Aromatic Hydroxylation Research Articles

Imidazolium bromo chromate: A new and efficient reagent for bromination of hydroxy aromatic compounds

A new Cr (VI) oxidizing agent Imidazolium Bromo chromate (IBC) has been used as an efficient and selective nuclear brominating agent for aromatic hydroxyl acetophenones, aldehyde, phenols as well as a brominating agent for unsaturated aromatic compounds. IBC has been found to be an efficient solid reagent that can be easily prepared in good yield.

Synthesis, Characterization, and Antibacterial Activity Study of Novel Curcuminoids Derivatives

Curcumin is a well-known compound with broad spectrum biological activities, but unfortunately rapid degradation properties and low bioavailability. Therefore, several attempts have been made to overcome these obstructions through chemical modifications. This investigation aimed to prepare several curcuminoids and their pyrazole derivatives and study their antibacterial activity. Curcuminoids and their pyrazole derivatives were synthesized, and their Chemical structures were established from their mass, 1H NMR, and 13C NMR spectra, followed by an in vitro study of the antibacterial activity of these compounds against the gram-negative Escherichia coli and the gram-positive Staphylococcus aureus using disc diffusion method. No compound has recorded any activity against Escherichia coli, while compounds 1-9 have shown anti-staphylococcus activity, compounds 11-14 didn’t present any activity, and compound 10 shows activity at the lowest studied concentration only. These findings suggest that the pyrazole substitution on curcumin derivatives that do not bear an aromatic hydroxyl group would diminish their anti-staphylococcal activity. More antibacterial activity studies are suggested regarding compound 10 activity

Direct C-H Hydroxylation of N-Heteroarenes and Benzenes via Base-Catalyzed Halogen Transfer.

Hydroxylated (hetero)arenes are valued in many industries as both key constituents of end products and diversifiable synthetic building blocks. Accordingly, the development of reactions that complement and address the limitations of existing methods for the introduction of aromatic hydroxyl groups is an important goal. To this end, we apply base-catalyzed halogen transfer (X-transfer) to enable the direct C-H hydroxylation of mildly acidic N-heteroarenes and benzenes. This protocol employs an alkoxide base to catalyze X-transfer from sacrificial 2-halothiophene oxidants to aryl substrates, forming SNAr-active intermediates that undergo nucleophilic hydroxylation. Key to this process is the use of 2-phenylethanol as an inexpensive hydroxide surrogate that, after aromatic substitution and rapid elimination, provides the hydroxylated arene and styrene byproduct. Use of simple 2-halothiophenes allows for C-H hydroxylation of 6-membered N-heteroarenes and 1,3-azole derivatives, while a rationally designed 2-halobenzothiophene oxidant extends the scope to electron-deficient benzene substrates. Mechanistic studies indicate that aromatic X-transfer is reversible, suggesting that the deprotonation, halogenation, and substitution steps operate in synergy, manifesting in unique selectivity trends that are not necessarily dependent on the most acidic aryl position. The utility of this method is further demonstrated through streamlined target molecule syntheses, examples of regioselectivity that contrast alternative C-H hydroxylation methods, and the scalable recycling of the thiophene oxidants.

Iron additions accelerate carbon loss from drained soil but promote carbon accumulation in waterlogged soil of Zoige plateau peatland

Iron (Fe), the fourth abundant element in soil, commonly exists as ferrous (Fe(II)) and ferric (Fe(Ⅲ)) forms, playing a crucial role carbon cycling. However, the effect of Fe(II) and Fe(Ⅲ) on soil organic carbon (SOC) remains unclear, especially in carbon-rich peatland soils. Therefore, this study added Fe (Ⅱ) and Fe (Ⅲ) into the drained and waterlogged soils sampled from the Zoige plateau peatland to conduct a 95-day incubation experiment to reveal the role of Fe forms in driving carbon cycling. The dynamics of carbon compositions (phenolics, dissolved organic carbon (DOC), SOC, Fe-bound SOC (Fe–SOC)) and enzyme activity (phenol oxidase and β-glucosidase) were tested along with incubation time. Moreover, soil functional groups and bacteria were determined over the incubation period. The results demonstrated that Fe(II) and Fe(Ⅲ) addition in the drained soil decreased phenolics, DOC and SOC but increased Fe–SOC, soil organic functional groups (i.e., aromatic hydroxyl), and chemical bonds (i.e., C–O bonds); the reduced DOC and phenolics by the increased Fe(III)/Fe(II) ratio (extracted by 0.5 M HCl solution) was the primary reason for SOC loss. In waterlogged soil, Fe(II) and Fe(Ⅲ) addition increased carbon compositions and soil functional groups; the increased DOC and phenolics by the reduced pH was the possible reason for SOC accumulation. It can be known that the wide existence of Fe(II) and Fe(Ⅲ) in peatland may accelerate carbon loss from drained soil but prevent carbon loss from waterlogged soil and enhance SOC stability.

