One Soai reaction, two mechanisms?

For over 25 years the chemistry community has puzzled over the mechanism of the Soai reaction, a fascinating chemical process which achieves chiral symmetry breaking by combining autocatalysis with asymmetric amplification. In 2020, the groups of Denmark and Trapp each made a proposal, based on extensive experimental work, on what is the catalytic species there: either a tetrameric product alkoxide aggregate (“SMS tetramer”) or a product-substrate dimer (“hemiacetal”). These models seemingly oppose and exclude each other; however, they might also be both valid since the studies were conducted on different substrates which are not necessarily equivalent. This is shown in this Viewpoint by an in-depth comparison of the two studies and of data from earlier reports, which opens up to a discussion on this scenario's far-reaching implications on the fundamental understanding of asymmetry-amplifying autocatalysis

Non-Linear Effects in Asymmetric Catalysis:Impact of Catalyst Precipitation

International audienceNon-linear effects between the enantiomeric excesses of both the ligand and the product are ubiquitous phenomena in asymmetric catalysis, allowing asymmetric amplification (or depletion) and are widely used tools for mechanistic investigations. Non-linear effects are caused by catalyst aggregation; however, the effect of catalyst precipitation on NLEs has not been systematically investigated to date, except in special cases such as ternary phase systems. In this article, we show through simulations and with several literature cases at hand how precipitation affects shape and amplitude of NLE curves. The limit of solubility of the homo- or heterochiral dimeric species causes broken-shaped NLE curves or very pronounced NLEs even though the equilibria between the different species in solution are not favorable, at first sight. Peculiar features such as horizontal segments, inverse S-shaped curves and a strong effect of total catalyst concentration are also observed. Overall, this study allows to get a better understanding of chiral catalytic systems and gives an outlook at other types of phase separation leading to NLEs

Enantioselective Self-Replicators

Self-replicating molecules provide a simple approach for investigating fundamental processes in scenarios of the emergence of life. Although homochirality is an important aspect of life and of how it emerged, the effects of chirality on self-replicators have received only little attention so far. Here, we report several self-assembled self-replicators with enantioselectivity that emerge spontaneously and grow only from enantiopure material. These require a relatively small number of chiral units in the replicators (down to eight) and in the precursors (down to a single chiral unit), compared to the only other enantioselective replicator reported previously. One replicator was found to incorporate material of its own handedness with high fidelity when provided with a racemic mixture of precursors, thus sorting (L)- and (D)-precursors into (L)- and (D)-replicators. Systematic studies reveal that the presence or absence of enantioselectivity depends on structural features (ring size of the replicator) that appear to impose constraints on its supramolecular organization. This work reveals new aspects of the little researched interplay between chirality and self-replication and represents another step toward the de novo synthesis of life.</p

Light-pulse atom interferometry in microgravity

We describe the operation of a light pulse interferometer using cold 87Rb atoms in reduced gravity. Using a series of two Raman transitions induced by light pulses, we have obtained Ramsey fringes in the low gravity environment achieved during parabolic flights. With our compact apparatus, we have operated in a regime which is not accessible on ground. In the much lower gravity environment and lower vibration level of a satellite, our cold atom interferometer could measure accelerations with a sensitivity orders of magnitude better than the best ground based accelerometers and close to proven spaced-based ones

Integrin α8β1 regulates adhesion, migration and proliferation of human intestinal crypt cells via a predominant RhoA/ROCK-dependent mechanism

Background. Integrins are transmembrane αβ heterodimer receptors that function as structural and functional bridges between the cytoskeleton and ECM (extracellular matrix) molecules. The RGD (arginine-glycine-aspartate tripeptide motif)-dependent integrin α8β1 has been shown to be involved in various cell functions in neuronal and mesenchymal-derived cell types. Its role in epithelial cells remains unknown

Complexes chiraux en catalyse et optique non-linéaire : étude d’effets non-linéaires en catalyse asymétrique et de génération de somme de fréquences

