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Review

Homochirality Emergence: A Scientific Enigma with Profound Implications in Origins of Life Studies

ICBMS—UMR5246, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Université de Lyon, Claude Bernard Lyon 1, 69100 Villeurbanne, France
Symmetry 2025, 17(3), 473; https://doi.org/10.3390/sym17030473
Submission received: 25 February 2025 / Revised: 17 March 2025 / Accepted: 17 March 2025 / Published: 20 March 2025
(This article belongs to the Special Issue Chemistry: Symmetry/Asymmetry—Feature Papers and Reviews)

Abstract

:
Homochirality, the ubiquitous preference of biological molecules, such as amino acids, sugars, and phospholipids, for a single enantiomeric form, is a fundamental characteristic of life. This consistent bias across the biosphere, where proteins predominantly utilize L-amino acids and nucleic acids predominantly utilize D-sugars, is not merely a biochemical peculiarity but a crucial aspect of life’s molecular architecture. However, the origin of this homochirality remains one of the most compelling and unresolved mysteries in the study of life’s origins, drawing inquiry from fields as diverse as cosmology, physics, chemistry, and biology. This article provides an overview of chirality’s pervasive influence across these domains, tracing its potential origins from early Earth’s conditions to its pivotal role in shaping both natural phenomena and the technological advancements that define our future.

1. Introduction

The emergence of homochirality in living systems is an enigma that has puzzled scientists for over a century [1,2]. It is well known that when chiral molecules are synthesized in the laboratory or natural processes unrelated to life, they typically form in equal mixtures of both enantiomers, known as racemic mixtures [1]. For example, when amino acids are synthesized under simple conditions, they are usually found in a racemic state, with equal numbers of left-handed and right-handed forms [3,4]. So, why did life emerge with a preference for only one enantiomer? One hypothesis is that homochirality arose early in the history of life and was preserved through a process of natural selection. Once a particular enantiomer was selected, the molecular processes involved in life (such as the synthesis of proteins and nucleic acids) may have become intrinsically biased toward that enantiomer, reinforcing the homochirality of the system [1,5]. However, the origin of this initial bias remains unclear. Scientists have proposed numerous mechanisms that could have contributed to the emergence of homochirality, each rooted in different areas of research. The significance of homochirality in the development of life is central to the very structure and function of biological molecules [6,7,8,9,10,11]. Proteins, which are composed of amino acids, and nucleic acids, which are made of sugars and bases, both rely on the precise three-dimensional shapes of their constituent molecules to function properly. The same happens for phospholipid and chiral amphiphiles [12,13]. The specific handedness of the building blocks ensures that these molecules can interact in highly predictable ways, a requirement for the complex biochemical processes that sustain life [14,15]. Moreover, homochirality influences the chemical and physical properties of biomolecules, including their ability to form stable structures and interact in highly specific ways. Any deviation from this uniformity could result in systems that are chemically incompatible or unstable, thus presenting a potential barrier to the development of life. Chirality transcends the realm of a mere chemical curiosity, emerging as a fundamental force that orchestrates not only the intricate molecular machinery of life but also serves as a critical lens through which we can decipher the enigmatic origins of life itself. The prebiotic emergence of a chiral bias, a phenomenon that remains one of the most compelling puzzles in astrobiology and biochemistry, is theorized to have played a pivotal role in the spontaneous assembly of life’s essential molecular building blocks. This initial symmetry breaking, the preferential selection of one enantiomer over its mirror image, is believed to have set the stage for the cascade of complex chemical processes that sustain living systems today. The establishment of a homochiral environment, where one enantiomeric form predominates, provided a critical advantage, facilitating the formation of stable and functional biomolecules. Without this initial chiral selection, the formation of complex, self-replicating systems might have been significantly hindered, if not impossible. Thus, the investigation of chirality’s origins is not merely an academic pursuit; it is a fundamental endeavor that seeks to illuminate the very conditions that allowed life to emerge and flourish on our planet [16]. From advancing the development of more effective pharmaceuticals to driving innovations in materials science and deepening our understanding of biological systems, the importance of chiral molecules cannot be overstated.

What Is Meant by Chirality?

