Deciphering Stereoselectivity in Hurd-Claisen Rearrangements: A Comprehensive Study of Electrostatic Interactions from Shubin's Energy Decomposition Analysis.

In this study, we explore the stereoselectivity of Hurd-Claisen Rearrangements, focusing on the influence of two electron-withdrawing groups and eight diverse substituents. Utilizing the Curtin-Hammett principle, we performed energy calculations for reactions, products, and transition states using the M062X/def2TZVPP compound model. Our analysis reveals that kinetic factors predominantly dictate the reaction equilibrium. A key aspect of our research is the application of Shubin's energy decomposition analysis to optimized transition states, highlighting the significant role of electrostatic interactions in determining stereoselectivity. We further dissected each transition state into four fragments: the electron-withdrawing groups ($CO_2Et$, $CN$), the Hurd group ($H$), various substituents ($CH_3$, $Et$, $SProp$, $TBut$, $IsoBut$, $NH_2Ph$, $NO_2Ph$, $Ph$), and the central fragment. This fragmentation approach enabled an in-depth analysis of group dipole moments, providing insights into the electrostatic forces at play. Our findings shed light on the intricate mechanisms driving stereoselectivity in Hurd-Claisen Rearrangements and enhance the understanding of molecular interactions, offering valuable implications for organic synthesis.

Cannabidiol induces systemic analgesia through activation of the PI3Kγ/nNOS/NO/KATP signaling pathway in neuropathic mice. A KATP channel S-nitrosylation-dependent mechanism.

BACKGROUND: Cannabidiol (CBD) is the second most abundant pharmacologically active component present in Cannabis sp. Unlike Δ-9-tetrahydrocannabinol (THC), it has no psychotomimetic effects and has recently received significant interest from the scientific community due to its potential to treat anxiety and epilepsy. CBD has excellent anti-inflammatory potential and can be used to treat some types of inflammatory and neuropathic pain. In this context, the present study aimed to evaluate the analgesic mechanism of cannabidiol administered systemically for the treatment of neuropathic pain and determine the endogenous mechanisms involved with this analgesia. METHODS: Neuropathic pain was induced by sciatic nerve constriction surgery, and the nociceptive threshold was measured using the paw compression test in mice. RESULTS: CBD produced dose-dependent antinociception after intraperitoneal injection. Selective inhibition of PI3Kγ dose-dependently reversed CBD-induced antinociception. Selective inhibition of nNOS enzymes reversed the antinociception induced by CBD, while selective inhibition of iNOS and eNOS did not alter this antinociception. However, the inhibition of cGMP production by guanylyl cyclase did not alter CBD-mediated antinociception, but selective blockade of ATP-sensitive K+ channels dose-dependently reversed CBD-induced antinociception. Inhibition of S-nitrosylation dose-dependently and completely reversed CBD-mediated antinociception. CONCLUSION: Cannabidiol has an antinociceptive effect when administered systemically and this effect is mediated by the activation of PI3Kγ as well as by nitric oxide and subsequent direct S-nitrosylation of KATP channels on peripheral nociceptors.

Revisiting Biginelli-like reactions: solvent effects, mechanisms, biological applications and correction of several literature reports.

This study critically reevaluates reported Biginelli-like reactions using a Kamlet-Abboud-Taft-based solvent effect model. Surprisingly, structural misassignments were discovered in certain multicomponent reactions, leading to the identification of pseudo three-component derivatives instead of the expected MCR adducts. Attempts to replicate literature conditions failed, prompting reconsideration of the described MCRs and proposed mechanisms. Electrospray ionization (tandem) mass spectrometry, NMR, melting points, elemental analyses and single-crystal X-ray analysis exposed inaccuracies in reported MCRs and allowed for the proposition of a complete catalytic cycle. Biological investigations using both pure and "contaminated" derivatives revealed distinctive features in assessed bioassays. A new cellular action mechanism was unveiled for a one obtained pseudo three-component adduct, suggesting similarity with the known dihydropyrimidinone Monastrol as Eg5 inhibitors, disrupting mitosis by forming monoastral mitotic spindles. Docking studies and RMSD analyses supported this hypothesis. The findings described herein underscore the necessity for a critical reexamination and potential corrections of structural assignments in several reports. This work emphasizes the significance of rigorous characterization and critical evaluation in synthetic chemistry, urging a careful reassessment of reported synthesis and biological activities associated with these compounds.

