Methyl Derivatives Research Articles

Unlocking the biological potential of methyl antcinate A: a new frontier in cancer and inflammation application.

Antrodia camphorata is a valued and scarce parasitic mushroom that exclusively proliferates on the inner cavity wall of the endangered tree Cinnamomum kanehirai Hay (Lauraceae), endemic to Taiwan. Historically, this fungus has been utilized in traditional medicine to treat liver cancer, diarrhea, abdominal pain, hypertension, and food and drug intoxication, among other ailments. Literature searches were performed in scientific databases. The results were compiled from peer-reviewed studies; the search was refreshed through January 2024 to incorporate the most recent research. In vitro studies have revealed that Antrodia camphorata possesses various pharmacological properties that prevent cancer, reduce inflammation, and improve liver function. This medicinal mushroom contains unique ergostane-type triterpenoids known as antcins, which exhibit numerous pharmacological properties. Seven naturally occurring methyl analogs of antcins have been identified so far. In this article, we reviewed and analyzed the properties of methyl antcinate A (MAA), a constituent of Antrodia camphorata and methyl derivative of antcin A. MAA has demonstrated important anti-apoptotic, anti-inflammatory, and gastro-protective properties, as well as significant anti-tumor, anti-cancer, and cytotoxic activities. The anti-cancer effect of MAA in various cancers is attributed to its ability to modulate signaling cascades in apoptotic pathways. A significant challenge is to initiate preclinical and clinical trials to assess its anti-tumor action in vivo, as this data is currently missing. Additionally, future research on the structure-activity relationship of antcins and their derivatives is expected to support their development as therapeutic agents for clinical use.

Bioassay-guided evaluation of antimicrobial properties and profile of bioactive compounds from leaf, peel and mesocarp of four apple cultivars (Malus domestica Borkh.) grown in Serbia: Application of HPTLC-EDA and UHPLC Q-ToF MS techniques

The aim of this study was to evaluate the antimicrobial properties and profile of bioactive compounds from mesocarp, peel and leaves of four autochthonous apple cultivars against human pathogens, Escherichia coli, Staphylococcus aureus and Bacillus subtilis and the apple pathogen Erwinia amylovora by direct detection on HPTLC plates and subsequent chemometric analysis. UHPLC Q-ToF MS was used for detailed characterization of the bioactive compounds with antimicrobial properties. Leaf extracts showed the highest antibacterial activity against all bacterial strains, followed by peel extracts, while the mesocarp extracts showed only weak and selective inhibition zones for E. coli and B. subtillis. The apple cultivars, ‘Kadumana’ and ‘Kopaoničanka’ showed the best antimicrobial properties. The active compounds were triterpenoids, coumaroylquinic acid and caffeoylquinic acid isomers and methyl derivatives, naringenin, kaempferol and quercetin aglycones and glycosides, phloretin and its glycosides and acylated derivatives that detected for the first time in the apple leaves and fruits.

Resveratrol and Its Derivatives Diminish Lipid Accumulation in Adipocytes In Vitro-Mechanism of Action and Structure-Activity Relationship.

