Enantiomers Of Compounds Research Articles

Analysis of the Volatile and Enantiomeric Compounds Emitted by Plumeria rubra L. Flowers Using HS-SPME-GC.

The volatile components emitted by fresh aromatic flowers of Plumeria rubra L., harvested in southern Ecuador during three different months were determined to evaluate the fluctuation of secondary metabolites. The volatile compounds were analyzed using headspace solid-phase microextraction (HS-SPME) followed by gas chromatography coupled to mass spectrometry (GC-MS) and a flame ionization detector (GC-FID) using two types of columns: a non-polar (DB-5ms) and polar column (HP-INNOWax). The principal chemical groups were hydrocarbon sesquiterpenes (43.5%; 40.0%), oxygenated sesquiterpenes (23.4%; 26.4%), oxygenated monoterpenes (14.0%; 11.2%), and hydrocarbon monoterpenes (12.7%; 9.3%). The most representative constituents were (E,E)-α-Farnesene (40.9-41.2%; 38.5-50.6%), (E)-nerolidol (21.4-32.6%; 23.2-33.0%), (E)-β-ocimene (4.2-12.5%; 4.5-9.1%), (Z)-dihydro-apofarnesol (6.5-9.9%; 7.6-8.6%), linalool (5.6-8.3%; 3.3-7.8%), and perillene (3.1-5.9%; 3.0-3.2%) in DB-5ms and HP-INNOWax, respectively. Finally, we reported for the first time the enantiomeric distribution of P. rubra flowers, where the enantiomers (1R,5R)-(+)-α-pinene, (S)-(-)-limonene, (S)-(+)-Linalool, and (1S,2R,6R,7R,8R)-(+)-α-copaene were present as enantiomerically pure substances, whereas (S)-(+)-(E)-Nerolidol and (R)-(+)-(E)-Nerolidol were observed as scalemic mixtures. This study provides the first comprehensive and comparative aroma profile of Plumeria rubra cultivated in southern Ecuador and gave us a clue to the variability of P. rubra chemotypes depending on the harvesting time, which could be used for future quality control or applications in phytopharmaceutical and food industries.

Phenolic Constituents with Glucose Uptake and GLUT4 Translocation Bioactivities from the Fruits of Cordia dichotoma.

From the fruits of Cordia dichotoma, 11 new phenolic compounds, dichotomins A-K, were isolated, together with 19 known compounds. Through the analysis of detailed NMR data and HRESIMS data, the planar structures of all compounds were confirmed. Using NMR calculations, the absolute configuration of dichotomins A-K was elucidated by comparing their observed and computed electronic circular dichroism (ECD) spectra. Dichotomin H (8) and dichotomin I (9) were determined as two pairs of enantiomers. The enantiomers of compounds 8 and 9 were separated using chiral-phase high-performance liquid chromatography (HPLC), and the stereostructure of each enantiomer was determined by similarly calculating the ECD. Compounds 3, 5, 7, 17, 18, 23-25, and 27-30 increased glucose uptake by 1.04- to 2.85-folds at concentrations of 30 μg/mL. Further studies revealed that compounds 3 and 5 had a moderate effect on glucose transporter 4 (GLUT4) translocation activity in L6 cells. At 30 μg/mL, compound 3 significantly enhanced AMPK phosphorylation and GLUT4 expression. As a whole, compound 3 has the potential to be a drug candidate for the treatment of type 2 diabetes mellitus (T2DM).

Electrochemical-assisted synthesis of molecularly imprinted graphene oxide/magnetite for highly selective enantiomer separation

Enantiomeric compounds have been reported to exhibit different biological and pharmacological activities. MIP-GO/Fe3O4 has been synthesized with L-glutamic acid (L-Glu) as template molecules and developed to separate amino acids enantiomeric compounds (AAs) especially for DL-glutamic acid (DL-Glu). The MIP-GO/Fe3O4 adsorbent material was synthesized in several stages, namely electrochemically synthesizing GO, co-precipitation for GO/Fe3O4, and surface imprinting polymerization to obtain MIP-GO/Fe3O4. The characterization results of MIP-GO/Fe3O4 show that the composite system has been successfully created with saturation magnetization (Ms) values of 49.37 emu/g. Adsorption tests are carried out on the racemic mixture of DL-Glu and show that the material worked effectively and selectively to separate D- and L-Glu with a %ee value of 97.86 % and an adsorption capacity for L of 9.9 mg g−1 on optimum conditions. In addition, the adsorbent developed shows good reusability values with a decreasing performance of no more than 2.0 % after 10-time use cycles and is easily separated in less than 15 s. This research contributes to developing advanced materials with extraordinary selectivity and efficiency, paving the way for advances in enantiomer separation technology.

