pairs of N—HS inter­actions, with graph-set motif R2²(8), into centrosymmetric dimers. The dimers are further connected by centrosymmetric pairs of ethanol mol­ecules, building mono-periodic hydrogen-bonded ribbons along [011]. The Hirshfeld surface analysis indicates that the major contributions for the crystal cohesion are [atoms with highest/lowest s.o.f.s considered separately]: HH (81.6/82.0%), HC/CH (6.5/6.4%), HN/NH (5.2/5.0%) and HS/SH (5.0/4.9%). [ABSTRACT FROM AUTHOR]

This study aimed to analyze the structural requirements for di- and tripeptides exhibiting a DPP IV-inhibitory effect. The sequences of 46 di- and 33 tripeptides, including their bioactivity (IC50; μM), were implemented from the BIOPEP-UWM database, whereas modeling was performed using SCIGRESS Explorer: Version FJ 3.5.1 software. Models included 336 (dipeptide dataset) and 184 descriptors (tripeptide dataset). The values of the determination coefficient (R2) defining model reliability were 0.782 and 0.829 for di- and tripeptides, respectively. Based on the implemented descriptors, it was concluded that increased numbers of nitrogen atoms, as well as the methyl groups, are required for dipeptides to enhance the DPP IV-inhibitory effect. This was indicated by the presence of amino acids with an aliphatic side chain (e.g., Leu, Val, Ile) and an aromatic ring (Trp). In the case of tripeptides, a correlation was found between their molecular weight (MW) and studied bioactivity. A tripeptide with a molecular weight of up to 500 Da was found suitable for the sequence to act as the DPP IV inhibitor. Although there is still a gap in explaining the relations between the structural nature and the DPP IV-inhibitory activity of peptides, and certain issues related to this topic still remain unknown, the results are in line with those reported by other authors. Additionally, the suitability of the SCIGRESS tool in the QSAR analysis of peptides derived from foods can be confirmed. Interpretable descriptors enabled the achievement of more unequivocal results concerning the main structural factors affecting the DPP IV inhibition of di- and tripeptides. [ABSTRACT FROM AUTHOR]

Internal modifications of mRNA have emerged as widespread and versatile regulatory mechanism to control gene expression at the post-transcriptional level. Most of these modifications are methyl groups, making S-adenosyl-L-methionine (SAM) a central metabolic hub. Here we show that metabolic labeling with a clickable metabolic precursor of SAM, propargyl-selenohomocysteine (PSH), enables detection and identification of various methylation sites. Propargylated A, C, and G nucleosides form at detectable amounts via intracellular generation of the corresponding SAM analogue. Integration into next generation sequencing enables mapping of N6-methyladenosine (m6A) and 5-methylcytidine (m5C) sites in mRNA with single nucleotide precision (MePMe-seq). Analysis of the termination profiles can be used to distinguish m6A from 2′-O-methyladenosine (Am) and N1-methyladenosine (m1A) sites. MePMe-seq overcomes the problems of antibodies for enrichment and sequence-motifs for evaluation, which was limiting previous methodologies. Metabolic labeling via clickable SAM facilitates the joint evaluation of methylation sites in RNA and potentially DNA and proteins. Methylation is the dominant modification in mRNA and occurs at a variety of sites. Here, Hartstock et al. show that a clickable analogue of the key cosubstrate S-adenosyl-L-methionine (SAM) can be produced in cells, allowing for identification and mapping of different methylated nucleosides in mRNA. [ABSTRACT FROM AUTHOR]