A Comparison between Bulgarian Tanacetum parthenium Essential Oil from Two Different Locations.

Tanacetum parthenium L. (Asteraceae) is a perennial herbaceous plant with a long-standing historical use in traditional medicine. Recently Tanacetum parthenium L. essential oil has been associated with a promising potential for future applications in the pharmaceutical industry, in the cosmetics industry, and in agriculture. Investigations on the essential oil (EO) have indicated antimicrobial, antioxidant, and repellent activity. The present study aimed to evaluate the chemical composition of Bulgarian T. parthenium essential oil from two different regions, to compare the results to those reported previously in the literature, and to point out some of its future applications. The essential oils of the air-dried flowering aerial parts were obtained by hydrodistillation using a Clevenger-type apparatus. The chemical composition was evaluated using gas chromatography with mass spectrometry (GC-MS). It was established that the oxygenated monoterpenes were the predominant terpene class, followed by the monoterpene hydrocarbons. Significant qualitative and quantitative differences between both samples were revealed. Camphor (50.90%), camphene (16.12%), and bornyl acetate (6.05%) were the major constituents in the feverfew EO from the western Rhodope Mountains, while in the EO from the central Balkan mountains camphor (45.54%), trans-chrysanthenyl acetate (13.87%), and camphene (13.03%) were the most abundant components.

The Odorant Receptor Recognizing Camphor in a Camphor Tree Specialist Orthaga achatina (Lepidoptera: Pyralidae).

Camphor has been used as an effective repellent and pesticide to stored products for a long history, but Orthaga achatina (Lepidoptera: Pyralidae) has evolved to specifically feed on the camphor tree Cinnamomum camphora. However, the behavioral response of O. achatina to camphor and the molecular basis of camphor perception are totally unknown. Here, we demonstrated that both male and female adults were behaviorally attracted to camphor, suggesting the adaptation of O. achatina to and utilization of camphor as a signal of C. camphora. Second, in 40 O. achatina OR genes obtained by analyzing antenna transcriptomes, only OachOR16/Orco significantly responded to camphor in the Xenopus oocyte system. Finally, by molecular docking analysis and site-directed mutagenesis, the Ser209 residue is confirmed to be essential for binding of the oachOR16 with camphor. This study not only reveals the camphor-based host plant choice and olfactory mechanisms of O. achatina but also provides a molecular target for screening more potential insect repellents.

In-silico molecular modelling studies of some camphor imine based compounds as anti-influenza A (H1N1) pdm09 virus agents.

The advent of influenza A (H1N1) drug-resistant strains led to the search quest for more potent inhibitors of the influenza A virus, especially in this devastating COVID-19 pandemic era. Hence, the present research utilized some molecular modelling strategies to unveil new camphor imine-based compounds as anti-influenza A (H1N1) pdm09 agents. The 2D-QSAR results revealed GFA-MLR (R2train = 0.9158, Q2=0.8475) and GFA-ANN (R2train = 0.9264, Q2=0.9238) models for the anti-influenza A (H1N1) pdm09 activity prediction which have passed the QSAR model acceptability thresholds. The results from the 3D-QSAR studies also revealed CoMFA (R2train =0.977, Q2=0.509) and CoMSIA_S (R2train =0.976, Q2=0.527) models for activity predictions. Based on the notable information derived from the 2D-QSAR, 3D-QSAR, and docking analysis, ten (10) new camphor imine-based compounds (22a-22j) were designed using the most active compound 22 as the template. Furthermore, the high predicted activity and binding scores of compound 22j were further justified by the high reactive sites shown in the electrostatic potential maps and other quantum chemical calculations. The MD simulation of 22j in the active site of the influenza hemagglutinin (HA) receptor confirmed the dynamic stability of the complex. Moreover, the appraisals of drug-likeness and ADMET properties of the proposed compounds showed zero violation of Lipinski's criteria with good pharmacokinetic profiles. Hence, the outcomes in this work recommend further in-depth in vivo and in-vitro investigations to validate these theoretical findings.Communicated by Ramaswamy H. Sarma.

Adjusting function of camphor on primary metabolism in Cinnamomum camphora stressed by high temperature.