Psychedelic Therapy: A Primer for Primary Care Clinicians-Ketamine.

Ketamine, an arylcyclohexylamine dissociative anesthetic agent, has evolved into a versatile therapeutic. It has a rapid-onset, well-understood cardiovascular effects and a favorable safety profile in clinical use. Its enantiomeric compound, esketamine, was approved by the Food and Drug Administration in 2019 for both treatment-resistant depression and major depressive disorder with suicidal ideation. Research indicates dose-dependent impacts on cognition, particularly affecting episodic and working memory following both acute administration and chronic use, albeit temporarily for the former and potentially persistent for the latter. Alongside acute risks to cardiovascular stability, ketamine use poses potential liver toxicity concerns, especially with prolonged or repeated exposure within short time frames. The drug's association with "ketamine cystitis," characterized by bladder inflammation, adds to its profile of physiological risks. Data demonstrate a single intravenous infusion of ketamine exhibits antidepressant effects within hours (weighted effect size averages of depression scores (N = 518) following a single 0.5 mg/kg infusion of ketamine is d = 0.96 at 24 hours). Ketamine is also effective at reducing posttraumatic stress disorder (PTSD) symptom severity following repeated infusions (Clinician-Administered PTSD Scale scores: -11.88 points compared with midazolam control). Ketamine also decreased suicidal ideation in emergency settings (Scale for Suicidal Ideation scores: -4.96 compared with midazolam control). Through its opioid-sparing effect, ketamine has revolutionized postoperative pain management by reducing analgesic consumption and enhancing recovery. Many studies indicate that ketamine's therapeutic effects may subside within weeks. Repeated administrations, given multiple times per week, are often required to sustain decreases in suicidality and depressive symptoms. Ketamine's comprehensive clinical profile, combined with its robust effects on depression, suicidal ideation, PTSD, chronic pain, and other psychiatric conditions, positions it as a substantial contender for transformative therapeutic application.

Discovery and characterization of novel TRPML1 agonists

Screening a library of >100,000 compounds identified the substituted tetrazole compound 1 as a selective TRPML1 agonist. Both enantiomers of compound 1 were separated and profiled in vitro and in vivo. Their selectivity, ready availability and CNS penetration should enable them to serve as the tool compounds of choice in future TRPML1 channel activation studies. SAR studies on conformationally locked macrocyclic analogs further improved the TRPML1 agonist potency while retaining the selectivity.

Unveiling tetrahydroquinolines as promising BVDV entry inhibitors: Targeting the envelope protein

Bovine viral diarrhea virus (BVDV) is known to cause financial losses and decreased productivity in the cattle industry worldwide. Currently, there are no available antiviral treatments for effectively controlling BVDV infections in laboratories or farms. The BVDV envelope protein (E2) mediates receptor recognition on the cell surface and is required for fusion of virus and cell membranes after the endocytic uptake of the virus during the entry process. Therefore, E2 is an attractive target for the development of antiviral strategies. To identify BVDV antivirals targeting E2 function, we defined a binding site in silico located in domain IIIc at the interface between monomers in the disulfide linked dimer of E2. Employing a de novo design methodology to identify compounds with the potential to inhibit the E2 function, compound 9 emerged as a promising candidate with remarkable antiviral activity and minimal toxicity. In line with targeting of E2 function, compound 9 was found to block the virus entry into host cells. Furthermore, we demonstrated that compound 9 selectively binds to recombinant E2 in vitro. Molecular dynamics simulations (MD) allowed describing a possible interaction pattern between compound 9 and E2 and indicated that the S enantiomer of compound 9 may be responsible for the antiviral activity. Future research endeavors will focus on synthesizing enantiomerically pure compounds to further support these findings. These results highlight the usefulness of de novo design strategies to identify a novel class of BVDV inhibitors that block E2 function inhibiting virus entry into the host cell.

