Specific Isomers Research Articles

Abstract P3-12-35: Industrial and ruminant trans fatty acid intakes and cancer risk: Results from the NutriNet-Santé cohort

Abstract Background Dietary trans fatty acids (TFAs) are either natural (from ruminant sources) or generated through industrial processes by partial hydrogenation of vegetable oils. Extended evidence demonstrated their role as cardiovascular risk factors. In contrast, their involvement in cancer etiology is suspected, but epidemiological evidence remains limited. Objectives Our objective was to investigate associations between TFA intake of different types (total, rumninant [rTFAs], industrial [iTFAs], and corresponding specific isomers) and the risk of cancer (overall and main cancer sites) in the NutriNet-Santé prospective cohort (2009-2020). Methods Overall, 104,909 participants were included. Usual TFA intake was estimated from validated repeated 24-h dietary records matched with detailed composition table. Associations between sex-specific quartiles of TFA intake and cancer risk were assessed using multi-adjusted Cox proportional hazard models. Results A total of 3,374 incident cancer cases occured during follow-up (among which 982 breast and 405 prostate cancers). Dietary intake of total TFAs was associated with higher prostate cancer risk (HRfor quartile 4 versus 1: 1.27, 1.11-1.77 Ptrend=0.005). rTFAs were associated with increased overall cancer risk (1.16, 1.02-1.32 Ptrend=0.07), in particular the conjugated linoleic acid isomers (CLA) (1.19, 1.04-1.36 Ptrend=0.04). These associations were specifically observed for breast cancer (rTFAs: 1.35, 1.06-1.72 Ptrend=0.01; CLA: 1.29, 1.00-1.66 Ptrend=0.048), in particular before menopause (rTFAs: 1.68, 1.06-2.67 Ptrend=0.02; CLA: 2.013, 1.25-3.23 Ptrend=0.003). Several iTFAs were associated with overall (1.18, 1.06-1.31 Ptrend=0.02 for transdocosenoic acid), breast (isomer 18:2t: 1.30, 1.06-1.58 Ptrend=0.01; hexadecenoic acid: 1.28, 1.05-1.56 Ptrend=0.02) and prostate (transdocosenoic acid: 1.52, 1.09-2.12 Ptrend=0.07) cancer risks. Conclusion In this large prospective study, several types of TFAs were associated with increased overall, breast and prostate cancer risks. Although further studies are needed to better understand underlying mechanisms, these results support the WHO's goal of achieving industrially produced TFAs elimination from food supplies. Meanwhile, the consumption of food products containing partially-hydrogenated oils should be avoided. Citation Format: Gaëlle Wendeu-Foyet, Véronique Chajes, Inge Huybrechts, Jean-Marie Bard, Charlotte Debras, Eloi Chazelas, Bernard Srour, Laurent Zelek, Chantal Julia, Emmanuelle Kesse-Guyot, Cédric Agaësse, Nathalie Druesne-Pecollo, Pilar Galan, Serge Hercberg, Mélanie Deschasaux-Tanguy, Mathilde Touvier. Industrial and ruminant trans fatty acid intakes and cancer risk: Results from the NutriNet-Santé cohort [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-35.

Formation of astrochemically relevant molecular ions: Reaction of translationally coldCCl+with benzene in a linear ion trap

