Methyl Group Research Articles

Bond lengths and band strengths of non-equivalent C-H bonds of 2-methyl-1,3-butadiene using density functional theory, Fourier transform IR, and cavity ringdown techniques

The C-H fundamental and overtone spectra (Δυ = 1- 4) of non-equivalent C-H bonds of isoprene (CH2=C(CH3)-CH=CH2) have been obtained using a Fourier transform infrared spectrometer. The C-H vibrational overtone spectra (Δυ = 5, 6) have been recorded using phase shift (PS) and exponential decay cavity ring down (CRD) techniques, respectively at 293 K. Theoretical density functional theory (DFT) calculations of bond lengths, harmonic, and anharmonic frequencies of isoprene and partially deuterated isoprene molecules, as well as computer deconvolution of the bands are used to identify transitions corresponding to non-equivalent C-H bonds. Harmonic frequencies ωe and anharmonicities ωexe are reported for theC-H (a) in plane and C-H (b) out of plane bonds of the methyl group, the single olefinic nonterminal C-H (o), and the four olefinic terminal C-H bonds that are defined in two groups as C-H (cis) and C-H (trans). From the Δυ = 6 peak wavenumbers, correlation functions are used to calculate C-H bond lengths, isolated frequencies, and dissociation energies. Band strengths, oscillator strengths, and transition moments are obtained experimentally for all transitions. The significance of the assigned vibrational transitions and integrated intensities of isoprene for research on Earth's atmosphere and as a potential indicator of life in exoplanets with oxygen-deprived atmospheres is examined.

Radical Cascade Cyclization of N-(o-Cyanobiaryl)acrylamides with Sulfonium Salts via Synergetic Photoredox and Copper Catalysis.

As the magic methyl effect is well acknowledged in pharmaceutical molecules, the development of simple and efficient methods for the installment of methyl groups on complex molecules is highly coveted. Hence, we provide a general strategy for radical cascade cyclization of N-(o-cyanobiaryl)acrylamides by utilizing sulfonium salts as the sources of methyl radical and merging photoredox and copper catalysis. This novel protocol can access a wide variety of methylation or remote thioether-substituted benzo-fused N-heterocycle derivatives, which can be easily transformed into diverse highly valuable sulfone and sulfoximine compounds via late-stage diversification. Moreover, to further demonstrate the synthetic utility of this conversion, the methyl(phenyl)sulfide, which serves as both raw material and byproduct, can be recovered and reused in this transformation. The scale-up experiment for the one-pot two-step process directly offers the target product in good yield under the standard conditions.

Effect of the alkyl chain length of α,ω-dichloroalkane on the Gibbs energy of transfer for functional groups.

Ion-transfer reactions of alkyl and perfluoroalkyl carboxylate ions (CH3(CH2)n-2COO- with n = 8-12 and CF3(CF2)n-2COO- with n = 3-9) were investigated at the polarized Cl-(CH2)m-Cl with m = 2, 4, 6, and 8 (O) | water (W) interface to evaluate the effects of n and m on the solvation energy of the ions, as well as on their methylene and terminal groups. These ions exhibited reversible or quasi-reversible voltammetric waves due to their transfer across the O | W interfaces, enabling the determination of formal potentials and formal Gibbs transfer energies from O to W, . The values for CH3(CH2)n-2COO- and CF3(CF2)n-2COO- increased linearly with n, allowing the estimation of for methylene and difluoromethylene groups, (CH2) and (CF2), and for their terminal groups, (COO- + CH3) and (COO- + CF3). Whereas the (CH2) and (CF2) hardly changed with the variation in m, the (COO- + CH3) and (COO- + CF3) decreased noticeably. These results suggest that the solvation energy for ions in Cl-(CH2)m-Cl increases with m, regardless of hydrophilic or lipophilic nature of the ions. Based on these findings, the advantage of using Cl-(CH2)m-Cl with a large m as a non-aqueous solvent for ion-transfer voltammetry was discussed.

Structural insight into the DNMT1 reaction cycle by cryo-electron microscopy.

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.