Cinnamomum camphora has great economic value for its wide utilization in traditional medicine and furniture material, and releases lots of monoterpenes to tolerate high temperature. To uncover the adjusting function of monoterpenes on primary metabolism and promoting their utilization as anti-high temperature agents, the photosynthetic capacities, primary metabolite levels, cell ultrastructure and associated gene expression were surveyed in C. camphora when it was blocked monoterpene biosynthesis with fosmidomycin (Fos) and fumigated with camphor (a typical monoterpene in the plant) under high temperature (Fos+38 °C+camphor). Compared with the control (28 °C), high temperature at 38 °C decreased the starch content and starch grain size, and increased the fructose, glucose, sucrose and soluble sugar content. Meanwhile, high temperature also raised the lipid content, with the increase of lipid droplet size and numbers. These variations were further intensified in Fos+ 38 °C treatment. Compared with Fos+ 38 °C treatment, Fos+ 38 °C+camphor treatment improved the starch accumulation by promoting 4 gene expression in starch biosynthesis, and lowered the sugar content by suppressing 3 gene expression in pentose phosphate pathway and promoting 15 gene expression in glycolysis and tricarboxylic acid cycle. Meanwhile, Fos+ 38 °C+camphor treatment also lowered the lipid content, which may be caused by the down-regulation of 2 genes in fatty acid formation and up-regulation of 4 genes in fatty acid decomposition. Although Fos+ 38 °C+camphor treatment improved the photosynthetic capacities in contrast to Fos+ 38 °C treatment, it cannot explain the variations of these primary metabolite levels. Therefore, camphor should adjust related gene expression to maintain the primary metabolism in C. camphora tolerating high temperature.

The impact of chitosan in experimental resin with different photoinitiator systems.

OBJECTIVE: to investigate the effect of different concentrations of chitosan added to experimental resins containing either BAPO or camphorquinone (CQ) as photoinitiators, regarding degree of conversion (DC), flexural strength (FS), flexural elastic modulus (E), Knoop microhardness (KHN), cytotoxicity, genotoxicity and antimicrobial activity. METHODS: Experimental resins with polymeric matrix of BisGMA and TEGDMA was added either 0.5 wt% BAPO or 0.5 wt% camphorquinone/0.2% amine along with and chitosan concentrations of 0.5%; 1.0% or 2.0%. Degree of conversion was measured using Fourier transformed infrared spectroscopy. Flexural strength and elastic modulus were obtained through three-point bending test and Knoop microhardness was measured in a microidenter. Direct cytotoxicity was performed in human keratinocytes and genotoxicity test was done in murine macrophages cells. Antimicrobial activity was acessed against Staphylococcus aureus and Streptococcus mutans through the inhibition halo. Data were analyzed using two-way ANOVA and Tukey teste (α = 0.05). RESULTS: The materials containing photoinitiator BAPO showed higher values of DC, FS, E, and KHN compared to resins with CQ. The addition of chitosan did not affect the properties of these materials. However, in resins containing CQ, the addition of chitosan improve these properties compared to control group. For the groups containing BAPO the chitosan reduced cytotoxicity and genotoxicity compared to materials with camphorquinone. The materials with 1.0% and 2.0% chitosan showed increased antibacterial activity in the materials containing BAPO as photoinitiator for both bacteria. SIGNIFICANCE: The alternative photoinitiator BAPO and chitosan can improve physical and biological properties of photoactivated resins when compared with the materials with photoinitiator camphorquinone.

Isolation and characterization of gut bacteria associated with the degradation of host-specific terpenoids in Pagiophloeus tsushimanus (Coleoptera: Curculionidae) larvae.

Insect intestinal bacteria play an important role in resisting defensive substances of host plants. Pagiophloeus tsushimanus (Coleoptera: Curculionidae) feeds exclusively on camphor trees (Cinnamomum camphora, Laurales: Lauraceae) in China, causing substantial economic and ecological losses. It is unclear how the larvae of P. tsushimanus outcome the main secondary metabolites of C. camphora such as D-camphor, eucalyptol, and linalool. In this study, we isolated terpenoid-degrading bacteria from the gut of P. tsushimanus larvae by using selective culture medium. Maximum likelihood phylogenetic analyses were performed with 16S rDNA sequences to identify the bacteria, and results showed ten strains belonged to four genera, including Pseudomonas, Enterobacter, Serratia, and Corynebacterium. Then, gas chromatography was employed to determine the degradability of D-camphor, eucalyptol, and linalool by the isolated strains, results showed that Z5 strain (i.e., Corynebacterium variabile, Actinomycetales: Corynebacteriaceae), F1 strain (i.e., Pseudomonas aeruginosa, Pseudomonadales: Pseudomonaceae), and A3 strain (i.e., Serratia marcescens, Enterobacterales: Enterobacteriaceae) had the highest degradation rates of D-camphor, linalool, and eucalyptol, respectively. The intestinal bacteria were capable of terpenoid degradation in vitro, which suggested that these gut bacteria associated with P. tsushimanus play an important role in overcoming host plant secondary metabolite defense, thereby facilitating the host specialization of this pest.