The gas-phase ion-neutral reaction of ${\mathrm{CCl}}^{+}$ $+$ benzene $({\mathrm{C}}_{6}{\mathrm{H}}_{6})$ is investigated using a linear Paul ion trap coupled to a time-of-flight mass spectrometer. Low collision energies are achieved by sympathetically cooling ${\mathrm{CCl}}^{+}$ reactant ions with cotrapped laser-cooled ${\mathrm{Ca}}^{+}$. The observed products include the astrochemically relevant carbocations ${\mathrm{C}}_{7}{\mathrm{H}}_{5}^{+}$, ${\mathrm{C}}_{5}{\mathrm{H}}_{3}^{+}$, and ${\mathrm{C}}_{3}{\mathrm{H}}_{3}^{+}$, as well as ${\mathrm{C}}_{3}{\mathrm{H}}_{2}{\mathrm{Cl}}^{+}$. Branching ratios of these products are measured, and ${\mathrm{C}}_{7}{\mathrm{H}}_{5}^{+}$, a carbon-growth species, is favored. Complementary electronic structure calculations provide thermodynamic limits for the reaction and allow for assignment of reaction products to specific structural isomers. Only one exoergic isomer is identified for each observed product with the exception of ${\mathrm{C}}_{7}{\mathrm{H}}_{5}^{+}$ where many identified structural isomers are exoergic. The results from this Letter broaden our understanding of the reactivity and possible role of ${\mathrm{CCl}}^{+}$ and ${\mathrm{C}}_{6}{\mathrm{H}}_{6}$ in interstellar chemistry. Furthermore, this Letter provides insight into a potential pathway to larger carbocations that may be precursors to more complex polycyclic aromatic hydrocarbons.

Quantum mechanical and molecular dynamics simulations of retinal systems utilizing novel artificial-intelligence-derived force fields

G-protein-coupled receptors (GPCRs) are a superfamily of transmembrane proteins that perform diverse signaling roles in organisms, including humans. This makes them an attractive target for pharmaceuticals, with 134 different GPCRs being currently targeted by roughly 700 drugs. Here we studied the retinylidene cofactor of GPCR rhodopsin that is responsible for initiating phototransduction in many organisms. The conformational energy landscape of this retinylidene is both complex and critical for the activation of the rhodopsin protein, which depends not only on specific isomers but on rotamers as well.

Photodegradation of hydroxyfluorenes in ice and water: A comparison of kinetics, effects of water constituents, and phototransformation by-products

The photochemical behavior of organic pollutants in ice is poorly studied in comparison to aqueous photochemistry. Here we report a detailed comparison of ice and aqueous photodegradation of two representative OH-PAHs, 2-hydroxyfluorene (2-OHFL) and 9-hydroxyfluorene (9-OHFL), which are newly recognized contaminants in the wider environment including colder regions. Interestingly, their photodegradation kinetics were clearly influenced by whether they reside in ice or water. Under the same simulated solar irradiation (λ > 290 nm), OHFLs photodegraded faster in ice than in equivalent aqueous solutions and this was attributed to the specific concentration effect caused by freezing. Furthermore, the presence of dissolved constituents in ice also influenced photodegradation with 2-OHFL phototransforming the fastest in ‘seawater’ ice (k = (11.4 ± 1.0) × 10−2 min−1) followed by ‘pure-water’ ice ((8.7 ± 0.4) × 10−2 min−1) and ‘freshwater’ ice ((8.0 ± 0.7) × 10−2 min−1). The presence of dissolved constituents (specifically Cl−, NO3−, Fe(III) and humic acid) influences the phototransformation kinetics, either enhancing or suppressing phototransformation, but this is based on the quantity of the constituent present in the matrixes, the specific OHFL isomer and the matrix type (e.g., ice or aqueous solution). Careful derivation of key photointermediates was undertaken in both ice and water samples using tandem mass spectrometry. Ice phototransformation exhibited fewer by-products and ‘simpler’ pathways giving rise to a range of hydroxylated fluorenes and hydroxylated fluorenones in ice. These results are of importance when considering the fate of PAHs and OH-PAHs in cold regions and their persistence in sunlit ice.

Photoelectron Circular Dichroism as a Probe of Chiral Hydrocarbons

The sensitivity of Photoelectron Circular Dichroism (PECD) in the angular distribution of photoelectrons, a recent chiral technique, to detect chirality in pure hydrocarbons is investigated in a number of benchmark molecules. It is found that a very large chiral signal is expected, surpassing most current examples, giving a sure fingerprint of absolute configuration. On the other hand, the sensitivity to specific isomers or closely related molecules is relatively modest.