Nitric oxide and potassium channels but not opioid and cannabinoid receptors mediate tramadol-induced peripheral antinociception in rat model of paw pressure withdrawal.

Tramadol, an analgesic classified as an "atypical opioid", exhibits both opioid and non-opioid mechanisms of action. This study aimed to explore these mechanisms, specifically the opioid-, cannabinoid-, nitric oxide-, and potassium channel-based mechanisms, which contribute to the peripheral antinociception effect of tramadol, in an experimental rat model. The nociceptive threshold was determined using paw pressure withdrawal. To examine the mechanisms of action, several substances were administered intraplantarly: naloxone, a non-selective opioid antagonist (50 µg/paw); AM251 (80 µg/paw) and AM630 (100 µg/paw) as the selective antagonists for types 1 and 2 cannabinoid receptors, respectively; nitric oxide synthase inhibitors L-NOArg, L-NIO, L-NPA, and L-NIL (24 µg/paw); and the enzyme inhibitors of guanylatocyclase and phosphodiesterase of cGMP, ODQ, and zaprinast. Additionally, potassium channel blockers glibenclamide, tetraethylammonium, dequalinium, and paxillin were used. The results showed that opioid and cannabinoid receptor antagonists did not reverse tramadol's effects. L-NOarg, L-NIO, and L-NPA partially reversed antinociception, while ODQ completely reversed, and zaprinast enhanced tramadol's antinociception effect. Notably, glibenclamide blocked tramadol's antinociception in a dose-dependent manner. These findings suggest that tramadol's peripheral antinociception effect is likely mediated by the nitrergic pathway and sensitive ATP potassium channels, rather than the opioid and cannabinoid pathways.

Anodal tDCS over the left DLPFC but not M1 increases muscle activity and improves psychophysiological responses, cognitive function, and endurance performance in normobaric hypoxia: a randomized controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been shown to have positive effects on exercise performance and cognitive function in the normal ambient condition. Hypoxia is deemed a stressful situation with detrimental effects on physiological, psychological, cognitive, and perceptual responses of the body. Nevertheless, no study has evaluated the efficacy of tDCS for counteracting the negative effects of hypoxic conditions on exercise performance and cognition so far. Hence, in the present study, we investigated the effects of anodal tDCS on endurance performance, cognitive function, and perceptual responses in hypoxia. PARTICIPANTS AND METHODS: Fourteen endurance-trained males participated in five experimental sessions. After familiarization and measuring peak power output in hypoxia, in the first and second sessions, through the 3rd to 5th sessions, participants performed a cycling endurance task until exhaustion after 30 min hypoxic exposure at resting position followed by 20 min of anodal stimulation of the motor cortex (M1), left dorsolateral prefrontal cortex (DLPFC), or sham-tDCS. Color-word Stroop test and choice reaction time were measured at baseline and after exhaustion. Time to exhaustion, heart rate, saturated O2, EMG amplitude of the vastus lateralis, vastus medialis, and rectus femoris muscles, RPE, affective response, and felt arousal were also measured during the task under hypoxia. RESULTS: The results showed a longer time to exhaustion (+ 30.96%, p=0.036), lower RPE (- 10.23%, p = 0.045) and higher EMG amplitude of the vastus medialis muscle (+ 37.24%, p=0.003), affective response (+ 260%, p=0.035) and felt arousal (+ 28.9%, p=0.029) in the DLPFC tDCS compared to sham. The choice reaction time was shorter in DLPFC tDCS compared to sham (- 17.55%, p=0.029), and no differences were seen in the color-word Stroop test among the conditions under hypoxia. M1 tDCS resulted in no significant effect for any outcome measure. CONCLUSIONS: We concluded that, as a novel finding, anodal stimulation of the left DLPFC might provide an ergogenic aid for endurance performance and cognitive function under the hypoxic condition probably via increasing neural drive to the working muscles, lowering RPE, and increasing perceptual responses.