Un effet non-linéaire (NLE) hyperpositif a été observé dans l’addition énantiosélective de dialkylzincs sur du benzaldéhyde catalysée par un ligand chiral éphédrine N-benzylé. Ceci est la première preuve expérimentale d’un NLE hyperpositif, où le ee de produit maximal n’est pas obtenu avec un catalyseur énantiopur mais scalémique. L’origine de ce NLE hyperpositif a été identifiée comme venant d’un double système catalytique où des catalyseurs monomériques mais aussi dimériques homochiraux catalysent la réaction, avec des énantiosélectivités différentes. Avec un ligand scalémique, la précipitation d’un aggrégat hétérochiral diminue la quantité de catalyseur homochiral actif et en solution, déplaçant ainsi l’équilibre du catalyseur agrégé vers son homologue monomérique et plus énantiosélectif. Le système catalytique a été étudié en variant la concentration de catalyseur et la température, en déterminant l’état d’agrégation du catalyseur par RMN 1H DOSY, par des études cinétiques et des courbes de Hammett. Une version ditopique du ligand a également été étudiée pour ces effets non-linéaires en catalyse, qui se sont avérés être en partie hyperpositifs. De nouveaux métallopolymères constitués d’un ligand ditopique chiral et d’un métal ont été développé pour l’application en génération de somme de fréquence (SFG). Les ligands sont préparés par la double addition d’un aminoalcool ou d’une diamine chirale sur du terephtaldehyde pour obtenir des bis-imine-1,4-phenylènes absorbant vers 300 nm. Certains de ces complexes montrent une très forte activité en SFG mais s’avèrent être sensible à l’humidité et donc être difficile à manipuler. Une variante plus stable à base d’une 2-aminoaniline chirale a été développée par la suite et ces propriétés en spectroscopie UV-visible ont été étudiées.A hyperpositive non-linear effect (NLE) was observed in the enantioselective addition of dialkylzincs to benzaldehyde catalyzed by chiral N-benzyl ephedrine. This is the first experimental evidence of such phenomenon were the maximum product ee is not achieved with an enantiopure, but a scalemic catalyst. The origin for this hyperpositive NLE was traced back to a joint catalysis by monomeric as well as homochiral aggregated catalysts which bear different enantioselectivities. With scalemic ligands, the precipitation of heterochiral aggregates decreases the amount of active homochiral catalyst in solution, thus shifting the equilibrium from the aggregated to the more enantioselective monomeric catalysts. The catalytic system was studied by varying catalyst concentration and reaction temperature, by analysis of the catalyst aggregation state via 1H DOSY NMR, by kinetic studies and Hammett plots. A ditopic version of the ligand was also studied for NLEs, which in part turned out to be also hyperpositive. New metallopolymers consisting of a ditopic, chiral ligand and a metal were developed for the application in sum-frequency generation (SFG). The ligands are prepared by the double addition of a chiral aminoalcohol or diamine on terephtaldehyde to obtain bis-imine-1,4-phenylenes absorbing at 300 nm. Some complexes exhibited a very strong activity in SFG but proved to be sensitive to moisture and thus were difficult to handle. A more stable variant based on a 2-aminoaniline was developed and its UV-vis-characteristics were studied

Complexes chiraux en catalyse et optique non-linéaire : étude d’effets non-linéaires en catalyse asymétrique et de génération de somme de fréquences

