Homochiral State Research Articles

Emergence of Homochirality via Template-Directed Ligation in an RNA Reactor

RNA in extant biological systems is homochiral; it consists exclusively of -ribonucleotides rather than -ribonucleotides. How the homochirality of RNA emerged is not known. Here we use stochastic simulations to quantitatively explore the conditions for RNA homochirality to emerge in the prebiotic scenario of an RNA reactor, in which RNA strands react in a nonequilibrium environment. These reactions include the hybridization, dehybridization, template-directed ligation, and cleavage of RNA strands. The RNA reactor is either closed, with a finite pool of ribonucleotide monomers of both chiralities ( and ), or the reactor is open, with a constant inflow of a racemic mixture of monomers. For the closed reactor, we also consider the interconversion between and monomers via a racemization reaction. We first show that template-free polymerization is unable to reach a high degree of homochirality, due to the lack of autocatalytic amplification. In contrast, in the presence of template-directed ligation, with base pairing and stacking between bases of the same chirality thermodynamically favored, a high degree of homochirality can arise and be maintained provided the nonequilibrium environment overcomes product inhibition, for instance, via temperature cycling. Indeed, if the experimentally observed kinetic stalling of ligation after chiral mismatches is also incorporated, the RNA reactor can evolve towards a fully homochiral state, in which one chirality is entirely lost. This is possible because the kinetic stalling after chiral mismatches effectively implements a chiral cross-inhibition process. Taken together, our model supports a scenario where the emergence of homochirality is assisted by template-directed ligation and polymerization in a nonequilibrium RNA reactor. Published by the American Physical Society 2024

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.

Tailoring energy barriers of Bloch-point-mediated transitions between topological spin textures

Magnetic skyrmions are nanoscale spin textures whose thermal stability originates from the nontrivial topology in nature. Recently, a plethora of topological spin textures have been theoretically predicted or experimentally observed, enriching the diversity of the skyrmionic family. In this work, we theoretically demonstrate the stabilities of various topological spin textures against homochiral states in chiral magnets, including chiral bobbers, dipole strings, and skyrmion tubes. They can be effectively classified by the associated topological Hall signals. Multiple transition paths are found among these textures, mediated by Bloch-point singularities, and the topological protection property here can be manifested by a finite energy barrier with the saddle point corresponding to the Bloch-point creation/destruction. By carefully modulating the local property of a surface, such as interfacial Dzyaloshinskii-Moriya interaction induced by breaking the structural symmetry, the energy landscape of a magnetic system can be tailored decisively. Significantly, the proposed scenario also enables the manipulation of stabilities and transition barriers of these textures, even accompanied by the discovery of ground-state chiral bobbers. This study may raise great expectations on the coexistence of topological spin textures as spintronics-based information carriers for future applications. Published by the American Physical Society 2024

The central dogma of biological homochirality: How does chiral information propagate in a prebiotic network?

Biological systems are homochiral, raising the question of how a racemic mixture of prebiotically synthesized biomolecules could attain a homochiral state at the network level. Based on our recent results, we aim to address a related question of how chiral information might have flowed in a prebiotic network. Utilizing the crystallization properties of the central ribonucleic acid (RNA) precursor known as ribose-aminooxazoline (RAO), we showed that its homochiral crystals can be obtained from its fully racemic solution on a magnetic mineral surface due to the chiral-induced spin selectivity (CISS) effect [Ozturk et al., arXiv:2303.01394 (2023)]. Moreover, we uncovered a mechanism facilitated by the CISS effect through which chiral molecules, such as RAO, can uniformly magnetize such surfaces in a variety of planetary environments in a persistent manner [Ozturk et al., arXiv:2304.09095 (2023)]. All this is very tantalizing because recent experiments with tRNA analogs demonstrate high stereoselectivity in the attachment of L-amino acids to D-ribonucleotides, enabling the transfer of homochirality from RNA to peptides [Wu et al., J. Am. Chem. Soc. 143, 11836 (2021)]. Therefore, the biological homochirality problem may be reduced to ensuring that a single common RNA precursor (e.g., RAO) can be made homochiral. The emergence of homochirality at RAO then allows for the chiral information to propagate through RNA, then to peptides, and ultimately through enantioselective catalysis to metabolites. This directionality of the chiral information flow parallels that of the central dogma of molecular biology-the unidirectional transfer of genetic information from nucleic acids to proteins [F. H. Crick, in Symposia of the Society for Experimental Biology, Number XII: The Biological Replication of Macromolecules, edited by F. K. Sanders (Cambridge University Press, Cambridge, 1958), pp. 138-163; and F. Crick, Nature 227, 561 (1970)].