Chemical Variation and Environmental Influence on Essential Oil of Cinnamomum camphora.

Cinnamomum camphora is a traditional aromatic plant used to produce linalool and borneol flavors in southern China; however, its leaves also contain many other unutilized essential oils. Herein, we report geographic relationships for the yield and compositional diversity of C. camphora essential oils. The essential oils of 974 individual trees from 35 populations in 13 provinces were extracted by hydrodistillation and analyzed qualitatively and quantitatively by gas chromatography-mass spectrometry and gas chromatography-flame ionization detection, respectively. Oil yields ranged from 0.01% to 3.46%, with a significantly positive correlation with latitude and a significantly negative correlation with longitude. In total, 41 compounds were identified, including 15 monoterpenoids, 24 sesquiterpenoids, and two phenylpropanoids. Essential oil compositions varied significantly among individuals and could be categorized into various chemotypes. The six main chemotypes were eucalyptol, nerolidol, camphor, linalool, selina, and mixed types. The other 17 individual plants were chemotypically rare and exhibited high levels of methyl isoeugenol, methyl eugenol, δ-selinene, or borneol. Eucalyptol-type plants had the highest average oil yield of 1.64%, followed in decreasing order by linalool-, camphor-, mixed-, selina-, and nerolidol-type plants. In addition, the five main compounds exhibited a clear geographic gradient. Eucalyptol and linalool showed a significantly positive correlation with latitude, while selina-6-en-4-ol was significantly and negatively correlated with latitude. trans-Nerolidol and selina-6-en-4-ol showed significantly positive correlations with longitude, whereas camphor was significantly and negatively correlated with longitude. Canonical correspondence analysis indicated that environmental factors could strong effect the oil yield and essential oil profile of C. camphora.

Hydroxylation Regiochemistry Is Robust to Active Site Mutations in Cytochrome P450cam (CYP101A1).

Cytochrome P450cam (CYP101A1) catalyzes the hydroxylation of d-camphor by molecular oxygen. The enzyme-catalyzed hydroxylation exhibits a high degree of regioselectivity and stereoselectivity, with a single major product, d-5-exo-hydroxycamphor, suggesting that the substrate is oriented to facilitate this specificity. In previous work, we used an elastic network model and perturbation response scanning to show that normal deformation modes of the enzyme structure are highly responsive not only to the presence of a substrate but also to the substrate orientation. This work examines the effects of mutations near the active site on substrate localization and orientation. The investigated mutations were designed to promote a change in substrate orientation and/or location that might give rise to different hydroxylation products, while maintaining the same carbon and oxygen atom balances as in the wild type (WT) enzyme. Computational experiments and parallel in vitro site-directed mutations of CYP101A1 were used to examine reaction products and enzyme activity. 1H-15N TROSY-HSQC correlation maps were used to compare the computational results with detectable perturbations in the enzyme structure and dynamics. We found that all of the mutant enzymes retained the same regio- and stereospecificity of hydroxylation as the WT enzyme, with varying degrees of efficiency, which suggests that large portions of the enzyme have been subjected to evolutionary pressure to arrive at the appropriate sequence-structure combination for efficient 5-exo hydroxylation of camphor.

Pseudo-polymorphism of a camphor α-cyclodextrin complex.

Crystalline products of vapor diffusion of an alcoholic solution of 1R,4R-camphor into an aqueous solution of α-cyclodextrin were prepared and subjected to X-ray structure analysis. Two different forms were obtained: a dimeric cavity formed by head-to-head association of cyclodextrin (phase A), and a complex set of monomeric cavities (phase B). Both contain camphor molecules orientationally disordered inside cavities. The structures are solvated by mixtures of water and ethanol. The structures significantly differ in chemical stabilities. Whilst phase A is relatively stable with respect to guest desorption, phase B rapidly reacts to change of its chemical environment manifested by cracking of crystals in solution. The phenomenon has been recorded and a short movie is included in the supplementary data.

Development and Validation of an HPLC Method for Simultaneous Determination of Capsaicinoids and Camphor in Over-the-Counter Medication for Topical Use.