The Role of Functional Groups in Tuning the Self-Assembly Modes and Physical Properties of Multicomponent Gels.

We have analyzed the nature and role of functional groups on the self-assembly modes and the physical properties of multicomponent gels with structurally similar individual components. The gelation properties of individual and mixed enantiomeric compounds of biphenyl bis-(amides) of alanine (BPA) or phenylalanine (BPP) methyl ester were analyzed in various solvent/solvent mixtures. Multicomponent gels were formed by mixing the enantiomeric BPP compounds at a lower concentration, but a higher concentration was required for mixed alanine-based BPA gels. The comparison of the mechanical strength of the individual and mixed BPP compounds indicated that the mixed BPP gels displayed enhanced mechanical strength (~2-fold increase) in p-xylene, but a weaker gel was observed in DMSO/water. However, a reverse trend was observed for BPA gels, indicating the role of functional groups in the gel network formation. X-ray diffraction analysis of the gelator and the xerogels in the solid state confirmed the formation of co-assembled networks in mixed enantiomeric gels. The stability of the gels towards anions was evaluated by analyzing the anion induced stimuli-responsive properties. These results indicate the effective modeling of the functional groups of the individual components could lead to multicomponent gels with tunable properties.

Investigation of Lactone Chiral Enantiomers and Their Contribution to the Aroma of Longjing Tea by Odor Activity Value and S-Curve

Odor activity value (OAV) and S-curve were used to study the content, proportion, and contribution of lactone chiral enantiomers in Longjing tea. A total of 10 enantiomers were identified in this study, among which (S)-(-)-δ-decalactone (45.4-84.4 μg/L), (S)-(-)-γ-decalactone (31.5-109 μg/L), (S)-(-)-γ-nonanolactone (23.4-72.8 μg/L), and (S)-(-)-γ-undecalactone (21.1-56.2 μg/L) presented the highest concentrations. Furthermore, (R)-(+)-γ-nonanolactone (OAV: 2-7), (S)-(-)-γ-nonanolactone (OAV: 1-5), (S)-(-)-δ-decalactone (OAV: 2-4), (R)-(+)-δ-decalactone (OAV: 1-3), and (R)-(+)-γ-undecalactone (OAV: 1-5) were determined as enantiomeric compounds that play an important role in the perceived aroma of Longjing tea. Compared with the aromatic reconstitution (AR), the threshold increased to different degrees after adding γ-nonanolactone, γ-decalactone, δ-decalactone, γ-undecalactone, and their chiral enantiomers. This finding indicated that these compounds exert significant effects on the overall aroma of the AR. The contribution of racemates and chiral enantiomers to the AR threshold and aroma is completely different. In view of the difference between racemic and enantiomers' aroma characteristics in Longjing tea, the analysis and identification of chiral enantiomers are necessary to enrich and improve the accurate analysis of the flavor profile of Longjing tea.

Varying chiral ratio of pinic acid enantiomers above the Amazon rainforest

Abstract. Chiral chemodiversity plays a crucial role in biochemical processes such as insect and plant communication. However, the vast majority of organic aerosol studies do not distinguish between enantiomeric compounds in the particle phase. Here we report chirally specified measurements of secondary organic aerosol (SOA) at the Amazon Tall Tower Observatory (ATTO) at different altitudes during three measurement campaigns at different seasons. Analysis of filter samples by liquid chromatography coupled to mass spectrometry (LC-MS) has shown that the chiral ratio of pinic acid (C9H14O4) varies with increasing height above the canopy. A similar trend was recently observed for the gas-phase precursor α-pinene but more pronounced. Nevertheless, the measurements indicate that neither the oxidation of (+/−)-α-pinene nor the incorporation of the products into the particulate phase proceeds with stereo preference and that the chiral information of the precursor molecule is merely transferred to the low-volatility product. The observation of the weaker height gradient of the present enantiomers in the particle phase at the observation site can be explained by the significant differences in the atmospheric lifetimes of reactant and product. Therefore, it is suggested that the chiral ratio of pinic acid is mainly determined by large-scale emission processes of the two precursors, while meteorological, chemical, or physicochemical processes do not play a particular role. Characteristic emissions of the chiral aerosol precursors from different forest ecosystems, in some cases even with contributions from forest-related fauna, could thus provide large-scale information on the different contributions to biogenic secondary aerosols via the analytics of the chiral particle-bound degradation products.