Automatization of theoretical kinetic data generation for tabulated TS models building - Part II: 1,2 to 1,5-H-shift reactions in alkyl radicals

Branched alkanes make up a significant fraction of sustainable alternative fuels. The accurate chemical kinetic modeling of the pyrolysis and oxidation of those fuels requires the availability of accurate kinetic data for branched structures. The accurate theoretical calculation of these data for substituted cyclic transition states (TS) is a challenge because of the large number of configurations that can be created, especially in the larger TS cycles. These configurations originate from all the possible combinations of the orientations of the substituents (axial or equatorial) on the cyclic TS and diastereomers in the reactants, which makes the rigorous counting of the multiple parallel pathways complicated. In this paper, the isomerisation reactions of branched alkyl radicals are theoretically investigated using the code presented in the Part I of this paper series. The 1,2 to 1,5-H-shift reactions are studied within the tabulated transition state models approach, where chain substituents are represented by methyl groups, and all combinations of substitutions in the model TSs are included in a table with their computed rate constants. The rate constants computed for hundreds of reactions with our code demonstrate the necessity to consider all the TS configurations in order to get accurate data. The presence of spectator substituents in the cyclic transition state is shown to have a major impact on the rate constants, increasing their values by more than a factor of 10 for some cases. The tabulated TS models (TMTS) method is validated by comparisons with available experimental data in the literature and is one of the only approach able to accurately capture the impact of branching on the rate constants of isomerizations for large alkyl radicals, which are still difficult to calculate with high-level on-the-fly ab initio calculations.

Formohyperins G-L, polycyclic prenylated benzoylphloroglucinols from the flowers of Hypericum formosanum.

Phytochemical study on the flowers of Hypericum formosanum Maxim. (Hypericaceae) led to the isolation of formohyperins G-L (1-6), whose structures were assigned by detailed spectroscopic analysis. Formohyperins G-L (1-6) are new benzoylphloroglucinols substituted by a C10 unit, a prenyl group, and a methyl group. Formohyperins G-J (1-4) possess a 6/6/6-tricyclic structure, while formohyperins K (5) and L (6) have a unique 6/6/5/4-tetracyclic structure consisting of cyclohexadienone, dihydropyrane, cyclopentane, and cyclobutane rings. The absolute configurations of 1-6 were deduced by analysis of the ECD spectra. Formohyperins G-J (1-4) and L (6) were found to show potent inhibitory activities against IL-1β release from LPS-treated murine microglial cells with EC50 values of 5.0, 10.9, 6.3, 10.8, and 13.7µM, respectively, without cytotoxicity. 6-O-Methylformohyperins G (1a) and I (3a) also exhibited the inhibitory activities with EC50 values of 4.7 and 2.7µM, respectively, although they were cytotoxic against microglial cells.

RNA methylation in neurodevelopment and related diseases.

Biological development and genetic information transfer are governed by genetic, epigenetic, transcriptional, and posttranscriptional mechanisms. RNA methylation, the attachment of methyl (-CH 3) groups to RNA molecules, is a posttranscriptional modification that has gained increasing attention in recent years because of its role in RNA epitranscriptomics. RNA modifications (RMs) influence various aspects of RNA metabolism and are involved in the regulation of diverse biological processes and diseases. Neural cell types emerge at specific stages of brain development, and recent studies have revealed that neurodevelopment, aging, and disease are tightly linked to transcriptome dysregulation. In this review, we discuss the roles of N6-methyladenine (m6A) and 5-methylcytidine (m5C) RNA modifications in neurodevelopment, physiological functions, and related diseases.

