Origin Of Biological Homochirality Research Articles

Origin of biological homochirality by crystallization of an RNA precursor on a magnetic surface.

Homochirality is a signature of life on Earth, yet its origins remain an unsolved puzzle. Achieving homochirality is essential for a high-yielding prebiotic network capable of producing functional polymers like RNA and peptides on a persistent basis. Because of the chiral-induced spin selectivity effect, which established a strong coupling between electron spin and molecular chirality, magnetic surfaces can act as chiral agents and be templates for the enantioselective crystallization of chiral molecules. Here, we studied the spin-selective crystallization of racemic ribo-aminooxazoline (RAO), an RNA precursor, on magnetite (Fe3O4) surfaces, achieving an unprecedented enantiomeric excess (ee) of about 60%. Following the initial enrichment, we then obtained homochiral (100% ee) crystals of RAO after a subsequent crystallization. Our results demonstrate a prebiotically plausible way of achieving system-level homochirality from completely racemic starting materials, in a shallow-lake environment on early Earth where sedimentary magnetite deposits are expected to be common.

Crystal Prediction via Genetic Algorithms in a Model Chiral System.

Chiral crystals and their constituent molecules play a prominent role in theories about the origin of biological homochirality and in drug discovery, design, and stability. Although the prediction and identification of stable chiral crystal structures is crucial for numerous technologies, including separation processes and polymorph selection and control, predictive ability is often complicated by a combination of many-body interactions and molecular complexity and handedness. In this work, we address these challenges by applying genetic algorithms to predict the ground-state crystal lattices formed by a chiral tetramer molecular model, which we have previously shown to exhibit complex fluid-phase behavior. Using this approach, we explore the relative stability and structures of the model's conglomerate and racemic crystals, and present a structural phase diagram for the stable Bravais crystal types in the zero-temperature limit.

A New Twist in Eutectic Composition: Deracemization of a Racemic Compound Amino Acid by Viedma Ripening and Temperature Fluctuation

AbstractViedma ripening and temperature fluctuation are processes based on solution phase racemization and dissolution‐growth of racemic or scalemic conglomerates resulting in solid‐phase deracemization. The dissolution‐growth process is performed by abrasive grinding in the first case and by the temperature fluctuation in the second. But both methods have the intrinsic drawback of being only applicable to conglomerates, accounting for only 10 % of all chiral molecules and are not suitable for the 90 % of chiral compounds that crystallize as racemic compound. Herein we show that the enantiomeric excess of the solution in the eutectic mixture formed by a racemic compound and one of its enantiomers in suspension changes dramatically by growth‐dissolution of the crystals through grinding and temperature fluctuation, converting the racemic compound into the desired enantiomer. With this new finding the scope of Viedma ripening and temperature fluctuation could be significantly expanded and can shed new ideas about the origin of biological homochirality on earth.

Asymmetric Autocatalysis as a Link Between Crystal Chirality and Highly Enantioenriched Organic Compounds

AbstractThe origin of biological homochirality has attracted much attention. Pyrimidyl alkanols exhibit asymmetric autocatalysis with significant amplification of enantiomeric excess in the reaction between pyrimidine‐5‐carbaldehyde and diisopropyl zinc (the Soai reaction). Chiral inorganic crystals such as quartz, cinnabar and sodium chlorate act as chiral triggers of asymmetric autocatalysis to afford highly enantioenriched pyrimidyl alkanol, with the absolute configurations corresponding to those of the chiral crystals. Chiral organic crystals composed of achiral organic compounds such as cytosine, adenine dinitrate, and γ‐glycine act as the chiral triggers of the Soai reaction to afford pyrimidyl alkanol with high ee that corresponds to the absolute configuration of the chiral trigger. This review describes that chiral minerals and chiral organic crystals act as the chiral triggers of the Soai reaction and that these chiral crystals are correlated to near‐enantiopure chiral organic compounds.