Expansion of white adipose tissue causes systemic inflammation and increased risk of metabolic diseases due to its endocrine function. Resveratrol was suggested to be able to prevent obesity-related disorders by mimicking caloric restriction; however, its structure-activity relationships and molecular targets are still unknown. We aimed to compare the effects of resveratrol and its analogues on adipocyte metabolism and lipid accumulation in vitro. Mouse embryonic fibroblasts were differentiated to adipocytes in the absence or presence of resveratrol or its derivatives (oxyresveratrol, monomethylated resveratrol, or trimethylated resveratrol). Intracellular lipid content was assessed by Oil Red O staining. Glucose uptake and its response to insulin were estimated by 2-NBDG, and mitochondrial activity was assayed via resazurin reduction. Involvement of potential molecular pathways was investigated by concurrent treatment with their inhibitors. Although lipid accumulation was significantly reduced by all analogues without altering protein content, oxyresveratrol was the most potent (IC50 = 4.2 μM), while the lowest potency was observed with trimethylated resveratrol (IC50 = 27.4 μM). Increased insulin-stimulated glucose uptake was restored by each analogue with comparable efficiency. The enhanced mitochondrial activity was normalized by resveratrol and its methylated derivatives, while oxyresveratrol had a minor impact on it. Among the examined pathways, inhibition of SIRT1, PGC-1α, and JNK diminished the lipid-reducing effect of the compounds. Autophagy appeared to play a key role in the effect of all compounds but oxyresveratrol. Resveratrol and its analogues can mimic caloric restriction with complex mechanisms, including activation of SIRT1, PGC-1α, and JNK, making them possible drug candidates to treat obesity-related diseases.

Metabolic engineering of Escherichia coli for N-methylserotonin biosynthesis

N-methylserotonin (NMS) is a valuable indole alkaloid with therapeutic potential for psychiatric and neurological disorders, and it is used in health foods, cosmetics, and weight loss supplements. However, environmental challenges and low reaction efficiencies significantly hinder cost-effective, large-scale production of NMS in plants or through chemical synthesis. Herein, we have successfully engineered Escherichia coli strains to enhance NMS production from L-tryptophan using whole-cell catalysis. We developed multiple biosynthesis pathways incorporating modules for serotonin (5-hydroxytryptamine, 5-HT), tetrahydromonapterin (MH₄), and S-adenosylmethionine (SAM) synthesis. To enhance MH₄ availability, we employed a high-activity Bacillus subtilis FolE and minimized carbon flux loss through targeted gene knockouts in competitive metabolic pathways, improving 5-HT production. Additionally, we constructed a comprehensive SAM biosynthesis module to facilitate transmethylation by a selected N-methyltransferase fused with ProS2. These engineered modules were coexpressed in two plasmids within the optimized strain NMS-19, producing 128.6 mg/L of NMS in a 5-L bioreactor using fed-batch cultivation—a 92-fold increase over the original strain. This study introduces a viable strategy for NMS production and provides insights into the biosynthesis of SAM-dependent methylated tryptamine derivatives.

Revealing the Role of Electronic Effect to Modulate the Photophysics and Z-Scan Responses of o-Locked GFP Chromophores.

Three novel core green fluorescent protein (GFP) chromophore analogues, based on a doubly locked conformation and variable electronic effects by replacing one hydrogen with bromine, iodine, and methyl, respectively, have been synthesized to modulate the push-pull effect. These chromophores exhibited intramolecular H-bonding, as evidenced by single-crystal X-ray and 1H NMR studies. The fluorescence quantum yields (ϕf) of all of the chromophores were found to be more than an order of magnitude higher (∼0.2) than the unlocked chromophores (∼0.01). It was found that the electronic effect did affect the nonradiative rates, as the quantum yields were found to vary with respect to different analogues in the same solvents. The effect of the push-pull effect was also evident by a higher Stokes-shifted emission in the case of the methyl derivative with respect to the bromo- and iodo-analogues. Furthermore, the emission spectra of these GFP chromophores were found to show positive solvatochromism, which was supported by a quantum chemical calculation. A detailed study, correlating the observed spectral changes with various solvent functions and supported by computational results, established a facile proton transfer, followed by twisted intramolecular charge transfer (TICT) to be the major nonradiative channels of these chromophores. Besides, a completely novel usage of these chromophores was explored for the first time by studying their third-order nonlinear optical characteristics in DMSO using a single-beam Z-scan technique. All of the chromophores exhibited tunable nonlinear refraction (NLR) and nonlinear absorption (NLA) properties that depend upon different substituent groups present in the chromophores. Here, the NLR was due to the effect of self-defocusing, whereas the NLA was triggered by reverse saturable absorption, which is attributed to the two-photon absorption (TPA) process. Surprisingly, the efficiency of the TPA ability of the chromophores was found to be a function of the induced electronic effect. Hence, this work opens a new route for the utility of the ortho-locked GFP chromophores in the field of nonlinear optical applications.

