Side Products Research Articles

CPGA hydrolase assay of DJ-1 in crude cell lysates: Implications for sensing of oxidative stress

Cyclic 3-phosphosphoglyceric anhydride (cPGA), a side product of glycolysis, acylates cellular amines and thiols to form amides and thioesters, respectively. Since these acylation reactions are harmful, organisms rely on a protein, known as DJ-1 in humans, to inactivate cPGA. Inactivation of cPGA likely plays a significant role in cytoprotection by DJ-1, but further progress in this direction is hampered by the lack of quantitative assays to measure the cPGA hydrolase activity of DJ-1 in biological samples. Here we report an optimized procedure for preparation of cPGA which is then used as a substrate to quantify enzymatic activity of DJ-1. The end-point assay for cPGA hydrolase uses dilute cell lysates to hydrolyze cPGA for 0.5–3.5 min followed by conversion of the remaining cPGA into thioester for spectrophotometric quantitation. We illustrate the utility of this assay by showing that higher levels of cPGA hydrolase activity result in better protection from acylation by cPGA. Moreover, the decrease of cPGA hydrolase activity due to oxidation of the catalytic cysteine of DJ-1 under oxidative stress and its subsequent recovery can be monitored using the assay. This relatively simple assay allows functional characterization of DJ-1 in biological samples through quantitative assessment of its cPGA hydrolase activity.

Tandem Condensation-Cycloaddition of Propargylic Amines with α-Azido Ketones and β-Alkoxy-γ-Azido Enones.

α-Azido ketones and their vinylogous relatives β-alkoxy-γ-azido enones are versatile building blocks for constructing diverse heterocyclic products, but are prone to azide decomposition. Here, we report their condensation with propargylic amines and investigate the fate of the intermediate azido-enamine condensation products, both experimentally and theoretically. Efficient intramolecular cycloaddition was observed for electron-poor azide substrates, and a range of diversely substituted [1,2,3]triazolo[1,5-a]pyrazine products is reported. For electron-rich substrates, azide decomposition predominated. Computational modeling of possible pathways from the azido-enamine intermediates revealed two alternative mechanisms for azide decomposition, which were consistent with observed side products.

Methane pyrolysis in molten salt slurry systems: Evaluation of activity and mechanism in binary salt mixtures with molybdenum disulfide suspensions

In this study we evaluated three binary salt mixtures of 50 wt% potassium bromide and 50 wt% sodium chloride, manganese chloride, or magnesium chloride for methane pyrolysis in a bubble column reactor configuration. Initial results confirm preferential mixtures of reciprocal salts that tune salt ionicity. This study focusses on the interactions of these binary salt mixtures with 5 wt% suspensions of 2-μm 2H-MoS2 with a 100 mm bubble path at 800 and 850 oC. Magnesium chloride and potassium bromide show a favourable enhancement with MoS2, with an apparent activation energy of 251 kJ mol−1 (salt mixture) decreasing to 96 kJ mol−1 (slurry mixture). Assessing the results indicates that MgCl2-KBr melts promote increased contact with MoS2 relative to NaCl-KBr and MnCl2-KBr, and this in turn improves hydrogen yield. Further investigation of slurry system through deuterium-methane exchange confirms molybdenum disulfide promotes methane decomposition to protium, hydrogen, methyl radical, and methylene, preferentially intensified by magnesium mixtures. Additional reaction steps vary depending on salt selection. At 850 oC, the salt effect is significant, leading to an inverse relationship between net increase of side products in the slurries and salt activity. In contrast, at 800 oC, the salt effect is small, and activity is dictated by the MoS2 suspension.