A reverse-phase high-performance liquid chromatography method was developed to determine and quantify capsaicin (trans-8-methyl-N-vanillyl-6- nonenamid), dihydrocapsaicin (8-methyl-N-vanillylnonanamide), and camphor (trimethylbicyclo[2.2.1]heptan-2-one). It is applicable in analyses of over-the-counter (OTC) medications for topical use and raw materials such as chili pepper oleoresin. Chromatographic separation was carried out on a C18 column using an isocratic flow of the mobile phase containing acetonitrile and ultrapure water in a ratio of 2:3, with pH adjusted to 3.2 using glacial acetic acid, and a flow rate of 1.5 mL/min. The concentration of the eluting compounds was monitored by a diode-array detector at a wavelength of 281 nm. The method was evaluated for several validation parameters, including selectivity, accuracy (confidence intervals < 0.05%), repeatability, and intermediate precision. The limit of detection (LOD) was determined to be 0.070 µg/mL for capsaicin, 0.211 µg/mL for dihydrocapsaicin, and 0.060 µg/mL for camphor. The limit of quantification (LOQ) was determined to be 0.212 µg/mL for capsaicin, 0.640 µg/mL for dihydrocapsaicin, and 0.320 µg/mL for camphor. Linearity was set in the range of 2.5-200 µg/mL for capsaicin and dihydrocapsaicin and 25-2000 µg/mL for camphor. The suggested analytical method can be used for quality control of formulated pharmaceutical products containing capsaicinoids, camphor, and propolis.

Partial Opening of Cytochrome P450cam (CYP101A1) Is Driven by Allostery and Putidaredoxin Binding.

Cytochrome P450cam (CYP101A1) catalyzes the regio- and stereo-specific 5-exo-hydroxylation of camphor via a multistep catalytic cycle that involves two-electron transfer steps, with an absolute requirement that the second electron be donated by the ferrodoxin, putidaredoxin (Pdx). Whether P450cam, once camphor has bound to the active site and the substrate entry channel has closed, opens up upon Pdx binding, during the second electron transfer step, or it remains closed is still a matter of debate. A potential allosteric site for camphor binding has been identified and postulated to play a role in the binding of Pdx. Here, we have revisited paramagnetic NMR spectroscopy data and determined a heterogeneous ensemble of structures that explains the data, provides a complete representation of the P450cam/Pdx complex in solution, and reconciles alternative hypotheses. The allosteric camphor binding site is always present, and the conformational changes induced by camphor binding to this site facilitates Pdx binding. We also determined that the state to which Pdx binds comprises an ensemble of structures that have features of both the open and closed state. These results demonstrate that there is a finely balanced interaction between allosteric camphor binding and the binding of Pdx at high camphor concentrations.

Investigation of the relaxing effect of a camphor nanoemulsion on rat isolated trachea.

Asthma is a chronic inflammatory disease that targeting lower airways, being characterized by bronchial smooth muscle hyper responsiveness and mucus hypersecretion. Asthma is considered the most common respiratory disease in the world, affecting approximately 235 million individuals. The main therapy sometimes fails to establish clinical improvement in patients, which leads to a constant search for new alternatives. Camphor is a transparent solid monoterpene with a strong aroma, which due to its high lipophilicity is insoluble in water. Nanostructured carrier systems have shown promise as a delivery system for lipophilic compounds such as monoterpenes. Therefore, the objective of this work was to evaluate the relaxant effect of nanoemulsified camphor (NEC), as well as the mechanism of action of that monoterpene, in isolated rat trachea. The results obtained demonstrated that NEC promote relaxation of the isolated rat trachea when smooth muscle contraction was induced by both carbachol (CCh) and KCl, presenting a pCE50 of 2.25 ± 0.27 and 3.30 ± 0.07, respectively. In the presence of dexamethasone (DEXA), tetraethylammonium (TEA), glibenclamide (GLIB), 1H-[1,2,4]-oxadiazole-[4,3,-a]-quinoxaline-1-one (ODQ) and ruthenium red (RR) there was a significant difference in at least one of the evaluated pharmacological parameters, such as concentration-response curves shape, Emax or pCE50. As conclusion, NEC may be involved with ß-adrenergic receptors, channels for K+ sensitive to ATP (KATP) or Channels for K+ opened by Ca2+ (KCa), increase in prostanoids and with receptor channel with transient potential (TRPv). In conclusion, ß-adrenergic receptors, prostanoids, nitric oxide (NO), ATP-sensitive K+ channels (KATP), Ca2+-opened K+ channels (KCa), and transient receptor potential cation channel subfamily V (TRPV) are involved in the relaxing effect of NEC. In addition, the mechanism of action of NEC may be involved with the signal transduction pathway Nitric Oxide/soluble guanylyl cyclase/cGMP/cGMP-activated protein kinase. NEC, therefore, demonstrates spasmolytic activity when presenting tracheal relaxation compared to CCh and KCl contracturants.