From a coenzyme-like mechanism to homochirality

Inspired in a coenzyme-like behavior, an alternative mechanism to induce homochirality within a small vesicle is proposed. The system includes six different chemical species: an achiral substrate A, the enantiomeric forms L and D, a coenzyme E and two intermediate catalytic forms LE and DE. Whereas the coenzyme and the intermediate catalytic forms are trapped within the vesicle, the substrate and the two enantiomeric forms are able to diffuse selectively across the vesicle boundary. Instead of using autocatalysis, the production of new enantiomers includes two different steps, the production of intermediate catalytic species (LE, DE) and the catalytic production of new enantiomers from the substrate. Using a suitable parameterization, we found that the chiral evolution of the system is highly dependent on the total amount of coenzyme within the vesicle, regardless of whether the surrounding membrane is permeable or not. However, the existence of large flows from the outside can destabilize the homochiral state inside the vesicle. In general, homochiral states tend to arise when the amount of coenzyme is quite low, a value that can vary according to the parametrization. On the other hand, the system tends to decrease the enantiomeric excess when the coenzyme levels are high enough. In general, the appearance of homochirality is conditioned by stochastic fluctuations in coenzyme levels within the vesicle, an effect that is gradually amplified throughout the entire process of enantiomer synthesis.

A robust transition to homochirality in complex chemical reaction networks

Homochirality, i.e. the dominance across all living matter of one enantiomer over the other among chiral molecules, is thought to be a key step in the emergence of life. Building on ideas put forward by Frank and many others, we proposed recently one such mechanism in Laurentet al.(Laurent, 2021Proc. Natl Acad. Sci. USA118, e2012741118. (doi:10.1073/pnas.2012741118)) based on the properties of large out of equilibrium chemical networks. We showed that in such networks, a phase transition towards a homochiral state is likely to occur as the number of chiral species in the system becomes large or as the amount of free energy injected into the system increases. This paper aims at clarifying some important points in that scenario, not covered by our previous work. We first analyse the various conventions used to measure chirality, introduce the notion of chiral symmetry of a network and study its implications regarding the relative chiral signs adopted by different groups of molecules. We then propose a generalization of Frank’s model for large chemical networks, which we characterize completely using methods of random matrices. This analysis is extended to sparse networks, which shows that the emergence of homochirality is a robust transition.

Chiral response of spin-spiral states as the origin of chiral transport fingerprints of spin textures

The transport properties of nontrivial spin textures are coming under closer scrutiny as the amount of experimental data and theoretical simulations is increasing. To extend the commonly accepted yet simplifying and approximate picture of transport effects taking place in systems with spatially varying magnetization, it is important to understand the transport properties of building blocks for spin textures---the homochiral spin-spiral states. In this work, by referring to phenomenological symmetry arguments based on the gradient expansion, and explicit calculations within the Kubo framework, we study the transport properties of various types of spin-spirals in a two-dimensional model with strong spin-orbit interaction. In particular, we focus on the contributions to the magnetoconductivity, the planar Hall effect, and the anomalous Hall effect, which are sensitive to the sense of chirality of the spiral states. We analyze the emergence, symmetry, and microscopic properties of the resulting chiral magnetoconductivity, chiral planar Hall effect, and chiral Hall effect in terms of spin-spiral propagation direction, cone angle, spiral pitch, and disorder strength. Our findings suggest that the presence of spin-spiral states in magnets can be readily detected in various types of magnetotransport setups. Moreover, the sizable magnitude of chiral contributions to the conductivity of skyrmions estimated from homochiral spirals implies that chiral, as opposed to topological, magnetotransport can play a prominent role for the detection of nontrivial spin textures.