OPTIMIZATION OF THE METHOD OF QUANTITATIVE DEFINITIONS OF FLAVONOIDS IN THE RAW MATERIALS OF "MENYANTHIDIS TRIFOLIATAE LEAVES"

The aim of the study is to optimize the methodology of quantitative determination of flavonoids in the leaves of Menyanthidis trifoliatae. In official medicine, the leaves of Menyanthidis trifoliatae are used for anorexia and dyspeptic disorders.
 In the current regulatory documentation (State Pharmacopoeia of the Russian Federation), it is proposed to evaluate the quality of raw materials by the content of the amount of flavonoids in terms of rutin using spectrophotometry. This technique is based on the ability of flavonoids containing free aromatic hydroxyl groups to form colored products with diazotized sulfanilic acid. The disadvantage of this technique is the long and time-consuming stage of cleaning raw materials from certain groups of lipophilic substances, which can also react with diazotized sulfanilic acid to form colored products.
 We have proposed a selective method for the quantitative determination of flavonoids in the herb trifoliate by the method of spectrophotometry in terms of rutin. The technique is based on the ability of flavonoids to form stable colored complexes with aluminum chloride. We have selected the optimal conditions for extraction and complexation reaction of aluminum chloride with flavonoids of M. trifoliatae extract. The proposed method has been validated and is suitable for use in an analytical laboratory.

Regioselective Hydroxylation of Unsymmetrical Ketones Using Cu, H2O2, and Imine Directing Groups via Formation of an Electrophilic Cupric Hydroperoxide Core.

Herein, we describe the regioselective functionalization of unsymmetrical ketones using imine directing groups, Cu, and H2O2. The C-H hydroxylation of the substrate-ligands derived from 2-substituted benzophenones occurred exclusively at the γ-position of the unsubstituted ring due to the formation of only one imine stereoisomer. Conversely, the imines derived from 4-substituted benzophenones produced E/Z mixtures that upon reacting with Cu and H2O2 led to two γ-C-H hydroxylation products. Contrary to our initial hypothesis, the ratio of the hydroxylation products did not depend on the ratio of the E/Z isomers but on the electrophilicity of the reactive [LCuOOH]1+. A detailed mechanistic analysis suggests a fast isomerization of the imine substrate-ligand binding the CuOOH core before the rate-determining electrophilic aromatic hydroxylation. Varying the benzophenone substituents and/or introducing electron-donating and electron-withdrawing groups on the 4-position of pyridine of the directing group allowed for fine-tuning of the electrophilicity of the mononuclear [LCuOOH]1+ to reach remarkable regioselectivities (up to 91:9 favoring the hydroxylation of the electron-rich arene ring). Lastly, we performed the C-H hydroxylation of alkyl aryl ketones, and like in the unsymmetrical benzophenones, the regioselectivity of the transformations (sp3 vs sp2) could be controlled by varying the electronics of the substrate and/or the directing group.

Exploring metabolic effects of dipeptide feed media on CHO cell cultures by in silico model-guided flux analysis