Evaluation of a decomposition-based interpolation method for fourth-order fiber-orientation tensors: An eigensystem approach

We propose and assess a new decomposition-based interpolation method on fourth-order fiber-orientation tensors. This method can be used to change the resolution of discretized fields of fiber-orientation tensors, e.g., obtained from flow simulations or computer tomography, which are common in the context of short- and long-fiber–reinforced composites. The proposed interpolation method separates information on structure and orientation using a parametrization which is based on tensor components and a unique eigensystem. To identify this unique eigensystem of a given fourth-order fiber-orientation tensor in the absence of material symmetry, we propose a sign convention on tensor coefficients. We explicitly discuss challenges associated with material symmetries, e.g., non-distinct eigenvalues of the second-order fiber-orientation tensor and propose algorithms to obtain a unique set of parameters combined with a minimal number of eigensystems of a given fourth-order fiber-orientation tensor. As a side product, we specify for the first time, parametrizations and admissible parameter ranges of cubic, tetragonal, and trigonal fiber-orientation tensors. Visualizations in terms of truncated Fourier series, quartic plots, and tensor glyphs are compared.

Bridging Targeted (Zeno MRM-HR) and Untargeted (SWATH) LC-HRMS in a Single Run for Sensitive Exposomics.

Traditionally, chemical exposure has been assessed by low-resolution mass spectrometry via targeted approaches due to the typically extremely low concentration of such compounds in biological samples. Nevertheless, untargeted approaches are now becoming a promising tool for a broader investigation of the exposome, covering additional compounds, their biotransformation products, and possible metabolic alterations (metabolomics). However, despite broad compound coverage, untargeted metabolomics still underperforms in ultratrace biomonitoring analysis. To overcome these analytical limitations, we present the development of the first combined targeted/untargeted LC-MS method, merging MRM-HR and SWATH experiments in one analytical run, making use of Zeno technology for improved sensitivity. Multiple reaction monitoring transitions were optimized for 135 highly diverse toxicants including mycotoxins, plasticizers, PFAS, personal care products ingredients, and industrial side products as well as potentially beneficial xenobiotics such as phytohormones. As a proof of concept, standard reference materials of human plasma (SRM 1950) and serum (SRM 1958) were analyzed with both Zeno MRM-HR + SWATH and SWATH-only methodologies. Results demonstrated a significant increase in sensitivity represented by the detection of lower concentration levels in spiked SRM materials (mean value: 2.2 and 3 times lower concentrations for SRMs 1950 and 1958, respectively). Overall, the detection frequency was increased by 68% (19 to 32 positive detections) in the MRM-HR + SWATH mode compared to the SWATH-only. This work presents a promising avenue for addressing the outstanding key challenge in the small-molecule omics field: finding a balance between high sensitivity and broad chemical coverage. It was demonstrated for exposomic applications but might be transferred to lipidomics and metabolomics workflows.

Investigation of column purified dye derived carbon nanomaterials for security printing and supercapacitor applications

