New esters from the essential oil of dry flowers of elder (Sambucus nigra L.).

BACKGROUND: Elder (Sambucus nigra L.) has relevance for the food, fragrance and pharmaceutical industries. Flowers of this species emit a very pleasant scent; for processing purposes, inflorescences are either collected from the wild or harvested from a cultivated crop. The study of elderflower-derived volatiles bears both phytochemical and commercial importance. RESULTS: Three samples of dry elderflower essential oil obtained from laboratory-scale hydrodistillations were analyzed. By use of gas chromatography-mass spectrometry, synthesis and NMR studies of chromatographic fractions of a distillation water extract prepared in a semi-industrial scale steam distillation, 252 constituents of the oil were identified; 115 compounds were not previously reported as elderflower volatiles, seven of which were new natural esters. Particularly interesting were those of isosenecioic (3-methylbut-3-enoic) acid because these were never before found in the plant kingdom. CONCLUSION: With these identifications, the known essential oil constituents accounted for 89.0-93.0% of the analyzed samples. Although the number of known S. nigra flower-derived volatiles is now quite high, further research (both analytical and olfactory) is needed to unveil all of the relevant contributions to the unique odor of elderflowers. © 2023 Society of Chemical Industry.

Wax Composition of Serbian Dianthus spp. (Caryophyllaceae): Identification of New Metabolites and Chemotaxonomic Implications.

Although ethnopharmacologically renowned, wax constituents of Dianthus species were sporadically studied. A combination of GC-MS analysis, synthesis, and chemical transformations enabled the identification of 275 constituents of diethyl-ether washings of aerial parts and/or flowers of six Dianthus taxa (Dianthus carthusianorum, D. deltoides, D. giganteus subsp. banaticus, D. integer subsp. minutiflorus, D. petraeus, and D. superbus) and one Petrorhagia taxon (P. prolifera) from Serbia. Seventeen of these constituents (nonacosyl benzoate, additional 12 benzoates with anteiso-branched 1-alkanols, eicosyl tiglate, triacontane-14,16-dione, dotriacontane-14,16-dione, and tetratriacontane-16,18-dione) and two additional synthesized eicosyl esters (angelate and senecioate) represent completely new compounds. The structures of the tentatively identified ß-ketones were confirmed by analysis of the mass fragmentation of the corresponding pyrazoles and silyl enol ethers obtained by transformations of crude extracts and extract fractions. Silylation allowed the identification of 114 additional constituents, including a completely new natural product (30-methylhentriacontan-1-ol). The results obtained by multivariate statistical analyses showed that the chemical profile of Dianthus taxa's surface waxes is subject to both genetic and ecological factors, whereas the latter seemingly takes a more important role for the studied Dianthus samples.

Synthesis of Small Libraries of Natural Products: Part II: Identification of a New Natural Product from the Essential Oil of Pleurospermum austriacum (L.) Hoffm. (Apiaceae).

Herein, comprehensive data of NMR, MS, IR, and gas chromatography (RI) obtained by GC-MS on commonly used capillary columns of different polarity (non-polar DB-5MS and polar HP-Innowax) of a series of esters of all constitutional isomers of hexanoic acid with a homologous series of ω-phenylalkan-1-ols (phenylmethanol, 2-phenylethanol, 3-phenylpropan-1-ol, 4-phenylbutan-1-ol, and 5-phenylpentan-1-ol) and phenol, in total 48 chemical entities, were collected. The created synthetic library allowed the identification of a new constituent of the P. austriacum essential oil (3-phenylpropyl 2-methylpentanoate). The accumulated spectral and chromatographical data, as well as the established correlation between RI values and structures of regioisomeric hexanoates, provide (phyto)chemists with a tool that will make future identification of related natural compounds a straightforward task.

The potential of lemon balm (Melissa officinalis L.) essential oil as an anti-anxiety agent - is the citronellal the activity carrier?

