An Extended Model for the Evolution of Prebiotic Homochirality: A Bottom-Up Approach to the Origin of Life

A generalized autocatalytic model for chiral polymerization is investigated in detail. Apart from enantiomeric cross-inhibition, the model allows for the autogenic (non-catalytic) formation of left and right-handed monomers from a substrate with reaction rates epsilon L and epsilon R, respectively. The spatiotemporal evolution of the net chiral asymmetry is studied for models with several values of the maximum polymer length, N. For N = 2, we study the validity of the adiabatic approximation often cited in the literature. We show that the approximation obtains the correct equilibrium values of the net chirality, but fails to reproduce the short time behavior. We show also that the autogenic term in the full N = 2 model behaves as a control parameter in a chiral symmetry-breaking phase transition leading to full homochirality from racemic initial conditions. We study the dynamics of the N--> infinity model with symmetric (epsilon L = epsilon R) autogenic formation, showing that it only achieves homochirality for epsilon > epsilon c, where epsilon c is an N-dependent critical value. For epsilon 相似文献   

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.     

Indications towards a stereoselectivity of the salt-induced peptide formation reaction

Different reaction yields for l- and d-alanine in the salt-induced peptide formation (SIPF) reaction, differences in the circular dichroism spectra and the complex formation constants of the involved chlorocuprate complexes point at a stereoselective differentiation between the two stereoisomers in the SIPF reaction and give a possible explanation towards the origin of homochirality in the process of the origin of life. An explanation of the observed effects can for the time being only be based on assumptions but could possibly be related to the inherent chirality of the Cu^II ion as a central atom of the [CuCl(gly)(glyH₂)(H₂O)₂]⁺ complex due to parity violation in weak interactions and to amplification of chirality related to the structural properties of the complex.     

Prebiotic Homochirality as a Critical Phenomenon

The development of prebiotic homochirality on early-Earth or another planetary platform may be viewed as a critical phenomenon. It is shown, in the context of spatio-temporal polymerization reaction networks, that environmental effects – be them temperature surges or other external disruptions – may destroy any net chirality previously produced. In order to understand the emergence of prebiotic homochirality it is important to model the coupling of polymerization reaction networks to different planetary environments. *Presented at: National Workshop on Astrobiology: Search for Life in the Solar System, Capri, Italy, 26 to 28 October, 2005.     

d-Amino acids in molecular evolution in space – Absolute asymmetric photolysis and synthesis of amino acids by circularly polarized light

Living organisms on the Earth almost exclusively use l-amino acids for the molecular architecture of proteins. The biological occurrence of d-amino acids is rare, although their functions in various organisms are being gradually understood. A possible explanation for the origin of biomolecular homochirality is the delivery of enantioenriched molecules via extraterrestrial bodies, such as asteroids and comets on early Earth. For the asymmetric formation of amino acids and their precursor molecules in interstellar environments, the interaction with circularly polarized photons is considered to have played a potential role in causing chiral asymmetry. In this review, we summarize recent progress in the investigation of chirality transfer from chiral photons to amino acids involving the two major processes of asymmetric photolysis and asymmetric synthesis. We will discuss analytical data on cometary and meteoritic amino acids and their potential impact delivery to the early Earth. The ongoing and future ambitious space missions, Hayabusa2, OSIRIS-REx, ExoMars 2020, and MMX, are scheduled to provide new insights into the chirality of extraterrestrial organic molecules and their potential relation to the terrestrial homochirality. This article is part of a Special Issue entitled: d-Amino acids: biology in the mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca.     

Simultaneous origin of homochirality, the genetic code and its directionality

The origin of homochirality in molecules characterizing living systems has remained a mystery since Pasteur's recognition of the problem some 150 years ago.(2-5) Most theories also assume that homochirality emerged in one class of molecules (e.g. ribose) from which it was enriched in other molecules (e.g. amino acids) as well.(2-5)I propose a novel, experimentally testable hypothesis describing a process by which selective chirality in amino acids and ribonucleotides emerged simultaneously and hand-in-hand with the origin and directionality of the genetic code within a system of interactions involving amino acids, peptides, nucleotide bases, their sugars and polynucleotides.     