To contextualize the subsequent discussion on homochirality’s origins, it is imperative to delineate the fundamental principles of chirality. In chemical terms, chirality denotes the property of a molecule that renders it non-superimposable upon its mirror image. Analogous to the relationship between left and right hands, chiral molecules exist as enantiomers, stereoisomers with identical atomic constitutions but distinct three-dimensional arrangements. The term “chiral”, derived from the Greek “χείρ” (hand), aptly illustrates this duality. Enantiomers, while exhibiting similar physical characteristics, diverge in their interaction with polarized light. One enantiomer, the dextrorotatory form, rotates polarized light clockwise (+ or D); whereas the other, the levorotatory form, induces a counterclockwise rotation (− or L, see Figure 1). However, optical rotation, influenced by environmental variables such as temperature, solvent, and concentration, provides only relative, non-absolute, configurational information. To address this limitation, the Cahn–Ingold–Prelog (CIP) sequence rule system was developed in 1956, offering a standardized nomenclature for the unambiguous assignment of absolute configurations to chiral molecules [17]. In this system, atoms attached to the chiral center are ranked by atomic number, with the highest priority given to the atom with the largest atomic number. If two atoms share the same atomic number, the priority determination moves to the next set of atoms until a clear order is established [18,19,20,21,22,23]. The molecule is then viewed from the side opposite the lowest-priority atom. If the priority sequence is clockwise, the configuration is assigned as (R) for rectus; if counterclockwise, it is (S) for sinister. When a 50:50 mixture of enantiomers is present, their optical rotations cancel each other out, resulting in an optically inactive racemic mixture. However, it is crucial to note that optical rotation does not necessarily correlate with the absolute configuration of a molecule. As a result, the terms (R) and (S) should not be confused with (+) and (−) as they refer to distinct concepts. A defining feature of chiral molecules is how dramatically their properties can differ depending on the enantiomer present. This is particularly significant in biological systems, where molecular shape and reactivity are closely tied to chirality. For example, the three-dimensional shape of biomolecules, such as proteins, is a critical determinant of their function, making chirality an essential factor in the biochemical processes that govern life. Thus, the question arises: how did life favor one specific enantiomeric form over the other, leading to homochirality? [24,25]. In addition to enantiomers, chiral molecules can also exist as diastereomers, which are stereoisomers that are not mirror images of each other. Unlike enantiomers, diastereomers have different physical properties, such as melting points, solubility, and reactivity, making them easier to distinguish experimentally. While enantiomers differ in only one aspect, i.e., how they rotate polarized light, diastereomers can vary in multiple properties due to their distinct spatial arrangements. For example, in a pair of diastereomers, one might interact differently with biological macromolecules, potentially affecting the molecule’s biological activity or function. This distinction is particularly important in the context of drug design, where the different interactions between diastereomers and receptors or enzymes can lead to vastly different physiological effects. Therefore, while homochirality refers to the preference for a single enantiomeric form in biological systems, understanding diastereomers adds a layer of complexity to how chirality influences molecular behavior and interactions within living organisms [12].
Even when a biomolecule contains only two chiral centers, such as in a dipeptide excluding the null contribution of glycine, its isomers are no longer simple mirror images of one another. Thus, two distinct dimers can exist, the L-L dimer (from naturally occurring chiral amino acids, and its mirror counterpart, the D-D) and D-L (or L-D) isomers. The former is an enantiomer dimer, while the latter a diastereomer one. A typical example, homochiral poly-alanine sequences, such as D-D-D-D-D-… or L-L-L-L-L-…, readily form alpha-helical structures, whereas a mixed sequence like D-L-D-L-L-D-L-… does not exhibit this behavior. The same loss of functionality occurs when ribose, the unique source of chirality in DNA, is substituted by glycerol; this is achiral [12].

