Small Enantiomeric Excess Research Articles

Enantioselective-GCxGC determination of α-terpinyl ethyl ether in wine: Quantitative analysis and identification of main terpene precursors

The present study investigates the presence of α-terpinyl ethyl ether in wine and gives insights on the chemical processes leading to its formation. The analytical determination of (S)-α-terpinyl ethyl ether and (R)-α-terpinyl ethyl ether enantiomers was obtained by enantioselective comprehensive two-dimensional gas chromatography. Applying the two isomers as variables in combination with closely related terpenes, an accurate classification model of wines for the grape variety was successfully applied to a representative set of single-variety wine samples. Although presenting relatively low absolute concentrations, α-terpinyl ethyl ether (along with α-terpineol) resulted to be an inevitable and irreversible degradation product of linalool. In fact, a conversion study from enantiomerically pure (R)-linalool showed a major loss of the initial chiral configuration, i.e. only a very small enantiomeric excess characterized the product. α-Terpineol itself was also confirmed to be a precursor of α-terpinyl ethyl ether, however this process showed a smaller conversion over two weeks than from linalool, and without losses of the initial chiral configuration. In the real samples, the concentration of α-terpinyl ethyl ether was found to be much lower than that of α-terpineol, regardless of the alcohol-to-water ratio. Finally, olfactory descriptors were qualitatively attributed to each α-terpinyl ethyl ether enantiomer.

Duplex Formation and the Origins of Homochirality.

The roots of biological homochirality remain unknown despite decades of study. A commonly proposed path includes an initial small enantiomeric excess that was amplified over time, but a satisfactory source of the excess and a plausible amplification process have yet to be described. We propose here a route to oligonucleotide homochirality from unactivated racemic sources based upon the facts that duplex structures are inherently homochiral and their synthesis from strands of complementary string nucleotide subunits is both uncommonly rapid and exergonic. Simulations employing available kinetic and thermochemical data in an iterated sequence of three equilibria in dry/wet cycles running from unactivated and racemic RNA monomers through oligonucleotides to duplex structures have shown that the exceptional association rate distorts the otherwise simple equilibrium string and overcomes the severe kinetic and stoichiometric barriers to the pairing of the statistically scant homochiral fractions. The simulations reveal widespread deracemization and the full conversion of racemic monomers to populations of L- and D-duplexes in a succession of growth in which the initially formed duplexes are replaced over time with increasingly larger descendants. This claim is open to experimental testing.

Relation between Morphology and Chiroptical Properties in Chiral Conducting Polymer Films: A Case Study in Chiral PEDOT.

The electronic properties of conducting polymers are influenced by their micro- and macrostructural orders, which can be tailored by substituent modification. However, while the effect of substituents on conducting polymers is extensively investigated, chiral substituents are far less studied. Furthermore, many chiral conducting polymers have regioirregular structures, which result in polymer films with inferior properties. In this work, we apply electronic circular dichroism (ECD) spectroscopy to study the morphological changes to the chiral polymers under different polymerization conditions. For this purpose, we investigated 3,4-ethylenedioxythiophene (EDOT) derivatives having two stereogenic centers on each monomer and bearing methyl or phenyl side groups (dimethyl-EDOT and diphenyl-EDOT, respectively). Polymerizing the enantiomerically pure monomers produces regioregular and stereoregular dimethyl-PEDOT and diphenyl-PEDOT, respectively. The effect of the electrolyte and solvent on polymer film morphology was studied using scanning electron microscopy (SEM) and ECD, showing a correlation between the polymer’s morphology and the chiroptical properties of its films. We found that, for diphenyl-PEDOT, the combination of perchlorate anion electrolyte and acetonitrile solvent resulted in a unique morphology characterized by significant intermolecular interactions. These interactions were clearly observable in the ECD spectra in the form of exciton couplings, whose presence was supported by TD-DFT calculations. A small enantiomeric excess was sufficient to induce very intense ECD signals, demonstrating chiral amplification in electropolymerized films.

In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis.