Topological spin/structure couplings in layered chiral magnet Cr1/3TaS2: The discovery of spiral magnetic superstructure

Chiral magnets have recently emerged as hosts for topological spin textures and related transport phenomena, which can find use in next-generation spintronic devices. The coupling between structural chirality and noncollinear magnetism is crucial for the stabilization of complex spin structures such as magnetic skyrmions. Most studies have been focused on the physical properties in homochiral states favored by crystal growth and the absence of long-ranged interactions between domains of opposite chirality. Therefore, effects of the high density of chiral domains and domain boundaries on magnetic states have been rarely explored so far. Herein, we report layered heterochiral Cr1/3TaS2, exhibiting numerous chiral domains forming topological defects and a nanometer-scale helimagnetic order interlocked with the structural chirality. Tuning the chiral domain density, we discovered a macroscopic topological magnetic texture inside each chiral domain that has an appearance of a spiral magnetic superstructure composed of quasiperiodic Néel domain walls. The spirality of this object can have either sign and is decoupled from the structural chirality. In weak, in-plane magnetic fields, it transforms into a nonspiral array of concentric ring domains. Numerical simulations suggest that this magnetic superstructure is stabilized by strains in the heterochiral state favoring noncollinear spins. Our results unveil topological structure/spin couplings in a wide range of different length scales and highly tunable spin textures in heterochiral magnets.

Spontaneous chiral self-assembly of CdSe@CdS nanorods

Spontaneous chiral self-assembly of CdSe@CdS nanorods

Noise-induced symmetry breaking of self-regulators: Nonequilibrium transition toward homochirality.

We present a theoretical model to study the origin of chiral symmetry breaking of a racemic mixture of optically active biomolecules. We consider a collection of Brownian particles, which can stay in any of the three possible isomeric states: one achiral and two enantiomers. Isomers are undergoing self-regulatory reaction along with chiral inhibition and achiral decay processes. The reaction rates of the isomeric states are guided by their neighbors as well as the thermal fluctuations of the system. We find that an alteration in the relative dominance of self-regulation, chiral inhibition, and achiral decay processes breaks the chiral symmetry of the system, which is either partial or complete. This results in four different asymmetric population states, viz., three-isomer coexistence, enantiomeric coexistence, chiral-achiral coexistence, and homochiral state. A change in the reaction condition induces nonequilibrium transition among these states. We also report that a fast stochastic self-regulation and a slow chiral inhibition and achiral decay process along with a threshold population of interacting neighbors suffice for the requisite for transition toward a completely symmetry broken state, i.e., homochirality.

Racemization in Post-Translational Modifications Relevance to Protein Aging, Aggregation and Neurodegeneration: Tip of the Iceberg.

Homochirality of DNA and prevalent chirality of free and protein-bound amino acids in a living organism represents the challenge for modern biochemistry and neuroscience. The idea of an association between age-related disease, neurodegeneration, and racemization originated from the studies of fossils and cataract disease. Under the pressure of new results, this concept has a broader significance linking protein folding, aggregation, and disfunction to an organism’s cognitive and behavioral functions. The integrity of cognitive function is provided by a delicate balance between the evolutionarily imposed molecular homo-chirality and the epigenetic/developmental impact of spontaneous and enzymatic racemization. The chirality of amino acids is the crucial player in the modulation the structure and function of proteins, lipids, and DNA. The collapse of homochirality by racemization is the result of the conformational phase transition. The racemization of protein-bound amino acids (spontaneous and enzymatic) occurs through thermal activation over the energy barrier or by the tunnel transfer effect under the energy barrier. The phase transition is achieved through the intermediate state, where the chirality of alpha carbon vanished. From a thermodynamic consideration, the system in the homo-chiral (single enantiomeric) state is characterized by a decreased level of entropy. The oscillating protein chirality is suggesting its distinct significance in the neurotransmission and flow of perceptual information, adaptive associative learning, and cognitive laterality. The common pathological hallmarks of neurodegenerative disorders include protein misfolding, aging, and the deposition of protease-resistant protein aggregates. Each of the landmarks is influenced by racemization. The brain region, cell type, and age-dependent racemization critically influence the functions of many intracellular, membrane-bound, and extracellular proteins including amyloid precursor protein (APP), TAU, PrP, Huntingtin, α-synuclein, myelin basic protein (MBP), and collagen. The amyloid cascade hypothesis in Alzheimer’s disease (AD) coexists with the failure of amyloid beta (Aβ) targeting drug therapy. According to our view, racemization should be considered as a critical factor of protein conformation with the potential for inducing order, disorder, misfolding, aggregation, toxicity, and malfunctions.