ETHNOPHARMACOLOGICAL RELEVANCE: Among the fewest drugs discovered are those belonging to the class of anxiolytics. Although some drug targets for anxiety disorders are established, it is hard to modify and selectively choose the active principle for those targets. Thus, the ethnomedical approach to treating anxiety disorders remains one of the most prevalent ways for (self)managing the symptoms. Melissa officinalis L. (lemon balm) has been extensively used as an ethnomedicinal remedy for the treatment of different psyche-related symptoms, especially dose related to restlessness. AIM OF THE STUDY: This work aimed to evaluate the anxiolytic activity, in several in vivo models, of the essential oil extracted from Melissa officinalis (MO) and its main constituent citronellal, a widespread plant utilized for managing anxiety. MATERIALS AND METHODS: In the present study several animal models were used to assess MO anxiolytic potential in mice. The effect of the MO essential oil applied in doses ranging from 12.5 to 100 mg/kg was estimated in light/dark, hole board, and marble burying tests. In parallel doses of citronellal corresponding to the ones in the MO essential oil were applied to animals to determine if this is the activity carrier. RESULTS: The results indicate that the MO essential oil exerts anxiolytic potential in all three experimental settings by significantly altering the traced parameters. The effects of citronellal are somewhat inconclusive and should not be interpreted only as anxiolytic but rather as a combination of anti-anxiety and motor-inhibiting effects. CONCLUSIONS: In conclusion, we could say that the results of the present study provide a base for future mechanistic studies that would evaluate the activity of M. officinalis essential oil on various neurotransmitter systems involved in the generation, propagation, and maintenance of anxiety.

An Atomistic Model of Field-Induced Resistive Switching in Valence Change Memory.

In valence change memory (VCM) cells, the conductance of an insulating switching layer is reversibly modulated by creating and redistributing point defects under an external field. Accurately simulating the switching dynamics of these devices can be difficult due to their typically disordered atomic structures and inhomogeneous arrangements of defects. To address this, we introduce an atomistic framework for modeling VCM cells. It combines a stochastic kinetic Monte Carlo approach for atomic rearrangement with a quantum transport scheme, both parametrized at the ab initio level by using inputs from density functional theory. Each of these steps operates directly on the underlying atomic structure. The model thus directly relates the energy landscape and electronic structure of the device to its switching characteristics. We apply this model to simulate field-induced nonvolatile switching between high- and low-resistance states in a TiN/HfO2/Ti/TiN stack and analyze both the kinetics and stochasticity of the conductance transitions. We also resolve the atomic nature of current flow resulting from the valence change mechanism, finding that conductive paths are formed between the undercoordinated Hf atoms neighboring oxygen vacancies. The model developed here can be applied to different material systems to evaluate their resistive switching potential, both for use as conventional memory cells and as neuromorphic computing primitives.

Assessing motivators and barriers to active healthy living among a multicultural college student body: A qualitative inquiry.

Lack of physical activity and poor eating habits have been associated with numerous negative health outcomes, including diabetes, cardiovascular disease, and obesity. Previous research demonstrated that physical activity decreases throughout young adulthood and adolescence. This was a qualitative investigation into potential barriers and motivators to healthy eating and being physically active among a diverse group of college students in a US institution in the Middle East. A total of six focus groups were conducted (N = 35) to discuss motivators and barriers to healthy eating and being physically active, perceptions, culture, and intervention ideas. Stress and time management emerged as barriers, while social supports were a motivating factor for students. Future research should investigate the unique effect of transitioning into college in the context of the Middle East. Interventions targeting factors that affect the physical activity and eating habits of young adults can help improve longer-term health outcomes.

Pulicaria dysenterica (L.) Bernh.-Rightfully Earned Name? Identification and Biological Activity of New 3-Methoxycuminyl Esters from P. dysenterica Essential Oil.

Motivated by the ethnopharmacological use of Pulicaria dysenterica, in the present study, the antimicrobial potential of the extracted essential oil was investigated against a panel of eighteen microorganism strains. Additionally, anti-acetylcholinesterase and antispasmodic (isolated rat distal colon) activities, general acute toxicity (Artemia salina model), and immunomodulatory properties (cytotoxicity on isolated mouse macrophages) were studied. Detailed analyses of the essential oil led to the identification of 3-methoxycuminyl 2-methylbutanoate (a new natural product) and 3-methoxycuminyl 3-methylbutanoate (a rare natural product). The obtained esters and intermediates in the synthesis of the starting alcohol (3-methoxycuminol) were subjected to a battery of 1D- and 2D-NMR experiments. The synthesized esters were additionally characterized by GC-MS, IR, and UV-Vis. The synthesized compounds (ten in total) were biologically tested in the same way as the extracted P. dysenterica essential oil. The obtained low acute toxicity and promising antimicrobial potential suggest that the P. dysenterica essential oil might partially explain the ethnopharmacological application of P. dysenterica plant material for the treatment of gastrointestinal infections.