Elution behavior of carbohydrates using core-shell ion-exchange resin St-60 with different numbers of methylene groups in the porous shell and a constant cross-linking degree of 55%

Elution behavior of carbohydrates using core-shell ion-exchange resin St-60 with different numbers of methylene groups in the porous shell and a constant cross-linking degree of 55%

Design, Synthesis and Evaluation of Photophysical and Biological Properties of Tetrafluoroacridine

Abstract1,4,5,8‐Tetrafluoroacridine was successfully synthesized from 1,4,5,8‐tetrafluoroacridone through transfer hydrogenation using an in‐house ruthenium pincer catalyst followed by in situ dehydration. The synthetic protocol involves the copper‐catalyzed coupling of 2‐amino‐3,6‐difluorobenzoic acid 1 and 1,4‐difluoro‐2‐iodobenzene 2 to obtain 3 followed by cyclization using polyphosphoric acid to get the 1,4,5,8‐tetrafluoroacridone 4. Common synthetic strategies for converting 4 to the 1,4,5,8‐tetrafluoroacridine 5 were unsuccessful and the transfer hydrogenation approach proved to be most fruitful. 1,4,5,8‐Tetrafluoroacridone 4 can be N‐methylated to give 9. The investigation into the photophysical properties of 4, 5, and 9 revealed that the average photoluminescence (PL) lifetime of the acridine derivatives was longer in the aqueous medium than in ethanol and methanol, indicating the influence of the solvent environment on the excited‐state dynamics. To assess their potential therapeutic applications, the cytotoxic activity of these compounds was evaluated against AGS and IMR‐32 cells, and compound 9 showed significant activity. The addition of methyl group to the acridone was found helpful in enhancing the solubility and biological activity.

Protective role of S-adenosylmethionine on high fat/high cholesterol diet-induced hepatic and aortic lesions and oxidative stress in guinea pigs.

S-adenosylmethionine (SAM) is the main methyl group donor and has antioxidant potential. In this study, preventive and regressive potential of SAM were investigated in high fat/high cholesterol (HFHC) diet-induced non-alcoholic fatty liver disease (NAFLD) in guinea pigs. They were injected with SAM (50 mg/kg, i.p.) for 6 weeks along with HFHC diet or 4 weeks after HFHC diet. Serum transaminase activities, total cholesterol (TC), triglyceride (TG), cytochrome p450-2E1 (CYP2E1) and hydroxyproline (Hyp) levels, prooxidative and antioxidative parameters, protein expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) together with histopathological changes were examined in the liver. SAM treatment diminished HFHC diet-induced increases in serum transaminase activities and hepatic TC, TG, CYP2E1, Hyp, α-SMA and TGF-β1 expressions and ameliorated prooxidant-antioxidant balance. Histopathological scores for hepatic steatosis, inflammation, and fibrosis were decreased by SAM treatment. Increases in TC, diene conjugate levels, and lipid vacuoles within the tunica media of the aorta were reduced in HFHC-fed animals treated with SAM. These protective effects were also detected in the regression period of HFHC-guinea pigs due to SAM. In conclusion, SAM treatment was found to be effective in prevention and regression of HFHC-induced hepatic and aortic lesions together with decreases in oxidative stress in guinea pigs with NAFLD.

Substituent effect on the chemical and biological properties of diisatin dihydrazone Schiff bases: DFT and docking studies

According to the considered role of lipophilicity-hydrophobicity on organic Schiff base hydrazones, different substituents of phenyl, ethyl, and methyl groups were inserted in the synthetic strategy of diisatin dihydrazones (L1–4). The biochemical enhancement was evaluated depending on their inhibitive potential of the growth power of three human tumor cells, fungi, and bacteria. The biochemical assays assigned the effected role of different substituents of phenyl, ethyl, and methyl groups on the effectiveness of their diisatin dihydrazone reagents. The interacting modes with calf thymus DNA (i.e. Ct-DNA) were studied via viscometric and spectrophotometric titration.The organo-reagent L1 with the oxalic derivative assigned a performed inhibitive action for the examined microbes and the human tumor cell lines growing up over the terephthalic (L4) > malonic (L2) > succinic (L3) ones. From Kb = binding constant, and ∆Gb≠ = Gibb’s free energy values, the binding of interaction within Ct-DNA was evaluated for all compounds (L1–4), in which L1, L3, and L4 assigned the highest reactivity referring to the covalent/non-covalent modes of interaction, as given for (L1–4), 14.32, 13.28, 10.87, and 12.41 × 107 mol−1 dm3, and −45.17, −43.24, −43.75, and −44.05 kJ mol−1, respectively. DFT and docking studies were achieved to support the current work.