Luminescence, CPL and magnetic properties of 1D enantiopure Ln3+ complexes with (S-) and (R-) α-methoxyphenylacetate ligand.

The reaction of Ln(NO3)2·6H2O (Ln = Eu, Tb, Dy and Sm) with (R)-(-)-α-methoxyphenylacetic acid (R-HMPA) and 1,10-phenanthroline (phen) in EtOH/H2O allows the isolation of 1D chiral compounds of formula [Ln(μ-R-MPA)(R-MPA)2(phen)]n in which Ln = Eu (R-Eu), Tb (R-Tb), Dy (R-Dy) and Sm (R-Sm). The same synthesis by using (S)-(+)-α-methoxyphenylacetic acid (S-HMPA) instead of (R)-(-)-α-methoxyphenylacetic acid allows the isolation of the enantiomeric compounds with formula [Ln(μ-S-MPA)(S-MPA)2(phen)]n where Ln = Eu (S-Eu), Tb (S-Tb), Dy (S-Dy) and Sm (S-Sm). Single crystal X-Ray diffraction measurements were performed for compounds R/S-Eu, R/S-Tb, S-Dy and S-Sm. The luminescence and the circular dichroism measured in the solid state are reported. All compounds show sensitized luminescence, notably the Eu3+ and Tb3+ ones, whose emission color can be perceived by the naked eye. For the Eu3+ and Tb3+ derivatives the quantum yield and the circular polarized luminescence have been measured. For the magnetic allowed transition 5D0 → 7F1 of the Eu3+ compound, the anisotropy factor glum is ±0.013 (+for S-Eu). Also, magnetic properties of all compounds were studied with the Dy3+ analogue showing slow relaxation of the magnetization under a direct current magnetic field of 1000 Oe.

Polymyxin Stereochemistry and Its Role in Antibacterial Activity and Outer Membrane Disruption.

With increasing rates of resistance toward commonly used antibiotics, especially among Gram-negative bacteria, there is renewed interested in polymyxins. Polymyxins are lipopeptide antibiotics with potent anti-Gram-negative activity and are generally believed to target lipid A, the lipopolysaccharide (LPS) anchor found in the outer membrane of Gram-negative bacteria. To characterize the stereochemical aspects of their mechanism(s) of action, we synthesized the full enantiomers of polymyxin B and the polymyxin B nonapeptide (PMBN). Both compounds were compared with the natural compounds in biological and biophysical assays, revealing strongly reduced antibacterial activity for the enantiomeric species. The enantiomeric compounds also exhibit reduced LPS binding, lower outer membrane (OM) permeabilization, and loss of synergetic potential. These findings provide new insights into the stereochemical requirements underlying the mechanisms of action of polymyxin B and PMBN.

One-stage chiral enrichment process by continuous flow electrodialysis with molecularly imprinted membrane

The purification and separation of amino acid enantiomeric compounds, such as dl-phenylalanine (dl-Phe), are attracting increasing attention in the biomedical and pharmaceutical fields. In this study, an enantioselective l-Phe molecularly imprinted membrane (l-Phe-MIM) was prepared via a surface grafting reaction. The membrane performances in the separation and enrichment of dl-Phe were investigated by using a continuous-flow electrodialysis system. The synthesis and electrodialysis parameters were optimized to obtain the maximum separation ratio. The selectivity for dl-Phe can be switched by changing the template from l-Phe to d-Phe. This suggests that the MIM is controlling the selectivity in the continuous flow electrodialysis system. The membrane prepared via a layer-by-layer process gave improved selectivity. The results show that excellent chiral separation and high stability were achieved, with a selectivity (l/d) of 2.95 ± 0.34. The results of this study offer new insights into, and perspectives on, obtaining enhanced chiral compound separation by continuous electrodialysis with a MIM in a single-pass process within ∼ 10 s.