Sensitive hydrazine detection and quantification with a fluorescent benzothiadiazole sensor: selective lipid droplets and in vivo imaging.

In this work, we describe the design, synthesis, characterization, photophysical evaluation, DFT calculations, and application of two novel fluorescent benzothiadiazole (BTD) sensors for hydrazine detection and quantification at the cellular and multicellular (in vivo) levels. The two probes were fully characterized, and their photophysical properties were evaluated. We tested the designed fluorogenic dye (named BTD-CHO) as a selective sensor for the rapid, sensitive, and selective detection of hydrazine. When treated with N2H4, the probe affords a new derivative named BTD-HZN, releasing water as the only byproduct. BTD-CHO exhibited a preference for lipid droplets (LDs) and accumulated inside these organelles. Hydrazine detection in LDs could be carried out by the in situ formation of BTD-HZN inside live cells. We efficiently visualized the lipids of a challenging cellular model, microalgae (Chlorella sorokiniana), using these sensors. In vivo experiments indicated rapid and efficient detection of the analyte using C. elegans and zebrafish (Danio rerio) as the multicellular models.

Effect of tDCS targeting the M1 or left DLPFC on physical performance, psychophysiological responses, and cognitive function in repeated all-out cycling: a randomized controlled trial.

BACKGROUND: Despite reporting the positive effects of transcranial direct current stimulation (tDCS) on endurance performance, very few studies have investigated its efficacy in anaerobic short all-out activities. Moreover, there is still no consensus on which brain areas could provide the most favorable effects on different performance modalities. Accordingly, this study aimed to investigate the effects of anodal tDCS (a-tDCS) targeting the primary motor cortex (M1) or left dorsolateral prefrontal cortex (DLPFC) on physical performance, psychophysiological responses, and cognitive function in repeated all-out cycling. METHODS: In this randomized, crossover, and double-blind study, 15 healthy physically active men underwent a-tDCS targeting M1 or the left DLPFC or sham tDCS in separate days before performing three bouts of all-out 30s cycling anaerobic test. a-tDCS was applied using 2 mA for 20 min. Peak power, mean power, fatigue index, and EMG of the quadriceps muscles were measured during each bout. Heart rate, perceived exertion, affective valence, and arousal were recorded two minutes after each bout. Color-word Stroop test and choice reaction time were measured at baseline and after the whole anaerobic test. RESULTS: Neither tDCS montage significantly changed peak power, mean power, fatigue index, heart rate, affective valence, arousal, and choice reaction time (p> 0.05). a-tDCS over DLPFC significantly lowered RPE of the first bout (compared to sham; p=0.048, Δ=-12.5%) and third bout compared to the M1 (p=0.047, Δ=-12.38%) and sham (p=0.003, Δ=-10.5%), increased EMG of the Vastus Lateralis muscle during the second (p=0.016, Δ= +40.3%) and third bout (p=0.016, Δ= +42.1%) compared to sham, and improved the score of color-word Stroop test after the repeated all-out task (p=0.04, Δ= +147%). The qualitative affective response (valence and arousal) was also higher under the M1 and DLPFC compared to the sham. CONCLUSION: We concluded that tDCS targeting M1 or DLPFC does not improve repeated anaerobic performance. However, the positive effect of DLPFC montage on RPE, EMG, qualitative affective responses, and cognitive function is promising and paves the path for future research using different tDCS montages to see any possible effects on anaerobic performance. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Razi University (IR.RAZI.REC.1400.023) and registered in the Iranian Registry of Clinical Trials (IRCT id: IRCT20210617051606N5; Registration Date: 04/02/2022).