There is a growing interest in perfusion or continuous processes to achieve higher productivity of biopharmaceuticals in mammalian cell culture, specifically Chinese hamster ovary (CHO) cells, towards advanced biomanufacturing. These intensified bioprocesses highly require concentrated feed media in order to counteract their dilution effects. However, designing such condensed media formulation poses several challenges, particularly regarding the stability and solubility of specific amino acids. To address the difficulty and complexity in relevant media development, the biopharmaceutical industry has recently suggested forming dipeptides by combining one from problematic amino acids with selected pairs to compensate for limitations. In this study, we combined one of the lead amino acids, L-tyrosine, which is known for its poor solubility in water due to its aromatic ring and hydroxyl group, with glycine as the partner, thus forming glycyl-L-tyrosine (GY) dipeptide. Subsequently, we investigated the utilization of GY dipeptide during fed-batch cultures of IgG-producing CHO cells, by changing its concentrations (0.125 × , 0.25 × , 0.5 × , 1.0 × , and 2.0 ×). Multivariate statistical analysis of culture profiles was then conducted to identify and correlate the most significant nutrients with the production, followed by in silico model-guided analysis to systematically evaluate their effects on the culture performance, and elucidate metabolic states and cellular behaviors. As such, it allowed us to explain how the cells can more efficiently utilize GY dipeptide with respect to the balance of cofactor regeneration and energy distribution for the required biomass and protein synthesis. For example, our analysis results uncovered specific amino acids (Asn and Gln) and the 0.5 × GY dipeptide in the feed medium synergistically alleviated the metabolic bottleneck, resulting in enhanced IgG titer and productivity. In the validation experiments, we tested and observed that lower levels of Asn and Gln led to decreased secretion of toxic metabolites, enhanced longevity, and elevated specific cell growth and titer.Key points• Explored the optimal Tyr dipeptide for the enhanced CHO cell culture performance• Systematically analyzed effects of dipeptide media by model-guided approach• Uncovered synergistic metabolic utilization of amino acids with dipeptideGraphical abstract

Q-RASTR modelling for prediction of diverse toxic chemicals towards T. pyriformis

ABSTRACT A series of diverse organic compounds impose serious detrimental effects on the health of living organisms and the environment. Determination of the structural aspects of compounds that impart toxicity and evaluation of the same is crucial before public usage. The present study aims to determine the structural characteristics of compounds for Tetrahymena pyriformis toxicity using the q-RASTR (Quantitative Read Across Structure–Toxicity Relationship) model. It was developed using RASTR and 2-D descriptors for a dataset of 1792 compounds with defined endpoint (pIGC50) against a model organism, T. pyriformis. For the current study, the whole dataset was divided based on activity/property into the training and test sets, and the q-RASTR model was developed employing six descriptors (three latent variables) having r 2, Q 2 F1 and Q 2 values of 0.739, 0.767, and 0.735, respectively. The generated model was thoroughly validated using internationally recognized internal and external validation criteria to assess the model’s dependability and predictability. It was highlighted that high molecular weight, aromatic hydroxyls, nitrogen, double bonds, and hydrophobicity increase the toxicity of organic compounds. The current study demonstrates the applicability of the RASTR algorithm in QSTR model development for the prediction of toxic chemicals (pIGC50) towards T. pyriformis.

A density functional theory study on interactions in water-bridged dimeric complexes of lignin.

Lignin is the main plant cell wall component responsible for recalcitrance in the process of lignocellulosic biomass conversion into biofuels. The recalcitrance and insolubility of lignin in different reaction media are due in part to the hydrogen bonds and π interactions that hold syringyl (S) and guaiacyl (G) units together and promote the formation of stable water-bridged dimeric complexes (WBDCs): S⋯G and S⋯S, in native lignin. The current understanding of how each type of interaction influences the stability of these complexes within lignin native cell walls is still limited. Here, we found by DFT calculations that hydrogen bonding is more dominant than π-stacking interaction between aromatic rings of WBDCs. Although there is a stronger interaction of hydrogen bonds between subunits and water and higher π-stacking interaction in the S⋯S complex compared to the S⋯G complex, the former complex is less thermodynamically stable than the latter due to the entropic contribution coming from the methoxy substituents in the S-unit. Our results demonstrate that the methoxylation degree of lignin units does not significantly influence the structural geometries of WBDCs; if anything, an enhanced dispersion interaction between ring aromatics results in quasi-sandwich geometries as found in "coiled" lignin structures in the xylem tissue of wood. In the same way as that with ionic liquids, polar solvents can dissolve S-lignin by favorable interactions with the aliphatic hydroxyl group in the α-position as the key site or the aromatic hydroxyl group as the secondary site.

High-valent nonheme Fe(IV)O/Ru(IV)O complexes catalyze C-H activation reactivity and hydrogen tunneling: a comparative DFT investigation.