Chemical reactions that lead to a spontaneous symmetry breaking or amplification of the enantiomeric excess are of fundamental interest in explaining the formation of a homochiral world. An outstanding example is Soai's asymmetric autocatalysis, in which small enantiomeric excesses of the added product alcohol are amplified in the reaction of diisopropylzinc and pyrimidine‐5‐carbaldehydes. The exact mechanism is still in dispute due to complex reaction equilibria and elusive intermediates. In situ high‐resolution mass spectrometric measurements, detailed kinetic analyses and doping with in situ reacting reaction mixtures show the transient formation of hemiacetal complexes, which can establish an autocatalytic cycle. We propose a mechanism that explains the autocatalytic amplification involving these hemiacetal complexes. Comprehensive kinetic experiments and modelling of the hemiacetal formation and the Soai reaction allow the precise prediction of the reaction progress, the enantiomeric excess as well as the enantiomeric excess dependent time shift in the induction period. Experimental structural data give insights into the privileged properties of the pyrimidyl units and the formation of diastereomeric structures leading to an efficient amplification of even minimal enantiomeric excesses, respectively.

Design of Chiral Supramolecular Polymers Exhibiting a Negative Nonlinear Response.

Many synthetic and supramolecular chiral polymeric systems are known to exhibit the "majority rules effect" (MRE), a positive nonlinear response in which a small enantiomeric excess (ee) of the chiral building blocks leads to unproportionally large chiroptical signals near zero ee. In contrast, the opposite "racemate rules effect" (RRE), a negative nonlinear response in which the chiroptical signals are flat near zero ee, while giving large nonlinear chiroptical responses to ee at high values, has only been occasionally observed. The origin of this unusual ee dependence remains elusive largely because few systems have been established that exhibit this effect. Herein, we present a design approach that enables the development of chiral supramolecular polymers with a pronounced negative nonlinear response akin to RRE. This is achieved by in situ generating a bidentate inducer for supramolecular polymerization that exists in both meso- and homochiral forms upon reacting with chiral guests. The presence of the meso-inducer creates an aggregate structure that has a little response in the circular dichroism (CD) spectra as a function of ee at a particular wavelength, but a homochiral inducer gives large changes in response to ee at this wavelength. This allowed for an RRE-like response to be observed when the CD intensity of the supramolecular polymers was plotted against the ee of the chiral guests that generate the meso- and homochiral inducers without the necessity of the racemic guest preferentially being incorporated into the polymer.

The Astrophysical Formation of Asymmetric Molecules and the Emergence of a Chiral Bias.

The biomolecular homochirality in living organisms has been investigated for decades, but its origin remains poorly understood. It has been shown that circular polarized light (CPL) and other energy sources are capable of inducing small enantiomeric excesses (ees) in some primary biomolecules, such as amino acids or sugars. Since the first findings of amino acids in carbonaceous meteorites, a scenario in which essential chiral biomolecules originate in space and are delivered by celestial bodies has arisen. Numerous studies have thus focused on their detection, identification, and enantiomeric excess calculations in extraterrestrial matrices. In this review we summarize the discoveries in amino acids, sugars, and organophosphorus compounds in meteorites, comets, and laboratory-simulated interstellar ices. Based on available analytical data, we also discuss their interactions with CPL in the ultraviolet (UV) and vacuum ultraviolet (VUV) regions, their abiotic chiral or achiral synthesis, and their enantiomeric distribution. Without doubt, further laboratory investigations and upcoming space missions are required to shed more light on our potential extraterrestrial molecular origins.

Spontaneous resolution in racemic solutions of N-trifluoroacetylated α-aminoalcohols

N-trifluoroacetylated α-aminoalcohol are low molecular weight (Mw ∼200 Da) gelators. Under cooling of the homochiral solutions, TFAAAs form highly elongated supramolecular structures (strings). In the racemic solution of TFAAA-6 in CCl4, we observed spontaneous resolution of enantiomers and formation of the conglomerate composed of the highly elongated strings. Herewith, in the racemic solution of TFAAA-5 in heptane, the spontaneous resolution was not observed, and we found the isometric precipitate instead of the strings. At the same time, in the TFAAA-5 solutions with small enantiomeric excess (EE), the homochiral strings were observed along with the isometric precipitate. In this case, the strings were formed from the excess of one of the enantiomers that remained in solution after precipitation of the racemic residual. This process leads to the enhancement of chiral polarization in systems close to racemic and can explain the chiral purity of the living cell.

A Concept for a Novel Test for Chemical Parity

Deviations from chemical parity (PV) were evaluated with the search for very small enantiomeric excesses in a racemate prepared from non chiral materials and were detected by means of the circular dichroism (CD). Thus, intensely light-absorbing perylenebiscarboximides were attached to axially chiral biphenyls for the amplification of CD effects by exciton interactions of the adjacent chromophores. A rapidly racemising system was applied for the exclusion of artifacts and compared with an analogous with locked chirally. A very slight enantiomeric excess was detected for the (M) enantiomer. Application of the method for other systems was suggested and relations to natural products discussed.