The effect of tyrosine supplementation on whole-body endurance performance in physically active population: A systematic review and meta-analysis including GRADE qualification.

Although tyrosine supplementation is well recognized to improve cognitive function, its impact on endurance performance is debatable and needs to be clarified further. The purpose of this systematic review and meta-analysis was to evaluate the effects of tyrosine supplementation on whole-body endurance performance in physically active population. The search strategy follow the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), using four databases (Cochrane Library, Web of Science, Scopus, PsycINFO, and PubMed) until 3 August 2023. The effect of tyrosine (experimental condition) was compared against placebo (control condition). The methodological quality of the included studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE Pro software) System was also used to assess the quality of evidence. A total of 10 interventions from 8 studies were included. The sub-group analysis revealed no significant differences between tyrosine and placebo conditions for time to exhaustion (SMD = 0.02; p = 0.94) and time trial performance (SMD = -0.04; p = 0.85). The level of evidence as qualified with GRADE was moderate. In conclusion, moderate-quality evidence suggests that tyrosine supplementation is ineffective on endurance performance in the physically active population, independently of the endurance task (TTE or ETT).

Lessons from the invasion front: Integration of research and management of the lionfish invasion in Brazil.

After successful invasions in the Caribbean and Mediterranean, lionfish (Pterois spp.) have recently invaded another important biogeographical region -the Brazilian Province. In this article, we discuss this new invasion, focusing on a roadmap for urgent mitigation of the problem, as well as focused research and management strategies. The invasion in Brazil is already in the consolidation stage, with 352 individuals recorded so far (2020-2023) along 2766 km of coastline. This includes both juveniles and adults, including egg-bearing females, ranging in length from 9.1 to 38.5 cm. Until now, most of the records in the Brazilian coast occurred in the equatorial southwestern Atlantic (99%), mainly on the Amazon mesophotic reefs (15% of the records), northeastern coast of Brazil (45%), and the Fernando de Noronha Archipelago (41%; an UNESCO World Heritage Site with high endemism rate). These records cover a broad depth range (1-110 m depth), twelve protected areas, eight Brazilian states (Amapá, Pará, Maranhão, Piauí, Ceará, Rio Grande do Norte, Paraíba, and Pernambuco) and multiple habitats (i.e., mangrove estuaries, shallow-water and mesophotic reefs, seagrass beds, artificial reefs, and sandbanks), indicating a rapid and successful invasion process in Brazilian waters. In addition, the lack of local knowledge of rare and/or cryptic native species that are potentially vulnerable to lionfish predation raises concerns regarding the potential overlooked ecological impacts. Thus, we call for an urgent integrated approach with multiple stakeholders and solution-based ecological research, real-time inventories, update of environmental and fishery legislation, participatory monitoring supported by citizen science, and a national and unified plan aimed at decreasing the impact of lionfish invasion. The experience acquired by understanding the invasion process in the Caribbean and Mediterranean will help to establish and prioritize goals for Brazil.

(Ro)vibrational Spectroscopic Constants, Lifetime and QTAIM Evaluation of Fullerene Dimers Stability.

The iconic caged shape of fullerenes gives rise to a series of unique chemical and physical properties; hence a deeper understanding of the attractive and repulsive forces between two buckyballs can bring detrimental information about the structural stability of such complexes, providing significant data applicable for several studies. The potential energy curves for the interaction of multiple van der Waals buckyball complexes with increasing mass were theoretically obtained within the DFT framework at ωB97xD/6-31G(d) compound model. These potential energy curves were employed to estimate the spectroscopic constants and the lifetime of the fullerene complexes with the Discrete Variable Representation and with the Dunham approaches. It was revealed that both methods are compatible in determining the rovibrational structure of the dimers and that they are genuinely stable, i.e., long-lived complexes. To further inquire into the nature of such interaction, Bader's QTAIM approach was applied. QTAIM descriptors indicate that the interactions of these closed-shell systems are dominated by weak van der Waals forces. This non-covalent interaction character was confirmed by the RDG analysis scheme. Indirectly, QTAIM also allowed us to confirm the stability of the non-covalent bonded fullerene dimers. Our lifetime calculations have shown that the studied dimers are stable for more than 1 ps, which increases accordingly with the number of carbon atoms.