Kinetics of thermal decomposition of methyl derivatives of 7<i>H</i>-difurazanofuxanoazepine and 7<i>H</i>-tryfurasanoazepine

The thermal stability of N-methyl derivatives of 7H-difurasanofuroxanoazepine and 7H-trifurazanoazepine in non-isothermal and isothermal modes has been studied. Formal-kinetic regularities of decomposition and temperature dependences of reaction rate constants have been determined. The thermal stability methyl, propargyl, cyanomethyl, allyl and amine derivatives of azepines is compared.

SDMA as a marker and mediator in cerebrovascular disease.

Symmetric dimethylarginine (SDMA) is a methylated derivative of arginine, generated by all cells as a by-product of cellular metabolism and eliminated via the kidney. For many years SDMA has been considered inert and of little biological significance. However, a growing body of evidence now suggests this view is outdated and that circulating SDMA levels may, in fact, be intricately linked to endothelial dysfunction and vascular risk. In this review, we specifically examine SDMA within the context of cerebrovascular disease, with a particular focus on ischaemic stroke. We first discuss pre-clinical evidence supporting the notion that SDMA has effects on nitric oxide signalling, inflammation, oxidative stress, and HDL function. We then appraise the most recent clinical studies that explore the relationship between circulating SDMA and cerebrovascular risk factors, such as chronic kidney disease, hypertension, atrial fibrillation, and atherosclerosis, exploring whether any associations may arise due to the existence of shared risk factors. Finally, we consider the evidence that elevated circulating SDMA is linked to poor outcomes following ischaemic and haemorrhagic stroke. We draw upon pre-clinical insights into SDMA function to speculate how SDMA may not only be a marker of cerebrovascular disease but could also directly influence cerebrovascular pathology, and we highlight the pressing need for more mechanistic pre-clinical studies alongside adequately powered, longitudinal clinical studies to fully evaluate SDMA as a marker/mediator of disease.

Identification of a polyphenol O-methyltransferase with broad substrate flexibility in Streptomyces albidoflavus J1074

Flavonoids are a large and important group of phytochemicals with a great variety of bioactivities. The addition of methyl groups during biosynthesis of flavonoids and other polyphenols enhances their bioactivities and increases their stability. In a previous study of our research group, we detected a novel flavonoid O-methyltransferase activity in Streptomyces albidoflavus J1074, which led to the heterologous biosynthesis of homohesperetin from hesperetin in feeding cultures. In this study, we identify the O-methyltransferase responsible for the generation of this methylated flavonoid through the construction of a knockout mutant of the gene XNR_0417, which was selected after a blast analysis using the sequence of a caffeic acid 3′-O-methyltransferase from Zea mays against the genome of S. albidoflavus J1074. This mutant strain, S. albidoflavus ∆XNR_0417, was no longer able to produce homohesperetin after hesperetin feeding. Subsequently, we carried out a genetic complementation of the mutant strain in order to confirm that the enzyme encoded by XNR_0417 is responsible for the observed O-methyltransferase activity. This new strain, S. albidoflavus SP43-XNR_0417, was able to produce not only homohesperetin from hesperetin, but also different mono-, di-, tri- and tetra-methylated derivatives on other flavanones, flavones and stilbenes, revealing a broad substrate flexibility. Additionally, in vitro experiments were conducted using the purified enzyme on the substrates previously tested in vivo, demonstrating doubtless the capability of XNR_0417 to generate various methylated derivatives.

Structural insights into phosphatidylethanolamine N-methyltransferase PmtA mediating bacterial phosphatidylcholine synthesis.