A comprehensive density functional theory investigation has been presented towards the comparison of the C-H activation reactivity between high-valent iron-oxo and ruthenium-oxo complexes. A total of four compounds, e.g., [Ru(IV)O(tpy-dcbpy)] (1), [Fe(IV)O(tpy-dcbpy)] (1'), [Ru(IV)O(TMCS)] (2), and [Fe(IV)O(TMCS)] (2'), have been considered for this investigation. The macrocyclic ligand framework tpy(dcbpy) implies tpy = 2,2':6',2''-terpyridine, dcbpy = 5,5'-dicarboxy-2,2'-bipyridine, and TMCS is TMC with an axially tethered -SCH2CH2 group. Compounds 1 and 2' are experimentally synthesized standard complexes with Ru and Fe, whereas compounds 1' and 2 were considered to keep the macrocycle intact when switching the central metal atom. Three reactants including benzyl alcohol, ethyl benzene, and dihydroanthracene were selected as substrates for C-H activation. It is noteworthy to mention that Fe(IV)O complexes exhibit higher reactivity than those of their Ru(IV)O counterparts. Furthermore, regardless of the central metal, the complex featuring a tpy-dcbpy macrocycle demonstrates higher reactivity than that of TMCS. Here, a thorough analysis of the reactivity-controlling characteristics-such as spin state, steric factor, distortion energy, energy of the electron acceptor orbital, and quantum mechanical tunneling-was conducted. Fe(IV)O exhibits the exchanged enhanced two-state-reactivity with the quintet reactive state, whereas Ru(IV)O has only a triplet reactive state. Both the distortion energy and acceptor orbital energy are low in the case of Fe(IV)O supporting its higher reactivity. All the investigated C-H activation processes involve a significant contribution from hydrogen tunneling, which is more pronounced in the case of Ru, although it cannot alter the reactivity pattern. Furthermore, it has also been found that, independent of the central metal, aliphatic hydroxylation is always preferable to aromatic hydroxylation. Overall, this work is successful in establishing and investigating the cause of enzymes' natural preference for Fe over Ru as a cofactor for C-H activation enzymes.

Proton-assisted activation of a MnIII-OOH for aromatic C-H hydroxylation through a putative [MnVO] species.

Adding HClO4 to [(BnTPEN)MnIII-OO]+ in MeOH generates a short-lived MnIII-OOH species, which converts to a putative MnVO species. The potent MnVO species in MeCN oxidizes the pendant phenyl ring of the ligand in an intramolecular fashion. The addition of benzene causes the formation of (BnTPEN)MnIII-phenolate. These findings suggest that high valent Mn species have the potential to catalyze challenging aromatic hydroxylation reactions.

Mechanism of Selective Aromatic Hydroxylation in the Metabolic Transformation of Paclitaxel Catalyzed by Human CYP3A4.

Paclitaxel (PTX) is heralded as one of the most successful natural-product drugs for the treatment of refractory cancers. In humans, the hepatic metabolic transformation of PTX is primarily mediated by two cytochrome P450 enzymes (P450s): CYP3A4 and CYP2C8. The impact of P450 metabolism on the anticancer effectiveness of PTX is significant. However, the precise mechanism underlying selective P450-catalyzed reactions in PTX metabolism remains elusive. To address this knowledge gap, we conducted molecular docking and molecular dynamics simulations using multiple crystal structures of CYP3A4, which originally contained other ligands. These methods enabled us to determine the most plausible binding structure of PTX within the enzyme. By further employing hybrid quantum mechanics and molecular mechanics calculations, we successfully identified two primary pathways for the reaction between compound I (Cpd I) of CYP3A4 and PTX. One of these pathways involves the formation of an epoxide, while the other proceeds through a ketone intermediate.

Molecular Docking, Synthesis and Antimicrobial Evaluation of 4-[(3 hydroxybenzalidene)amino]antipyrine and its Copper Complex

