Homochirality In Life Research Articles

Chiroptical properties of membrane glycerophospholipids and their chiral backbones.

Glycerophospholipid membranes are one of the key cellular components. Still, their species-dependent composition and homochirality remain an elusive subject. In the context of the astrophysical circularly polarized light scenario likely involved in the generation of a chiral bias in meteoritic amino and sugar acids in space, and consequently in the origin of life's homochirality on Earth, this study reports the first measurements of circular dichroism and anisotropy spectra of a selection of glycerophospholipids, their chiral backbones and their analogs. The rather low asymmetry in the interaction of UV/VUV circularly polarized light with sn-glycerol-1/3-phosphate indicates that chiral photons would have been unlikely to directly induce symmetry breaking to membrane lipids. In contrast, the anisotropy spectra of d-3-phosphoglyceric acid and d-glyceraldehyde-3-phosphate unveil up to 20 and 100 times higher maximum anisotropy factor values, respectively. This first experimental report, targeted on investigating the origins of phospholipid symmetry breaking, opens up new avenues of research to explore alternative mechanisms leading to membrane lipid homochirality, while providing important clues for the search for chiral biosignatures of extant and/or extinct life in space, in particular for the ExoMars 2028 mission.

The Formation of Supramolecular Chiral Materials from Achiral Molecules Using a Liquid-Crystallin System: Symmetry Breaking, Amplification, and Transfer

Recently, the formation of chiral materials by the self-organization of achiral small molecules has attracted much attention. How can we obtain chirality without a chiral source? Interesting approaches, such as mechanical rotation, circularly polarized light, and asymmetric reaction fields, have been used. We describe recent research developments in supramolecular chirality in liquid crystals, focusing primarily on our group’s experimental results. We present the following concepts in this review. Spontaneous mirror symmetry breaking in self-assembled achiral trimers induces supramolecular chirality in the soft crystalline phase. Two kinds of domains with opposite handedness exist in non-equal populations. The dominant domain is amplified to produce a homochiral state. Chirality is transferred to a polymer film during the polymerization of achiral monomers by using the homochiral state as a template. Finally, we discuss how the concepts obtained from this liquid crystal research relate to the origin of homochirality in life.

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

Phenomena 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.

Spontaneous Resolution of Racemic Cage-Catenanes via Diastereomeric Enrichment at the Molecular Level and Subsequent Narcissistic Self-Sorting at the Supramolecular Level.

The spontaneous resolution of racemates, from natural compounds to artificial structures, has long been pursued to shed light on the origin of homochirality in life. Even though diverse synthetic systems have been elegantly devised to elaborate the underlying principles of spontaneous symmetry breaking, their complexity is still unparalleled to the natural masterpieces including DNA helix and proteins, which convey remarkable coalescence at both molecular and supramolecular levels. Here, we report on the spontaneous resolution of a pair of homochiral entities from a racemic mixture of a triply interlocked cage-catenane comprising 720 possible stereoisomers. This cage-catenane comprises six methyldithiane ring-containing linkers (denoted rac-2). As each methyldithiane ring has two chiral centers, it exhibits four possible diastereomers. These otherwise equimolar diastereomers are preferentially differentiated with the equatorial conformers over their axial analogues, leading to the dominant formation of (S, R)-2 and (R, S)-2, i.e., diastereomeric enrichment at the molecular level. This diastereomeric enrichment is unbiasedly transferred from precursor rac-2 to cage-catenane rac-4, from which a pair of homochirals (S, R)6-4 and (R, S)6-4 is narcissistically self-sorted upon crystallization. This powerful symmetry breaking is attributed to a supramolecular synergy of directional π-π stacking with the multivalency of erstwhile weak S···S contacts (with an unusual distance of 3.09 Å) that are cooperatively arranged in a helical fashion. This work highlights the attainability of complex homochiral entities by resorting to coalesced covalent and noncovalent contributions and therefore provides additional clues to the symmetry breaking of sophisticated yet well-defined architectures.

Evidence for new enantiospecific interaction force in chiral biomolecules

Evidence for new enantiospecific interaction force in chiral biomolecules

The Case for Non-Cryogenic Comet Nucleus Sample Return

Comets hold answers to mysteries of the Solar System by recording presolar history, the initial states of planet formation and prebiotic organics and volatiles to the early Earth. Analysis of returned samples from a comet nucleus will provide unparalleled knowledge about the Solar System starting materials and how they came together to form planets and give rise to life: 1. How did comets form? 2. Is comet material primordial, or has it undergone a complex alteration history? 3. Does aqueous alteration occur in comets? 4. What is the composition of cometary organics? 5. Did comets supply a substantial fraction of Earth's volatiles? 6. Did cometary organics contribute to the homochirality in life on Earth? 7. How do complex organic molecules form and evolve in interstellar, nebular, and planetary environments? 8. What can comets tell us about the mixing of materials in the protosolar nebula?