Phosphatidylethanolamine N-methyltransferase (PmtA) catalyzes the biosynthesis of phosphatidylcholine (PC) from phosphatidylethanolamine (PE). Although PC is one of the major phospholipids constituting bilayer membranes in eukaryotes, certain bacterial species encode PmtA, a membrane-associated methyltransferase, to produce PC, which is correlated with cellular stress responses, adaptability to environmental changes, and symbiosis or virulence with eukaryotic hosts. Depending on the organism, multiple PmtAs may be required for producing monomethyl- and dimethyl-PE derivatives along with PC, whereas in organisms such as Rubellimicrobium thermophilum, a single enzyme is sufficient to direct all three methylation steps. In this study, we present the x-ray crystal structures of PmtA from R. thermophilum in complex with dimethyl-PE and S-adenosyl-l-homocysteine, as well as in its lipid-free form. Moreover, we demonstrate that the enzyme associates with the cellular membrane via electrostatic interactions facilitated by a group of critical basic residues and can successively methylate PE and its methylated derivatives, culminating in the production of PC.

Evolution of the biochemistry underpinning purine alkaloid metabolism in plants.

Purine alkaloids are naturally occurring nitrogenous methylated derivatives of purine nucleotide degradation products, having essential roles in medicine, food and various other aspects of our daily lives. They are generated through convergent evolution in different plant species. The pivotal reaction steps within the purine alkaloid metabolic pathways have been largely elucidated, and the convergent evolution of purine alkaloids has been substantiated through bioinformatic, biochemical and other research perspectives within S-adenosyl-ʟ-methionine-dependent N-methyltransferases. Currently, the biological and ecological roles of purine alkaloids, further refinement of the purine alkaloid metabolic pathways and the investigation of purine alkaloid adaptive evolutionary mechanisms continue to attract widespread research interest. The exploration of the purine alkaloid metabolic pathways also enhances our comprehension of the biochemical mechanism, providing insights into inter-species interactions and adaptive evolution and offering potential value in drug development and agricultural applications. Here, we review the progress of research in the distribution, metabolic pathway elucidation and regulation, evolutionary mechanism and ecological roles of purine alkaloids in plants. The opportunities and challenges involved in elucidating the biochemical basis and evolutionary mechanisms of the purine alkaloid metabolic pathways, as well as other research aspects, are also discussed. This article is part of the theme issue 'The evolution of plant meta-bolism'.

Kinetic Assessment of the Catalytic Effect of Halide Ions on the Halogenations of Thiazole and Its Methyl Derivatives in Aqueous Medium

Kinetic Assessment of the Catalytic Effect of Halide Ions on the Halogenations of Thiazole and Its Methyl Derivatives in Aqueous Medium

Identification of Antioxidant Methyl Derivatives of Ortho-Carbonyl Hydroquinones That Reduce Caco-2 Cell Energetic Metabolism and Alpha-Glucosidase Activity.

α-glucosidase, a pharmacological target for type 2 diabetes mellitus (T2DM), is present in the intestinal brush border membrane and catalyzes the hydrolysis of sugar linkages during carbohydrate digestion. Since α-glucosidase inhibitors (AGIs) modulate intestinal metabolism, they may influence oxidative stress and glycolysis inhibition, potentially addressing intestinal dysfunction associated with T2DM. Herein, we report on a study of an ortho-carbonyl substituted hydroquinone series, whose members differ only in the number and position of methyl groups on a common scaffold, on radical-scavenging activities (ORAC assay) and correlate them with some parameters obtained by density functional theory (DFT) analysis. These compounds' effect on enzymatic activity, their molecular modeling on α-glucosidase, and their impact on the mitochondrial respiration and glycolysis of the intestinal Caco-2 cell line were evaluated. Three groups of compounds, according their effects on the Caco-2 cells metabolism, were characterized: group A (compounds 2, 3, 5, 8, 9, and 10) reduces the glycolysis, group B (compounds 1 and 6) reduces the basal mitochondrial oxygen consumption rate (OCR) and increases the extracellular acidification rate (ECAR), suggesting that it induces a metabolic remodeling toward glycolysis, and group C (compounds 4 and 7) increases the glycolysis lacking effect on OCR. Compounds 5 and 10 were more potent as α-glucosidase inhibitors (AGIs) than acarbose, a well-known AGI with clinical use. Moreover, compound 5 was an OCR/ECAR inhibitor, and compound 10 was a dual agent, increasing the proton leak-driven OCR and inhibiting the maximal electron transport flux. Additionally, menadione-induced ROS production was prevented by compound 5 in Caco-2 cells. These results reveal that slight structural variations in a hydroquinone scaffold led to diverse antioxidant capability, α-glucosidase inhibition, and the regulation of mitochondrial bioenergetics in Caco-2 cells, which may be useful in the design of new drugs for T2DM and metabolic syndrome.

