Chirality最新文献

Chirality is an essential geometric property unifying small molecules, biological macromolecules, inorganic nanomaterials, biological microparticles, and many other chemical structures. Numerous chirality measures have attempted to quantify this geometric property of mirror asymmetry and to correlate these measures with physical and chemical properties. However, their utility has been widely limited because these correlations have been largely notional. Furthermore, chirality measures also require prohibitively demanding computations, especially for chiral structures comprised of thousands of atoms. Acknowledging the fundamental problems with quantification of mirror asymmetry, including the ambiguity of sign-variable pseudoscalar chirality measures, we revisit this subject because of the significance of quantifying chirality for quantitative biomimetics and describing the chirality of nanoscale materials that display chirality continuum and scale-dependent mirror asymmetry. We apply the concept of torsion within the framework of differential geometry to the graph theoretical representation of chiral molecules and nanostructures to address some of the fundamental problems and practical limitations of other chirality measures. Chiral gold clusters and other chiral structures are used as models to elaborate a graph-theoretical chirality (GTC) measure, demonstrating its applicability to chiral materials with different degrees of chirality at different scales. For specific cases, we show that GTC provides an adequate description of both the sign and magnitude of mirror asymmetry. The direct correlations with macroscopic properties, such as chiroptical spectra, are enhanced by using the hybrid chirality measures combining parameters from discrete mathematics and physics. Taking molecular helices as an example, we established a direct relation between GTC and optical activity, indicating that this chirality measure can be applied to chiral metamaterials and complex chiral constructs.

An N-centered epimeric mixture of chlorophyll-a derivatives methylated at the inner nitrogen atom was separated by reverse-phase high-performance liquid chromatography. Circular dichroism (CD) spectroscopic analyses of the epimerically pure N22-methyl-chlorins revealed that the minor first-eluted and major second-eluted stereoisomers were (22S)- and (22R)-configurations, respectively. Their visible absorption and CD spectra in solution were dependent on the N22-stereochemistry. The epimer-dependent spectral changes were independent of the substituents at the peripheral 3-position of the core chlorin chromophore.

Obtaining optically pure compounds in an eco-friendly and cost-efficient manner plays an important role in human health and pharmaceutical industry. Racemic separation using multistage stereoselective liquid–liquid extraction has become one of the most practical and effective approach to access homochiral enantiomers. Currently, chiral ionic liquids (CILs) with structural designability have become a promising chiral additive and enable them as adjustable candidates for racemic separation. Herein, a high-effective stereoselective liquid–liquid extraction process composed of imidazolium cations and amino acid-derived anions as the chiral additive was established for racemic 2-cyclohexylmandelic acid (CHMA) separation. We have systematically investigated the choice of organic solvent, concentration of CIL, extraction temperature, and the pH of aqueous phase. For three-stage stereoselective extraction, the maximum enantiomeric excess (e.e.) for CHMA was reached up to 40.6%. Furthermore, the mechanism of steric effect and stereoselective capacity between the CILs and racemic CHMA was discussed and simulated. We envision that the work will facilitate the development of CILs in multistage liquid–liquid extraction and promote the large-scale production of optically pure enantiomers.

Truxillines are a group of tropane alkaloids present in coca leaves that are formed by photochemical dimerization of cinnamoylcocaine(s). Proportion of different truxilline forms present in cocaine serves as its geographical, manufacture, and storage “fingerprint”; thus, the quantitative determination of truxilline content represents one of the powerful methods of analysis and characterization of cocaine samples. Contrary to the statements repeatedly presented in the literature, namely, that there exist exactly 11 truxillines and that every single truxilline is diastereomer of any other, here we show that, in fact, a total of 15 truxillines exist, which can be divided in two structurally isomeric groups—five mutually diastereomeric truxillates and 10 mutually diastereomeric truxinates.

Electrons in circular motion emit electromagnetic radiation and lose their energy and angular momentum, both of which are carried away by the radiation field. Electromagnetic radiation from such electrons is not only circularly polarized but also, in general, possessing helical phase structure, the former of which corresponds to spin angular momentum and the latter orbital angular momentum. Based on the classical electrodynamics, we show that the chiral topological property related to the orbital angular momentum arises from deformation of the electromagnetic field due to the relativistic effect.

Each year, new psychoactive substances appear on the global drug market leading to constant changes. Most of these compounds with stimulating effect possess a chiral center, thus leading to two enantiomers with presumably different pharmacological properties. Among them, synthetic cathinones, often misleadingly traded as “bath salts,” play an important role. There is little knowledge about the distinct effect of the enantiomers. The aim of this study was to test a commercially available Lux® i-Amylose-3 column by HPLC-UV for enantiorecognition of cathinone derivatives. Overall, 80 compounds were tested in normal phase mode, where 75 substances were separated under initial conditions. After method optimization, at least partial separation was achieved for the remaining compounds. The same set of substances was measured in polar-organic mode, where 63 analytes were resolved into their enantiomers under initial conditions with very short retention times. Both modes showed complementary results for the individual compounds. Furthermore, the tested methods proved to be suitable for differentiation of positional isomers, which can be useful for drug checking programs. All measurements were carried out under isocratic conditions, and intraday and interday repeatability tests were performed.

The aim of this study was to investigate the chiral inversion and the stereoselective pharmacokinetic profiles of desmethyl-phencynonate hydrochloride after administration of the single isomer and its racemate to beagle dogs. A liquid chromatography with tandem mass spectrometry (LC–MS/MS) method was established for determination of the stereoisomers on chiral columns in beagle dog plasma, which met all the requirements. The chiral inversion in dogs of the desmethyl-phencynonate hydrochloride were studied after administration of the single isomer or the racemic modification. The stereoselective pharmacokinetic profiles of the desmethyl-phencynonate hydrochloride were studied by assays for simultaneous isomers after administration of the racemic modification. The results showed that the absorption of the R­configuration dosed as the single isomer was higher than it dosed as the racemic modification. The AUC_(0-t), AUC_(0-∞), and C_max of the S­configuration were much higher than those of R­configuration after oral administration of the racemic desmethyl-phencynonate hydrochloride. The chiral inversion of desmethyl-phencynonate isomers could not occur in dogs after administration of the R­configuration.

The absolute configuration of three chiral eugenol derivatives was assigned by a multi-step methodology based on enantioselective HPLC combined with spectroscopic and theoretical calculations. Milligram amounts of enantiopure forms used for stereochemical characterization were isolated by HPLC on the immobilized amylose-based chiral stationary phase Chiralpak IG using normal phase elution conditions. The absolute configuration was indirectly determined for one of the three compounds by ¹H NMR via methoxy-α-trifluoromethyl-α-phenylacetic acid derivatization (Mosher's acid). Comparison of the experimental and predicted electronic circular dichroism spectra confirmed the stereochemical assignment by Mosher's method and extended the absolute configuration assignment to two other chiral compounds.

Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class.

Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® Chiraldex™ G-PN column containing 2,6-di-O-pentyl-3-propionyl-γ-cyclodextrin and a Lipodex™ D column containing heptakis-(2,6-di-O-pentyl-O-acetyl)-β-cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS-QP2010 SE system.

Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.¹ As a result, 35 amphetamines were tested as their TFAA-derivatives.

A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the Chiraldex™ G-PN column. Six baseline and nine partial separations were observed with the Lipodex™ D column, respectively.