Electroantennogram responses of Batocera horsfieldi (Hope) to the selected volatile components of host plants, Rosa cymosa Tratt. and Rosa multiflora Thunb.

To screen for host volatile components for effectively monitoring and trapping Batocera horsfieldi Hope (Coleoptera: Cerambycidae), Headspace Solid Phase Microextraction (HS-SPME) and Gas Chromatograph-Mass Spectrometry (GC-MS) were combined to analyze volatiles emitted from Rosa cymosa Tratt. and Rosa multiflora Thunb. The results showed that alcohols (55.519%) and aldehydes (81.387%) were the primary chemicals emitted by R. cymosa and R. multiflora , respectively. An electroantennogram response (EAG) test was used to compare and analyze the responses of male and female beetles to each of the selected fifteen components, and the results showed that only nine of these components triggered significant EAG responses. Sex and volatile concentration-specific responses were observed in B. horsfieldi . Male adults showed the strongest EAG response to 1-octen-3-ol, while female adults expressed the most powerful EAG responses to salicylaldehyde and linalool. These results indicated that the sensitivity of B. horsfieldi to host volatile components was different, and the EAG response was positively correlated with the concentration of the volatile components in a certain range. Male and female adults showed different preferences for the volatile components. Furthermore, B. horsfieldi showed different preferences for volatile components and exhibited diverse recognition reactions to specific functional groups and homologous isomers. This work provided favorable data support for the development of insect attractant, and laid a theoretical foundation for the local forestry ecological protection. • R. cymosa and R. multiflora mainly contain aldehydes and alcohols. • EAG response had positive correlation with concentration. • B. horsfieldi could identify different functional groups and homologous isomers. • Male and female showed different preferences for volatile components.

Analysis of Specific Perfluorohexane Sulfonate Isomers by Liquid Chromatography-Tandem Mass Spectrometry: Method Development and Application in Source Apportionment

Analysis of Specific Perfluorohexane Sulfonate Isomers by Liquid Chromatography-Tandem Mass Spectrometry: Method Development and Application in Source Apportionment

Ensemble representation of catalytic interfaces: soloists, orchestras, and everything in-between.

Catalytic systems are complex and dynamic, exploring vast chemical spaces on multiple timescales. In this perspective, we discuss the dynamic behavior of fluxional, heterogeneous thermal and electrocatalysts and the ensembles of many isomers which govern their behavior. We develop a new paradigm in catalysis theory in which highly fluxional systems, namely sub-nano clusters, isomerize on a much shorter timescale than that of the catalyzed reaction, so macroscopic properties arise from the thermal ensemble of isomers, not just the ground state. Accurate chemical predictions can only be reached through a many-structure picture of the catalyst, and we explain the breakdown of conventional methods such as linear scaling relations and size-selected prevention of sintering. We capitalize on the forward-looking discussion of the means of controlling the size of these dynamic ensembles. This control, such that the most effective or selective isomers can dominate the system, is essential for the fluxional catalyst to be practicable, and their targeted synthesis to be possible. It will also provide a fundamental lever of catalyst design. Finally, we discuss computational tools and experimental methods for probing ensembles and the role of specific isomers. We hope that catalyst optimization using chemically informed descriptors of ensemble nature and size will become a new norm in the field of catalysis and have broad impacts in sustainable energy, efficient chemical production, and more.

Edge Decoration of Anthracene Switches Global Diatropic Current That Controls the Acene Reactivity.

The 14π-electron system of anthracene has been merged with the unsaturated Z-1,2-difurylethene to form a macrocycle(s) with the retained local conjugation of all incorporated subunits that were substantially modulated with a redox activation, opening a global delocalization involving all integrated aromatics. In addition, the edge modulation of acene via the attachment of a specific isomer of the conjugated system gives steric confinements that are characteristic of small macrocycles, forcing substantially short C(H)···O electrostatic interactions that are documented spectroscopically with the support of X-ray analysis.