The synthesis and characterization of Schiff base-containing transition metal complexes have gained increasing importance due to their catalytic roles in various reactions and their biological activities. These metal complexes have become crucial in drug design, leading to a growing interest in metal-based drugs. The study aimed to synthesize copper metal complex with a new Schiff base ligand 4-[(3-hydroxybenzalidene)amino]antipyrine derived from 4-aminoantipyrine and 3-hydroxybenzaldehyde, as well as evaluate their antimicrobial activity against gram positive and gram-negative bacterial strains. The ligand and its copper complex were assessed for antimicrobial activity against gram-positive and gram-negative strains utilizing disc diffusion and broth dilution methods. Spectroscopic techniques (UV-Vis, FT-IR, XRD, and EDXRF), solubility tests, and elemental analysis were employed to investigate the ligand and copper complex. The ligand displayed high insolubility in various solvents but had limited solubility in chloroform and methyl chloride. The FTIR spectrum of the Schiff base reveals the presence of aromatic hydrocarbons, imine (C=N), hydroxyl (-OH), secondary amine (C-N), carbonyl (C=O), and vibrations associated with C-O and C-C bonds, reflecting its molecular structure. In the EDXRF analysis, a prominent peak at 7.80 keV corresponding to copper was detected, indicating that copper is the most abundant element found in the ligand. XRD analysis demonstrated distinct crystal structures for both the ligand and its copper complex. The UV-Vis spectra of the ligand exhibited an absorption peak at a UV lambda max of 220 nm, indicating a π→π* transition. In contrast, the absorption peaks observed in the copper complex indicated different transitions compared to the Schiff base. The MIC results indicated the copper complex's stronger antimicrobial activity than the Schiff base against tested bacteria. Molecular docking studies showed that the interaction energies of the synthesized compounds, particularly the ligand and copper complex, surpassed that of the well-known anti-diabetic drug, metformin.

Review: immunomodulatory effects induced by phenolic compounds

Recently, the population has turned its attention to a healthier diet, with a diet richer in fruits, vegetables and vegetables. The search for a healthy diet is derived from the nutraceutical capacity of natural foods, and the beneficial effects of these, are attributed, at least in part, to the presence of phenolic compounds. Phenolic compounds are secondary metabolites present in plants, biologically active and have aromatic rings and hydroxyl groups in their structure. The objective of this work was to carry out a survey on the interaction capacity of phenolic compounds with the immune system, as well as to evaluate the current status of this topic in the academic community. The keywords “phenolic compounds” and “immunomodulatory activity” were used on three research platforms (Scielo, PubMed and Periódicos CAPES). The results showed that there is a growing interest in the academic community in the topic addressed, which is justified by the ability of these compounds to interact with various immunological responses, such as inflammatory activity and oxidative balance, proliferation and action of white cells, among others.

Ether Bond Formation in Waste Biomass–Derived, Value-Added Technical Hardwood Kraft Lignin Using Glycolic Acid

Ether bond formation in technical hardwood kraft lignin (THKL) by crosslinking using glycolic acid was investigated for bio-adhesive applications. Industrial hardwood kraft black liquor was used to extract the THKL utilized by acidification. Chemical and thermal properties of the THKL with and without crosslinking were analyzed by Fourier transform infrared (FTIR) spectroscopy, solid-state 13C cross-polarization/magic angle spinning nuclear magnetic resonance (13C CP/MAS NMR) spectroscopy, X-ray photoelectron spectroscopy (XPS), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). FTIR results revealed a new peak corresponding to the ether bond and hemiacetal formation due to crosslinking at 1075 cm-1 and 1324 cm-1. 13C CP/MAS NMR spectra revealed the presence of a higher number of ether bonds due to the reduced aromatic and aliphatic hydroxyl groups in THKL and new bonds formed at 62-64 ppm and 168-191 ppm due to crosslinking. XPS results revealed that new bonds were formed between glycolic acid and THKL, leading to increased atomic oxygen percentage and carbon–oxygen bonds in crosslinked THKL detected by peak intensity changes at 287.7 and 288.8 related to O–C–O and O–C=O. Also, the oxygen content increased from 14.88% to 31.76% due to bond formation. GPC confirmed a higher molecular weight and broader molecular-weight distribution of THKL. DSC and TGA curves of crosslinked THKL revealed exothermic behavior, high thermal stability, and low thermal degradation rate. Owing to a significant amount of kraft black liquor being generated by wood pulp industries and attractive chemical properties of THKL, THKL demonstrates promise as a raw material to produce green, sustainable bio-adhesives via the crosslinking of its different hydroxyl groups using glycolic acid.