An HPLC-based assay for improved measurement of glutamate decarboxylase inhibition/activation.

L-Glutamic acid decarboxylase (GAD) is an enzyme that ensures the balance between the levels of two neurotransmitters, γ-aminobutyric acid (GABA) and L-glutamic acid (L-Glu), necessary for proper brain functioning. A reduction in the concentrations of GABA and/or GAD activity has been implicated in the symptoms associated with epilepsy, which could be plausibly alleviated by the application of GAD activators. As any unnecessary interference in GAD catalytic activity could be detrimental, it is important to study whether CNS (or other) drug candidates act on GAD or not. The ability to identify and reduce this risk early could significantly improve the process of drug development. Although many methods for measuring GAD activity in various biological samples have been described, only few (such as manometric and radiometric) were adopted as in vitro assays for the screening of potential GAD inhibitors/activators. However, these methods require specialized equipment and/or an expensive radiolabeled substrate, and may have sensitivity and/or reliability issues. Therefore, this study aimed to develop an HPLC-DAD-based assay that would allow a simple and more accurate measurement of GAD inhibition or activation using unpurified mice or rat brain homogenates. This assay is based on the quantification of GABA, formed during the enzymatic reaction, after its derivatization with dansyl chloride. Various parameters were evaluated to optimize the assay procedure (e.g. homogenate volume, incubation time, DMSO content, GAD, GABA, and dansyl-GABA stabilities). This assay was validated for pharmacological screenings using 3-mercaptopropionic acid and gallic acid and GAD obtained from different experimental animals.

Interplay of Kinetic and Thermodynamic Reaction Control Explains Incorporation of Dimethylammonium Iodide into CsPbI3.

CsPbI3 is a promising material for optoelectronics owing to its thermal robustness and favorable bandgap. However, its fabrication is challenging because its photoactive phase is thermodynamically unstable at room temperature. Adding dimethylammonium (DMA) alleviates this instability and is currently understood to result in the formation of DMA x Cs1-x PbI3 perovskite solid solutions. Here, we use NMR of the 133Cs and 13C local structural probes to show that these solid solutions are not thermodynamically stable, and their synthesis under thermodynamic control leads to a segregated mixture of yellow one-dimensional DMAPbI3 phase and δ-CsPbI3. We show that mixed-cation DMA x Cs1-x PbI3 perovskite phases only form when they are kinetically trapped by rapid antisolvent-induced crystallization. We explore the energetics of DMA incorporation into CsPbI3 using first-principles calculations and molecular dynamics simulations and find that this process is energetically unfavorable. Our results provide a complete atomic-level picture of the mechanism of DMA-induced stabilization of the black perovskite phase of CsPbI3 and shed new light on this deceptively simple material.

New neryl esters from Helichrysum italicum (Roth) G. Don (Asteraceae) essential oil.

Helichrysum italicum (immortelle) is a dwarf aromatic shrub native to the Mediterranean region. The typical subspecies (italicum) produces an essential oil rich in neryl acetate and characteristic ß-diketones, italidiones, highly valued in the perfume industry. As esters are an important group of aroma-active volatiles, herein the composition of the ester fraction of this immortelle chemotype essential oil was studied in detail. Chromatographic separation of Corsican immortelle essential oil enabled the discovery of numerous potentially olfactory-interesting esters of nerol and/or angelic acid, undetectable by direct GC-MS analyses of the unfractioned oil. Four esters of nerol and medium-chain branched fatty acids represent new natural products, while several other esters have a rather restricted occurrence in the Plant Kingdom.