A highly effective "turn-on" camphor-based fluorescent probe for rapid and sensitive detection and its biological imaging of Fe2.

In this work, a novel fluorescent probe CBO was synthesized for detecting Fe2+ using the natural monoterpenketone camphor as the starting material. The probe CBO displayed turn-on fluorescence to Fe2+ accompanied by the solution change from colorless to green. As expected, there was an excellent linear relationship between the fluorescence intensity of probe CBO and the concentration of Fe2+ (0-20 µM), and the detection limit was as low as 1.56×10-8 M. In particular, CBO could selectively sense Fe2+ more than other analytes (Fe3+ included) through the N-oxide strategy, and quickly responded to Fe2+ (60 s) over a wide pH (4-14) range. Additionally, based on the rapid fluorescence response of CBO to Fe2+, a simple test strip-based detector was designed for boosting practical applicability. The probe CBO had been successfully applied to the fluorescence imaging of Fe2+ in onion cells and living zebrafish. The probe CBO was a powerful tool of detecting Fe2+ level in organisms, which was of significance to understand the role of Fe2+ in Fe2+-related physical processes and diseases.

Simple Plug-In Synthetic Step for the Synthesis of (-)-Camphor from Renewable Starting Materials.

Racemic camphor and isoborneol are readily available as industrial side products, whereas (1R)-camphor is available from natural sources. Optically pure (1S)-camphor, however, is much more difficult to obtain. The synthesis of racemic camphor from α-pinene proceeds via an intermediary racemic isobornyl ester, which is then hydrolyzed and oxidized to give camphor. We reasoned that enantioselective hydrolysis of isobornyl esters would give facile access to optically pure isoborneol and camphor isomers, respectively. While screening of a set of commercial lipases and esterases in the kinetic resolution of racemic monoterpenols did not lead to the identification of any enantioselective enzymes, the cephalosporin Esterase B from Burkholderia gladioli (EstB) and Esterase C (EstC) from Rhodococcus rhodochrous showed outstanding enantioselectivity (E>100) towards the butyryl esters of isoborneol, borneol and fenchol. The enantioselectivity was higher with increasing chain length of the acyl moiety of the substrate. The kinetic resolution of isobornyl butyrate can be easily integrated into the production of camphor from α-pinene and thus allows the facile synthesis of optically pure monoterpenols from a renewable side-product.

Active Site Hydrogen Bonding Induced in Cytochrome P450cam by Effector Putidaredoxin.

Cytochrome P450s are diverse and powerful catalysts that can activate molecular oxygen to oxidize a wide variety of substrates. Catalysis relies on effective uptake of two electrons and two protons. For cytochrome P450cam, an archetypal member of the superfamily, the second electron must be supplied by the redox partner putidaredoxin (Pdx). Pdx also plays an effector role beyond electron transfer, but after decades the mechanism remains under investigation. We applied infrared spectroscopy to heme-ligated CN- to examine the influence of Pdx binding. The results indicate that Pdx induces the population of a conformation wherein the CN- ligand forms a strong hydrogen bond to a solvent water molecule, experimentally corroborating the formation of a proposed proton delivery network. Further, characterization of T252A P450cam implicates the side chain of Thr252 in regulating the population equilibrium of hydrogen-bonded states within the P450cam/Pdx complex, which could underlie its role in directing activated oxygen toward product formation and preventing reaction uncoupling through peroxide release.

Acute toxicity and ecological risk assessment of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC in ultraviolet (UV)-filters.

Ultraviolet (UV) filters are used in cosmetics, personal care products and packaging materials to provide sun protection for human skin and other substances. Little is known about these substances, but they continue to be released into the environment. The acute toxicity of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC to Chlorella vulgaris and Daphnia magna were analyzed in this study. The 96 h-EC50 values of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC on C. vulgaris were 183.60, 3.50 and 0.16874 mg/L, respectively. The 48 h-LC50 of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC on D. magna were 12.50, 3.74 and 0.54445 mg/L, respectively. The toxicity of a mixture of 4,4'-dihydroxybenzophenone and 4-MBC showed addictive effect on C. vulgaris, while the toxicity of mixtures of 4,4'-dihydroxybenzophenone and 2,4,4'-trihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC as well as 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC all showed antagonistic effect on C. vulgaris. The induced no-effect concentrations of 4,4'-dihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone and 4-MBC by the assessment factor (AF) method were 0.0125, 0.00350 and 0.000169 mg/L, respectively.