Chirality and life

The crucial role of homochirality and chiral homogeneity in the self-replication of contemporary biopolymers is emphasized, and the experimentally demonstrated advantages of these chirality attributes in simpler polymeric systems are summarized. The implausibility of life without chirality and hence of a biogenic scenario for the origin of chiral molecules is stressed, and chance and determinate abiotic mechanisms for the origin of chirality are reviewed briefly in the context of their potential viability on the primitive Earth. It is concluded that all such mechanisms would be non-viable, and that the turbulent prebiotic environment would require an ongoing extraterrestrial source for the accumulation of chiral molecules on the primitive Earth. A scenario is described wherein the circularly polarized ultraviolet synchrotron radiation from the neutron star remnants of supernovae engenders asymmetric photolysis of the racemic constituents in the organic mantles on interstellar dust grains, whereupon these chiral constituents are transported repetitively to the primative Earth by direct accretion of the interstellar dust or through impacts of comets and asteroids.     

Origin of amino acid homochirality: relationship with the RNA world and origin of tRNA aminoacylation

The origin of homochirality of l-amino acids has long been a mystery. Aminoacylation of tRNA might have provided chiral selectivity, since it is the first process encountered by amino acids and RNA. An RNA minihelix (progenitor of the modern tRNA) was aminoacylated by an aminoacyl phosphate oligonucleotide that exhibited a clear preference for l- as opposed to d-amino acids. A mirror-image RNA system with l-ribose exhibited the opposite selectivity, i.e., it exhibited an apparent preference for the d-amino acid. The selectivity for l-amino acids is based on the stereochemistry of RNA. The side chain of d-amino acids is located much closer to the terminal adenosine of the minihelix, causing them collide and interfere during the amino acid-transfer step. These results suggest that the putative RNA world that preceded the protein theatre determined the homochirality of l-amino acids through tRNA aminoacylation.     

Chirality as an inherent general property of matter

A statement has been formulated that chirality is an indispensable inherent property of all material objects, at one level of organization of matter or another. The translation of chirality from one level of material objects to another deserves our attention. The parity violation of weak interactions can be discussed in terms of the homochirality of the pool of fundamental particles, as it translates into optical activity of metal vapors. Individual photons and energy quanta are considered to be chiral entities, too, since they can be separated into beams of circularly polarized radiation. The chiral structure of the universe has been proposed and a method of determining the orientation of the axis of rotation of the universe suggested.     

A new theoretical model for the origin of amino acid homochirality

Amino acid homochirality, as a unique behavior of life, could have originated synchronously with the genetic code. In this paper, phosphoryl amino-acid-5′-nucleosides with P-N bond are postulated to be a chiral origin model in prebiotic molecular evolution. The enthalpy change in the intramolecular interaction between the nucleotide base and the amino-acid side-chain determines the stability of the particular complex, resulting in a preferred conformation associated with the chirality of amino acids. Based on the theoretical model, our experiments and calculations show that the chiral selection of the earliest amino acids for L-enantiomers seems to be a strict stereochemical/physicochemical determinism. As other amino acids developed biosynthetically from the earliest amino acids, we infer that the chirality of the later amino acids was inherited from the precursor amino acids. This idea probably goes far back in history, but it is hoped that it will be a guide for further experiments in this area.     

The asymmetry of existence: do we owe our existence to cold dark matter and the weak force?

A common theme throughout biology is homochirality, including its origin and especially implications. Homochirality has also intrigued scientists because of the hypothesis that life, as it currently exists, could not have occurred without it. In this review, we discuss several hypotheses regarding homochirality and their linkage to processes that range from subatomic in scale to processes that help define the structure of the universe. More importantly, this exploration begins with the knowledge that humans inhabit the universe in which there is an excess of normal matter over antimatter. It is a universe characterized by homochirality but is nonetheless contained in what is most easily described as a 3+1 dimensional spacetime wherein most laws of physics are invariant under spacetime transformations. This restriction on spacetime poses significant constraints on the processes that can be invoked to explain homochirality. However, in dealing with such restraints, including the total mass contained in the universe, the concepts of cold dark matter and dark energy can be incorporated into cosmological models with resultant behaviors and predictions very much in accord with the findings of the cosmic background surveys. Indeed, the introduction of cold dark matter and dark energy to solve problems relating to the mass found in the universe may provide a means for generating the needed asymmetry to allow homochirality to arise.     