Chiral Recognition with Broad Selective Sensor Arrays

The detection and discrimination of chiral analytes has always been a topical theme in food and pharmaceutical industries and environmental monitoring, especially when dealing with chiral drugs and pesticides, whose enantiomeric nature assessment is of crucial importance. The typical approach matches novel chiral receptors designed ad hoc for the discrimination of a target enantiomer with emerging nanotechnologies. The massive synthetic efforts requested and the difficulty of analyzing complex matrices warrant the ever-growing exploitation of sensor array as an alternative route, using a limited number of chiral or both chiral and achiral sensors for the stereoselective identification and dosing of chiral compounds. This review aims to illustrate a little-explored winning strategy in chiral sensing based on sensor arrays. This strategy mimics the functioning of natural olfactory systems that perceive some couples of enantiomeric compounds as distinctive odors (i.e., using an array of a considerable number of broad selective receptors). Thus, fundamental concepts related to the working principle of sensor arrays and the role of data analysis techniques and models have been briefly presented. After the discussion of existing examples in the literature using arrays for discriminating enantiomers and, in some cases, determining the enantiomeric excess, the remaining challenges and future directions are outlined for researchers interested in chiral sensing applications.

Aromatic Profiles and Enantiomeric Distributions of Chiral Volatile Compounds in Pu-Erh Tea.

Pu-Erh tea, as a typical post-fermented tea, can be divided into raw Pu-Erh tea (RAPT) and ripened Pu-Erh tea (RIPT) according to the processing technology. It is famous for its unique aroma after aging. Although previous research on the aroma characteristics of Pu-Erh tea mostly focused on the aroma compounds, little research on chiral compounds in RAPT and RIPT has been performed. Therefore, the current work aims to explore the aroma characteristics of Pu-Erh tea from the perspective of enantiomers of chiral compounds. A total of 15 enantiomers were determined in this study, among which (R)-(-)-2,2,6-trimethylcyclohexanone, (R)-(-)-linalool, (S)-(+)-linalool, (R)-(+)-δ-octanolactone, (R)-(+)-γ-nonanolactone, (2R,5R)-(+)-theaspirone A, and (R)-(-)-dihydroactinidiolide were identified as enantiomeric compounds that play an important role in the aroma of RAPT and RIPT. Furthermore, (2S,5R)-trans-linalool oxide and (R)-(+)-α-terpineol were important contributors to the aroma profile of RAPT, while (S)-(+)-2-methylbutanal, (S)-(-)-limonene, S-(-)-α-terpineol, and (1R,2R)-(-)-methyl jasmonate contributed to the characteristic aroma of RIPT. The addition of these enantiomeric compounds brings the aroma closer to that of the original tea sample. In addition, the analysis of chiral enantiomers of linalool, limonene, theaspirone A, and γ-nonanolactone can provide guidance for the quality and flavor control of Pu-Erh tea aroma.

Chemical Characterization and Biological Activity of the Essential Oil from Araucaria brasiliensis Collected in Ecuador.

The purpose of this study was to determine the chemical composition, physical properties, enantiomeric composition and cholinesterase inhibitory activity of the essential oil (EO) steam-distilled from the leaves of the plant Araucaria brasiliensis Loud. collected in Ecuador. The chemical composition was determined by gas chromatography coupled to mass spectrometry (GC-MS) analysis on two capillary GC columns (DB5-ms and HP-INNOWax). Thirty-three compounds were identified in the EO; the main compounds were beyerene (26.08%), kaurene (24.86%), myrcene (11.02%), α-pinene (9.99%) and 5,15-rosadiene (5.87%). Diterpene hydrocarbons (65.41%), followed by monoterpene hydrocarbons (21.11%), were the most representative components of the EO. Enantioselective analysis of the EO showed four pairs of enantiomeric compounds, α-pinene, camphene, γ-muurolene and δ-cadinene. In an in vitro assay, the EO showed moderate inhibitory activity towards the enzyme butyrylcholinesterase (BuChE) (95.7 µg/mL), while it was inactive towards acetylcholinesterase (AChE) (225.3 µg/mL). Further in vivo studies are needed to confirm the anticholinesterase potential of the EO.