Hydroxylamine-mediated C\u2013C amination via an aza-hock rearrangement

Despite the widespread use of anilines, synthetic challenges to these targets still exist. Selectivity is often an issue, when using the traditional nitration-reduction sequence or more modern approaches, including arene C–H aminations catalyzed by transition metals, photosensitizers, or electrodes. Accordingly, there is still a need for general methods to rapidly, directly access specific isomers of substituted anilines. Here, we report a simple route towards the synthesis of such motifs starting from benzyl alcohols, which are converted to anilines by the use of arylsulfonyl hydroxylamines, via an aza-Hock rearrangement. Good to excellent yields are observed. The method is applicable to various benzyl alcohol surrogates (such as ethers, esters, and halides) as well as simple alkylarenes. Functionalizations of pharmaceutically relevant structures are feasible under the reaction conditions. Over ten amination reagents can be used, which facilitates the rapid assembly of a vast set of compounds.

Changes in Brain Matrix Glycan Sulfation Associate With Reactive Gliosis and Motor Coordination in Mice With Head Trauma.

Perineuronal nets (PNNs) are extracellular matrix (ECM) structures that enmesh and regulate neurocircuits involved in motor and sensory function. Maladaptive changes to the composition and/or abundance of PNNs have been implicated in preclinical models of neuroinflammation and neurocircuit destabilization. The central nervous system (CNS) is limited in its capacity to repair and reorganize neural networks following traumatic brain injury (TBI) and little is known about mechanisms of ECM repair in the adult brain after TBI. In this study, adult male C57BL/6 mice were subjected to a TBI via a controlled cortical impact (CCI) to the right motor and somatosensory cortices. At 7 days following CCI, histological analysis revealed a loss of Wisteria floribunda agglutinin (WFA) positive PNN matrices in the ipsilateral cortex. PNNs are comprised of chondroitin sulfate (CS) and dermatan sulfate (DS)-glycosaminoglycans (GAGs), the composition of which are known to influence neuronal integrity and repair. Using an innovative liquid chromatography tandem mass spectrometry (LC-MS/MS) method, we analyzed the relative abundance of six specific CS/DS-GAG isomers (Δ4S-, Δ6S-, Δ4S6S-, Δ2S6S-, Δ0S-CS, and Δ2S4S-DS) from fixed-brain sections after CCI injury. We report a significant shift in CS/DS-GAG sulfation patterns within the rostro-caudal extent of the injury site from mice exposed to CCI at 7 days, but not at 1 day, post-CCI. In the ipsilateral thalamus, the appearance of WFA+ puncta occurred in tandem with gliosis at 7 days post-CCI, but weakly colocalized with markers of gliosis. Thalamic WFA+ puncta showed moderate colocalization with neuronal ubiquitin C-terminal hydrolase L1 (UCHL1), a clinical biomarker for TBI injury. A shift in CS/DS-GAG sulfation was also present in the thalamus including an increase of 6S-CS, which is a specific isomer that associates with the presence of glial scarring. Upregulation of the 6S-CS-specific sulfotransferase (CHST3) gene expression was accompanied by reactive gliosis in both the ipsilateral cortex and thalamus. Moreover, changes in 6S-CS extracted from the thalamus positively correlated with deficits in motor coordination after CCI. Collectively, these data argue that CCI alters CS/DS-GAG sulfation in association with the spatiotemporal progression of neurorepair. Therapeutic interventions targeting restoration of CS/DS-GAG sulfation patterns may improve outcomes from TBI.