Active centrum hypothesis: The origin of chiral homogeneity and the RNA-world

I propose a hypothesis on the origin of chiral homogeneity of bio-molecules based on chiral catalysis. The first chiral active centre may have formed on the surface of complexes comprising metal ions, amino acids, other coenzymes and oligomers (short RNAs). The complexes must have been dominated by short RNAs capable of self-reproduction with ligation. Most of the first complexes may have catalysed the production of nucleotides. A basic assumption is that such complexes can be assembled from their components almost freely, in a huge variety of combinations. This assumption implies that “a few” components can constitute “a huge” number of active centre types. Moreover, an experiment is proposed to test the performance of such complexes in vitro.If the complexes were built up freely from their elements, then Darwinian evolution would operate on the assembly mechanism of complexes. For the production of complexes, first their parts had to appear by forming a proper three-dimensional structure. Three possible re-building mechanisms of the proper geometric structure of complexes are proposed. First, the integration of RNA parts of complexes was assisted presumably by a pre-intron. Second, the binding of RNA parts of a complex may give rise to a “polluted” RNA world. Third, the pairing of short RNA parts and their geometric conformation may have been supported by a pre-genetic code.Finally, an evolutionary step-by-step scenario of the origin of homochirality and a “polluted” RNA world is also introduced based on the proposed combinatorial complex chemistry. Homochirality is evolved by Darwinian selection whenever the efficiency of the reflexive autocatalysis of a dynamical combinatorial library increases with the homochirality of the active centres of reactions cascades and the homochirality of the elements of the dynamical combinatorial library. Moreover, the potential importance of phospholipid membrane is also discussed.     

A periodic system of chiral structures in molecular biology

A systemic regularity of molecular biology is considered: the tendency towards alternating of the sense of chirality of intramolecular structural levels of DNA and proteins, namely, D–L–D–L for DNA and L–D–L–D for proteins, is observable starting from the level of asymmetric carbon in deoxyribose and amino acids. Helicity is a special case of chirality. In intermolecular interactions, the sense of chirality of the highest intramolecular structural level directly involved in the interaction prevails in each of the participants. The interaction of molecules of the same nature (protein–protein, DNA–RNA, tRNA–mRNA, and ribozymes) mainly occurs in the case of the same sense of chirality, either L–L or D–D, and for molecules of different types (DNA–protein, tRNA–amino acids, and enzyme–substrate), in the case of different senses of chirality, either D–L or L–D. An alternating sense of the chiral hierarchy of conjugated levels of macromolecular structures in proteins and nucleic acids is of general biological importance: it determines the discreteness of levels, serves as a tool of folding, and provides a structural basis for “preferred collective” (or “macroscopic mechanical”) degrees of freedom in the design of macromolecular machines, as well as being one of the mechanisms of blockwise/saltatory development of the evolutionary process. A new fundamental concept is proposed: the homochirality of primary structures of DNA and proteins determines the amount of the entropic component of the free energy, which is used in the processes of folding and molecular rearrangements.     

Molecular chirality and the fundamental symmetries of physics: influence of parity violation on rovibrational frequencies and thermodynamic properties.

We introduce the topic of fundamental symmetries of physics in relation to molecular chirality by a brief review of the development and current status of the theory of parity violation in chiral molecules. We then discuss in some detail CHBrClF (bromochlorofluoromethane) as a test case, to which the work of André Collet has contributed importantly. For this molecule and its isotopomers, we report here the first detailed theoretical calculations of the influence of parity violation on statistical thermodynamic properties. High-quality ab initio calculations (RPA, random phase approximation, and CASSCF, complete-active-space self-consistent-field) were performed to determine the small energy difference between R- and S-enantiomers of H and D isotopomers of bromochlorofluoromethane (CHBrClF, CDBrClF), and fluorooxirane ((1)H(3)C(2)OF) introduced by the parity-violating weak interaction. Together with vibrational and rotational frequency shifts caused by parity violation, these were used to determine the statistical thermodynamic quantities from the corresponding partition functions within the separable harmonic and in part also anharmonic adiabatic approximation. Temperature-dependent equilibrium constants for the stereomutation were calculated and are discussed in relation to biochemical homochirality.     

A new theoretical model for the origin of amino acid homochirality

Amino acid homochirality, as a unique behavior of life, could have originated synchronously with the genetic code. In this paper, phosphoryl amino-acid -5′-nucleosides with P－N bond are postulated to be a chiral origin model in prebiotic molecular evolution. The enthalpy change in the intramolecular interaction between the nucleotide base and the amino-acid side-chain determines the sta-bility of the particular complex, resulting in a preferred conformation associated with the chirality of amino acids. Based on the theoretical model, our experiments and calculations show that the chiral selection of the earliest amino acids for L-enantiomers seems to be a strict stereochemi-cal/physicochemical determinism. As other amino acids developed biosynthetically from the earliest amino acids, we infer that the chirality of the later amino acids was inherited from the precursor amino acids. This idea probably goes far back in history, but it is hoped that it will be a guide for further ex-periments in this area.     