Petrographic and geochemical analysis of Barmer Basin Paleogene lignite deposits: Insights into depositional environment and paleo-climate

The current study attempts to characterize the samples from Kapurdi, Giral and Sonari lignite mines of Barmer Basin within Rajasthan Tertiary Lignite deposits using petrographic and geochemical techniques. The data generated has been studied in order to better understand the geochemical properties, hydrocarbon potential, depositional environment and paleo-climatic condition of the paleo-mires of these lignites. The proximate analysis of the samples reveals that the average ash content of the Barmer Basin is 11.93 %, the average moisture content is 14.08 %, average volatile matter yield is 42.03 % and the average fixed carbon is 31.95 %, which suggesting that the physical properties of lignite are dominated by volatile matter on dry basis. The ultimate investigation reveals the chemical properties of the lignite with the average carbon content found to be 58.79 wt%, hydrogen value 3.83 wt%, nitrogen percentage 1.60 wt% and sulphur content 2.75 wt%. This clearly indicates high sulphur concentration in Barmer lignite deposits, based on dry basis. The lignite samples subjected to FTIR studies identified aliphatic CH group, aromatic CO group, hydroxyl OH and Aldehyde HCO group. The Rock-Eval pyrolysis studies have been carried out to know the coalification profile of the deposits and hydrocarbon source rock potential. The varying behaviour between brown coal lithotype are primarily reflected by changes in oxygen index values, whereas hydrogen index values demonstrate a more pronounced correlation with coal type rather than the level of maturation. The results show the average total organic carbon (TOC) 47.29 %, S1 peak 2.18 mg HC/g, S2 peak 88.70 mg HC/g, S3 peak 19.22 % mg CO2/g, Tmax 410.53 °C, hydrogen index 219.2 mg HC/g TOC and oxygen index 46.33 mg CO2/g TOC. According to petrographic investigations, the huminite macerals dominate followed by liptinite and inertinite maceral groups in mineral matter-free basis. In all the three different lignite mines, the huminite group dominates with preserved sub-maceral ulminite indicating less transformation of structured plant matter. Reconstruction of depositional environment and paleo-climatic condition of the paleo-mires has been attempted by using organic petrographic indices. The high gelification index (GI) and low tissue preservation index (TPI) values suggest a prolonged wet environment during the decomposition of organic material, accompanied by a gradual subsidence process. The ground water influence index (GWI) and vegetation index (VI) denote ombrotrophic to mesotrophic hydrological conditions of basin at the time of deposition.

Novel phenolate salts of bioactive agents: Cannabidiol phenolate salts

Bioactive phenolic compounds are commonly found in medications, with examples including apomorphine, estrone, thymol, estradiol, propofol, o-phenylphenol, l-Dopa, doxorubicin, tetrahydrocannabinol (THC), and cannabidiol (CBD). This study is the first to explore the creation and assessment of metal and ammonium phenolate salts using CBD as an example. CBD is used in medicine to treat anxiety, insomnia, chronic pain, and inflammation, but its bioavailability is limited due to poor water solubility. In this study exploit a synthetic route to convert CBD into anionic CBD-salts to enhance water solubility. Various CBD-salts with metal and ammonium counterions such as lithium (Li+), sodium (Na+), potassium (K+), choline hydroxide ([(CH3)3NCH2CH2OH]+), and tetrabutylammonium ([N(C4H9)4]+) have been synthesized and characterized. These salts are obtained in high yields, ranging from 74 % to 88 %, through a straightforward dehydration reaction between CBD and alkali metal hydroxides (LiOH, NaOH, KOH) or ammonium hydroxides (choline hydroxide, tetrabutylammonium hydroxide). These reactions are conducted in either ethanol, methanol, or a methanol:water mixture, maintaining a 1:1 molar ratio between the reactants. Comprehensive characterization using Fourier-Transform Infrared Spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR) spectroscopy, and elemental (CHN) analysis confirms the formation of CBD-salts, as evidenced by the absence of aromatic hydroxyl resonances or stretching frequencies. The molecular formulas of CBD salts were determined based on CHN analysis, and CBD quantification from acid regeneration experiments. Characterization data confirms that each CBD phenolate in a specific CBD salt was electrostatically stabilized by one of the either alkali metal or ammonium ion. The CBD-salts are highly susceptible to acidic conditions, readily reverting back to the original CBD. The percentage and purity of CBD in the CBD-metal/ammonium salts have been studied using High-Performance Liquid Chromatography (HPLC) analysis. Solubility studies indicate that the conversion of CBD into CBD salts significantly enhances its solubility in water, ranging from 110 to 1606 folds greater than pure CBD. Furthermore, the pharmacokinetic evaluation of oral administration of CBD-salts compared to CBD were determined in rats.