Structural basis for promiscuous action of monoterpenes on TRP channels.

Monoterpenes are major constituents of plant-derived essential oils and have long been widely used for therapeutic and cosmetic applications. The monoterpenes menthol and camphor are agonists or antagonists for several TRP channels such as TRPM8, TRPV1, TRPV3 and TRPA1. However, which regions within TRPV1 and TRPV3 confer sensitivity to monoterpenes or other synthesized chemicals such as 2-APB are unclear. In this study we identified conserved arginine and glycine residues in the linker between S4 and S5 that are related to the action of these chemicals and validated these findings in molecular dynamics simulations. The involvement of these amino acids differed between TRPV3 and TRPV1 for chemical-induced and heat-evoked activation. These findings provide the basis for characterization of physiological function and biophysical properties of ion channels.

(+)-Camphor and (-)-borneol derivatives as potential anti-orthopoxvirus agents.

Although the World Health Organisation had announced that smallpox was eradicated over 40 years ago, the disease and other related pathogenic poxviruses such as monkeypox remain potential bioterrorist weapons and could also re-emerge as natural infections. We have previously reported (+)-camphor and (-)-borneol derivatives with an antiviral activity against the vaccinia virus. This virus is similar to the variola virus (VARV), the causative agent of smallpox, but can be studied at BSL-2 facilities. In the present study, we evaluated the antiviral activity of the most potent compounds against VARV, cowpox virus, and ectromelia virus (ECTV). Among the compounds tested, 4-bromo-N'-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)benzohydrazide 18 is the most effective compound against various orthopoxviruses, including VARV, with an EC50 value of 13.9 µM and a selectivity index of 206. Also, (+)-camphor thiosemicarbazone 9 was found to be active against VARV and ECTV.

Sedative effects of l-menthol, d-camphor, phenylethyl alcohol, and geraniol.

Various essential oils from plants and fragrance components such as monoterpenes have been discovered to reduce spontaneous movements in mice; thus, it has been made clear that the odor itself has the sedative activity. In the present study, we examined the sedative activity of the odors of fragrance components added to eye drops; l-menthol, d-camphor, phenylethyl alcohol, and geraniol, which are often used as refreshers or preservatives. Each fragrance component was administered by the inhalation route to mice, and the sedative effects were evaluated using an open field test. The results showed that four components administered via inhalation to mice significantly decreased the amount of spontaneous motor activity in a dose-dependent manner, indicating that all four components have a sedative effect. The optimal concentrations at which l-menthol, d-camphor, phenylethyl alcohol, and geraniol showed the highest sedative activity were 4 × 10-2 mg per cage, 4 × 10-4 mg per cage, 4 × 10-2 mg per cage, and both 4 × 10-4 and 4 × 10-2 mg per cage, respectively. The AUC graph of geraniol was represented as a W-shaped curve, suggesting that the sedative action of geraniol was biphasic. The present finding demonstrates a new perspective on a possible pharmacological property of eye drop additives used with no expected pharmacological functions.

Self-Assembly of Supramolecular Architectures by the Effect of Amino Acid Residues of Quaternary Ammonium Pillar[5]arenes.

Novel water-soluble multifunctional pillar[5]arenes containing amide-ammonium-amino acid moiety were synthesized. The compounds demonstrated a superior ability to bind (1S)-(+)-10-camphorsulfonic acid (S-CSA) and methyl orange dye depending on the nature of the substituent, resulting in the formation one-to-one complexes with both guests. The formation of host-guest complexes was confirmed by ultraviolet (UV), circular dichroism (CD) and 1H NMR spectroscopy. This work demonstrates the first case of using S-CSA as a chiral template for the non-covalent self-assembly of architectures based on pillar[5]arenes. It was shown that pillar[5]arenes with glycine or L-alanine fragments formed aggregates with average hydrodynamic diameters (d) of 165 and 238 nm, respectively. It was established that the addition of S-CSA to the L-alanine-containing derivative led to the formation of micron-sized aggregates with d of 713 nm. This study may advance the design novel stereoselective catalysts and transmembrane amino acid channels.