Anomalous fluctuations and selective extinction in primordial replicators: a ‘struggle for life’ at the origin of biological homochirality

AbstractThe prevalent presence of a single chiral variant of molecules in live organisms is one of the most distinctive signs of life as a global phenomenon. One of the greatest ambitions of biochemistry and astrobiology is to provide an explanation of this predominance. Several mechanisms were proposed in the past, from the propagation of chirality from a homo-chiral substrate to the amplification of effects associated with electro-weak interactions. Here, a different scenario is proposed: anomalous fluctuations associated with a self-replication scenario can lead to the selective extinction of primordial organisms using one of two enantiomers as an enzyme. These fluctuations arise spontaneously under very general conditions. The idea is based on three key points: (a) the simulation of early biological processes as a ‘board game’; (b) the presence of large fluctuations during an autocatalytic process; (c) the presence of a limited source of chemical energy, inducing a form of competition in a primordial replicator population. In order to demonstrate this mechanism, a computational model is developed, describing the ‘struggle for life’ of two different kinds of primordial replicators on a ‘chessboard’ with periodic boundary conditions; each replicator employs enzymes of different chirality on a non-chiral substrate, thereby with no selective advantage. The replication occurs randomly and with a fixed probability, providing that a sufficient amount of chemical energy is locally available. For the first time, our model includes the local balance of chemical energy in a molecular form on the substrate. The correlation between the chemical energy and the local populations is shown. Results clearly show that strong fluctuations in the number of individuals of each species and subsequent selective extinction events of one of the two species are observed. These studies may contribute to shed light on the most mysterious phase transition that occurred during the biochemical evolution of our planet.

Demystifying the asymmetry-amplifying, autocatalytic behaviour of the Soai reaction through structural, mechanistic and computational studies.

The Soai reaction has profoundly impacted chemists’ perspective of chiral symmetry breaking, absolute asymmetric synthesis and its role in the origin of biological homochirality. Herein, we describe the unprecedented observation of asymmetry amplifying autocatalysis in the alkylation of 5-(trimethylsilylethynyl)pyridine-3-carbaldehyde using diisopropylzinc. Kinetic studies with a surrogate substrate and spectroscopic analysis of a series of zinc-alkoxides that incorporate specific structural mutations reveal a ‘pyridine-assisted cube escape’. The new tetrameric cluster functions as a catalyst that activates the substrate through a two point binding mode and poises a coordinated diisopropylzinc moiety for alkyl group transfer. Transition-state models leading to both the homochiral and heterochiral products were validated by density functional theory calculations. Moreover, experimental and computational analysis of the heterochiral complex provides a definitive explanation for the non-linear behavior of this system. Our deconstruction of the Soai system reveals the structural logic for autocatalyst evolution, function and substrate compatibility – a central mechanistic aspect of this iconic transformation.

Acceleration of amino acid racemization by isovaline: possible implications for homochirality and biosignature search

AbstractIn nature, abiotically formed amino acids are usually racemic. However, this is not true for the α,α-dialkyl amino acid isovaline (Iva), which has an L-enantiomeric excess in some specimens of carbonaceous meteorites. On the early Earth and Mars, such meteorites were sources of amino acids, including Iva. Therefore, a connection may exist between the possible chiral influence of non-racemic Iva and the origin of biological homochirality. On the surface of a young terrestrial planet, amino acids can be chemically altered in many ways. For example, high temperatures from geothermal heating can lead to racemization. Four billion years ago, active volcanism and volcanic islands provided suitable conditions for such reactions and perhaps even for early microbial life on Earth. In the current study, we investigated the influence of D- and L-Iva on the thermal racemization of L-alanine (L-Ala) and L-2-aminobutyric acid (L-Abu) in a simulated hot volcanic environment. The amino acids were intercalated in the clay mineral calcium montmorillonite (SAz-1). While Iva was resistant to racemization, partial racemization was observed for Ala and Abu after 8 weeks at 150°C. The experimental results – for example, accelerated racemization in the presence of Iva and different influences of the Iva enantiomers – suggest that the amino acid molecules interacted with each other, possibly in hydrogen-bonded dimers. Accelerated racemization of amino acids could have been an obstacle to the development of homochirality. Besides, it is also detrimental to the use of homochirality as a biosignature, for example, in the search for microbial life on Mars.

The origin of biological homochirality along with the origin of life.

