Search Results (78)

Crystal molecular structure of 3-(anthracen-2′-yl)-ortho-carborane was determined by single crystal X-ray diffraction study at 100 K. The asymmetric cell unit contains two enantiomeric pairs of molecules, in one of which the intramolecular dihydrogen bond CH...HB is formed with the participation of the C(1)H hydrogen of the anthracene substituent, and in the other with the participation of the C(3)H hydrogen. In all molecules, the polycyclic aromatic and carborane fragments are rotated relative to each other in such a way that the C-C bond of the ortho-carborane cage is approximately parallel to the plane of the aromatic substituent. According to quantum chemical calculations, the minimum energy corresponds to the formation of an intramolecular dihydrogen bond C(1)H...HB(4/7), whereas the C(3)H...HB(4/7) bond is formed rather as a result of intermolecular interactions in the crystal lattice. Full article

The present research describes the chemical composition and the enantiomeric profile of a spicy green aroma essential oil, distilled from the dry leaves of Baccharis sinuata Kunth (Asteraceae). The distillation yield was as high as 3.0% by weight. The chemical analysis was conducted on two columns, coated with stationary phases of different polarity (5% phenyl—95% methyl polysiloxane, expressed by weight, and 100% polyethylene glycol). Major components (≥2.0% as an average value between the two columns) were as follows: β-pinene (4.9%), limonene (39.0%), (E)-β-caryophyllene (2.0%), bicyclogermacrene (2.7%), γ-cadinene (4.0%), δ-cadinene (7.3%), β-eudesmol (2.0%), α-eudesmol (3.0%), and α-cadinol (2.0%). For the enantioselective analysis, 10 enantiomeric pairs were investigated, using two capillary columns coated with different chiral selectors. As a result, (1R,5R)-(−)-α-thujene, (1S,5S)-(−)-α-pinene, and (1R,2S,6S,7S,8S)-(−)-α-copaene were enantiomerically pure, whereas (R)-(+)-limonene presented a 90.0% enantiomeric excess. All the other analysed chiral compounds were scalemic mixtures. The high distillation yield, its aroma, and the bibliographic bioactivity profile make this essential oil potentially interesting from a commercial point of view. To the best of the authors’ knowledge, this is the first description of an essential oil distilled from leaves of B. sinuata. Full article

The control of crystal form in chiral active pharmaceutical ingredients (APIs) is a critical challenge in pharmaceutical development, as differences in solid-state structure can significantly influence physical properties and manufacturing performance. Troglitazone, a molecule with two chiral centers, exists as four stereoisomers (RR, SS, RS, SR) that crystallize as two enantiomeric pairs: RR/SS and RS/SR. This study aims to elucidate the relationship between solution-state molecular interactions and crystallization behavior of these diastereomeric pairs. Antisolvent crystallization experiments were conducted for both mixed solutions containing all four isomers and solutions of individual pairs. Crystallization kinetics were monitored by HPLC, and the resulting solids were characterized by PXRD, DSC, TG, and microscopic observation. Nucleation induction times were determined over a range of supersaturation levels. To probe intermolecular interactions in solution, NOESY and targeted NOE NMR experiments were performed, and the results were compared with crystallographic data. The RS/SR crystals(H-form) consistently exhibited shorter induction times and faster crystallization rates than the RR/SS crystals (L-form), even under conditions where RR/SS solutions were more supersaturated. In mixed solutions, H-form crystallized preferentially, with L-form either remaining in solution or being incorporated into H-form crystals as a solid solution. NOESY and NOE analyses revealed intermolecular proximities between protons that are distant in the molecular structure, indicating the presence of ordered aggregates in solution. These aggregates were more structurally compatible with the H-form than with the L-form crystal lattice, as supported by crystallographic distance analysis. The results demonstrate that differences in nucleation kinetics between troglitazone diastereomers are closely linked to solution-state molecular arrangements. Understanding these relationships provides a molecular-level basis for the rational design of selective crystallization processes for chiral APIs. Full article