Chiral Selectivities of Permethylated α-, β-, and γ-Cyclodextrins Containing Gas Chromatographic Stationary Phases towards Ibuprofen and Its Derivatives.

Ibuprofen is a well-known and broadly used, nonsteroidal anti-inflammatory and painkiller medicine. Ibuprofen is a chiral compound, and its two isomers have different biological effects, therefore, their chiral separation is necessary. Ibuprofen and its derivatives were used as model compounds to establish transportable structure chiral selectivity relationships. Chiral selectors were permethylated α-, β-, and γ-cyclodextrins containing gas chromatographic stationary phases. The chiral selectivity of ibuprofen as a free acid and its various alkyl esters (methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and isoamyl esters) derivatives were tested at different temperatures. Every tested stationary phase was capable of the chiral separations of ibuprofen in its free acid form. The less strong included S optical isomers eluted before R optical isomers in every separate case. The results offer to draw transportable guidelines for the chiral selectivity vs. analyte structures. It was recognized that the S isomers of free ibuprofen acid showed an overloading phenomenon, but the R isomer did not. The results were supported by molecular modeling studies.

Kinetic Study and Reaction Mechanism of the Gas-Phase Thermolysis Reaction of Methyl Derivatives of 1,2,4,5-Tetroxane.

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.

Cholinesterase Inhibition and Antioxidative Capacity of New Heteroaromatic Resveratrol Analogs: Synthesis and Physico-Chemical Properties.

The targeted compounds in this research, resveratrol analogs 1-14, were synthesized as mixtures of isomers by the Wittig reaction using heterocyclic triphenylphosphonium salts and various benzaldehydes. The planned compounds were those possessing the trans-configuration as the biologically active trans-resveratrol. The pure isomers were obtained by repeated column chromatography in various isolated yields depending on the heteroaromatic ring. It was found that butyrylcholinesterase (BChE) was more sensitive to the heteroaromatic resveratrol analogs than acetylcholinesterase (AChE), except for 6, the methylated thiophene derivative with chlorine, which showed equal inhibition toward both enzymes. Compounds 5 and 8 achieved the highest BChE inhibition with IC50 values of 22.9 and 24.8 μM, respectively. The same as with AChE and BChE, methylated thiophene subunits of resveratrol analogs showed better enzyme inhibition than unmethylated ones. Two antioxidant spectrophotometric methods, DPPH and CUPRAC, were applied to determine the antioxidant potential of new heteroaromatic resveratrol analogs. The molecular docking of these compounds was conducted to visualize the ligand-active site complexes' structure and identify the non-covalent interactions responsible for the complex's stability, which influence the inhibitory potential. As ADME properties are crucial in developing drug product formulations, they have also been addressed in this work. The potential genotoxicity is evaluated by in silico studies for all compounds synthesized.