How homochirality concerning biopolymers (DNA/RNA/proteins) could have originally occurred (i.e., arisen from a non-life chemical world, which tended to be chirality-symmetric) is a long-standing scientific puzzle. For many years, people have focused on exploring plausible physic-chemical mechanisms that may have led to prebiotic environments biased to one chiral type of monomers (e.g., D-nucleotides against L-nucleotides; L-amino-acids against D-amino-acids)-which should have then assembled into corresponding polymers with homochirality, but as yet have achieved no convincing advance. Here we show, by computer simulation-with a model based on the RNA world scenario, that the biased-chirality may have been established at polymer level instead, just deriving from a racemic mixture of monomers (i.e., equally with the two chiral types). In other words, the results suggest that the homochirality may have originated along with the advent of biopolymers during the origin of life, rather than somehow at the level of monomers before the origin of life.

Symmetry Breaking in Self-Assembled Nanoassemblies

The origin of biological homochirality, e.g., life selects the L-amino acids and D-sugar as molecular component, still remains a big mystery. It is suggested that mirror symmetry breaking plays an important role. Recent researches show that symmetry breaking can also occur at a supramolecular level, where the non-covalent bond was crucial. In these systems, equal or unequal amount of the enantiomeric nanoassemblies could be formed from achiral molecules. In this paper, we presented a brief overview regarding the symmetry breaking from dispersed system to gels, solids, and at interfaces. Then we discuss the rational manipulation of supramolecular chirality on how to induce and control the homochirality in the self-assembly system. Those physical control methods, such as Viedma ripening, hydrodynamic macro- and micro-vortex, superchiral light, and the combination of these technologies, are specifically discussed. It is hoped that the symmetry breaking at a supramolecular level could provide useful insights into the understanding of natural homochirality and further designing as well as controlling of functional chiral materials.

Spontaneous mirror symmetry breaking and origin of biological homochirality.

Recent reports on both theoretical simulations and on the physical chemistry basis of spontaneous mirror symmetry breaking (SMSB), that is, asymmetric synthesis in the absence of any chiral polarizations other than those arising from the chiral recognition between enantiomers, strongly suggest that the same nonlinear dynamics acting during the crucial stages of abiotic chemical evolution leading to the formation and selection of instructed polymers and replicators, would have led to the homochirality of instructed polymers. We review, in the first instance, which reaction networks lead to the nonlinear kinetics necessary for SMSB, and the thermodynamic features of the systems where this potentiality may be realized. This could aid not only in the understanding of SMSB, but also the design of reliable scenarios in abiotic evolution where biological homochirality could have taken place. Furthermore, when the emergence of biological chirality is assumed to occur during the stages of chemical evolution leading to the selection of polymeric species, one may hypothesize on a tandem track of the decrease of symmetry order towards biological homochirality, and the transition from the simple chemistry of astrophysical scenarios to the complexity of systems chemistry yielding Darwinian evolution.

Homochirality of Organic Matter – Objective Law or Curious Incident?

AbstractOf the many hypotheses on the origin of biological homochirality on the Earth, the combination of the notion of subatomic particles composing a homochiral pool of primary matter, on the one hand, with the suggestion of the synthesis of chiral organic molecules in the plasma torch generated by super‐high‐velocity impacts (SHVI) of meteorites, on the other hand, was chosen as the working assumption.

Absolute asymmetric synthesis in enantioselective autocatalytic reaction networks: theoretical games, speculations on chemical evolution and perhaps a synthetic option.

The Soai reaction and the Viedma deracemization of racemic conglomerate crystal mixtures are experimental pieces of evidence of the ability of enantioselective autocatalytic coupled networks to yield absolute asymmetric synthesis. Thermodynamically open systems or systems with non-uniform energy distributions may lead to chiral final states and, in systems able to come into thermodynamic equilibrium with their surroundings, to kinetically controlled absolute asymmetric synthesis. The understanding of network parameters and of the thermodynamic scenarios that may lead to spontaneous mirror symmetry breaking (SMSB) could assist in the development of new methods for asymmetric synthesis and enantioselective polymerizations (e.g., replicators), and to frame reasonable speculations on the origin of biological homochirality.

The origin of biological homochirality

The single handedness of biological molecules has fascinated scientists and laymen alike since Pasteur's first painstaking separation of the enantiomorphic crystals of a tartrate salt over 150 years ago. More recently, a number of theoretical and experimental investigations have helped to delineate models for how one enantiomer might have come to dominate over the other from what presumably was a racemic prebiotic world. Mechanisms for enantioenrichment that include either chemical or physical processes, or a combination of both, are discussed in the context of experimental studies in autocatalysis and in the phase behaviour of chiral molecules.