Chiral analysis is becoming increasingly important across various scientific fields, including chemistry, pharmaceuticals, biosciences, and more recently, metabolomics. In this context, a high-resolution and high-throughput method was developed for the simultaneous determination of the enantiomeric ratio (er) of seven pairs of amino acid (AA) enantiomers (Arg, Gln, His, Met, Pro, Tyr, and Trp) using flow injection analysis coupled with ion mobility-mass spectrometry (FIA-IM-MS) technology. Specifically, the Single Ion Mobility Monitoring (SIM²) mode on a TIMS-Tof^TM instrument enabled the rapid relative quantification of chiral compound mixtures. A linear model accurately described the relationship between enantiomeric ratio and IM-MS response for Arg, Gln, and Pro enantiomers, as evidenced by high R² values and unbiased residuals. In contrast, non-linear trends were observed for His, Tyr, and Trp, where a quadratic model significantly improved the fit. However, the linear model was retained for Met, despite an R² of about 0.98, due to its comparable performance and simplicity. Measurement accuracy was confirmed with very good recovery rates for er values of 0.95 and 0.99 across all AAs. Finally, the potential of the FIA-SIM²-MS approach in chiral analysis was demonstrated, particularly its ability to provide a reliable and efficient high-throughput tool for accurate er determination. Full article

Citrus x limonia is an aromatic species, known locally in Ecuador as limón mandarina or limón chino. In the present study, the chemical composition and biological activity of the essential oil isolated from this species were determined. The essential oil was extracted through hydrodistillation. The chemical composition and enantiomeric distribution of the essential oil were determined by gas chromatography. Antimicrobial activity was determined using the broth microdilution method against tree Gram-positive cocci, a Gram-positive bacillus, four Gram-negative bacilli, a fungus, and a yeast. The antioxidant activity was determined through ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and DPPH (2,2-diphenyl-1-picrylhydrazyl) methods. The spectrophotometric method was used to determine anticholinesterase activity. In the essential oil, thirty-nine compounds were identified, which represented 99.35% of the total composition. Monoterpene hydrocarbons were the most representative group in terms of number of compounds (thirteen) and in terms of relative abundance (91.39%). The main constituents were found to be limonene (57.38 ± 1.09%), γ-terpinene (13.01 ± 0.37%), and β-pinene (12.04 ± 0.63%). Five pairs of enantiomers were identified in the essential oil from fruits of Citrus x limonia. The essential oil presented a minimum inhibitory concentration of 4000 μg/mL against Aspergillus niger. The antioxidant activity of essential oil was weak per the ABTS method, with a SC₅₀ of 1.26 mg/mL. Additionally, the essential oil exhibited moderate anticholinesterase activity, with an IC₅₀ of 203.9 ± 1.03 µg/mL. This study provides the first comprehensive analysis of the chemical composition and biological activities of the essential oil from fruits of Citrus x limonia. Full article

Citrus x limonia is an aromatic species belonging to the Rutaceae family. In the present study, the chemical composition, enantiomeric distribution, and biological activity of the essential oil isolated from leaves of Citrus x limonia were determined. The essential oil was extracted through hydrodistillation. The chemical composition of the essential oil was determined by gas chromatography (GC) coupled to a flame ionization detector (GC-FID), and a mass spectrometer detector (GC-MS) using a nonpolar column. The enantiomeric distribution was performed using two enantioselective chromatographic columns. Antimicrobial activity was determined using the broth microdilution method. The antimicrobial activity was tested against eight bacteria and two fungi. The antioxidant activity was determined through ABTS and DPPH methods. The spectrophotometric method was used to determine anticholinesterase activity. In the essential oil, forty-three compounds were identified. These compounds represent 99.13% of the total composition. Monoterpene hydrocarbons were the most representative group in number of compounds (fourteen) and in terms of relative abundance (65.67%). The main constituent is found to be limonene (25.37 ± 0.80%), β-pinene (23.29 ± 0.15%) and sabinene (8.35 ± 0.10%). Six pairs of enantiomers were identified in the essential oil from fruits of Citrus x limonia. The essential oil showed moderate antibacterial activity against Gram-positive cocci Enterococcus faecalis, and Gram-positive bacillus Lysteria monocytogenes with a MIC of 1000 μg/mL. The oil exhibited strong antifungal activity against fungi Aspergillus niger, and yeasts Candida albicans with a MIC of 250 and 500 μg/mL, respectively. The antioxidant activity of essential oil was weak in ABTS method with a SC₅₀ of 9.12 mg/mL. Additionally, the essential oil presented moderate anticholinesterase activity with an IC₅₀ of 71.02 ± 1.02 µg/mL. Full article