2. Possible Chiral Influence Form Space?

One of the most intriguing suggestions comes from the realm of astrophysics. It has been proposed that chiral molecules or processes may have influenced homochirality in space [2]. Some findings, recently discussed, suggest that chiral forces may have played a significant role in this process, offering additional evidence for the potential influence of extraterrestrial factors on the emergence of homochirality. Initial studies [25] have investigated the impact of chiral environments, particularly highlighting how light could bias the synthesis of chiral molecules, supporting the theory that such phenomena might have contributed to the origins of homochirality. Additionally, the discovery of chiral organic molecules in meteorites, space bodies, and comets has led some researchers to propose that homochirality could have first originated on prebiotic Earth by delivering these molecules from space [26,27,28]. Such an effect has been observed in laboratory experiments, where circularly polarized light can influence the synthesis of chiral molecules, potentially providing a mechanism for the initial skewing of enantiomers. Particularly, Meierhenrich, Meinert, and co-workers [27,28] have explored the role of chiral catalysts and circularly polarized light in asymmetric synthesis, emphasizing how polarized radiation from cosmic sources may have influenced the formation of chiral molecules both in space and on early Earth [29].

3. Autocatalytic Processes

Autocatalytic processes are a fundamental concept in chemistry, especially when discussing complex systems, prebiotic chemistry, and the origins of life [30]. Autocatalysis occurs when one or more products of a chemical reaction act as catalysts, accelerating the same reaction that produces them. In an autocatalytic process, product C could act as a catalyst, enabling more of the reactant A or B to be converted into C. Mathematically, autocatalysis can be modeled with differential equations. If we define the concentrations of the reactants and products as [A], [B], and [C], the rate of change in the concentration of C over time could be expressed as follows:
d C d t = k + m C n A B
where k is the rate constant for the initial reaction, [A] and [B] are the concentrations of reactants, and m[C]n represents the autocatalytic effect, where C accelerates its own production (with n being the order of the autocatalytic feedback). In such a system, as [C] increases, the autocatalytic term becomes more significant, leading to a rapid increase in the production of C, characteristic of an exponential growth phase. In addition to the direct autocatalytic process, chemical feedback loops refer to the broader concept where chemical reactions interact in a network, influencing each other’s rates and direction. There are two primary types of feedback:
  • Amplifying Reaction Mechanisms: Certain reaction pathways exhibit a characteristic where the products generated serve to increase the rate or extent of the reaction itself. This self-reinforcing dynamic can result in a rapid escalation of product formation, potentially leading to a state of uncontrolled progression under specific environmental parameters.
  • Regulatory Reaction Mechanisms: Conversely, other reaction pathways are characterized by a product-mediated deceleration. In these systems, the accumulation of reaction products acts to diminish the reaction rate, effectively establishing a self-limiting process. This type of regulatory control is frequently observed in complex systems, where it functions to maintain a stable internal state by preventing excessive product accumulation and ensuring system equilibrium.
Autocatalytic processes often combine both positive and negative feedback mechanisms to regulate their activity and prevent instability, creating a dynamic and self-regulating system.
In the origin of life (OOL) theories, autocatalytic networks are often considered essential for the transition from simple organic molecules to more complex life-like systems [23]. Once basic molecules were able to catalyze their formation, this could have led to the development of “molecular cooperation” in prebiotic chemistry, setting the stage for the biochemical networks seen in living organisms [30,31,32,33]. Autocatalytic networks may provide insight into how the first life forms emerged from simple molecules. In many theories of abiogenesis [34], the first life forms were likely based on simple, self-replicating molecules. These molecules could have been autocatalytic, meaning that their production was facilitated by the products they generated. This mechanism would have allowed them to increase in number and complexity over time, eventually evolving into the complex molecular systems that form the basis of cellular life. One hypothesis, largely criticized [35,36], is the “RNA world” hypothesis [37,38], where RNA molecules (i.e., ribozymes), perhaps encapsulated into a lipidic envelope, capable of both carrying genetic information and catalyzing their replication, could have been the first forms of life [39].
In the context of homochirality, it is hypothesized that an initial imbalance between the two enantiomers could have led to a self-reinforcing cycle. This creates a positive feedback loop that can potentially lead to an exponential growth of products under the right conditions. For instance, if one enantiomer of a molecule were capable of catalyzing the production of more molecules of the same enantiomer, this imbalance could progressively intensify, eventually leading to a homochiral environment. One such concept is the “chirality-driven autocatalysis” hypothesis, which suggests that minor asymmetries in the initial materials (potentially influenced by external factors like radiation, vide supra) could be magnified through autocatalytic reactions [6]. Over time, this process might result in the dominance of a single enantiomer, contributing to the homochirality observed in living systems. In this scenario, the autocatalytic replication of RNA molecules would have led to an exponential increase in the complexity of life, eventually evolving into the proteins and DNA-based life forms we see today.