Chromosome Gene, Hsl7 Gene in Vitro Studies

Chromosome gene can expression many functions in human body. Eukaryotic cells are presence in yeast and human, in order to more understanding human gene, we use yeast as a model to research. The ORF (open reading frame) position of the Hsl7 gene is in yeast Saccharomyces YBR133C between 501804bp~504287bp of Chromosome II, with a total length of 2483bp, and the protein size is 95 kDa. Hsl7 gene is a methyltransferase. Protein-arginine N-methyltransferase involved in protein catabolism and regulation of the G2/M transition of mitosis; localizes to the septin collar of the bud neck, and the outer plaque of the spindle pole body in the G1 phase of the cell cycle (Saccharomyces Genome Database), Hsl7 (histone synthetic lethal 7) represent protein methylation, protein methylation is a type of post-translational modification that involves the addition of methyl groups to proteins, Protein methylation, including histone methylation and non-histone protein methylation, is one of the most important forms of posttranscriptional and epigenetic modifications.

Molecular origin of viscoelasticity and influence of methylation in mesophase pitch

The viscoelastic and thermomechanical properties of pitches are responsible for their melt-spinning behavior, a critical step for manufacturing high-performance pitch-based carbon fibers. Here, we systematically explore the impact of methyl group modifications on the viscoelastic and thermal properties of mesophase pitches. We employ a range of atomistic modeling approaches, including Density Functional Theory (DFT), Density Functional Tight Binding (DFTB), and Classical Molecular Mechanics (MM), to provide detailed insights into the molecular interactions and structural changes. Our results revealed the molecular mechanisms that promote layered structures leading to the anisotropic nature of the viscoelastic behavior of mesophase pitch. Furthermore, we propose a modified molecular representation of naphthalene-based mesophase pitch based on the analysis of x-ray diffraction measurements. This study provides fundamental insights into the molecular structures of mesophase pitch and the role of methyl groups controlling its viscosity, which offer valuable insights into mesophase-based carbon fiber production.

Differences in humic acid structure extracted from different types of peat

ABSTRACT Peat is an organic mineral resource. Peat contains a large amount of humic acid, and extracting humic acid from peat is a way to efficiently utilize peat. This article mainly studies the effects of using woody, herbaceous, and mossy peat as raw materials on the yield, content, and especially molecular structure of humic acid extraction, including that the oxygen-containing functional groups of humic acids, aromatic carbon content, microcrystalline structure, carbon chain structure, and degree of aromatization. The results showed that the highest yield of humic acid in woody peat was 54.33%, the yield of humic acid in herbaceous peat and mossy peat are relatively low, at 44.67% and 15.00%, respectively. while the woody peat humic acid has the lowest content, that is 38.38%. The content of humic acid in herbaceous peat was 77.33%. and the content of humic acid in mossy peat is 57.85%. Through comprehensive consider, herbaceous peat is more suitable for extracting humic acid. At the same time, this article studies the molecular structures of three peat humic acids and concludes as follows. Woody peat humic acid has the highest degree of aromatization, the highest content of benzene ring, and more functional groups such as methyl, phenol, aromatic ether, carbonyl, and hydroxyl groups. The content of methoxy and methylene groups in herbaceous peat humic acid is relatively high. Through XPS characterization analysis, it was found that the main forms of oxygen element in humic acid are C = O, C-O, and -COOH, without inorganic oxygen. The humic acid extracted from different types of peat has significant differences in yield, purity, and functional group content. Compared to woody peat and mossy peat, herbaceous peat is the most suitable raw material for extracting humic acid from peat.