BM7, a derivative of benzofuran, effectively fights cancer by promoting cancer cell apoptosis and impacting IL-6 levels

The BM7 compound, a bromo derivative of methyl 6-acetyl-5-hydroxy-2-methyl-1-benzofuran-3-carboxylate, was previously identified as cytotoxic to human leukaemia cells (K562 and HL60) and human cervical cancer (HeLa), while showing no toxicity to non-cancerous primary endothelial cells (HUVEC). In this study, we present the first demonstration of BM7's anticancer efficacy in vivo using a mouse chronic myeloid leukaemia xenograft model. Administered intraperitoneally in a mixture of 10% Solutol HS 15/10% ethanol, BM7 exhibited no visible toxicity and significantly reduced tumor weight, comparable to standard drugs imatinib and hydroxyurea. Further supporting its anticancer potential, a multi-model in vitro study involving seven human cancer cell lines revealed the most promising responses in colon cancer (SW480, SW620, HCT116), liver cancer (HEPG2), and breast adenocarcinoma (MDA-MB-231) cells. BM7 demonstrated multifaceted anticancer mechanisms, inducing apoptosis while elevating reactive oxygen species (ROS) levels and suppressing interleukin-6 (IL-6) release in these cell lines. These findings position BM7 as a candidate of significant interest for cancer therapy. Its ability to not only induce apoptosis but also modulate cellular processes such as ROS levels and immune responses, specifically IL-6 suppression, makes BM7 a versatile and promising agent for further exploration in the realm of cancer treatment.

Exploring novel benzene sulfonamide derivatives: Synthesis, ADME studies, anti-proliferative activity, docking simulation, and emphasizing theoretical investigations

In this investigation, we elucidated the different heterocyclic containing benzenesulphonamide utilizing Microwave irradiation as a green energy source. Firstly the synthesis of (E)-N-(4-(3-(4-bromophenyl)acryloyl)phenyl)-4-methylbenzene sulfonamide (4) from the nucleophilic substitution reaction between 4-methylbenzenesulfonyl chloride and 1-(4-aminophenyl)ethan-1-one in pyridine, yielding N-(4-acetylphenyl)-4-methylbenzenesulfonamide (3), then the aldol condensation with bromobenzaldehyde in basic condition to afford the corresponding benzene sulfonamide chalcone 4 which is building block for different heterocycles. So its reactivity with different active methylene derivatives such as ethyl cyanoacetate and acetylacetone and nitrogen nucleophiles such as hydrazine hydrate and hydroxylamine using microwave irradiation in excellent yield. All synthesized compounds were investigated through spectral analysis such as FT-IR, 1HNMR, 13C NMR, and mass spectrum. Moreover, the synthesized compounds were screened through their ADME properties and were tested for antitumor activity against HepG2 hepatocellular carcinoma and MCF-7 breast cancer, exhibiting excellent efficacy compared to standard drugs, especially the heterocycles 6,8, 10, and 13 compared with Doxorubicin drug Furthermore, Molecular simulations with different proteins confirmed these results with PDBID:4hdq and 5H38. Additionally, the DFT analysis of optimized structures investigated their physical descriptors, Frontier Molecular Orbitals (FMO) which correlated them with the biological evaluation and showed the stabilities of these compounds.

Intramolecular Cyclopropanation of Active Methylene Derivatives Based on FeCl2 or FeCl3-Promoted Radical-Polar Crossover Reactions.

Radical-polar crossover reactions were studied for the intramolecular cyclopropanation of active methylene derivatives. In the presence of FeCl3 as a stoichiometric oxidant and K2HPO4 as a base, the dehydrogenative cyclopropanation of active methylenes proceeded through the FeCl3-promoted oxidative radical cyclization followed by the ionic cyclization to give the bicyclic cyclopropanes. The use of α-chloro-active methylenes leads the subcatalytic cyclopropanation involving two redox pathways. In the presence of K2HPO4, the redox cyclopropanation proceeded by using FeCl2 (20 mol%) in combination with ligand (20 mol%).