Turning off the majority-rules effect in two-dimensional hierarchical chiral assembly by introducing a chiral mismatch.

Understanding the mechanism in chiral transmission from a single molecule to a supramolecular level is fundamentally important to decipher the nonlinear amplification effect in the two-dimensional (2D) chiral assembly process. In this contribution, we report on the dramatically different nonlinear amplification effect in the chiral co-adsorber induced homochiral assemblies constructed by a series of homologous achiral building blocks on the graphite surface under control of the majority-rules principle. Homologous hexagonal networks are formed for 5-(benzyloxy)-isophthalic acid (BIC) derivatives with different alkyl lengths. While globally homochiral monolayers of BIC-C6 or BIC-C16 can be obtained by using a mixture of chiral co-adsorber 2-octanol with a small enantiomeric excess, such majority-rules principle based nonlinear chiral amplification is inoperative for the assembly of BIC-C10. Molecular mechanistic analysis indicates that BIC-C10 assembly can accommodate a chiral mismatched motif to form long-range ordered but short-range disordered crystalline networks, leading to the co-adsorption of enantiomers without enantioselectivity. The present results shed important insights into the significance of chirality mismatch during chiral transmission and benefit the understanding of chiral communication in a surface monolayer.

Adsorption-induced auto-amplification of enantiomeric excess on an achiral surface.

The homochirality of biomolecules is a signature of life on Earth and has significant implications in, for example, the production of pharmaceutical compounds. It has been suggested that biomolecular homochirality may have arisen from the amplification of a spontaneously formed small enantiomeric excess (e.e.). Many minerals exhibit naturally chiral surfaces and so adsorption has been proposed as one possible mechanism for such an amplification of e.e. Here we show that when gas-phase mixtures of D- and L-aspartic acid are exposed to an achiral Cu(111) surface, a small e.e. in the gas phase, e.e.g, leads to an amplification of the e.e. on the surface, e.e.s, under equilibrium conditions. Adsorption-induced amplification of e.e. does not require a chiral surface. The dependence of e.e.s on e.e.g has been modelled successfully using a Langmuir-like adsorption isotherm that incorporates the formation of homochiral adsorbate clusters on the surface.

Stereoselection in the diels–alderase ribozyme: A molecular dynamics study

The Diels-Alderase ribozyme is an in vitro-evolved ribonucleic acid enzyme that catalyzes a [4 + 2] cycloaddition reaction between an anthracene diene and a maleimide dienophile. The ribozyme can in principle be used to selectively synthesize only one product enantiomer, depending on which of the two entrances to the catalytic pocket, "front" or "back", the substrate is permitted to use. Here, we investigate stereoselection and substrate recognition in the ribozyme by means of multiple molecular dynamics simulations, performed on each of the two substrates individually in the pocket, on the reactant state, and on the product state. The results are consistent with a binding mechanism in which the maleimide likely binds first followed by the anthracene, which enters preferentially through the front door. The free energy profiles for anthracene binding indicate that the pre-(R,R)-enantiomer conformation is slightly preferred, in agreement with the experimentally observed small enantiomeric excess of the (R,R)-enantiomer of the product. The reactant state is stabilized by the simultaneous presence of both substrates bound to their binding sites in the hydrophobic pocket as well as by stacking interactions between them.

Nanocrystalline MgO catalysts for the Henry reaction of benzaldehyde and nitromethane

Nanocrystalline MgO particles of about 3 nm were examined as catalysts for the Henry reaction between benzaldehyde and nitromethane at 273 K. The surface area of nanocrystalline MgO was greater than 600 m 2 g −1 except after thermal treatment in N 2 at 823 K, which reduced the surface area to 359 m 2 g −1. The areal rate of the Henry reaction over nanocrystalline MgO at 273 K was 0.015 ± 0.002 μmol m −2 s −1 and was independent of pretreatment temperature over the range of 523–823 K. Addition of (S)-BINOL to nanocrystalline MgO has been reported previously to favor the production of one enantiomer of the Henry reaction. In the current work, negligible enantiomeric excess was observed on (S)-BINOL-modified nanocrystalline MgO catalysts, regardless of the source of nanocrystalline MgO, the MgO activation temperature, the reaction temperature, the sequence of reactant addition or the loading of (S)-BINOL. Adsorption of l-proline onto nanocrystalline MgO catalyst induced a small enantiomeric excess in the Henry reaction products, but the catalytic activity of the catalyst was low.

ChemInform Abstract: A Concise Summary of Experimental Facts About the Soai Reaction

AbstractReview: 61 refs.