The pronounced NTC behavior of 1,2,4-trimethylbenzene at high-pressure oxidation

This study presents experimental and modeling results of the 1,2,4-trimethylbenzene (T124MBZ) oxidation in a jet-stirred reactor at equivalence ratios of 0.4 and 2.0, temperature range of 450–1000 K, and pressure of 12.0 atm. Compared with the oxidation at atmospheric pressure, a pronounced negative temperature coefficient (NTC) behavior of T124MBZ was observed between 622 K and 773 K under fuel-lean condition. A detailed chemical kinetic model involving 865 species and 5092 reactions was developed. In addition, the model was validated against experimental results of laminar burning velocities and ignition delay times. The present model reasonably reproduces these experimental data. The dominant consumption channels for T124MBZ are H-abstraction reactions on methyl groups by OH radicals. The H-abstraction reactions on the 1- and 2- methyl sites by OH radicals are the most promoting in pre- and mid- NTC phases, and H2O2(+M) = 2OH(+M) is the most promoting in the post-NTC phase, while the reaction on the 4-methyl site is the most inhibiting across pre-, mid-, and post-NTC phases. This difference arises from the fact that the dominant consumption pathway for 2,4-dimethylbenzyl and 2,5-dimethylbenzyl involves H-transfer, while the 4-methyl site cannot undergo an H-transfer reaction due to the absence of adjacent methyl groups. The competition between the two consumption channels of ·QOOH radicals (decomposition and second O2 addition), resulting in the reduction of OH radicals as temperature increases, leads to diminished OH production. This causes the emergence of pronounced NTC behavior at high pressure.

Exposure to prenatal excess or imbalanced micronutrients leads to long-term perturbations in one-carbon metabolism, trimethylamine-N-oxide and DNA methylation in Wistar rat offspring.

Prenatal multivitamins, including folic acid, are commonly consumed in excess, whereas choline, an essential nutrient and an important source of labile methyl groups, is underconsumed. Here, we characterized profiles of one-carbon metabolism and related pathways andpatterns of DNA methylation in offspring exposed to excess or imbalanced micronutrients prenatally. Pregnant Wistar rats were fed either recommended 1× vitamins (RV), high 10× vitamins (HV), high 10× folic acid with recommended choline (HFolRC), or high 10× folic acid with no choline (HFolNC). Offspring were weaned to a high-fat diet for 12 weeks. Circulating metabolites were analyzed with a focus on the hypothalamus, an area known to be under epigenetic regulation. HV, HFolRC, and HFolNC males had higher body weight (BW) and lower plasma choline and methionine consistent with lower hypothalamic S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) and global DNA methylation compared with RV. HV and HFolNC females had higher BW and lower plasma 5-methyltetrahydrofolate and methionine consistent with lower hypothalamic global DNA methylation compared with RV. Plasma dimethylglycine (DMG) and methionine were higher as with hypothalamic SAM:SAH and global DNA methylation in HFolRC females without changes in BW compared with RV. Plasma trimethylamine and trimethylamine-N-oxide were higher in males but lower in females from HFolRC compared with RV. Network modeling revealed a link between the folate-dependent pathway and SAH, with most connections through DMG. Final BW was negatively correlated with choline, DMG, and global DNA methylation. In conclusion, prenatal intake of excess or imbalanced micronutrients induces distinct metabolic and epigenetic perturbations in offspring that reflect long-term nutritional programming of health.

A structural and functional model for alkene dioxygenases

In this article, we report sterically-controlled iron sites based on non-chelating bulky imidazole ligands. Adding 6 equiv. of 1,2-dimethylimidazole (1,2-Me2Im) to Fe(OTf)2⋅2CH3CN affords the first example of a 5-coordinate imidazole‑iron complex ([Fe(1,2-Me2Im)5](OTf)2, 1). The structure is distorted square pyramidal (τ5 = 0.41). When an iPr group is substituted for the methyl group at the 2-position on the imidazole (2-iPr-1-MeIm), the 14-electron complex ([Fe(2-iPr-1-MeIm)4](OTf)2, 2) is obtained. This complex exhibits slightly distorted tetrahedral geometry (τ'4 = 0.93) with four N-donors and serves as a 4-His iron structural model complex for carotenoid cleavage dioxygenases (CCD). The electronic structure of 1 and 2 were characterized by Mössbauer spectroscopy. Reactions of 1 and 2 with model olefin substrates (1-R-4-(1-methoxyprop-1-en-2-yl)benzene; R = Me or Br) in the presence of oxygen result in olefin cleavage yielding ketone and aldehyde products, although 2 yields more products than 1. Support for a proposed reaction mechanism for 2 is offered from Density Functional Theory (DFT) calculations.