Unveiling the dynamic and thermodynamic interactions of hydrocortisone with β-cyclodextrin and its methylated derivatives through insights from molecular dynamics simulations

Cyclodextrins (CDs) can enhance the stability and bioavailability of pharmaceutical compounds by encapsulating them within their cavities. This study utilized molecular dynamics simulations to investigate the interaction mechanisms between hydrocortisone (HC) and various methylated CD derivatives. The results reveal that the loading of HC into CD cavities follows different mechanisms depending on the degree and position of methylation. Loading into βCD and 6-MeβCD was more complete, with the hydroxyl groups of HC facing the primary hydroxyl rim (PHR) and the ketone side facing the secondary hydroxyl rim (SHR). In contrast, 2,3-D-MeβCD and 2,6-D-MeβCD showed a different loading mechanism, with the ketone side facing the PHR and the hydroxyl groups facing the SHR. The root mean square fluctuation (RMSF) analysis demonstrated that methylation increases the flexibility of CD heavy atoms, with 3-MeβCD and 2,3-D-MeβCD exhibiting the highest flexibility. However, upon inclusion of HC, 3-MeβCD, 2,3-D-MeβCD, 2-MeβCD, and 6-MeβCD showed a significant reduction in flexibility, suggesting a more rigid structure that effectively retains HC within their cavities. The radial distribution function revealed a significant reduction in the number of water molecules within the innermost layer of the methylated CD cavities, particularly in TMeβCD, indicating a decrease in polarity. The presence of HC led to the release of high-energy water molecules, creating more favorable conditions for HC loading. Conformational analysis showed that methylation caused a partial decrease in the area of the PHR, a significant decrease in the area of the middle rim, and a notable decrease in the area of the SHR. The loading of HC increased the area of the PHR in most derivatives, with the most pronounced increase observed in 2,6-D-MeβCD and 6-MeβCD. The analysis of interaction energies and binding free energies demonstrated that the binding of HC to methylated CD derivatives is thermodynamically more favorable than to βCD, with the strongest association observed for 6-MeβCD, 2-MeβCD, and 2,3-D-MeβCD.

Thin layer chromatography of methylated derivatives of sodium alkylbenzenesulfonates in water analysis by GC-MS

Sodium alkylbenzene sulfonates or linear alkyl benzene sulfonates (LAS) are the most common synthetic anionic surfactants and water pollutants. They can cause both acute and chronic toxic effects on water organisms. Selective determination of sodium alkylbenzene sulfonates as a separate class of anionic surfactants is possible using gas chromatography coupled with mass spectrometry (GC-MS) in the form of linear alkylbenzenesulfonic acid methyl esters (LABSA ME). In order to purify the extracts and concentrate the analytes, we studied the behaviour of these compounds by ascending high-performance thin-layer chromatography using Kieselgel 60 F254 and Sorbfil plates. A mixture of n-hexane and methanol solvents in a ratio of 23:1 (by volume) was used as the mobile phase. Under these conditions, sodium alkylbenzenesulphonates remain on the start line, while their derivatives (ME ABSC), obtained by methylation with trimethyl orthoformate in the presence of trifluoroacetic acid (with a yield of η=98%), form zones characterised by retention coefficient values of Rf = 0.62 and Rf = 0.71 on Kieselgel 60 F254 and Sorbfil plates, respectively. The repeatability of the Rf values was characterised by a standard deviation of 6.1 and 5.9 %, respectively (n=16). The completeness of extraction (95.0–100.0 %) of analytes from the plates by descending TLC with acetonitrile was noted. The applicability of the TLC method for the concentration of analytes and pretreatment of extracts on the example of real water samples was shown. Using GC-MS with electron impact ionisation, we determined the concentrations of sodium alkylbenzenesulphonates in water sampled in the southern basin of Lake Baikal from a depth of 400 m (0.24±0.02 µg/dm3) and in snowmelt water from the ice of the Krestovka River where it flows into Lake Baikal near the village of Listvyanka (31.1 ± 1.0 µg/dm3).