A good chiral separation usually results in a trial-and-error process; however, through systematic studies, certain principles can be established to correlate structure with chiral selectivity. These principles can then be applied to other chiral separations, reducing the time of developing chiral selective analytical methods. Using the model compounds, the established principles can be applied to a wider range of compounds. In this study, mandelic acid and its substituted derivatives were selected as model compounds to establish transferable rules. The chiral selectivity of 13 compounds was measured on various permethylated cyclodextrin selectors. Comparing the chiral selectivity of permethylated cyclodextrins with different ring sizes (α, β, and γ) provides further insight into the role of inclusion in the chiral selectivity of the cyclodextrin-based stationary phases. Different derivatives of acidic and hydroxyl functions of mandelic acids were tested. Ring- and alkyl-substituted mandelic acid enantiomeric pairs were also tested. By using these compounds, the role of hydrogen donor–acceptor interactions and dipole–dipole interactions and inclusions in chiral recognition processes were investigated. The chiral selectivity values were measured and extrapolated to the same temperature, for the sake of the comparison. Several general tendencies were concluded, which can be used for chiral separation of other enantiomer pairs. Full article

Optically active heterodimeric 5,5′-linked bis-isochromans, containing a stereogenic ortho-trisubstituted biaryl axis and up to four chirality centers, were synthesized stereoselectively by using a Suzuki–Miyaura biaryl coupling reaction of optically active isochroman and 1-arylpropan-2-ol derivatives, providing the first access to synthetic biaryl-type isochroman dimers. Enantiomeric pairs and stereoisomers up to seven derivatives were prepared with four different substitution patterns, which enabled us to test how OR, ECD, and VCD measurements and DFT calculations can be used to determine parallel central and axial chirality elements in three isolated blocks of chirality. In contrast to natural penicisteckins A–D and related biaryls, the ECD spectra and OR data of (aS) and (aR) atropodiastereomers did not reflect the opposite axial chirality, but they were characteristic of the central chirality. The atropodiastereomers showed consistently near-mirror-image VCD curves, allowing the determination of axial chirality with the aid of DFT calculation or by comparison of characteristic VCD transitions. Full article

Two enantiomeric pairs of new 3d–4f heterometallic clusters have been synthesized from two enantiomer Schiff base derivatives: (R/S)-2-[(2-hydroxy-1-phenylethylimino)methyl] phenol (R-/S-H₂L). The formulae of the series clusters are Co₃Ln(R-L)₆ (Ln = Dy (1R), Gd (2R)), Co₃Ln (S-L)₆ (Ln = Dy (1S), Gd (2S)), whose crystal structures and magnetic properties have been characterized. Structural analysis indicated that the above clusters crystallize in the chiral P2₁3 group space. The central lanthanide ion has a coordination geometry of D₃ surrounded by three [Co^III(L)₂]^– anions using six aliphatic oxygen atoms of L²⁻ featuring a star-shaped [Co^III₃Ln^III] configuration. Magnetic measurements showed the presence of slow magnetic relaxation with an effective energy barrier of 22.33 K in the Dy^III derivatives under a zero-dc field. Furthermore, the circular dichroism (CD) spectra of 1R and 1S confirmed their enantiomeric nature. Full article