Dietary trans fatty acid intakes and cancer risk: results from the NutriNet-Santé cohort

Abstract Dietary trans fatty acids (TFAs) are either natural (ruminant sources) or industrially generated by partial hydrogenation of vegetable oils. Increasing evidence demonstrated their role as cardiovascular risk factors. Their involvement in cancer etiology is suspected, but epidemiological evidence is limited so far. We aimed to investigate the associations between different types of TFAs (total, ruminant [rTFAs], industrial [iTFAs] and corresponding specific isomers) and the risk of cancer in the NutriNet-Santé prospective cohort (2009-2020). Overall, 104,909 participants were included. Usual TFA intake was estimated from validated repeated 24-h dietary records. Associations between sex-specific quartiles of dietary intake of TFA and cancer risk were assessed using multi-adjusted Cox proportional hazard models. A total of 3,374 incident cancer cases occured during follow-up (including 982 breast and 405 prostate cancers). Total TFAs was associated with higher prostate cancer risk (1.34[1.25;1.87] Ptrend=0.005). rTFAs were associated with increased overall cancer risk (HRfor quartile 4 versus 1: 1.21[1.06;1.39] Ptrend=0.03), in particular the conjugated linoleic acid isomer (CLA) (1.19[1.04;1.36] Ptrend=0.04). These associations were specifically observed for breast cancer, in particular before menopause (rTFAs: 1.78[1.11;2.87] Ptrend=0.006; CLA: 2.013[1.25;3.23] Ptrend=0.003). Several iTFAs were associated with overall (1.18[1.06;1.31] Ptrend=0.02 for transdocosenoic acid), breast (isomer 18:2t: 1.30[1.06;1.58] Ptrend=0.01; hexadecenoic acid: 1.28[1.05-1.56] Ptrend=0.02) and prostate (transdocosenoic acid: 1.52[1.09;2.12] Ptrend=0.07) cancer risks. In this large prospective study, several types of TFAs were associated with increased overall, breast and prostate cancer risks. Although further studies are needed to better understand underlying mechanisms, these results support the WHO's goal of achieving industrially produced TFAs elimination from food supplies. Key messages Higher intake of dietary trans fatty acids is associated with an increased risk of various cancers. Our findings support WHO’s global recommendation of eliminating industrially produced TFAs by 2023.

Trans-10 18:1 in ruminant meats: A review.

Trans (t) fatty acids (TFA) from partially hydrogenated vegetable oils (i.e., industrial trans) have been phased out of foods in many countries due to their promotion of cardiovascular disease. This leaves ruminant-derived foods as the main source of TFA. Unlike industrial TFA where catalytic hydrogenation yields a broad distribution of isomers, ruminant TFA are enzymatically derived and can result in enrichment of specific isomers. Comparisons between industrial and ruminant TFA have often exonerated ruminant TFA due to their lack or at times positive effects on health. At extremes, however, ruminant-sourced foods can have either high levels of t10- or t11-18:1, and when considering enriched sources, t10-18:1 has properties similar to industrial TFA, whereas t11-18:1 can be converted to an isomer of conjugated linoleic acid (cis(c)9,t11-conjugated linoleic acid), both of which have potential positive health effects. Increased t10-18:1 in meat-producing ruminants has not been associated with negative effects on live animal production or meat quality. As such, reducing t10-18:1 has not been of immediate concern to ruminant meat producers, as there have been no economic consequences for its enrichment; nevertheless at high levels, it can compromise the nutritional quality of beef and lamb. In anticipation that regulations regarding TFA may focus more on t10-18:1 in beef and lamb, the present review will cover its production, analysis, biological effects, strategies for manipulation, and regulatory policy.

Effects of Wounding Stress and Storage Temperature on the Accumulation of Chlorogenic Acid Isomers in Potatoes (Solanum tuberosum)

Wounding stress is an effective strategy to increase the content of bioactive compounds in horticultural crops. Potato tubers subjected to wounding stress accumulate chlorogenic acid (CGA) and CGA isomers (neo-CGA and crypto-CGA), which are phenolics that prevent and treat different chronic and degenerative diseases. In this study, the effects of wounding stress and storage temperature (10 °C and 20 °C for 168 h) on the accumulation of CGA isomers in potatoes were evaluated. Results indicated that CGA accumulation was favored when wounded potatoes were stored at 20 °C for 120 h, obtaining a 1923.1% higher concentration when compared with samples before storage. Furthermore, wounded potatoes stored at 10 °C for 120 h showed the highest neo-CGA increase in concentration (712.2%). Likewise, the highest crypto-CGA concentration (84.9% higher than control samples) was quantified in wounded potatoes stored at 20 °C for 144 h. Based on the results from both the present study and previous reports, a strategy that summarizes effective postharvest stress conditions that induce the accumulation of specific CGA isomers in potatoes is presented. The tissue with an increased content of bioactive compounds could be used as raw material to produce functional foods or could be subjected to downstream processing to produce dietary supplements.