A New Inorganic−Organic Hybrid Zinc Phosphate Prepared with l-Histidine with an Unusual Stability in Water

A new layered zinc phosphate (Mu-39) has been synthesized by hydrothermal treatment with biomolecules as original templates. It was synthesized with the l-histidine amino acid (C6H9N3O2). The structure was determined by a single crystal X-ray diffraction study combined with exhaustive solid-state NMR experiments. These last ones [1H → 13C HETCOR, 1H single quantum/double quantum (DQ), 31P, 1H → 31P CPMAS, 1H → 31P HETCOR] ascertained the formulation of Mu-39 as {[C6H10N3O2+][Zn2(HPO4)(PO4)−]·H2O}n with a hydrogen phosphate and phosphate ligands, and ruled out partial protonation such as (H1−xPO4)(HxPO4). A 31P magic angle spinning (MAS) NMR study supported the almost complete racemization of l-histidine during the hydrothermal synthesis with only a small enantiomeric excess of 25% remaining. The compound crystallizes in the triclinic symmetry (space group P1) with a = 8.6109(6) A, b = 9.0319(6) A, c = 9.9523(7) A, and α = 84.481(2)°, β = 83.279(2)°, γ = 74.652(2)°, V = 739.56(9) A3, Z = 2. The inorganic ...

ChemInform Abstract: Amplification of Chirality at Solid Surfaces

AbstractReview: 45 refs.

ChemInform Abstract: Enantioselectivity in a Free-Radical Oxidation: Measurement of Small Enantiomeric Excesses.

ChemInform Abstract: Enantioselectivity in a Free-Radical Oxidation: Measurement of Small Enantiomeric Excesses.

A concise summary of experimental facts about the Soai reaction

The Soai reaction amplifies small enantiomeric excesses in a spectacular manner. Being known for 20 years, it has drawn the attention of many scientists in different fields as it is to date the only chemical reaction offering the chance to study the phenomenon of asymmetric autocatalysis in conjunction with high amplification of enantiomeric excess (ee). This mini-review comprises an introduction to the discovery of asymmetric autocatalysis with amplification of ee and a concise summary of published experimental results showing which starting materials and reaction parameters play an important role in this reaction and which influences are understood. It is addressed especially to scientists entering the field of the Soai reaction to get a quick overview of important aspects.

Amplification of chirality at solid surfaces.

Symmetry-breaking phenomena in two-dimensional crystallization at surfaces are reviewed and the potential impact to chiral amplification in three-dimensional systems in connection with the origin of homochirality in the biomolecular world is discussed. Adsorption of prochiral molecules leads to two-dimensional conglomerates, i.e., on a local scale spontaneously to homochiral crystal structures. Small enantiomeric excess or chiral impurities in this environment install homochirality on a global scale, that is, on the entire surface.

Homochirality in life: two equal runners, one tripped.

Strong arguments can be found in the literature addressed to the question of the origin of homochirality in life, supporting the hypothesis that primordial life could have evolved in both homochiral forms and that early on when life was still rarely found, random events led to the survival of only one of these living mirror images. This proposal is an alternative to the generally accepted view that small enantiomeric excesses of biologically important molecules were amplified to homochirality prior to life's origin. Acceptance of the possibility of "two equal runners" leads to the importance of research investigations on routes to formation of ensembles of racemic mixtures of isotactic biologically interesting polymers, supramolecular entities and aggregates.

Systematic Studies using 2‐(1‐Adamantylethynyl)pyrimidine‐5‐carbaldehyde as a Starting Material in Soai’s Asymmetric Autocatalysis

Herein, we present a new substrate for the Soai reaction, which has an adamantylethynyl residue (1 g) and exhibits asymmetric autocatalysis, yielding products with enantiomeric excesses above 99%. For the first time, all reactions were performed on a parallel synthesizer system to ensure identical reaction conditions. A detailed systematic study of reaction parameters was performed and we report the highest enhancements of enantiomeric excess reported so far in the Soai reaction in one reaction cycle (7.2-->94.1% ee or 3.1-->92.1% ee). Our results led to a set of reaction parameters that yield reproducible results. Therefore, our new starting material 1 g is suitable for systematic and mechanistic studies on this remarkable reaction. A series of experiments designed to quantify the amplification of enantiomeric excess demonstrated that the reaction can be used in principle as a tool for the detection of low enantiomeric excesses: under definite conditions, an unknown low enantiomeric excess (0.1-7%) was amplified to a detectable one. A back calculation to the original value offers a new method for the determination of small enantiomeric excesses.