Spectroscopic analysis of 1.75 MeV N5+ ions irradiated polystyrene film and the quest for the reaction mechanisms of fullerene and other products

The effects of 1.75 MeV N5+ ion beams of varying fluences, ranging from 1 × 1011 to 1 × 1014 ions/cm2, have been used to investigate the structural, optical, and chemical properties of polystyrene using X-ray diffraction (XRD), UV–Visible spectroscopic, and Fourier transform infrared (FTIR) spectroscopic techniques. The changes in polystyrene polymer depend on ion fluence. The crystallinity has been increased drastically up to the ion fluence of 5 × 1012 ions/cm2, and decreases further up to 1 × 1014 ions/cm2. The energy of the direct bandgap is found to be reduced by up to 50% when compared to the pristine one. The shift in absorption maxima towards a higher wavelength supports color development in polymer films and is due to the formation of extended conjugation. The developments of FTIR peaks at 1601, 1697, 3321, and 3723 cm−1 support the existence of aromatic rings, carbonyl (>CO), acetylenic (-CC-), and hydroxyl functional groups in the irradiated polystyrene. Functional group generation is exponentially dependent on the quantity of ion fluences. The reaction mechanism of degradation products formation chemistry has been discussed.

Melatonin Activation by Human Cytochrome P450 Enzymes: A Comparison between Different Isozymes.

Cytochrome P450 enzymes in the human body play a pivotal role in both the biosynthesis and the degradation of the hormone melatonin. Melatonin plays a key role in circadian rhythms in the body, but its concentration is also linked to mood fluctuations as well as emotional well-being. In the present study, we present a computational analysis of the binding and activation of melatonin by various P450 isozymes that are known to yield different products and product distributions. In particular, the P450 isozymes 1A1, 1A2, and 1B1 generally react with melatonin to provide dominant aromatic hydroxylation at the C6-position, whereas the P450 2C19 isozyme mostly provides O-demethylation products. To gain insight into the origin of these product distributions of the P450 isozymes, we performed a comprehensive computational study of P450 2C19 isozymes and compared our work with previous studies on alternative isozymes. The work covers molecular mechanics, molecular dynamics and quantum mechanics approaches. Our work highlights major differences in the size and shape of the substrate binding pocket amongst the different P450 isozymes. Consequently, substrate binding and positioning in the active site varies substantially within the P450 isozymes. Thus, in P450 2C19, the substrate is oriented with its methoxy group pointing towards the heme, and therefore reacts favorably through hydrogen atom abstraction, leading to the production of O-demethylation products. On the other hand, the substrate-binding pockets in P450 1A1, 1A2, and 1B1 are tighter, direct the methoxy group away from the heme, and consequently activate an alternative site and lead to aromatic hydroxylation instead.

Phenotypic Test of Benzo[4,5]imidazo[1,2-c]pyrimidinone-Based Nucleoside and Non-Nucleoside Derivatives against DNA and RNA Viruses, Including Coronaviruses.

Emerging and re-emerging viruses periodically cause outbreaks and epidemics around the world, which ultimately lead to global events such as the COVID-19 pandemic. Thus, the urgent need for new antiviral drugs is obvious. Over more than a century of antiviral development, nucleoside analogs have proven to be promising agents against diversified DNA and RNA viruses. Here, we present the synthesis and evaluation of the antiviral activity of nucleoside analogs and their deglycosylated derivatives based on a hydroxybenzo[4,5]imidazo[1,2-c]pyrimidin-1(2H)-one scaffold. The antiviral activity was evaluated against a panel of structurally and phylogenetically diverse RNA and DNA viruses. The leader compound showed micromolar activity against representatives of the family Coronaviridae, including SARS-CoV-2, as well as against respiratory syncytial virus in a submicromolar range without noticeable toxicity for the host cells. Surprisingly, methylation of the aromatic hydroxyl group of the leader compound resulted in micromolar activity against the varicella-zoster virus without any significant impact on cell viability. The leader compound was shown to be a weak inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase. It also inhibited biocondensate formation important for SARS-CoV-2 replication. The active compounds may be considered as a good starting point for further structure optimization and mechanistic and preclinical studies.