Spontaneous Deracemizations.

Spontaneous deracemizations is a challenging, multidisciplinary subject in current chirality research. In the absence of any chiral inductors, an achiral substance or a racemic composition is driven into an enantioenriched or even homochiral state through a selective energy input, e.g., chemical potential, photoirradiation, mechanical grinding, ultrasound waves, thermal gradients, etc. The most prominent examples of such transformations are the Soai reaction and the Viedma deracemization. In this review, we track the most recent developments in this topic and recall that many other deracemizations have been reported for solutions from mesophases to conglomerate crystallizations. A compiled set of simply available achiral organic, inorganic, organometallic, and MOF compounds, yielding conglomerate crystals, should give the impetus to realize new experiments on spontaneous deracemizations. Taking into account thermodynamic constraints, modeling efforts have shown that structural features alone are not sufficient to describe spontaneous deracemizations. As a guideline of this review, particular attention is paid to the physicochemical origin and symmetry requirements of such processes.

Emergence of homochirality in large molecular systems

The selection of a single molecular handedness, or homochirality across all living matter, is a mystery in the origin of life. Frank's seminal model showed in the '50s how chiral symmetry breaking can occur in nonequilibrium chemical networks. However, an important shortcoming in this classic model is that it considers a small number of species, while there is no reason for the prebiotic system, in which homochirality first appeared, to have had such a simple composition. Furthermore, this model does not provide information on what could have been the size of the molecules involved in this homochiral prebiotic system. Here, we show that large molecular systems are likely to undergo a phase transition toward a homochiral state, as a consequence of the fact that they contain a large number of chiral species. Using chemoinformatics tools, we quantify how abundant chiral species are in the chemical universe of all possible molecules of a given length. Then, we propose that Frank's model should be extended to include a large number of species, in order to possess the transition toward homochirality, as confirmed by numerical simulations. Finally, using random matrix theory, we prove that large nonequilibrium reaction networks possess a generic and robust phase transition toward a homochiral state.

Chiral Oscillations and Spontaneous Mirror Symmetry Breaking in a Simple Polymerization Model

The origin of biological homochirality—defined as the preference of biological systems for only one enantiomer—has widespread implications in the study of chemical evolution and the origin of life. The activation—polymerization—epimerization—depolymerization (APED) model is a theoretical model originally proposed to describe chiral symmetry breaking in a simple dimerization system. It is known that the model produces chiral and chemical oscillations for certain system parameters, in particular, the preferential formation of heterochiral polymers. In order to investigate the effect of higher oligomers, our model adds trimers, tetramers, and pentamers. We report sustained oscillations of all chemical species and the enantiomeric excess for a wide range of parameter sets as well as the periodic chiral amplification of a small initial enantiomeric excess to a nearly homochiral state.

Chirality in Self-Assembling Rod-Coil Copolymers: Macroscopic Homochirality Versus Local Chirality

We study chiral mesophases arising as a result of the interplay between microphase separation and orientational ordering in diblock rod-coil copolymers. It is shown that nearly compositionally symmetric copolymers form a columnar structure with twisted rod-rich domains, whereas there is a suppression of the lamellar morphologies with respect to the columnar one. Using high-resolution three-dimensional self-consistent field simulations, we show that chirality in the unit cell of the hexagonal phase develops in two different ways, leading to either homochiral state or heterochiral (locally chiral) state. Thus, chiral polarization, which occurs when the rigid and flexible blocks are segregated, causes a transition to two degenerate chiral states. In a system with many twisted domains, the magnitude of the chirality charge obeys the binomial distribution with random selection of the twist direction for each of the rod-rich domains. We suggest a model of pseudodynamical structural evolution aimed at understanding of how chirality arises from the achiral state and how it evolves. At the initial stage of the evolutionary process, there exists some waiting time for the onset of irreversible changes in chirality; during this time the system flips between the two chirality states.

Proline autocatalysis in the origin of biological enantioenriched chirality.