Transcranial direct current stimulation during a prolonged cognitive task: the effect on cognitive and shooting performances in professional female basketball players.

The negative effect of prolonged cognitive demands on psychomotor skills in athletes has been demonstrated. Transcranial direct current stimulation (tDCS) could be used to mitigate this effect. This study examined the effects of tDCS over the left dorsolateral prefrontal cortex (DLPFC) during a 30-min inhibitory Stroop task on cognitive and shooting performances of professional female basketball players. Following a randomised, double-blinded, sham-controlled, cross-over design, players were assigned to receive anodal tDCS (a-tDCS, 2 mA for 20 min) or sham-tDCS in two different sessions. Data from 8 players were retained for analysis. Response Time decreased significantly over time (p < 0.001; partial η2 = 0.44; no effect of condition, or condition vs. time interaction). No difference in mean accuracy and shooting performance was observed between tDCS conditions. The results suggest that a-tDCS exert no additional benefits in reducing the negative effects of prolonged cognitive demands on technical performance compared to sham (placebo).Practitioner summary: Prolonged cognitive demands can negatively affect the athletes' performance. We tested whether transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) could attenuate these effects on cognitive and shooting performance in professional female basketball players. However, tDCS did not exert any additional benefits compared to sham.Abbreviations: tDCS: transcranial direct current stimulation; a-tDCS: anodal transcranial direct current stimulation; PFC: prefrontal cortex; DLPFC: dorsolateral prefrontal cortex; PCT: prolonged cognitive task; TT: time trial; RT: response time; NASA-TLX: National Aeronautics and Space Administration Task Load Index; RPE: ratings of perceived exertion; CR-10 scale: category rating scale; EEG: electroencephalogram; AU: arbitrary units.

Metabolic memory underlying minimal residual disease in breast cancer.

Tumor relapse from treatment-resistant cells (minimal residual disease, MRD) underlies most breast cancer-related deaths. Yet, the molecular characteristics defining their malignancy have largely remained elusive. Here, we integrated multi-omics data from a tractable organoid system with a metabolic modeling approach to uncover the metabolic and regulatory idiosyncrasies of the MRD. We find that the resistant cells, despite their non-proliferative phenotype and the absence of oncogenic signaling, feature increased glycolysis and activity of certain urea cycle enzyme reminiscent of the tumor. This metabolic distinctiveness was also evident in a mouse model and in transcriptomic data from patients following neo-adjuvant therapy. We further identified a marked similarity in DNA methylation profiles between tumor and residual cells. Taken together, our data reveal a metabolic and epigenetic memory of the treatment-resistant cells. We further demonstrate that the memorized elevated glycolysis in MRD is crucial for their survival and can be targeted using a small-molecule inhibitor without impacting normal cells. The metabolic aberrances of MRD thus offer new therapeutic opportunities for post-treatment care to prevent breast tumor recurrence.

Theoretical Model of Polarization Effects on Third-Order NLO Properties of the Stilbazolium Derivative Crystal.

The linear and nonlinear properties of the stilbazolium derivative, 2-[2-(3-hydroxy-4-methoxy-phenyl)-vinyl]-1-methyl-pyridinium naphthalene-2-sulfonate dihydrate crystal (VSNS), were investigated using an iterative electrostatic embedding scheme and density functional theory (DFT). The dipole moment and second hyperpolarizability of the VSNS molecule are sharply influenced by its crystalline phase. Standard DFT global hybrids such as B3LYP and M06 are strongly benefited by the effects of crystalline polarization. The performance can be further improved by making small changes in the amount of Hartree-Fock exchange included in the hybrid, delivering good hyperpolarizability and spectroscopy.