Un effet non-linéaire (NLE) hyperpositif a été observé dans l’addition énantiosélective de dialkylzincs sur du benzaldéhyde catalysée par un ligand chiral éphédrine N-benzylé. Ceci est la première preuve expérimentale d’un NLE hyperpositif, où le ee de produit maximal n’est pas obtenu avec un catalyseur énantiopur mais scalémique. L’origine de ce NLE hyperpositif a été identifiée comme venant d’un double système catalytique où des catalyseurs monomériques mais aussi dimériques homochiraux catalysent la réaction, avec des énantiosélectivités différentes. Avec un ligand scalémique, la précipitation d’un aggrégat hétérochiral diminue la quantité de catalyseur homochiral actif et en solution, déplaçant ainsi l’équilibre du catalyseur agrégé vers son homologue monomérique et plus énantiosélectif. Le système catalytique a été étudié en variant la concentration de catalyseur et la température, en déterminant l’état d’agrégation du catalyseur par RMN 1H DOSY, par des études cinétiques et des courbes de Hammett. Une version ditopique du ligand a également été étudiée pour ces effets non-linéaires en catalyse, qui se sont avérés être en partie hyperpositifs. De nouveaux métallopolymères constitués d’un ligand ditopique chiral et d’un métal ont été développé pour l’application en génération de somme de fréquence (SFG). Les ligands sont préparés par la double addition d’un aminoalcool ou d’une diamine chirale sur du terephtaldehyde pour obtenir des bis-imine-1,4-phenylènes absorbant vers 300 nm. Certains de ces complexes montrent une très forte activité en SFG mais s’avèrent être sensible à l’humidité et donc être difficile à manipuler. Une variante plus stable à base d’une 2-aminoaniline chirale a été développée par la suite et ces propriétés en spectroscopie UV-visible ont été étudiées.A hyperpositive non-linear effect (NLE) was observed in the enantioselective addition of dialkylzincs to benzaldehyde catalyzed by chiral N-benzyl ephedrine. This is the first experimental evidence of such phenomenon were the maximum product ee is not achieved with an enantiopure, but a scalemic catalyst. The origin for this hyperpositive NLE was traced back to a joint catalysis by monomeric as well as homochiral aggregated catalysts which bear different enantioselectivities. With scalemic ligands, the precipitation of heterochiral aggregates decreases the amount of active homochiral catalyst in solution, thus shifting the equilibrium from the aggregated to the more enantioselective monomeric catalysts. The catalytic system was studied by varying catalyst concentration and reaction temperature, by analysis of the catalyst aggregation state via 1H DOSY NMR, by kinetic studies and Hammett plots. A ditopic version of the ligand was also studied for NLEs, which in part turned out to be also hyperpositive. New metallopolymers consisting of a ditopic, chiral ligand and a metal were developed for the application in sum-frequency generation (SFG). The ligands are prepared by the double addition of a chiral aminoalcohol or diamine on terephtaldehyde to obtain bis-imine-1,4-phenylenes absorbing at 300 nm. Some complexes exhibited a very strong activity in SFG but proved to be sensitive to moisture and thus were difficult to handle. A more stable variant based on a 2-aminoaniline was developed and its UV-vis-characteristics were studied

Observation of Hyperpositive Non-Linear Effect in Asymmetric Organozinc Alkylation in Presence of N-Pyrrolidinyl Norephedrine

International audiencePhenomena related to asymmetric amplification are considered to be key to understanding the emergence of homochirality in life. In asymmetric catalysis, theoretical and experimental models have been studied to understand such chiral amplification, in particular based on non-linear effects. Three decades after the theoretical demonstration that a chiral catalyst, when not enantiopure, could be more enantioselective than its enantiopure counterpart, we show here a new experimental example of nonlinear hyperpositive effect. We report here our investigations in the enantioselective zinc-catalyzed alkylation of benzaldehyde with N-pyrrolidinyl norephedrine as partially resolved chiral ligand, which shows a significant hyperpositive non-linear effect. A study of the underlying mechanism was conducted, which allows us to confirm a mechanism that implies a monomeric and a dimeric complex both catalyzing the reaction at a steady state and giving different enantioselectivities

Catalyst or Catalyst System? Nonlinear Behaviour and the Limits of Mechanistic Understanding in Proline-Based Asymmetric Catalysis.

Asymmetric catalysis has expanded the range of chiral products readily accessible through increasingly efficient synthetic catalysts. The development of these catalysts often starts with a result obtained by systematic screening of known privileged chiral structures and is based on the assumption that the active species would be an isolated monomolecular species. Here, we have studied the activity of three proline-derived ligands that differ in minor chemical modifications. In the zinc-catalysed alkylation of benzaldehyde, we found that they exhibit completely different systems-level behaviours, characterized by multiple aggregation levels that are catalytically active simultaneously. Notably, we were able to establish the possibility of at least trimeric active species in equilibrium with less aggregated active species. These results were obtained through a combination of nonlinear effect studies and other related studies such as product ee versus catalyst loading and temperature as well as in situ NMR studies. Simulations using a mathematical model have confirmed the possibility of such systems-level behaviour. This indicates that the chiral structure alone does not necessarily correlate with systems-level behaviour that could alter the outcome of a given catalytic reaction