Rhodium(III)-Catalyzed [4 + 2] Annulation of N-Arylbenzamidines with Propargyl Alcohols: Highly Regioselective Synthesis of 1-Aminoisoquinolines Controlled by Noncovalent Interaction

A highly regioselective synthesis of 1-aminoisoquinolines has been explored via rhodium(III)-catalyzed C-H bond activation/annulation reactions of propargyl alcohols with N-arylbenzamidines. The imidamide was used as the directing group and the nitrogen source of the heterocycle and for regulating the regioselective migratory insertion of propargyl alcohol through a hydrogen bond. In this transformation, a specific isomer was obtained that would provide a new strategy for the synthesis of 1-aminoisoquinolines with biological activity.

Study of rapeseed oil gelation induced by commercial monoglycerides using a chemometric approach

Commercial oleogelators rich in monoglycerides (MGs) are complex mixtures of acylglycerides with variable gelling properties, depending on the oil used and their concentration. In this study we developed a chemometric approach to identify the key parameters involved in gelling process. Analytical parameters have been defined, using GC and NMR analysis to identify fatty acids and acylglycerides composing the mixtures. Specific acylglyceride families and compound ratios were calculated to streamline the analytical results. To determine the key analytical parameters, artificial neural networks were used in a QSPR study related to the gelling properties measured by rheology through oscillatory experiments. At low oleogelator concentrations, the MGs especially rich in C16:0 and the ratio of specific isomers both have a positive influence on G′. For high oleogelator concentrations, C18:0-rich acylglycerides and unsaturated/saturated fatty acid ratios have a positive influence on G′. Conversely, at low concentrations, C18:0-rich acylglycerides show a lesser effect on G′.

Phenyl argentate aggregates [AgnPhn+1]- (n = 2-8): Models for the self-assembly of atom-precise polynuclear organometallics.

Electrospray ionization of phenyl argentates formed by transmetalation reactions between phenyl lithium and silver cyanide provides access to the argentate aggregates, [AgnPhn+1]-, which were individually mass-selected for n = 2-8 in order to generate their gas-phase Ultraviolet Photodissociation (UVPD) "action" spectra over the range 304-399nm. A strong bathochromic shift in optical spectra was observed with increasing size/n. Theoretical calculations allowed the assignment of the experimental UVPD spectra to specific isomer(s) and provided crucial insights into the transition from the 2D to 3D structure of the metallic component with the increasing size of the complex. The [AgnPhn+1]- aggregates contain neither pronounced metallic cluster properties nor ligated metallic cluster features and are thus not superatom complexes. They therefore represent novel organometallic characteristics built from Ag2Ph subunits.

Structural Basis of Ligand Selectivity by a Bacterial Adhesin Lectin Involved in Multispecies Biofilm Formation.