3.1. Thermodinamic Limits

At the deterministic thermodynamic limit, the spontaneous emergence of racemic biases in energy-dissipative autocatalytic systems can be rigorously examined through bifurcation theory [40]. This framework reveals that under specific conditions, these systems can undergo transitions from a racemic steady-state to a state exhibiting enantiomeric excess. Specifically, as a critical parameter, such as substrate influx or energy dissipation rate, surpasses a bifurcation threshold, the system’s stability landscape undergoes a qualitative change [41]. The previously stable racemic state becomes unstable, and two symmetry-broken states, corresponding to enantiomeric enrichment in either the R or S configuration, emerge as stable attractors. This bifurcation scenario is thermodynamically justified by the minimization of a generalized potential, reflecting the system’s tendency to maximize entropy production or minimize free energy dissipation at steady-state. The selection of one enantiomeric excess over the other is stochastic at the bifurcation point, but once established, the system is driven towards a stable, non-racemic state by the inherent thermodynamic forces governing its behavior. This thermodynamic justification underscores the potential for spontaneous chiral symmetry breaking in far-from-equilibrium systems, even in the absence of stochastic fluctuations, highlighting the inherent capacity of energy dissipation to drive the evolution of molecular asymmetry.

3.2. Models: One Mathematical and One Experimental

In the early 1950s, Frank proposed a foundational mathematical framework elucidating the emergence of homochirality in chemical synthesis. This model posits an autocatalytic mechanism wherein a chiral molecule preferentially catalyzes its own formation while simultaneously exerting inhibitory effects on the production of its antipode. Consequently, the model predicts the selective generation of either the R or S enantiomer from an achiral precursor (Figure 2). This paradigm, which continues to hold significant currency within the field, underscores the critical role of asymmetric amplification in chiral reactions. Specifically, it demonstrates how a minute initial enantiomeric excess can be magnified to achieve a state of near-absolute homochirality, thereby providing a plausible mechanism for the observed dominance of single enantiomers in various chemical processes [42,43,44].
Frank’s seminal contribution to the understanding of homochiral amplification lies in the recognition that autocatalytic systems, where the catalyst and product are congruent, necessitate not only self-replication but also a mechanism for enantiomeric suppression, termed “mutual antagonism” [42]. This insight fundamentally distinguishes asymmetric autocatalysis from conventional asymmetric catalysis, offering critical advantages. Specifically, the autocatalytic process exhibits the following: (i) unparalleled efficiency through self-replication, enabling exponential amplification of chirality; (ii) sustained catalytic activity, as the catalyst’s concentration is inherently maintained and amplified alongside product formation, eliminating catalyst decay; and (iii) simplified product isolation, obviating the need for separation due to the structural identity between catalyst and product. These features collectively underscore the profound implications of Frank’s model, revealing how autocatalytic systems can drive the evolution of homochirality with remarkable selectivity and efficiency, a departure from the limitations imposed by non-autocatalytic processes. In keeping with Frank model, the Soai reaction, discovered by Kenzo Soai, is a striking example of asymmetric synthesis that produces chiral compounds with high enantiomeric excess (ee) from achiral substrates (Figure 3) [45,46]. The Soai reaction provides a model for how a slight initial chirality bias, potentially from random events or external chiral influences, could be amplified through autocatalysis to establish the homochirality observed in living organisms today. This reaction is characterized by autocatalysis, where a small initial enantiomeric excess of a chiral product triggers the amplification of its chirality, leading to a dramatic enrichment of one enantiomer over the other. This self-amplifying process has captivated researchers, particularly for its implications in understanding the origin of homochirality, a key feature of biological systems. In recent years, advancements in the Soai reaction have focused on optimizing its efficiency, broadening its substrate scope, and exploring novel catalytic systems, including the use of transition metals and organocatalysts. These developments continue to shed light on the reaction’s underlying mechanism, including the role of transient intermediates and external factors that influence chiral amplification [9,11,47,48,49]. The Soai reaction provides insights into homochirality’s emergence in prebiotic chemistry, suggesting how small chirality imbalances could evolve into enantiomeric excesses, offering clues about the origin of life’s homochirality and advancing asymmetric synthesis studies [50].