Fluorogenic Chemical Probe Strategy for Precise Tracking of Mitochondrial Polarity.

Mitochondrial polarity is a critical indicator of numerous pathological and biological processes; thus, the development of fluorescent probes capable of targeting mitochondria and visually monitoring its polarity is of great significance. In this study, fluorescent probes were designed with a N, N-dialkylamino rhodol scaffold as the fluorophore sensitive to polarity environments, in which the alkyl chain length was adjusted rationally to obtain distinct polarity recognition modes. By integrating mitochondria targeting groups, three fluorogenic chemical probes ROML-1, ROML-2, and ROML-3 have been obtained, featuring the capability to target mitochondria and monitor its polarity precisely, dynamically and visually. The probes displayed a distinctive response to the alterations in polarity. ROML-1 and ROML-2 followed a turn-on pattern while ROML-3 was ratiometric. It has been demonstrated that the hypersensitivity to polarity and ratio fluorescence property of ROML-3 was attributed to methyl groups rather than ethyl or butyl groups. The introduction of short methyl chains made the dihedral angle between the dialkylamino substituent and fluorophore of ROML-3 (spirocyclic form) rotatable and enlarged the energy gap between the ground state and excited state, which has been validated by the results of density functional theory (DFT) calculations. Furthermore, ROML-3 was used to monitor mitochondrial polarity via confocal microscopy imaging, which revealed that compared to healthy cells the polarity of mitochondria in cancer cells was enhanced; meanwhile, the polarity of mitochondria in senescent cells was higher in contrast with young cells. The present probe ROML-3 has been proven to be an efficient tool to monitor mitochondrial polarity dynamics, which demonstrated potential significance in biomedical research and disease diagnosis.

The Preparation and Crystal Structures of Octaoxoketocalix[8]arene Derivatives: The Ketocalixarene Counterparts of the Largest "Major" Calixarene.

The purpose of this study was to synthesize and structurally characterize ketocalixarenes (i.e., calixarenes where the bridging methylene bridges are replaced by carbonyl groups) derived from the largest "major" calixarene, namely p-tert-butylcalix[8]arene 3a. Ketocalix[8]arenes were synthesized by the oxidation of protected p-tert-butylcalix[8]arene derivatives. Octamethoxy-p-tert-butylketocalix[8]arene 6b was prepared by the photochemical reaction of the calixarene 3b with NBS in a CHCl3/H2O mixture. The oxidation of the methylene groups of octaacetoxy-p-tert-butylcalix[8]arene 3c was conducted by a reaction with CrO3 in Ac2O/AcOH. The basic hydrolysis of the acetate groups of the oxidation product yielded octahydroxy-p-tert-butylketocalix[8]arene 6a. In the crystal, the molecule adopts a saddle-like conformation of crystallographic C2 and idealized S4 symmetry. Strikingly, the array of OH/OH intramolecular hydrogen bonds present in the parent 3a is completely disrupted in 6a.

RNA Methylation and Tumor Occurrence

RNA methylation is a post-transcriptional modification involving the addition of methyl groups to RNA molecules, playing a crucial role in gene expression regulation. Recent studies have highlighted the importance of RNA methylation, particularly N6-methyladenosine (m6A) modification, in cancer development and progression. RNA methylation affects mRNA stability, splicing, transport, and translation, thereby regulating various aspects of tumor cell biology, including proliferation, migration, and apoptosis. Abnormal RNA methylation patterns are closely linked to tumor aggressiveness and drug resistance, with dysregulation of methylation writers, erasers, and readers contributing to cancer onset and progression. Moreover, RNA methylation plays a significant role in cancer immunotherapy by influencing tumor cell immune evasion, offering new therapeutic targets. Future research should focus on elucidating the specific mechanisms of RNA methylation in different cancer types and its interactions with the tumor microenvironment. As technologies advance, RNA methylation modulators hold promising potential for cancer treatment, providing new strategies and therapeutic targets.