Literature evidence reveals versatile applications of carbon dots (CDs), but generally mixtures of various types of carbon nanomaterials, molecular intermediates as well as side products are obtained upon hydrothermal treatment of the precursor material. This demands isolation of pure components and their complete characterization before these nano carbonaceous materials are chosen for suitable applications. In the present study, perylenetetracarboxylic dianhydride (PTCDA) is subjected to hydrothermal treatment and the mother liquor obtained is separated using column chromatography technique using dichloromethane-methanol solvent system to isolate fractions of various fluorescent carbonaceous nanostructures. The TEM imaging of nano carbonaceous particles of all five fractions indicated that the first and third fractions were composed of nanoribbons, while the latter two fractions largely contained quasi-spherical nanoparticles of both lesser (carbon quantum dots) and greater (carbon nanodots) than 10 nm dimensions. The XPS results of all the fractions suggested separation based on polarity difference. The ID/IG ratios obtained from Raman spectra implied the presence of several defects on the CDs. The time resolved fluorescence spectra of third, fourth and fifth fractions revealed mono-exponential decay of fluorophores with excitation independent average lifetime values. The fifth fraction exhibited good biocompatibility and the highest absolute fluorescence quantum yield of 58.47 % among all the isolated samples. As these CDs displayed a remarkable rise in the quantum yield to 88.60 % when dispersed in water, a water-based flexo-ink was formulated. The photostable pale yellow flexo print proofs obtained on UV dull paper exhibited a green fluorescence under 365 nm illumination, whereas a yellow glow when shined with blue light, which can serve as an authentication feature for security documents and currency notes. Moreover, as the third fraction constitutes mainly of carbon nanoribbons (CNRs), an optimized polymer electrolyte was prepared along with sodium alginate (SA), and MgCl2 to understand their potential use in energy storage application. A supercapacitor was fabricated and tested for its electrochemical performance such as cyclic voltammtery (CV), electrochemical impedance spectroscopy (EIS) and galvanostatic charge/discharge (GCD). An enhanced current window was observed in the CV of SA/CNRs compared to pure SA and SA/CNRs/Mg films, which indicated a structural interaction of CNRs with SA. The conductivity of SA/CNRs/Mg was lesser than SA/CNRs in EIS studies due to the presence of Mg ions, while pure SA showed lesser conductivity. The dual ionic interaction of Na and Mg along with enhanced structural stability due to doped CNRs favors its convenient supercapacitor application. The fabricated eco-friendly supercapacitor showed a specific capacitance of 84 F/g. The GCD of the device displayed pseudocapacitance behaviour and was quite stable for 2000 cycles with coulombic efficiency of 96 %.

Broadening the Scope of van Leusen Reaction: Investigation of Benzofuro[2,3‐d]imidazole Formation

AbstractThe van Leusen reaction utilizes p‐toluenesulfonylmethyl isocyanide as a versatile synthon for constructing nitrogen‐containing heterocycles, such as oxazoles, imidazoles, thiazoles, and pyrroles. In this study, the van Leusen imidazole reaction, employed for synthesizing potential Hsp90 inhibitors, yielded unexpected side products containing novel condensed tricycles, specifically 3a,8b‐dihydro‐1H‐benzofuro[2,3‐d]imidazoles. The mechanism behind the formation of this unprecedented fragment was further analyzed through quantum mechanical calculations and experimental investigations of the reaction outcome under different reaction conditions and with various substituents. Additionally, the stabilities of the products were evaluated.

Silylium-Ion-Initiated Twofold Halodealkylation of Fully Alkylated Silanes

AbstractThe synthesis of silanes starting from multifunctionalized precursors often suffers from low chemoselectivity due to the similar kinetic reaction profiles, leading to the formation of difficult to separate side products. The opposite approach, which is an access based on unreactive tetraalkylsilanes as starting materials, is far less developed. Making use of the silylium-ion-initiated chemoselective halodealkylation of tetraalkylsilanes recently developed by our laboratory, an extension of this protocol, namely the direct synthesis of dihalosilanes from tetraalkylsilanes, is reported. Following a sequence of halodehydrogenation and halodealkylation, trialkylhydrosilanes can also be converted into dihalosilanes. Commercially available 1,2-dihaloethane acts as the halogen source and is involved in the generation of the catalytically active arenium ion by an SEAr substitution of the benzene solvent. The formation of an uncommon halogen-substituted silylium ion as an intermediate is assumed, likely accounting for the need of an elevated reaction temperature.

Preparation of Oil Palm Leaves Ash-Supported Titania for the Elimination of Safranin-O Dye in Water