3.3. The Role of Autocatalysis in Evolution

Autocatalytic processes are hypothesized to have been instrumental in the emergence and evolution of molecular complexity, particularly within the context of prebiotic chemistry and the origins of life [52]. The establishment of self-replicating molecules or autocatalytic molecular systems would have provided a critical substrate for the onset of Darwinian selection. By intrinsically enhancing the propagation of self-replicating entities, autocatalytic systems would have conferred a selective advantage, thereby facilitating evolutionary trajectories analogous to those observed in biological systems [53]. This mechanism could have driven the progressive elaboration of molecular architectures and functionalities, ultimately leading to the complex biochemical networks characteristic of living organisms

3.4. The Case of Seryl-Histidine

Seryl-histidine (Ser-Hys) provides a fascinating example of how chirality, molecular recognition, and catalytic activity can converge in the context of prebiotic chemistry and the origins of life. The peptide bond formation between amino acids like serine and histidine, as well as their autocatalytic behavior, has been studied as a potential mechanism for self-replicating processes that could have contributed to the emergence of life. The importance of this dipeptide lies not only in its catalytic potential but also in its role as an example of how simple molecules could have initiated the complex processes needed for life’s origin. Histidine is an imidazole-containing amino acid, and its side chain can participate in acid–base reactions, making it a good candidate for catalyzing chemical reactions in a prebiotic environment (Figure 4).
The formation of a peptide bond between serine and histidine is a process that could have been catalyzed by ribozymes or other molecules in early Earth environments, but in a more simplified model, it can be catalyzed by the imidazole group of histidine itself. The structure of Ser-Hys allows it to potentially serve as a building block for more complex biochemical systems [54]. In the case of Ser-Hys, research has demonstrated that the dipeptide can exhibit “autocatalytic behavior”, where the presence of the dipeptide in a reaction mixture could facilitate the formation of additional Ser-Hys molecules [55,56]. This kind of feedback loop is a key concept in the study of self-replicating systems. For example, seryl-histidine can catalyze the formation of more peptide bonds between serine and histidine molecules by providing a template or a catalyst that accelerates the reaction. This self-promoting reaction could have been an important step toward more complex self-replicating systems that might have led to the development of life. One of the interesting features of Ser-Hys in the context of autocatalysis is how chirality could influence the reaction. The formation of Ser-Hys via autocatalysis could have been influenced by the “preference” for one enantiomer over the other, which would have been critical in setting the stage for the homochirality of life. In a prebiotic setting, the presence of an excess of one enantiomer of Ser-Hys could have provided an environment where this chirality was reinforced, leading to the eventual dominance of homochiral molecules in early biochemical systems. The autocatalytic nature of Ser-Hys could have been a key factor in amplifying this chirality bias, thus enabling the selective build-up of chiral molecules in the prebiotic world. Autocatalytic processes like those demonstrated by Ser-Hys may have provided a pathway toward more complex catalytic networks, which are essential for life [54,55,57]. These networks of interconnected catalytic reactions could have evolved from simple, autocatalytic processes like peptide bond formation into more intricate systems capable of carrying out a variety of metabolic and replication functions. In a way, the self-replicating and autocatalytic properties of Ser-Hys could serve as a building block for the complex biochemical cycles that sustain living systems today. For example, these early autocatalytic peptides may have acted as “protocatalysts”, facilitating the synthesis of other peptides or small molecules that could have contributed to early metabolic processes. This type of network could have led to the emergence of metabolism-first theories of life’s origin, which propose that life began with a simple, self-sustaining chemical system before evolving the ability to replicate genetic information [58]. Furthermore, the autocatalytic nature of seryl-histidine could have contributed to the self-organization of early molecular systems, where simple molecules gradually evolved into more sophisticated and functionally specialized compounds, eventually leading to the first self-replicating molecules capable of evolving and passing on genetic information [59].