Enantioselective C-C bond formation as a result of the oriented prochirality of an achiral aldehyde at the single-crystal face upon treatment with a dialkyl zinc vapor.

Enantioselective C-C bond formation as a result of the oriented prochirality of an achiral aldehyde at the single-crystal face upon treatment with a dialkyl zinc vapor.

Enantioselective CC Bond Formation as a Result of the Oriented Prochirality of an Achiral Aldehyde at the Single‐Crystal Face upon Treatment with a Dialkyl Zinc Vapor

Enantioselective CC Bond Formation as a Result of the Oriented Prochirality of an Achiral Aldehyde at the Single‐Crystal Face upon Treatment with a Dialkyl Zinc Vapor

On the evolution of homochirality

This work reconsiders recent ideas on the origin of biological homochirality by formally invoking the standard groupoid approach to stereochemistry in a thermodynamic context that generalizes Landau's spontaneous symmetry breaking arguments. On Earth, limited metabolic free energy density may have served as a low temperature-analog to ‘freeze’ the system in the lowest energy state, i.e., the set of simplest homochiral transitive groupoids representing reproductive chemistries. These engaged in Darwinian competition until a single configuration survived. Subsequent path-dependent evolutionary process locked-in this initial condition. Astrobiological outcomes, in the presence of higher initial metabolic free energy densities, could well be considerably richer, for example, of mixed chirality. One result would be a complicated distribution of biological chirality across a statistically large sample of extraterrestrial stereochemistry, in marked contrast with recent published analyses predicting a racemic average.

ChemInform Abstract: When Chiral Product and Catalyst Are the Same: Discovery of Asymmetric Organoautocatalysis

AbstractReview: 64 refs.

When chiral product and catalyst are the same: discovery of asymmetric organoautocatalysis

The process of asymmetric organoautocatalysis appears to be a natural extension to asymmetric organocatalysis, and holds implications for models on the origin of biological homochirality. The discovery of asymmetric organoautocatalysis (i.e. the process in which the chiral product of a purely organic reaction acts as an organocatalyst for its own formation under conservation of its absolute configuration) and more recent reports on related systems are discussed in this review.

Spontaneous Emergence of Homochirality via Coherently Coupled Antagonistic and Reversible Reaction Cycles

Asymmetric synthesis aims at obtaining enantio-enriched products in stereoselective reactions under a chiral influence. We demonstrate both mathematically and numerically that, even under nominally achiral conditions, fully homochiral steady states can be obtained in open reactive systems by spontaneous mirror-symmetry breaking in the homogenous solution phase when the autocatalytic reaction network is closed in the form of coherently coupled antagonistic reversible reaction cycles which, paradoxically, allow for complete recycling of the reactant. We show that the fully reversible Frank mechanism for spontaneous mirror-symmetry breaking is closely related to the Lotka-Volterra system, which models predator-prey relations in ecosystems. Amplification of total enantiomeric excess and the principle of microscopic reversibility are not in conflict for all conceivable reactions. A viable and widely applicable reaction protocol is introduced and discussed, and it permits the theoretical implications to be applied to practical laboratory examples. Implications for the possible origin of biological homochirality on early earth are discussed.

Re-Examination of Reversibility in Reaction Models for the Spontaneous Emergence of Homochirality

The concept of reversibility in complex chemical reaction networks has recently been introduced in discussions concerning the origin of biological homochirality. In computational studies drawing on an analogy to recent experimental studies involving reversible crystallization processes, recycling of reaction educts has been suggested to provide a driving force for the spontaneous emergence of homochirality. We demonstrate here that reversible reaction networks closed to mass flow lead inexorably to a racemic state for thermally driven reactions, which must adhere to the principle of microscopic reversibility. This conclusion was reached for analogous "triangle reaction" networks studied by Onsager in 1931. Special cases such as photochemical reactions offer an exception that may have prebiotic relevance. Fundamental differences between physical and chemical systems are discussed in order to clarify the role of reversibility in each case.