ABSTACT. The objective of this study was to develop an approach for incorporating titanium oxide or titania into oil palm leaves ash (OPLA) using a simple procedure. The study process comprised the mixing of oil palm leaves (OPL) powder and titanium tetraisopropoxide in chloroform solvent, followed by the elimination of the solvent to obtain a solid residue. Subsequently, the residue obtained was calcined at 500 °C for 5 hours, leading to the production of a yellow-light powder. The results of product characterization using X-ray diffraction (XRD) and scanning electron microscopy analysis showed the presence of titanium oxide in OPLA. In addition, the wide diffractogram detected in XRD analysis revealed the presence of a silica peak. The un-sharp peaks in the regions of 25.6°, 38.2°, 47.9°, 54.5°, and 62.9° showed that the TiO2 particles were pure anatase, and no peaks of other TiO2-anatase phases were detected. Analysis using SEM showed that the surface of the material obtained was irregular and tended to have a hollow shape, while energy dispersive X-ray analysis revealed a SiO2 content of approximately 73%. However, the titanium element or titania was not detected possibly due to its small concentration. The material obtained also had a good catalytic activity for safranin-O dye elimination under sunlight irradiation, which served as the activation energy source. Based on these findings, the use of OPLA (a side product of oil palm plantations) could be evaluated economically due to its effective role in the catalytic process despite the addition of a small amount of titania catalyst. Keywords: Oil palm leaves ash, titania, safranin-O, sunlight irradiation.

Green Synthesis of Thiazoles and Thiadiazoles Having Anticancer Activities under Microwave Irradiation

Abstract: Sulfur and nitrogen-containing heterocycles have received a great deal of attention due to their unique structures and therapeutic relevance. Thiazoles and thiadiazoles are important five-membered heterocycles containing sulfur and nitrogen atoms that draw the special attention of re-searchers due to their synthetic diversity and potent pharmacological properties. Thiazoles and thi-adiazoles are used in agrochemicals, liquid crystals, sensors, the cosmetic industry, cyanine dyes, etc. Sometimes, organic synthesis, including thiazoles and thiadiazoles syntheses with the help of conventional methods, is laborious work, while synthesis of promising organic molecules using microwave irradiation provides better yields, diminishes the reaction time, and reduces unwanted side products. The major causes of death worldwide are due to cancer. Current research demands the design and preparation of novel compounds, including thiazoles and thiadiazoles, that may help to combat cancer, as chemotherapy or chemo drugs suffer from some demerits, including toxicity, lack of selectivity, resistance, and side effects. Hence, the review focuses on the microwave-assisted synthesis of thiazoles and thiadiazoles as a sustainable technique for the first time, and it also aims to highlight the anticancer activities of thiazoles and thiadiazole derivatives elegantly.

Sustainable synthesis of carbon dots via bio-waste recycling for biomedical imaging.

Bio-waste is a side product of biomedical research containing carbon, which can be utilized for developing carbon dots (CDs). CDs are known to be useful for a variety of applications because of their unique photoluminescence, low toxicity, and straightforward synthesis. In this paper, we employed a one-step hydrothermal method to prepare CDs from bio-waste as the only reactant. The as-synthesized Cell-CDs were found to be chemically stable and biocompatible. In addition, the spectra of Cell-CDs' emissions covered the visible light, which is ideal for super-resolution imaging. Particularly, dual-color imaging can be achieved, for example, by staining the plasma membrane with Cell-CDs emitting one color and staining cytosolic organelles with Cell-CDs emitting a different color of fluorescence. Here, we demonstrate such applications by studying the subcellular dynamics of live cells.

Directed Arylation of 7‐Oxabicyclo[2.2.1]heptane to Prepare 3D Fragments

AbstractDirected Pd‐catalysed β‐(hetero)arylation of the 7‐oxabicyclo[2.2.1]heptane framework is described. Arylated products were formed in up to 99 % yield, and heteroarylated products in up to 88 % yield with complete diastereoselectivity. Different minor diarylated side products were formed, depending on whether electron deficient aryl or pyridyl iodides were used as the coupling partners. Cleavage of the 8‐aminoquinoline directing group provided small bridged compounds that may be of value in fragment based drug discovery.