2D Ising Model for Adsorption-induced Enantiopurification of Racemates.

Mechanisms for the spontaneous transformation of achiral chemical systems into states of enantiomeric purity have important ramifications in modern pharmacology and potential relevance to the origins of homochirality in life on Earth. Such mechanisms for enantiopurification are needed for production of chiral pharmaceuticals and other bioactive compounds. Previously proposed chemical mechanisms leading from achiral systems to near homochirality are initiated by a symmetry-breaking step resulting in a minor excess of one enantiomer via statistical fluctuations in enantiomer concentrations. Subsequent irreversible processes then amplify the majority enantiomer concentration while simultaneously suppressing minority enantiomer production. Herein, equilibrium adsorption of amino acid enantiomer mixtures onto chiral and achiral surfaces reveals amplification of surface enantiomeric excess relative to the gas phase; i. e. enantiopurification of chiral adsorbates by adsorption. This adsorption-induced amplification of enantiomeric excess is shown to be well-describe by the 2D Ising model. More importantly, the 2D-Ising model predicts formation of homochiral monolayers from adsorption of racemic mixtures or prochiral molecules on achiral surfaces; i. e. enantiopurification with no apparent chiral driving force.

Observation of hyperpositive non‐linear effect in catalytic asymmetric organozinc additions to aldehydes

Asymmetric amplification is a phenomenon that is believed to play a key role in the emergence of homochirality in life. In asymmetric catalysis, theoretical and experimental models have been investigated to provide an understanding of how chiral amplification is possible, in particular based on non-linear effects. Interestingly, it has been proposed a quarter century ago that chiral catalysts, when not enantiopure might even be more enantioselective than their enantiopure counterparts. We show here that such hyperpositive non-linear effect in asymmetric catalysis is indeed possible. An in-depth study into the underlying mechanism was carried out, and the scheme we derive differs from the previous proposed models.

Formation of homochiral helical nanostructures in diblock copolymers under the confinement of nanopores.

The control of the homochirality of helical structures formed in achiral systems is of great interest as it is helpful for understanding the origin of homochirality in life. In this work, we introduce a spiral arrangement of patches into the inner surface of a nanopore to guide the self-assembly of a cylinder-forming AB diblock copolymer melt into a homochiral single helix. We calculate the free energy of the single-helical structures with different handedness using self-consistent field theory (SCFT). Moreover, we simulate the self-assembly process using an iterative process of SCFT solution starting from a disordered state, and count the formation probability of different helical structures. We find that the formation probability of the homochiral helix with favorable free energy increases rapidly, leading to the conclusion that a minuscule difference of 0.5-1.0 × 10-4kBT per chain is enough to obtain the homochiral helix by suppressing its counterpart of a higher free energy. However, for a stronger chiral guiding field, other homochiral helical structures with unfavorable handedness and thus increasingly higher free energy become more likely to be formed. Morphological snapshots during the self-assembly process reveal that the formation of these metastable helical structures is induced by their kinetic pathways, which are altered to be favorable by the strong chiral field of the patch pattern. Therefore, our work suggests that both thermodynamics and kinetics are important for controlling the chirality of helical structures.

Control over the emerging chirality in supramolecular gels and solutions by chiral microvortices in milliseconds

The origin of homochirality in life is a fundamental mystery. Symmetry breaking and subsequent amplification of chiral bias are regarded as one of the underlying mechanisms. However, the selection and control of initial chiral bias in a spontaneous mirror symmetry breaking process remains a great challenge. Here we show experimental evidences that laminar chiral microvortices generated within asymmetric microchambers can lead to a hydrodynamic selection of initial chiral bias of supramolecular systems composed of exclusively achiral molecules within milliseconds. The self-assembled nuclei with the chirality sign affected by the shear force of enantiomorphic microvortices are subsequently amplified into almost absolutely chirality-controlled supramolecular gels or nanotubes. In contrast, turbulent vortices in stirring cuvettes fail to select the chirality of supramolecular gels. This study reveals that a laminar chiral microflow can induce enantioselection far from equilibrium, and provides an insight on the origin of natural homochirality.

Transfer of chiral information from a chiral solvent to a two-dimensional network.