Stereospecific antiseizure activity in mouse and rat epilepsy models by a pyridinium inhibitor of TNFα/NFκB signaling

Epilepsy affects over 50 million people worldwide and increases the risk of death. An intrinsic state of central inflammation, mainly driven by TNFα/NFκB signaling, may contribute to the refractory nature of some epilepsies. We have therefore hypothesized that inhibitors of this signaling pathway might be therapeutic. To test this hypothesis, we have measured the antiseizure properties of the enantiomeric compounds MRS-2481 and MRS-2485 in rodent seizure model systems. In the 6 ​Hz (44 ​mA) induced seizure test in mice, the (S) species, MRS-2485, was found to have higher protective potency and lower toxicity than the (R) species MRS-2481. However, neither of these enantiomers were protective in the MES-induced seizure test. MRS-2485 was also found to be protective in the corneal kindled mouse test. Finally, MRS-2485 reduced the post-kainate rat hippocampal slice electrical burst rate and duration. We conclude that MRS-2485, the (S)-enantiomer, is a potent inhibitor of seizure activity in mouse and rat models of epilepsy.

Dual-Functional Enantiomeric Compounds as Hole-Transporting Materials and Interfacial Layers in Perovskite Solar Cells.

In this paper, we describe the application of the enantiomeric compounds YLC-1-YLC-4, each featuring a bulky spiro[fluorene-9,9'-phenanthren]-10'-one moiety, as both hole-transporting materials (HTMs) and interfacial layers in both n-i-p and p-i-n perovskite solar cells (PSCs). These HTMs contain an enantiomeric mixture and a variety of core units linked to triarylamine donors to extend the degree of π-conjugation. The n-i-p PSCs incorporating YLC-1(a) exhibited a power conversion efficiency (PCE) of 19.15% under AM 1.5G conditions (100 mW cm-2); this value was comparable with that obtained using spiro-OMeTAD as the HTM (18.25%). We obtained efficient and stable p-i-n PSCs having the dopant-free structure indium tin oxide (ITO)/NiOx/interfacial layer (YLC)/perovskite/PC61BM/BCP/Ag. The presence of the spiro-based compounds YLC-1 and YLC-2 efficiently passivated the interfacial and grain boundary defects of the perovskite and enhanced the sizes of its grains, more so than did YLC-3 and YLC-4. These spiro-based YLC derivatives packed densely and functioned as Lewis bases to coordinate Pb and Ni ions in the perovskite and NiOx layers, respectively. Together, the effects of smaller grain boundaries and defect passivation of the perovskite enhanced the optoelectronic properties of the PSCs. The photoinduced charge carrier extraction in the linearly increasing voltage (photo-CELIV) curves of NiOx/YLC-1(a) showed the faster carrier transport 3.3 × 10-3 cm2 V-1 s-1, which improved the carrier mobility, supporting the notion of defect passivation of the perovskite. The best-performing NiOx/YLC-1(a) device provided a short-circuit current density (JSC) of 22.88 mA cm-2, an open-circuit voltage (VOC) of 1.10 V, and a fill factor (FF) of 80.93%, corresponding to an overall PCE of 20.37%. In addition, the PCEs of the NiOx/YLC-1(a) and NiOx/YLC-4(b) PSC devices underwent decays of only 98.1 and 97.0% of their original values after 41 days under an Ar atmosphere. Thus, these YLC derivatives passivated the NiOx surface and optimized the film quality of perovskites, thereby leading to superior PCEs of their respective PSCs.

Chemical Composition, Enantiomeric Distribution and Anticholinesterase and Antioxidant Activity of the Essential Oil of Diplosthephium juniperinum.