An efficient approach to produce flavonoid monophosphate by a coupled bienzymatic system

Flavonoids, with therapeutic potential, often encounter challenges due to poor aqueous solubility, which limits their oral bioavailability and efficacy. Phosphorylation presents a promising solution, yet current chemical methods require protective agents to mitigate side product formation. Here, we developed a coupled bienzymatic system using an ATP-dependent dikinase, flavonoid phosphate synthetase (BsFPS), for selective synthesis of flavonoid monophosphates. This system integrates a class III polyphosphate kinase 2 (PPK2-III) for ATP regeneration from AMP, thereby reducing costly ATP consumption and enhancing economic viability. Through PPK2-III screening, ErPPK was identified as a compatible candidate, facilitating a streamlined one-pot system. Structural analysis revealed that the residue at the equivalent site of Arg75ErPPK influences the binding pocket entry distance and flavonoid derivative inhibition propensity on PPK2-III, confirming the compatibility of ErPPK and providing structural insights for identifying PPK2-III with reduced inhibition likelihood. Further optimization strategies, including balancing Mg2+ and polyphosphate ratios, incorporating Tween surfactants for enhanced substrate solubilization without compromising enzyme stability, and increasing the rate-limiting enzyme amount, significantly elevated the conversion rate. Notably, pH control was crucial due to pH decline caused by BsFPS catalysis. pH-stat conversion achieved a 99.0 % conversion of luteolin, the flavonoid target, within 8 h, yielding up to 21.5 mM (7.9 g/L) luteolin monophosphates with up to 95 % reduction in ATP requirement. This enzymatic phosphorylation approach shows promise for advancing polyphenolic monophosphate bioproduction and transforming their functional applications.

Understanding the Social Determinants of Household Carbon Emissions for Carbon Mitigation Policies: The Case of Mersin, Turkey

Households are the main consumer-side source of carbon emissions. In Europe, consumer-based CO2 consumption per capita fell from 10.8 tons to 7.8 tons between 1990 and 2022, but in Turkey, the same data showed a rise from 4 tons to 5 tons. Strategies to reduce carbon emissions have recently shifted their focus from the production side to the consumption side. However, because different social segments have varying levels of price sensitivity and differing levels of necessity regarding consuming different items, a simple tax policy only targeting the consumption side is doomed to fail. This has prompted a discussion of the factors influencing carbon emissions on the consumption side and how those factors affect the amount of emissions. This study aims to identify the social determinants affecting household carbon emission levels and to demonstrate that such differences play an important role in effective and efficient carbon emission reduction strategies. In this case study, an appropriate testing method was used to test whether there are significant differences in dependent variables (carbon emissions) between categories of independent variables (the social determinants of households). As our literature review demonstrates, the social determinants of households and the local context were found to have an impact on carbon emissions in the case study. Nevertheless, we found that the degree of association lessens when the relationship between the dependent variables and the independent variables is re-evaluated while controlling for income level. Consequently, it may be concluded that the primary element influencing carbon emissions is income. In our field study, on the other hand, poverty stood out as another important factor affecting the level of carbon emissions. Poverty affects total household carbon emissions in two different ways, causing both carbon-intensive consumer goods and household appliances with low energy efficiency to be preferred because they are cheap to purchase. Therefore, the fight against poverty should be recognized as an important component of carbon reduction policies in Turkey, and the issue of environmental justice should not be ignored, because we know that 30% of the population was living in poverty (compared to the other 70% receiving the national median income) in 2022.

Water peaking with a three‐pillar analysis in China: Exploring the interplay of resource utilization and industrial structure

AbstractThis study introduces the innovative concept of water‐peaking theory, drawing inspiration from the theories of “peak oil” and “carbon peaking.” Employing the Environmental Kuznets Curve, Tapio's decoupling theory, and Logarithmic Mean Divisia Index decomposition, we analyze data spanning from 2006 to 2020, yielding significant findings. First, China's three industries exhibit an imbalanced structure in the utilization of water resources, necessitating the reallocation of water from the primary industry to the secondary and tertiary industries. Second, although China has not yet attained absolute water peaking, it confronts a predicament in sustainable development. Third, the primary and secondary industries demonstrate favorable decoupling of water consumption from economic growth, while the tertiary industry faces challenges in achieving historical water peaking. Fourth, drivers on the production side (technological effects, structural effects, output effects) substantially reduce water consumption across all industries, contributing to progress toward water peaking. Conversely, factors on the consumer side (population effects) play a minor role with untapped potential. This research provides valuable insights for nations worldwide in identifying historical inflection points in water resource management, pursuing sustainable pathways for industrial water usage and economic growth, and achieving environmental quality and sustainable economic development objectives. China's experiences serve as a guiding exemplar in this endeavor.