Chiral induction in self-assembled monolayers has garnered considerable attention in the recent past, not only due to its importance in chiral resolution and enantioselective heterogeneous catalysis but also because of its relevance to the origin of homochirality in life. Here, we demonstrate the emergence of homochirality in a supramolecular low-density network formed by achiral molecules at the interface of a chiral solvent and an atomically-flat achiral substrate. We focus on the impact of structure and functionality of the adsorbate and the chiral solvent on the chiral induction efficiency in self-assembled physisorbed monolayers, as revealed by scanning tunneling microscopy. Different induction mechanisms are proposed and evaluated, with the assistance of advanced molecular modeling simulations.

Chirality in adsorption on solid surfaces.

In the present review we survey the main advances made in recent years on the understanding of chemical chirality at solid surfaces. Chirality is an important topic, made particularly relevant by the homochiral nature of the biochemistry of life on Earth, and many chiral chemical reactions involve solid surfaces. Here we start our discussion with a description of surface chirality and of the different ways that chirality can be bestowed on solid surfaces. We then expand on the studies carried out to date to understand the adsorption of chiral compounds at a molecular level. We summarize the work published on the adsorption of pure enantiomers, of enantiomeric mixtures, and of prochiral molecules on chiral and achiral model surfaces, especially on well-defined metal single crystals but also on other flat substrates such as highly ordered pyrolytic graphite. Several phenomena are identified, including surface reconstruction and chiral imprinting upon adsorption of chiral agents, and the enhancement or suppression of enantioselectivity seen in some cases upon adsorption of enantiomixtures of chiral compounds. The possibility of enhancing the enantiopurity of adsorbed layers upon the addition of chiral seeds and the so-called "sergeants and soldiers" phenomenon are presented. Examples are provided where the chiral behavior has been associated with either thermodynamic or kinetic driving forces. Two main approaches to the creation of enantioselective surface sites are discussed, namely, via the formation of supramolecular chiral ensembles made out of small chiral adsorbates, and by adsorption of more complex chiral molecules capable of providing suitable chiral environments for reactants by themselves, via the formation of individual adsorbate:modifier adducts on the surface. Finally, a discussion is offered on the additional effects generated by the presence of the liquid phase often required in practical applications such as enantioselective crystallization, chiral chromatography, and enantioselective catalysis.

Chiral selection of single helix formed by diblock copolymers confined in nanopores.

Chiral selection has attracted tremendous attention from the scientific communities, especially from biologists, due to the mysterious origin of homochirality in life. The self-assembly of achiral block copolymers confined in nanopores offers a simple but useful model of forming helical structures, where the helical structures possess random chirality selection, i.e. equal probability of left-handedness and right-handedness. Based on this model, we study the stimulus-response of chiral selection to external conditions by introducing a designed chiral pattern onto the inner surface of a nanopore, aiming to obtain a defect-free helix with controllable homochirality. A cell dynamics simulation based on the time-dependent Ginzburg-Landau theory is carried out to demonstrate the tuning effect of the patterned surface on the chiral selection. Our results illustrate that the chirality of the helix can be successfully controlled to be consistent with that of the tailored surface patterns. This work provides a successful example for the stimulus response of the chiral selection of self-assembled morphologies from achiral macromolecules to external conditions, and hence sheds light on the understanding of the mechanism of the stimulus response.

Abiotic synthesis of amino acids and self-crystallization under prebiotic conditions.

Building on previous research on the origin and homochirality of life, this study focuses on analyses profiling important building blocks of life: the natural amino acids. The spark discharge variation of the iconic Miller experiment was performed with a reducing gas mixture of ammonia, methane, water and hydrogen. Amino acid analysis using liquid chromatography coupled with tandem mass spectrometry after pre-column derivatizaiton revealed the generation of several amino acids including those essential for life. Re-crystallization of the synthetic products and enantiomeric ratio analysis were subsequently performed. Results from liquid chromatography coupled with either fluorescent detector or tandem mass spectrometry after pre-column derivatization with chiral reagent revealed spontaneous and effective asymmetric resolution of serine and alanine. This work describes a useful analytical platform for investigation of hypotheses regarding the origin and homochirality of amino acids under prebiotic conditions. The formation of numerous amino acids in the electric discharge experiment and the occurrence of high enantiomeric ratios of amino acids in re-crystallization experiment give valuable implications for future studies in unraveling fundamental questions regarding origins and evolution of life.

New studies on molecular chirality in the gas phase: enantiomer differentiation and determination of enantiomeric excess.