A complete and comprehensive chemical and biological study of Drimys granadensis, a native Ecuadorian aromatic plant, was conducted. By conventional steam distillation from dried leaves, a yellowish, translucent essential oil (EO) with a density of 0.95 and a refractive index of 1.5090 was obtained. The EO was analyzed by gas chromatography coupled to a mass spectrometer (GC/MS) and an FID detector (GC/FID), respectively. Enantiomeric distribution was also carried out by GC/MS using a chiral selective column (diethyl tert-butylsilyl-BETA-cyclodextrin). The microdilution broth method was employed to assess the antibacterial and antifungal activity of the EO against a panel of opportunistic microorganisms. Antioxidant capacity was measured using diphenyl picryl hydrazyl (DPPH) and azino-bis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals. Finally, the inhibitory potential of the EO against acetylcholinesterase was also valued. Sixty-four chemical compounds, constituting 93.27% of the total composition, were identified, with major components including γ-muurolene (10.63%), spathulenol (10.13%), sabinene (5.52%), and δ-cadinene (4.22%). The characteristic taxonomic marker of the Drimys genus, Drimenol, was detected at very low percentages (<2%). Two pairs of enantiomers ((1S,5R)-(+)-α-pinene/(1S,5S)-(–)-α-pinene; (1S,5R)-(+)-β-pinene/(1S,5S)-(–)-β-pinene) and one pure enantiomer (1R,4S)-(–)-camphene were identified. Regarding antimicrobial potency, the EO exhibited a significant moderate effect on Listeria monocytogenes with a minimal inhibitory concentration (MIC) value of 250 µg/mL, while with the remaining microorganisms, it exerted less potency, ranging from 500 to 2000 µg/mL. The EO displayed moderate effects against the ABTS radical with a half scavenging capacity of 210.48 µg/mL and no effect against the DPPH radical. The most notable effect was noticed for acetylcholinesterase, with a half inhibition concentration (IC₅₀) of 63.88 ± 1.03 µg/mL. These antiradical and anticholinesterase effects hint at potential pharmacological applications in Alzheimer’s disease treatment, although the presence of safrole, albeit in low content (ca. 2%), could limit this opportunity. Further in vivo studies are necessary to fully understand their potential applications. Full article

The DNA building blocks 2′-deoxynucleotides are enantiomeric, with their natural β-D-configuration dictated by the sugar moiety. Their synthetic β-L-enantiomers (βLdNs) can be used to obtain L-DNA, which, when fully substituted, is resistant to nucleases and is finding use in many biosensing and nanotechnology applications. However, much less is known about the enzymatic recognition and processing of individual βLdNs embedded in D-DNA. Here, we address the template properties of βLdNs for several DNA polymerases and the ability of base excision repair enzymes to remove these modifications from DNA. The Klenow fragment was fully blocked by βLdNs, whereas DNA polymerase κ bypassed them in an error-free manner. Phage RB69 DNA polymerase and DNA polymerase β treated βLdNs as non-instructive but the latter enzyme shifted towards error-free incorporation on a gapped DNA substrate. DNA glycosylases and AP endonucleases did not process βLdNs. DNA glycosylases sensitive to the base opposite their cognate lesions also did not recognize βLdNs as a correct pairing partner. Nevertheless, when placed in a reporter plasmid, pyrimidine βLdNs were resistant to repair in human cells, whereas purine βLdNs appear to be partly repaired. Overall, βLdNs are unique modifications that are mostly non-instructive but have dual non-instructive/instructive properties in special cases. Full article