Palladium-Catalyzed Amination of Aryl Halides with Aqueous Ammonia and Hydroxide Base Enabled by Ligand Development.

The conversion of aryl halides to primary arylamines with a convenient and inexpensive source of ammonia has been a long-standing synthetic challenge. Aqueous ammonia would be the most convenient and least expensive form of ammonia, but such a palladium-catalyzed amination reaction with a high concentration of water faces challenges concerning catalyst stability and competing hydroxylation, and palladium-catalyzed reactions with this practical reagent are rare. Further, most reactions with ammonia to form primary amines are conducted with tert-butoxide base, but reactions with ammonium hydroxide would contain hydroxide as base. Thus, ammonia surrogates, ammonia in organic solvents, and ammonium salts have been used under anhydrous conditions instead with varying levels of selectivity for the primary amine. We report the palladium-catalyzed amination of aryl and heteroaryl chlorides and bromides with aqueous ammonia and a hydroxide base to form the primary arylamine with high selectivity. The palladium catalyst containing a new dialkyl biheteroaryl phosphine ligand (KPhos) suppresses both the formation of aryl alcohol and diarylamine side products. Mechanistic studies with a soluble hydroxide base revealed turnover-limiting reductive elimination of the arylamine and an equilibrium between arylpalladium amido and hydroxo complexes prior to the turnover-limiting step.

Microkinetic analysis of the CO2 effect on OCM over a La‐Sr/CaO catalyst

AbstractGiven its role as a primary side product and a potential soft oxidant in the oxidative coupling of methane (OCM), understanding the effect of CO2 co‐feeding on OCM emerges as a key milestone to optimize the process. To grasp the molecular impact of CO2, a mechanistic investigation over a La‐Sr/CaO catalyst was carried out via microkinetic modeling. Seven catalyst descriptors with a precise physico‐chemical meaning were regressed for both pure O2 and CO2 co‐feeding in order to assess eventual structural changes induced in the catalyst by the presence of CO2 in the feed. Global significance was achieved in both regressions and experimental trends were successfully reproduced by the specifically determined catalyst descriptors. CO2 co‐feeding is deemed responsible for generating a new active phase, for example, by converting metal oxides into (oxy‐)carbonates, among others, resulting in a decrease in active site density (D16) from 10 × 10−5 mol/m2 to 7 × 10−5 mol/m2. In the presence of the CO2‐induced phase, the catalyst exhibits higher attraction for unsaturated hydrocarbons as indicated by the higher initial sticking probabilities of CH3• (D11) and C2H4 (D15), which increase from 4.9 × 10−4 to 8 × 10−2 and from 2.1 × 10−2 to 3 × 10−2, respectively. Additionally, there are also lower the overall energy barriers for the activation of hydrocarbons on the catalyst, stemming from the decrease in the H abstraction enthalpy from CH4 (D1) from 14 to 6 kJ/mol. The operating conditions, in particular the O2 content, are critical in distinguishing the effect of CO2 co‐feeding. While at typical operating conditions, CO2 promotes the total oxidation of methane, in the prerequisite of reduced amount of O2, it may also act as an additional oxygen donor. This work provides molecular details on the CO2 induced changes in catalyst properties but also provides unprecedent quantified insights of the reaction mechanism underlying experimental observations.