Carbohydrate recognition by lectins governs critical host-microbe interactions. MpPA14 (Marinomonas primoryensis PA14 domain) lectin is a domain of a 1.5-MDa adhesin responsible for a symbiotic bacterium-diatom interaction in Antarctica. Here, we show that MpPA14 binds various monosaccharides, with l-fucose and N-acetylglucosamine being the strongest ligands (dissociation constant [Kd ], ∼150 μM). High-resolution structures of MpPA14 with 15 different sugars bound elucidated the molecular basis for the lectin's apparent binding promiscuity but underlying selectivity. MpPA14 mediates strong Ca2+-dependent interactions with the 3,4-diols of l-fucopyranose and glucopyranoses, and it binds other sugars via their specific minor isomers. Thus, MpPA14 only binds polysaccharides like branched glucans and fucoidans with these free end groups. Consistent with our findings, adhesion of MpPA14 to diatom cells was selectively blocked by l-fucose, but not by N-acetyl galactosamine. The MpPA14 lectin homolog present in a Vibrio cholerae adhesin was produced and was shown to have the same sugar binding preferences as MpPA14. The pathogen's lectin was unable to effectively bind the diatom in the presence of fucose, thus demonstrating the antiadhesion strategy of blocking infection via ligand-based antagonists.IMPORTANCE Bacterial adhesins are key virulence factors that are essential for the pathogen-host interaction and biofilm formation that cause most infections. Many of the adhesin-driven cell-cell interactions are mediated by lectins. Our study reveals for the first time the molecular basis underlying the binding selectivity of a common bacterial adhesin lectin from the marine bacterium Marinomonas primoryensis, homologs of which are found in both environmental and pathogenic species. The lectin-ligand interactions illustrated at the atomic level guided the identification of a ligand that serves as an inhibitor to block bacterium-host adhesion. With conventional bactericidal antibiotics losing their potency due to resistance, our work gives critical insight into an antiadhesion strategy to treat bacterial infections.

Determination of organic sulfur markers in crude oils by gas chromatography triple quadrupole mass spectrometry

Organic sulfur compounds, such as benzothiophene and dibenzothiophene, are present in crude oils, and specific isomers of these classes are known to be geochemical markers of maturity, lithology and biodegradation. Thus, knowledge of the individual concentrations of these target molecules enables us to characterize petroleum basins for better exploration. In this work, a simple and effective gas chromatography–triple quadrupole mass spectrometry method without preliminary fractionation was developed and validated for the determination of 14 organic sulfur compounds assumed to be geochemical markers for crude oils. The research was focused on the optimization of a highly selective GC-based analytical strategy using triple quadrupole MS in multiple reaction monitoring. Sample preparation was carried out by simple dilution in DCM. The method was validated, and the following parameters were expressed in terms of intraday precision: linearity, limit of detection, accuracy and precision. The limit of detection ranged from 0.005 μg mL−1 (benzothiophene) to 0.159 μg mL−1 (benzonaphthothiophene). Intraday assay precision was lower than 20% in all cases. Recoveries ranged from 78.2% (1,4-dimethyldibenzothiophene) to 117% (2,4,7-trimethyldibenzothiophene). After validation, the procedure was successfully applied to the determination of S-markers in 8 crude oil samples, and the method was determined to be precise, accurate, and suitable. Diagnostic ratios based on benzothiophenes to dibenzothiphenes were applied as tools to evaluate maturity, biodegradation and depositional ambient conditions. A cross-plot of methyldibenzothiophene versus dimethyldibenzophene ratio was utilized to classify oils according to their maturity.

Serotonin 2A Receptor (5-HT2AR) Activation by 25H-NBOMe Positional Isomers: In Vitro Functional Evaluation and Molecular Docking.

Serotonergic psychedelics are defined as compounds having serotonin 2A receptor (5-HT2AR) activation as an important pharmacological mechanism. These compounds include the phenylalkylamine class, containing substances with e.g. 2C-X structures (phenethylamines) or their N-methoxybenzyl analogues (NBOMes). Besides their abuse potential, psychedelics are increasingly recognized for having therapeutic benefits. However, many psychedelics remain incompletely characterized, even concerning their structure-activity relationships. Here, five positional isomers of 25H-NBOMe, with two methoxy groups on the different positions of the phenyl ring of the phenethylamine moiety, were subjected to split-nanoluciferase assays assessing the in vitro recruitment of cytosolic proteins to the 5-HT2AR. Furthermore, molecular docking at the 5-HT2AR allowed estimation of which residues interact with the specific isomers' methoxy groups. Although the optimal substitution pattern of N-unsubstituted phenylalkylamines has been extensively studied, this is the first comparative evaluation of the functional effects of the positioning of the methoxy groups in the phenethylamine moiety of NBOMes.