Harnessing Greenhouse Gases Absorption by Doped Fullerenes with Externally Oriented Electric Field.

In this work, a theoretical investigation of the effects caused by the doping of C20 with silicon (Si) atom as well as the adsorption of CO, CO2 and N2 gases to C20 and C19Si fullerenes was carried out. In concordance with previous studies, it was found that the choice of the doping site can control the structural, electronic, and energetic characteristics of the C19Si system. The ability of C20 and C19Si to adsorb CO, CO2 and N2 gas molecules was evaluated. In order to modulate the process of adsorption of these chemical species to C19Si, an externally oriented electric field was included in the theoretical calculations. It was observed that C19Si is highly selective with respect to CO adsorption. Upon the increase of the electric field intensity the adsorption energy was magnified correspondingly and that the interaction between CO and C19Si changes in nature from a physical adsorption to a partial covalent character interaction.

Positive Implicit Associations for Physical Activity Predict Physical Activity and Affective Responses During Exercise.

The purpose of this study was to investigate the relationships of implicit associations and explicit evaluations with affective responses during an aerobic exercise session, physical activity, and sedentary behavior in adults. Fifty adults (70% women; median age = 31 years; 25th, 75th percentiles: 24.50, 40.50 years old; body mass index = 25.29 ± 4.97 kg/m2) not engaged in regular physical activity completed an implicit association test and a questionnaire of explicit evaluations and wore an accelerometer for 7 days. After the 7-day period, the participants performed 30 min of moderate-intensity aerobic exercise. Every 5 min, the affective response and the perception of effort were recorded. Participants who had more positive implicit associations toward physical activity (vs. sedentary behavior) reported higher affective responses during exercise and engaged in more moderate to vigorous physical activity. Encouraging pleasant physical activity may act to partially improve future physical activity through automatic motivational processes.

Transcranial Stimulation Improves Volume and Perceived Exertion but does not Change Power.

This study aimed to analyze the acute effect of anodal transcranial direct current stimulation (a-tDCS) over the primary motor cortex (M1) on the volume, perceived exertion, and neuromuscular performance measurements in trained and untrained adults. Twenty-four male adults (12 trained and 12 untrained) participated in this single-blind, randomized, and sham-controlled study. The participants performed three back squat repetitions using the 15RM load with maximal concentric velocity to assess neuromuscular performance before tDCS and 30-min after resistance exercise. Next, they were randomly assigned to a-tDCS over M1 or the sham condition. Participants performed ten sets of parallel back squat with 15RM load and repetitions sustained to momentary muscular failure. The total number of repetitions was higher (p<0.05) and perceived exertion was lower (p<0.05) after a-tDCS in both groups. Peak power, velocity, and force decreased in both groups after the RE session (p<0.05), but with a higher rate in untrained individuals (p<0.05). No significant effect was found for peak power, peak velocity, and peak force (p>0.05). This study suggests that using a-tDCS may improve the total volume of repetitions and perceived exertion in trained and untrained individuals.

Clotrimazole reduces endometriosis and the estrogen concentration by downregulating aromatase.

This study aimed to analyse the effects of clotrimazole (CTZ) on estrogen production pathway in endometriosis progression. Experimental endometriosis was induced by autologous transplantation in female Wistar rats, and then the rats were treated with clotrimazole (200 mg/kg) or vehicle, both orally and intraperitoneally, for 15 consecutive days. Serum estrogen levels and vaginal smear analyses were performed and ERα (estrogen receptor alpha) and CYP19 (cytochrome P450 aromatase) levels in the endometriotic lesions were analysed morphologically and immunohistochemically. The clotrimazole group presented a reduction in serum estrogen levels, which were not influenced by the estrous cycle of the animals. The expression of ERα and CYP19 in endometriotic lesions was also reduced in the clotrimazole group compared to the control group. Moreover, clotrimazole treatment decreased the size of the lesions, as confirmed by histological examination, which showed glandular atrophy for both routes of administration. These results suggest that clotrimazole interferes with the estrogen production pathway by downregulating CYP19 and, therefore, reducing serum estrogen levels. Thus, the drug decreases endometriotic lesion size and consequently disease progression.