Lemon balm (Melissa officinalis L.) essential oil and citronellal modulate anxiety-related symptoms - In vitro and in vivo studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Besides psyche-related symptoms, patients with anxiety disorders can have a large number of somatic symptoms as well. Although the treatment of these disorders is mainly focused on resolving their mental component, one cannot neglect the need for the treatment of accompanying somatic symptoms. Melissa officinalis L. (lemon balm), in various formulations, has been extensively used as an ethnomedicinal remedy for the treatment of different psyche-related symptoms, and its use is considered relatively safe. AIM OF THE STUDY: In the present study, the activity of M. officinalis (MO) essential oil was evaluated in several in vitro and in vivo models mimicking or involving anxiety-related somatic symptoms. MATERIALS AND METHODS: To address the effect of MO essential oil on the gastrointestinal and heart-related symptoms accompanying anxiety disorders, in vitro models were utilized that follow the function of the isolated mouse ileum and atria tissues, respectively, after exposure to MO essential oil. Effects of MO essential oil on BALB/c mice motor activity was estimated using the open field, rota-rod, and horizontal wire tests. Additionally, the essential oil was assayed for its potential in inhibiting acetylcholinesterase activity. RESULTS: The performance of mice treated with 25 mg/kg of the oil showed a statistically significant decrease in the motor impairment arising from acute anxiety (open field test), while there was a prolonged latency and a reduction of the frequency of falling from a rotating rod and/or a horizontal wire (signs of muscle weakness/spasms). Concentrations of the essential oil higher than 1 µg/mL were found to inhibit both spontaneous and induced ileum contractions. Moreover, the essential oil and citronellal were found to decrease isolated mouse atria contraction frequency, as well as contraction force. However, the oil was found to be a very weak acetylcholinesterase inhibitor. CONCLUSION: The modulation of anxiety-related symptoms by the oil was found not to be mediated through the inhibition of the acetylcholinesterase, nonetheless, the mechanistic studies involving the ileum and cardiac tissues, revealed that the activity of MO and citronellal might be related to the modification of either voltage-gated Ca2+ channels or muscarinic receptors. Mice locomotion, balance, and muscle strength were not impacted by the essential oil; however, its main constituent, citronellal, was found to exert a certain degree of muscle function inhibition. All these results suggest that the activity of MO essential oil arises from synergistic and/or antagonistic interactions of its constituents, and is not completely dependent on the oil's main constituent.

Multimodal host-guest complexation for efficient and stable perovskite photovoltaics.

Formamidinium lead iodide perovskites are promising light-harvesting materials, yet stabilizing them under operating conditions without compromising optimal optoelectronic properties remains challenging. We report a multimodal host-guest complexation strategy to overcome this challenge using a crown ether, dibenzo-21-crown-7, which acts as a vehicle that assembles at the interface and delivers Cs+ ions into the interior while modulating the material. This provides a local gradient of doping at the nanoscale that assists in photoinduced charge separation while passivating surface and bulk defects, stabilizing the perovskite phase through a synergistic effect of the host, guest, and host-guest complex. The resulting solar cells show power conversion efficiencies exceeding 24% and enhanced operational stability, maintaining over 95% of their performance without encapsulation for 500 h under continuous operation. Moreover, the host contributes to binding lead ions, reducing their environmental impact. This supramolecular strategy illustrates the broad implications of host-guest chemistry in photovoltaics.

Nanoscale Phase Segregation in Supramolecular π-Templating for Hybrid Perovskite Photovoltaics from NMR Crystallography.

The use of layered perovskites is an important strategy to improve the stability of hybrid perovskite materials and their optoelectronic devices. However, tailoring their properties requires accurate structure determination at the atomic scale, which is a challenge for conventional diffraction-based techniques. We demonstrate the use of nuclear magnetic resonance (NMR) crystallography in determining the structure of layered hybrid perovskites for a mixed-spacer model composed of 2-phenylethylammonium (PEA+) and 2-(perfluorophenyl)ethylammonium (FEA+) moieties, revealing nanoscale phase segregation. Moreover, we illustrate the application of this structure in perovskite solar cells with power conversion efficiencies that exceed 21%, accompanied by enhanced operational stability.

Immunomodulatory Constituents of Conocephalum conicum (Snake Liverwort) and the Relationship of Isolepidozenes to Germacranes and Humulanes.