The Schiff base condensation of 5-methyl-4-imidazole carboxaldehyde, 5Me4ImCHO, and the anion of an amino acid, H₂N-CH(R)CO₂⁻ (R = -CH₃, -CH(CH₃)₂ and -CH₂CH(CH₃)₂), gives the aldimine tautomer, Im-CH=N-CH(R)CO₂⁻, while that of 5-methylimidazole-4-methanamine, 5MeIm-4-CH₂NH₂, with a 2-oxocarboxylate anion, R-C(O)-CO₂⁻, gives the isomeric ketimine tautomer, Im-CH₂-N=C(R)CO₂⁻. All are isolated as the neutral nickel(II) complexes, NiL₂, and are characterized by single crystal structure determination, IR, and positive ion ESI MS. In the cases of the 4 substituted imidazoles, either 5MeIm-4-CHO or 5MeIm-4-CH₂NH₂, both the aldimine and ketimine complexes are isolated cleanly with no evidence of an equilibrium between the two tautomers under the experimental conditions. The aldimines are blue while the tautomeric ketimines are green. In contrast, for the 2-substituted imidazoles, with either Im-2-CHO or Im-2-CH₂NH₂, the isolated product from the Schiff base condensation is the ketimine, which in the solid is green, as observed for the 4-isomer. These results suggest that for the 2-substituted imidazoles, there is a facile equilibrium between the aldimine and ketimine tautomers, and that the ketimine form is the thermodynamically favored tautomer. The aldimine tautomers of the 4-substituted imidazoles have three stereogenic centers, the nickel (Δ or Ʌ) and the two alpha carbon atoms (R or S). The observed pair of enantiomers is the ɅRR/ΔSS enantiomeric pair, suggesting that this pair is lower in energy than the others and that this is in general the preferred chiral correlation in these complexes. Full article

The determination of natural product stereochemistry plays a significant role in drug discovery and development. Understanding the stereochemistry of natural products is essential for predicting and optimizing their interactions with biological targets, which, in turn, influences their therapeutic efficacy, safety, and overall impact on living organisms. Here, we present the first application of competitive enantioselective acylation (CEA) reactions in conjunction with LC/MS analysis for determining the absolute configuration of secondary alcohols in natural products which were purified as a mixture. This approach utilizes the enantiomeric pair of HBTM (homobenzotetramisole) catalysts, demonstrating sufficient kinetic resolution for the acylation of secondary alcohols. The rapid reaction kinetics were quantitatively estimated with LC/MS analysis as the characterization technique for the enantioselective transformations. Our study has expanded the application of the CEA reaction coupled with LC/MS analysis to mixtures. Utilizing LC/MS analysis, the CEA reaction offers a sensitive and simple method for stereochemistry determination. Additionally, the application of the CEA reaction is cost/time-effective since only small quantities of substrates and a short reaction time are required for characterizing the absolute configuration of secondary alcohols in natural products compared to other conventional methods. Full article

A series of unsymmetrical phenyl β-carbonyl selenides with o-amido function substituted on the nitrogen atom with chiral alkyl groups was obtained. The compounds form a series of enantiomeric and diastereomeric pairs and present the first examples of this type of chiral Se derivatives. All obtained selenides were further evaluated as antioxidants and anticancer agents to define the influence of the particular stereochemistry of the attached functional groups on the bioactivity of the molecules. The highest H₂O₂ reduction potential was observed for N-(cis-2-hydroxy-1-indanyl)-2-((2-oxopropyl)selanyl)benzamide, and the best radical scavenging properties for N-(-1-hydroxy-2-butanyl)-2-((2-oxopropyl)selanyl)benzamide. Also, both enantiomers of the N-(1-hydroxy-2-butanyl) selenide expressed the highest cytotoxic potential towards human promyelocytic leukemia HL-60 cell line with similar IC₅₀ values 14.4 ± 0.5 and 16.2 ± 1.1 µM, respectively. On the other hand, breast cancer cell line MCF-7 was most sensitive to N-((R)-(-)-1-hydroxy-2-butanyl)- 2-((2-oxopropyl)selanyl)benzamide (IC50 of 35.7 ± 0.6 µM). The structure–activity dependence of the obtained Se derivatives was discussed, and the most potent compounds were selected. Full article