3.5. Biological Amplification: From Randomness to Selection

The establishment of homochirality in early molecular systems likely triggered a feedback loop with biological processes [52]. Enzymes, chiral themselves, preferentially catalyze reactions favoring one enantiomer, amplifying the homochiral bias. This evolutionary interplay was crucial, as life evolved to exploit molecular asymmetry for functional specificity [60]. Autocatalysis is not merely a mechanism for life’s origin; it is a fundamental driver of evolution [61]. Darwinian evolution hinges on variation, heritability, and differential survival. Autocatalytic systems inherently generate variation through the emergence of diverse self-replicating molecules [62,63]. Environmental fluctuations or mutations can alter autocatalytic reaction rates, leading to the selection of advantageous variants. In biochemical evolution, autocatalysis facilitates rapid molecular population shifts, enabling adaptation to changing conditions. These dynamic fuels the diversification of life forms as autocatalytic networks evolve to exploit diverse environmental niches. The concept of autocatalysis aligns with “chemical Darwinism”, where natural selection acts upon evolving chemical systems, driven by the success of autocatalytic cycles [64]. As autocatalytic systems grew in complexity, they became more efficient at harnessing energy, culminating in the development of sophisticated molecular machinery [39].

3.6. The Power of Chirality in Modern Science

Chirality plays a crucial role in the interactions and information exchange between chemical entities, particularly in the fields of biochemistry and pharmacology. Chiral molecules, which are non-superimposable mirror images of each other, can exhibit vastly different behaviors despite having the same molecular formula. This is because biological systems, such as enzymes and receptors, are often stereoselective, meaning they preferentially interact with one enantiomer over the other. In this way, chirality encodes vital information that influences molecular recognition, catalysis, and signaling processes. For instance, in drug design, one enantiomer of a chiral compound may have therapeutic effects, while its mirror image may be inactive or even harmful. This delicate relationship between chirality and biological information underscores the importance of stereochemistry in the specificity and efficacy of molecular interactions, shaping the behavior of chemical entities in living systems.
Though it may appear abstract at first, the impact of chiral molecules is profound, shaping everything from the design of life-saving pharmaceuticals to the development of advanced materials and biotechnological innovations [65]. The significance of chirality extends far beyond chemistry itself, influencing biology, medicine, and materials science in ways that are fundamental to the very essence of life and the future of human health.
In the realm of medicinal chemistry, chirality governs the efficacy and safety of therapeutic drugs [66]. The two mirror-image forms of chiral molecules, called enantiomers, can have drastically different effects on the human body. While one enantiomer may provide the intended therapeutic benefit, the other could be inert or even harmful. This understanding has driven the development of drugs that are not only more effective but also safer, with fewer side effects. The precision with which chiral molecules interact with biological systems has become a cornerstone of drug design, making chirality an essential consideration in the creation of targeted therapies.
In polymer science, chiral molecules have opened up new possibilities for advanced materials with unique properties. Chiral polymers, which arise from chiral monomers, exhibit distinct mechanical, optical, and chemical behaviors that set them apart from their non-chiral counterparts. This is the typical case of monotactic macromolecules having one stereoisomeric atom per repeat, unit where ditactic to n-tactic macromolecules have more than one stereoisomeric atom per unit. Indeed, monotactic polymers in the origin of life studies are DNA and RNA. These materials are central to cutting-edge applications such as drug delivery systems, biosensors, and even materials used in environmental monitoring. Chiral polymers can selectively interact with specific enantiomers of other molecules, enabling innovations in separation technologies and creating new tools for both scientific research and industry [67].
In the world of biology, chirality is nothing short of foundational. The very building blocks of life—proteins, nucleic acids, and enzymes—are all chiral. The precision of molecular interactions driven by chirality is essential for maintaining the structure and function of these biomolecules. The shape and behavior of enzymes, which catalyze virtually every biochemical reaction in living organisms, depend entirely on their chiral nature. Understanding how chirality dictates these interactions is vital for fields such as synthetic biology, genetic engineering, and the burgeoning area of enzyme-based therapeutics.