Chirality plays a fundamental role in the activity of biological molecules and broad classes of chemical reactions. The chemistry of life is built almost exclusively on left-handed amino acids and right-handed sugars, a phenomenon known as "homochirality of life". Furthermore, most drugs developed in the last decade are of specified chirality. Thus, fast and reliable methods that can differentiate molecules of different handedness, determine the enantiomeric excess of even molecular mixtures, and allow for an unambiguous determination of molecular handedness are of great interest, in particular with respect to complex mixtures. In this perspective article, we discuss the recent developments, with an emphasis on modern spectroscopic methods using gas-phase samples, such as photoelectron circular dichroism, Coulomb explosion imaging, and microwave three-wave mixing.

Colloquium: Homochirality: Symmetry breaking in systems driven far from equilibrium

Subsequent to the discovery of chirality of organic molecules by Pasteur, living organisms have been found to utilize biomolecules of only one handedness. The origin of this homochirality in life still remains unknown. It is believed that homochirality is attained in two stages: the initial creation of a chirality bias and its subsequent amplification to pure chirality. In the last two decades, two novel experiments have established the second stage in different fields: Soai and co-workers achieved the amplification of enantiomeric excess in the production of chiral organic molecules, and Viedma obtained homochirality in the solution growth of sodium chlorate crystals. These experiments are explained by a theory with a nonlinear evolution equation for the chiral order parameter; nonlinear processes in reactions or in crystal growth induce enantiomeric excess amplification, and the recycling of achiral elements ensures homochirality. Recycling drives the system to a state far from equilibrium with a free energy higher than that of the equilibrium state.

Solvent-Induced Homochirality in Surface-Confined Low-Density Nanoporous Molecular Networks

Induction of chirality in achiral monolayers has garnered considerable attention in the recent past not only due to its importance in chiral resolutions and enantioselective heterogeneous catalysis but also because of its relevance to the origin of homochirality in life. In this contribution, we demonstrate the emergence of macroscopic chirality in multicomponent supramolecular networks formed by achiral molecules at the interface of a chiral solvent and an achiral substrate. The solvent-mediated chiral induction provides a simple, efficient, and versatile approach for the fabrication of homochiral surfaces using achiral building blocks.

Life's chirality from prebiotic environments

AbstractA key open question in the study of life is the origin of biomolecular homochirality: almost every life-form on Earth has exclusively levorotary amino acids and dextrorotary sugars. Will the same handedness be preferred if life is found elsewhere? We review some of the pertinent literature and discuss recent results suggesting that life's homochirality resulted from sequential chiral symmetry breaking triggered by environmental events. In one scenario, autocatalytic prebiotic reactions undergo stochastic fluctuations due to environmental disturbances, in a mechanism reminiscent of evolutionary punctuated equilibrium: short-lived destructive events may lead to long-term enantiomeric excess. In another, chiral-selective polymerization reaction rates influenced by environmental effects lead to substantial chiral excess even in the absence of autocatalysis. Applying these arguments to other potentially life-bearing platforms has implications to the search for extraterrestrial life: we predict that a statistically representative sampling of extraterrestrial stereochemistry will be racemic (chirally neutral) on average.

ChemInform Abstract: Understanding Prebiotic Chemistry Through the Analysis of Extraterrestrial Amino Acids and Nucleobases in Meteorites

AbstractReview: 66 refs.

Understanding prebiotic chemistry through the analysis of extraterrestrial amino acids and nucleobases in meteorites

The discoveries of amino acids of extraterrestrial origin in many meteorites over the last 50 years have revolutionized the Astrobiology field. A variety of non-terrestrial amino acids similar to those found in life on Earth have been detected in meteorites. A few amino acids have even been found with chiral excesses, suggesting that meteorites could have contributed to the origin of homochirality in life on Earth. In addition to amino acids, which have been productively studied for years, sugar-like molecules, activated phosphates, and nucleobases have also been determined to be indigenous to numerous meteorites. Because these molecules are essential for life as we know it, and meteorites have been delivering them to the Earth since accretion, it is plausible that the origin(s) of life on Earth were aided by extraterrestrially-synthesized molecules. Understanding the origins of life on Earth guides our search for life elsewhere, helping to answer the question of whether biology is unique to Earth. This tutorial review focuses on meteoritic amino acids and nucleobases, exploring modern analytical methods and possible formation mechanisms. We will also discuss the unique window that meteorites provide into the chemistry that preceded life on Earth, a chemical record we do not have access to on Earth due to geologic recycling of rocks and the pervasiveness of biology across the planet. Finally, we will address the future of meteorite research, including asteroid sample return missions.