Deciphering the Dynamics of Organic Nanoaggregates with AIEE Effect and Excited States: Lipophilic Benzothiadiazole Derivatives as Selective Cell Imaging Probes.

An aggregation-induced emission enhancement (AIEE) effect in fluorescent lipophilic 2,1,3-benzothiadiazole (BTD) derivatives and their organic nanoaggregates were studied. A set of techniques such as single-crystal X-ray, dynamic light scattering (DLS), electron paramagnetic resonance (EPR), UV-vis, fluorescence, and density functional theory (DFT) calculations have been used to decipher the formation/break (kinetics), properties, and dynamics of the organic nanoaggregates of three BTD small organic molecules. An in-depth study of the excited-state also revealed the preferential relaxation emissive pathways for the BTD derivatives and the dynamics associated with it. The results described herein, for the first time, explain the formation of fluorescent BTD nanoaggregate derivatives and allow for the understanding of their dynamics in solution as well as the ruling forces of both aggregation and break processes along with the involved equilibrium. One of the developed dyes could be used at a nanomolar concentration to selectively stain lipid droplets emitting an intense and bright fluorescence at the red channel. The other two BTDs could also stain lipid droplets at very low concentrations and were visualized preferentially at the blue channel.

Non-covalent interactions and their impact on the complexation thermodynamics of noble gases with methanol.

Accurate ab initio calculations provide the reliable information needed to study the potential energy surfaces that control the non-covalent interactions (NCIs) responsible for the formation of weak van der Waals complexes. In this work, relying on the state of the art method for NCI computations, namely symmetry adapted perturbation theory (SAPT), we calculated the potential energy curves for the interaction of noble gases (Ng = He, Ne, Ar and Kr) with methanol in three different interaction sites to account for orientational anisotropy of the interaction potential. Different levels of the SAPT and basis set were employed to disclose the nature of the stabilizing forces acting upon formation of the Ng-CH3OH adducts. SAPT-derived NCIs indicate that dispersion forces are indeed the dominating component of the total energy, but also that induction and electrostatic effects are important to counterbalance the steric repulsions. By solving the Radial Nuclear Schrödinger Equation for the complexes, we also determined the rovibrational structure of the interaction wells to extract invaluable information about the thermodynamic stability of the adducts and how different temperature conditions affect the structure of the dimers. Although SAPT calculations reveal net attractive forces, these do not afford a spontaneous complexation process even at temperatures as low as 40 K.

Fast automated reconstruction of genome-scale metabolic models for microbial species and communities.

Genome-scale metabolic models are instrumental in uncovering operating principles of cellular metabolism, for model-guided re-engineering, and unraveling cross-feeding in microbial communities. Yet, the application of genome-scale models, especially to microbial communities, is lagging behind the availability of sequenced genomes. This is largely due to the time-consuming steps of manual curation required to obtain good quality models. Here, we present an automated tool, CarveMe, for reconstruction of species and community level metabolic models. We introduce the concept of a universal model, which is manually curated and simulation ready. Starting with this universal model and annotated genome sequences, CarveMe uses a top-down approach to build single-species and community models in a fast and scalable manner. We show that CarveMe models perform closely to manually curated models in reproducing experimental phenotypes (substrate utilization and gene essentiality). Additionally, we build a collection of 74 models for human gut bacteria and test their ability to reproduce growth on a set of experimentally defined media. Finally, we create a database of 5587 bacterial models and demonstrate its potential for fast generation of microbial community models. Overall, CarveMe provides an open-source and user-friendly tool towards broadening the use of metabolic modeling in studying microbial species and communities.