The aim of this study was to extract and identify the chemical compounds of Diplosthephium juniperinum essential oil (EO) from Ecuador and to assess its anticholinesterase and antioxidant properties. The EO chemical composition was determined by GC–MS. A total of 74 constituents of EO were identified, representing 97.27% in DB-5ms and 96.06% in HP-INNOWax of the total EO. The major constituents (>4.50%) identified were: α-pinene (21.52, 22.04%), geranyl acetate (10.54, 7.78%), silphiper-fol-5-ene (8.67, 7.38%), α-copaene (8.26, 8.18%), 7-epi-silphiperfol-5-ene (4.93, 5.95%), and germacrene D (4.91, 6.00%). Enantioselective analysis of the volatile fraction of D. juniperinum showed: (+)-α-pinene as a pure enantiomer and 5 pairs of enantiomeric compounds. Among them, (−)-β-Pinene and (−)-Germacrene D presented a high enantiomeric excess of 93.23 and 84.62%, respectively, while (−)-α-Thujene, (−)-Sabinene and (S)-4-Terpineol with a lower enantiomeric excess of 56.34, 47.84 and 43.11%, respectively. A moderate inhibitory effect was observed for Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) enzymes with IC50 values of 67.20 ± 7.10 and 89.00 ± 9.90 µg/mL, respectively. A lower antioxidant potential was observed for the EO measured through DPPH and ABTS radical scavenging assays with SC50 values of 127.03 and >1000 µg/mL, respectively. To the best of our knowledge, this is the first report of the chemical composition, enantiomeric distribution and, anticholinesterase and antioxidant potential of the EO of D. juniperinum. As future perspective, further in-vivo studies could be conducted to confirm the anticholinesterase potential of the EO.

An examination of the effects of water on normal phase enantioseparations

Superficially porous silica bonded with macrocyclic glycopeptides can separate enantiomers in various chromatographic formats, including normal phase liquid chromatography (NPLC). The conventional wisdom in NPLC is to avoid intentionally adding water in the eluents. Herein we examine the effects of small quantities of water as an additive on chiral separations in NPLC with the n-hexane-ethanol system. A phase diagram (n-hexane-ethanol-water) is used to analyze the physicochemical properties of the mobile phase. The relative polarity change of solvents upon adding water was determined by using bathochromic shifts of dissolved Nile Red dye. The effectiveness of chiral NPLC with water traces is demonstrated for various pharmaceutically relevant enantiomeric compounds. It is postulated that water molecules weaken stationary phase-solute interactions, resulting in lower retention times for both enantiomers in addition to significantly higher efficiencies. Gibbs free energy changes provided an understanding of the different enantioselectivity shifts caused by water addition. Some interesting kinetic effects also were observed. Classical van Deemter curves are not observed on macrocyclic glycopeptide stationary phases due to slow mass transfer kinetics and thermal effects at high flow rates. The most significant advantage of adding water in NPLC is reducing mass transfer kinetics and altering the mass overloading properties which is highly beneficial on macrocyclic glycopeptide phases. By overloading a 10 × 0.46-cm column with up to 0.6 mg alprenolol, it was found that the relative adsorption isotherm of the first eluting enantiomer was switched from Langmuir to anti-Langmuir type by water addition. The peak shape tuning effect demonstrated the strong influence of water on specific interaction sites of the chiral stationary phases. Water addition effects were most beneficial for enantiomeric and preparative separations in NP mode.

Allosteric modulation of dopamine D2L receptor in complex with Gi1 and Gi2 proteins: the effect of subtle structural and stereochemical ligand modifications

BackgroundAllosteric modulation of G protein-coupled receptors (GPCRs) is nowadays one of the hot topics in drug discovery. In particular, allosteric modulators of D2 receptor have been proposed as potential modern therapeutics to treat schizophrenia and Parkinson’s disease.MethodsTo address some subtle structural and stereochemical aspects of allosteric modulation of D2 receptor, we performed extensive in silico studies of both enantiomers of two compounds (compound 1 and compound 2), and one of them (compound 2) was synthesized as a racemate in-house and studied in vitro.ResultsOur molecular dynamics simulations confirmed literature reports that the R enantiomer of compound 1 is a positive allosteric modulator of the D2L receptor, while its S enantiomer is a negative allosteric modulator. Moreover, based on the principal component analysis (PCA), we hypothesized that both enantiomers of compound 2 behave as silent allosteric modulators, in line with our in vitro studies. PCA calculations suggest that the most pronounced modulator-induced receptor rearrangements occur at the transmembrane helix 7 (TM7). In particular, TM7 bending at the conserved P7.50 and G7.42 was observed. The latter resides next to the Y7.43, which is a significant part of the orthosteric binding site. Moreover, the W7.40 conformation seems to be affected by the presence of the positive allosteric modulator.ConclusionsOur work reveals that allosteric modulation of the D2L receptor can be affected by subtle ligand modifications. A change in configuration of a chiral carbon and/or minor structural modulator modifications are solely responsible for the functional outcome of the allosteric modulator.Graphical abstract