Production of biodiesel from Pistacia atlantica (PA) oil seeds using nano-catalyst of alumina/sludge of stone cutting factory (Al2O3/SSCF) and separation of biodiesel and glycerol phases by high voltage

Biodiesel is a renewable fuel and a suitable alternative to fossil fuels. However, the cost of its production and purification has prevented the commercialization and industrialization of this fuel. One economic solution for producing biodiesel fuel is the profit from the sale of glycerin, which is produced as a side product in various processes. In addition to the economic aspects, there are problems caused by the presence of glycerin residues in raw biodiesel before the purification process and the low speed of its separation from biodiesel. Biodiesel is produced by the transesterification method from Pistacia atlantica (PA) oil seeds of the Lorestan Mountains and methanol (1:6) using nano-catalysts of alumina/sludge from a stone cutting factory (Al2O3/SSCF). In this study, to investigate cost reduction and pure and quick separation of glycerin from biodiesel produced, a high-voltage electric method has been used. In this method, negative charges are absorbed by glycerin, separating it from biodiesel. The resulting biodiesel is produced in 10 min with 99% efficiency. The Fourier-transform infrared spectroscopy (FTIR) spectrum of biodiesel is investigated to ensure the formation of the reaction. This method can replace traditional methods.

In situ Crystallization of Methanesulfonic Acid, CH3SO3H, and Serendipitous Single Crystal Formation of its Anhydride, (CH3)2S2O5

AbstractMethanesulfonic acid, CH3SO3H, has been crystallized using an in situ technique on a single crystal diffractometer. The crystal structure is monoclinic (P21/c, Z=4, a=842.07(4) pm, b=582.20(3) pm, c=820.38(4) pm, β=106.459(2)°) and stamped by the presence of strong hydrogen bonds. Single crystals of the anhydride of methanesulfonic acid, (CH3)2S2O5, formed as a side product in the reaction of bis‐trimethylsilyl‐sulfate, [(CH3)3SiO]2SO2 with SO3 in a sealed glass ampoule. The monoclinic crystal structure (P21/n, Z=12, a=1794.5(2) pm, b=831.75(7) pm, 1383.4(1) pm, β=110.630(4)°) shows three crystallographically different (CH3)2S2O5 molecules in the unit cell. According to the orientation of the CH3 groups with respect to each other the (CH3)2S2O5 molecule appears as the so‐called trans‐conformer. The structure of both molecules is corroborated by quantum mechanical DFT calculations.

Isolation and characterization of synthesis intermediates and side products in hexahydrocannabiphorol

AbstractAfter the Swiss ban of hexahydrocannabinol (HHC) in March 2023, other semisynthetic dibenzopyran cannabinoids emerged on the Swiss gray market. Hexahydrocannabiphorol (HHCP) was the most prominent of them due to its potent cannabimimetic effects, as anecdotal reports from recreational users suggest. In October 2023, a class wide ban of dibenzopyran cannabinoids was introduced in Switzerland to prevent new similar substances from entering the drug market. Various vendors in online shops claim that HHCP is made from CBD, even though they possess different alkyl chain lengths. An HHCP sample was analyzed by gas chromatography coupled to mass spectrometry (GC‐MS), showing that a mixture of molecules with the same or a similar molecular mass as HHCP was present. Six different substances could be isolated from this sample using column chromatography. Four phenols ((9R)‐HHCP, iso‐HHCP, cis‐HHCP, and abn‐HHCP) and two ketones (possible intermediates to (9R)‐HHCP and abn‐HHCP) were identified by various nuclear magnetic resonance spectroscopy (NMR) techniques. (9S)‐HHCP was obtained in an impure fraction. In addition, a fraction was obtained that showed characteristic molecular and fragment ions consistent with bisalkylated products from the synthesis of similar compounds. The presence of abnormal cannabinoids (abn‐HHCP) and bisalkylated cannabinoids is a confirmation that this sample was produced purely synthetically as initially suspected, as these compounds have not been reported in Cannabis. Chiral derivatization of the phenols with Mosher acid chlorides showed that only iso‐HHCP was present as a scalemic mixture, indicating a good stereocontrol of this synthetic procedure.