Structural elucidation of three new sesquiterpenoids, namely, (1Z,4E)-lepidoza-1(10),4-dien-14-ol (1), rel-(1(10)Z,4S,5E,7R)-germacra-1(10),6 diene-11,14-diol (2), and rel-(1(10)Z,4S,5E,7R)-humula-1(10),5-diene-7,14-diol (3), isolated from the liverwort Conocephalum conicum, was accomplished by a combination of extensive NMR experiments, 1H NMR simulation, and other means. Additionally, the change of the identity of bicyclogermacren-14-al, previously reported as a C. conicum constituent, to isolepidozen-14-al is proposed. Compounds 2 and 3 appear to be related to 1 via hydration involving a shared intermediate, a substituted cyclopropylmethyl cation, formed by a highly regio- and stereoselective protonation of 1, followed by a stereospecific fission of the three-membered ring. In other words, an isolepidozene derivative might be a branchpoint to humulanes and germacranes; this transformation could be of, up to now, unknown, biosynthetic and/or synthetic relevance. Multivariate statistical analysis of the compositional data of C. conicum extract constituents was used to probe the hypothesized biochemical relations. The immunomodulatory effect of 1-3 and conocephalenol (4) was evaluated in an in vitro model on both nonstimulated and mitogen-stimulated rat splenocytes. The compounds displayed varying degrees of cytotoxicity to nonstimulated splenocytes, whereas 2 and 3 were found to exert immunosuppressive effects on concanavalin A-stimulated splenocytes while not being cytotoxic at the same concentrations.

Crown Ether Modulation Enables over 23% Efficient Formamidinium-Based Perovskite Solar Cells.

The use of molecular modulators to reduce the defect density at the surface and grain boundaries of perovskite materials has been demonstrated to be an effective approach to enhance the photovoltaic performance and device stability of perovskite solar cells. Herein, we employ crown ethers to modulate perovskite films, affording passivation of undercoordinated surface defects. This interaction has been elucidated by solid-state nuclear magnetic resonance and density functional theory calculations. The crown ether hosts induce the formation of host-guest complexes on the surface of the perovskite films, which reduces the concentration of surface electronic defects and suppresses nonradiative recombination by 40%, while minimizing moisture permeation. As a result, we achieved substantially improved photovoltaic performance with power conversion efficiencies exceeding 23%, accompanied by enhanced stability under ambient and operational conditions. This work opens a new avenue to improve the performance and stability of perovskite-based optoelectronic devices through supramolecular chemistry.

Why choosing the right partner is important: stabilization of ternary CsyGUAxFA(1-y-x)PbI3 perovskites.

Lead halide perovskites with mixtures of monovalent cations have attracted wide attention due to the possibility of preferentially stabilizing the perovskite phase with respect to photovoltaically less suitable competing phases. Here, we present a theoretical analysis and interpretation of the phase stability of binary (CH6N3)x[HC(NH2)2](1-x)PbI3 = GUAxFA(1-x)PbI3 and ternary CsyGUAxFA(1-y-x)PbI3 mixtures. We first estimate if such mixtures are stable and if they lead to a stabilization of the perovskite phase based on static Density Functional Theory (DFT) calculations. In order to investigate the finite temperature stability of the phases, we also employ first-principles molecular dynamics (MD) simulations. It turns out that in contrast to the FA+-rich case of FA/Cs mixtures, although mixing of FA/GUA is possible, it is not sufficient to stabilize the perovskite phase at room temperature. In contrast, stable ternary mixtures that contain 17% of Cs+ can be formed that lead to a preferential stabilization of the perovskite phase. In such a way, the enthalpic destabilization due to the introduction of a too large/too small cation that lies outside the Goldschmidt tolerance range can be (partially) compensated through the introduction of a third cation with complementary size. This allows to suggest a new design principle for the preparation of stable perovskite structures at room temperature with cations that lie outside the Goldschmidt range through mixtures with size-complementary cations in such a way that the effective average cation radius of the mixture lies within the stability range.

A new longipinane ketone from Achillea abrotanoides (Vis.) Vis.: chemical transformation of the essential oil enables the identification of a minor constituent.