4. Conclusions: The Continuing Mystery

Despite the significant strides made in elucidating the molecular mechanisms underpinning homochirality, the ultimate genesis of this fundamental biological phenomenon remains a profound and unresolved enigma. This persistent question, central to our understanding of life’s origins, continues to challenge researchers across diverse scientific disciplines. While a multitude of hypotheses have been advanced, encompassing a spectrum of potential causative factors, a singular, universally accepted explanation has yet to emerge. Some investigators advocate for a synergistic model, suggesting that the resolution of this puzzle may necessitate the integration of diverse influences, including extraterrestrial chiral biases, autocatalytic amplification, and the stochastic events of early molecular chemistry. Conversely, other researchers propose that a paradigm shift may be required, necessitating a re-evaluation of the very processes that culminated in the emergence of life. This perspective underscores the intrinsic connection between the quest for homochirality’s origin and the broader, equally compelling pursuit of understanding life’s initial spark. Homochirality, therefore, occupies a unique position, serving simultaneously as an essential hallmark of life and a formidable scientific conundrum. As researchers delve deeper into this phenomenon, employing increasingly sophisticated experimental and theoretical approaches, they are progressively uncovering the intricate network of forces and processes that sculpted the molecular asymmetry at the core of terrestrial life. Whether the initial impetus stemmed from subtle chiral biases imparted by cosmic radiation, the self-organizing capabilities of chemical systems, or the emergent properties of early biological evolution, the investigation of homochirality’s origins provides an unparalleled window into the complex interplay of factors that may have orchestrated the very genesis of life on Earth.

Funding

This research received no external funding.

Acknowledgments

This work is dedicated to my beloved daughter Océane.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. A visual representation (in Fischer) of enantiomers of the amino acid serine, a representation of the enantiomer of the ribose, and a representation of the possible diastereoisomer (*) of the L-ribose. All molecules are in the Fisher representation, with the top carbon (COOH) numbered as 1 in accordance with CIP rules.
Figure 1. A visual representation (in Fischer) of enantiomers of the amino acid serine, a representation of the enantiomer of the ribose, and a representation of the possible diastereoisomer (*) of the L-ribose. All molecules are in the Fisher representation, with the top carbon (COOH) numbered as 1 in accordance with CIP rules.
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Figure 2. Provides a visual representation of Frank’s seminal contribution to the understanding of symmetry breaking in chemical systems. The model elucidates an autocatalytic cycle wherein the chiral catalyst and its product are indistinguishable in terms of molecular architecture and absolute configuration, thereby establishing a pathway for the evolution of a homochiral state from an initially racemic or near-racemic mixture; (*) means that the product is chiral and act as the catalyst.
Figure 2. Provides a visual representation of Frank’s seminal contribution to the understanding of symmetry breaking in chemical systems. The model elucidates an autocatalytic cycle wherein the chiral catalyst and its product are indistinguishable in terms of molecular architecture and absolute configuration, thereby establishing a pathway for the evolution of a homochiral state from an initially racemic or near-racemic mixture; (*) means that the product is chiral and act as the catalyst.
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Figure 3. A significant advance in understanding asymmetric autocatalysis is the elucidated mechanism of the pyrimidine-5-carbaldehyde alkylation with diisopropylzinc. This reaction, known for its asymmetry-amplifying properties, has been the subject of detailed investigations, including the role of chiral initiators, as recently reviewed in refs. [49,51]. In this specific example, the initiator is the S enantiomer.
Figure 3. A significant advance in understanding asymmetric autocatalysis is the elucidated mechanism of the pyrimidine-5-carbaldehyde alkylation with diisopropylzinc. This reaction, known for its asymmetry-amplifying properties, has been the subject of detailed investigations, including the role of chiral initiators, as recently reviewed in refs. [49,51]. In this specific example, the initiator is the S enantiomer.
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Figure 4. The chemical structure of the catalytic dipeptide serine hystidine.
Figure 4. The chemical structure of the catalytic dipeptide serine hystidine.
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Fiore, M. Homochirality Emergence: A Scientific Enigma with Profound Implications in Origins of Life Studies. Symmetry 2025, 17, 473. https://doi.org/10.3390/sym17030473

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Fiore M. Homochirality Emergence: A Scientific Enigma with Profound Implications in Origins of Life Studies. Symmetry. 2025; 17(3):473. https://doi.org/10.3390/sym17030473

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Fiore, Michele. 2025. "Homochirality Emergence: A Scientific Enigma with Profound Implications in Origins of Life Studies" Symmetry 17, no. 3: 473. https://doi.org/10.3390/sym17030473

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Fiore, M. (2025). Homochirality Emergence: A Scientific Enigma with Profound Implications in Origins of Life Studies. Symmetry, 17(3), 473. https://doi.org/10.3390/sym17030473

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