Biological enantioenriched chirality is a phenomenon that in living organisms, amino acids and carbohydrates typically have the same absolute configuration. Perhaps one of the earliest attempts to delineate the origins of this phenomenon was a theory known as asymmetric autocatalysis, a reaction in which the structures of the chiral catalyst and the product are the same, and in which the chiral product acts as a chiral catalyst for its own production. In theory, this would mean that small asymmetries in the product will propagate rapidly. However, autocatalysis also relies on the cross-inhibition of chiral states, something that would not likely be possible on primordial Earth. But recently, theories on asymmetric autocatalysis have begun to resurface as more recent findings indicate that other mechanisms exist to stabilize the homochiral states. In this study, I propose an autocatalytic cycle, and using density functional theory, prove that (1) it is plausible on primordial Earth, and (2) it propagates arbitrary asymmetries in proline. Thus, facilitating asymmetry in proline and allowing access to a wide variety of asymmetric proline-catalyzed reactions, including those involved in the synthesis of amino acids and carbohydrates from achiral precursors.

Diastereoselective Ullmann Coupling to Bishelicenes by Surface Topochemistry.

The comparison of the self-assembly 9,9'-bisheptahelicene on the Au(111) surface, studied with scanning tunneling microscopy, with the self-assembly of the same species obtained by on-surface synthesis via Ullmann coupling from 9-bromoheptahelicene reveals a diastereomeric excess for the ( M, P)- meso-form of 50%. The stereoselectivity is explained by a topochemical effect, in which the surface-alignment of the starting material and the organometallic intermediate sterically favor the ( M, P)-transition state over the homochiral transition states.

Noise-induced symmetry breaking far from equilibrium and the emergence of biological homochirality.

The origin of homochirality, the observed single-handedness of biological amino acids and sugars, has long been attributed to autocatalysis, a frequently assumed precursor for early life self-replication. However, the stability of homochiral states in deterministic autocatalytic systems relies on cross-inhibition of the two chiral states, an unlikely scenario for early life self-replicators. Here we present a theory for a stochastic individual-level model of autocatalytic prebiotic self-replicators that are maintained out of thermal equilibrium. Without chiral inhibition, the racemic state is the global attractor of the deterministic dynamics, but intrinsic multiplicative noise stabilizes the homochiral states. Moreover, we show that this noise-induced bistability is robust with respect to diffusion of molecules of opposite chirality, and systems of diffusively coupled autocatalytic chemical reactions synchronize their final homochiral states when the self-replication is the dominant production mechanism for the chiral molecules. We conclude that nonequilibrium autocatalysis is a viable mechanism for homochirality, without imposing additional nonlinearities such as chiral inhibition.

A Novel Design Approach To Scale Up the Temperature Cycle Enhanced Deracemization Process: Coupled Mixed-Suspension Vessels

An improved process for the deracemization of a racemic conglomerate suspension of enantiomorphs has been created based on principles developed in an earlier method using temperature fluctuations. The method consists of circulating the suspension between two vessels, each controlled at a specific temperature in order to make the process more effective and faster to achieve a homochiral solid state. Crystals in the suspension were partially dissolved in the hot vessel, and the remaining crystals were regrown in the cold vessel. The crystals in the cold vessel have a longer residence time than those in the hot vessel to allow more time for the crystal growth process. The results show that complete deracemization can be achieved via this process far more rapidly than by using the previous temperature cycling (one-vessel) process. Moreover, the new process could easily be scaled up to an industrial scale. The current process can be an effective alternative to currently used enantiopurification methods, with s...

Noise-Induced Mechanism for Biological Homochirality of Early Life Self-Replicators.

The observed single-handedness of biological amino acids and sugars has long been attributed to autocatalysis. However, the stability of homochiral states in deterministic autocatalytic systems relies on cross inhibition of the two chiral states, an unlikely scenario for early life self-replicators. Here, we present a theory for a stochastic individual-level model of autocatalysis due to early life self-replicators. Without chiral inhibition, the racemic state is the global attractor of the deterministic dynamics, but intrinsic multiplicative noise stabilizes the homochiral states, in both well-mixed and spatially extended systems. We conclude that autocatalysis is a viable mechanism for homochirality, without imposing additional nonlinearities such as chiral inhibition.