INTRODUCTION: Minor plant constituents are difficult to identify due to the challenging isolation and acquiring of reliable spectral data. Essential oils abound in such minor constituents that might be of high importance for their (e.g. olfactory) properties. The presence of new minor constituents is usually inferred from gas chromatography mass spectrometry (GC-MS) analyses that provide only a mass spectrum and retention data, which are insufficient to allow a positive identification. OBJECTIVE: To identify a minor unknown constituent of the essential oil of Achillea abrotanoides (Vis.) Vis. (Asteraceae). METHODOLOGY: The application of chemical transformations (oxidation and reduction) performed directly on crude essential-oil samples, followed by preparative chromatography and detailed spectral analysis, to identify a new longipinane ketone from the mentioned sample. RESULTS: GC-MS analyses of the essential oil revealed, among other constituents, the presence of a known rare longipinane alcohol (α-longipinen-7ß-ol) representing 2.5% of the total GC-peak areas, and a related unidentified oxygenated sesquiterpene (3.8%). Interpretation of their mass spectra led to an assumption that the unidentified one could represent α-longipinen-7-one. Oxidation of the entire essential-oil sample by pyridinium chlorochromate confirmed the assumed relationship among the compounds and gave a simplified enriched mixture containing the ketone (ca. 16%). A straightforward chromatographic separation of the ketone was followed by corroboration of its structure by nuclear magnetic resonance (NMR) (one- and two-dimensional), infrared (IR) and MS. CONCLUSIONS: The complementing use of chemical transformations of crude essential oils, chromatographic separations, and detailed spectral analysis could have a more general application in the identification of new natural products.

Guanine-Stabilized Formamidinium Lead Iodide Perovskites.

Formamidinium (FA) lead iodide perovskite materials feature promising photovoltaic performances and superior thermal stabilities. However, conversion of the perovskite α-FAPbI3 phase to the thermodynamically stable yet photovoltaically inactive δ-FAPbI3 phase compromises the photovoltaic performance. A strategy is presented to address this challenge by using low-dimensional hybrid perovskite materials comprising guaninium (G) organic spacer layers that act as stabilizers of the three-dimensional α-FAPbI3 phase. The underlying mode of interaction at the atomic level is unraveled by means of solid-state nuclear magnetic resonance spectroscopy, X-ray crystallography, transmission electron microscopy, molecular dynamics simulations, and DFT calculations. Low-dimensional-phase-containing hybrid FAPbI3 perovskite solar cells are obtained with improved performance and enhanced long-term stability.

Atomic-Level Microstructure of Efficient Formamidinium-Based Perovskite Solar Cells Stabilized by 5-Ammonium Valeric Acid Iodide Revealed by Multinuclear and Two-Dimensional Solid-State NMR.

Chemical doping of inorganic-organic hybrid perovskites is an effective way of improving the performance and operational stability of perovskite solar cells (PSCs). Here we use 5-ammonium valeric acid iodide (AVAI) to chemically stabilize the structure of α-FAPbI3. Using solid-state MAS NMR, we demonstrate the atomic-level interaction between the molecular modulator and the perovskite lattice and propose a structural model of the stabilized three-dimensional structure, further aided by density functional theory (DFT) calculations. We find that one-step deposition of the perovskite in the presence of AVAI produces highly crystalline films with large, micrometer-sized grains and enhanced charge-carrier lifetimes, as probed by transient absorption spectroscopy. As a result, we achieve greatly enhanced solar cell performance for the optimized AVA-based devices with a maximum power conversion efficiency (PCE) of 18.94%. The devices retain 90% of the initial efficiency after 300 h under continuous white light illumination and maximum-power point-tracking measurement.

Toxic essential oils, part VI: Acute oral toxicity of lemon balm (Melissa officinalis L.) essential oil in BALB/c mice.

Despite being renowned for its volatiles, the data on the toxicity of the essential oil of lemon balm (Melissa officinalis L., Lamiaceae) is rather limited compared to its solvent/water-soluble extractibles. In this study, the aerial parts essential oil of M. officinalis, with over 130 constituents identified herein, 26 of which detected for the first time, was investigated for acute oral toxicity in BALB/c mice. The oil, composed of predominantly monoterpene aldehydes, citronellal (21.2-21.8%), neral (17.8-18.4%), and geranial (22.9-23.5%), which were assayed in parallel with the oil in some tests, induced significant changes in animal behavior, as well as altered biochemical parameters reflecting liver and kidney functions. Different pathological changes in the stomach, duodenum, liver, and kidneys were detected when the oil was administered in doses higher than 1 g kg-1. A depletion in the liver/kidney antioxidant capacities and an increased rate of lipid peroxidation was noted for animals treated with lemon balm oil. The calculated value of the oral LD50 in BALB/c mice (2.57 g kg-1) infers that the essential oil is only moderately toxic.