Emerging subject for chiral separation science: cluster boron compounds

The structural chirality is an inherent feature of fully synthetic boron cluster compounds that sometimes exhibit unique biochemical effects. HPLC studies with zwitter-ionic cluster boron compounds and electrophoretic studies with boron cluster anions reveal that the chiral separability of these species is remarkably dissimilar to that of organic species, if uncharged cyclodextrins are used as chiral selectors. Furthermore, marked differences were found between the analytical characteristics of the chiral separations of the boron cluster species and those of the organic species with uncharged cyclodextrins. The present-day experimental database indicates that the rules valid for the chiral separations of the organic species cannot be applied to the chiral separations of the boron cluster species without experimental verification. The current extent of research work devoted to the investigation of chirality and chiral separations of boron cluster species is negligibly small in comparison with that devoted to the investigation of chirality and chiral separations of organic species. This makes difficult a reliable explanation of both the particularities observed in chiral separations of boron cluster species with cyclodextrins as chiral selectors and the strange effects related to these separations at the moment.     

X-ray studies on crystalline complexes involving amino acids and peptides: Part XVIII. Crystal structure of a new form of L-arginine D-glutamate and a comparative study of amino acid crystal structures containing molecules of the same and mixed chirality

The new form of L-arginine D-glutamate is monoclinic, P2₁, witha = 9.941(1),b = 4.668(2),c = 17.307(1) Å,β = 95.27(1)°, and Z = 2. In terms of composition, the new form differs from the old form in that the former is a monohydrate whereas the latter is a trihydrate. The structure has been solved by the direct methods and refined to R = 0.085 for 1012 observed reflections. The conformation of the arginine molecule is the same in both the forms whereas that of the glutamate ion is different. The change in the conformation of the glutamate ion is such that it facilitates extensive pseudosymmetry in the crystals. The molecules arrange themselves in double-layers stabilised by head-to-tail sequences involving main chains, in both the forms. However, considerable differences exist between the two forms in the interface, consisting of side chains and water molecules, between double-layers. A comparative study of the relationship between the crystal structures of L and DL amino acids on the one hand and that between the structures of LL and LD amino acid-amino acid complexes on the other, provides interesting insights into amino acid aggregation and the effect of chirality on it. The crystal structures of most hydrophobic amino acids are made up of double-layers and those of most hydrophilic amino acids contain single layers, irrespective of the chiralities of the amino acids involved. In most cases, the molecules tend to appropriately rearrange themselves to preserve the broad features of aggregation patterns when the chirality of half the molecules is reversed as in the structures of DL amino acids. The basic elements of aggregation in the LL and the LD complexes, are similar to those found in the crystals of L and DL amino acids. However, the differences between the LL and the LD complexes in the distribution of these elements are more pronounced than those between the distributions in the structures of L and DL amino acids.     

Chirality as a tool in nucleic acid recognition: principles and relevance in biotechnology and in medicinal chemistry

The understanding of the interaction of chiral species with DNA or RNA is very important for the development of new tools in biology and of new drugs. Several cases in which chirality is a crucial point in determining the DNA binding mode are reviewed and discussed, with the aim of illustrating how chirality can be considered as a tool for improving the understanding of mechanisms and the effectiveness of nucleic acid recognition. The review is divided into two parts: the former describes examples of chiral species interacting with DNA: intercalators, metal complexes, and groove binders; the latter part is dedicated to chirality in DNA analogs, with discussion of phosphate stereochemistry and chirality of ribose substitutes, in particular of peptide nucleic acids (PNAs) for which a number of works have been published recently dealing with the effect of chirality in DNA recognition. The discussion is intended to show how enantiomeric recognition originates at the molecular level, by exploiting the enormous progresses recently achieved in the field of structural characterization of complexes formed by nucleic acid with their ligands by crystallographic and spectroscopic methods. Examples of application of the DNA binding molecules described and the role of chirality in DNA recognition relevant for biotechnology or medicinal chemistry are reported.     

Deracemization of Amino Acids by Partial Sublimation and via Homochiral Self-Organization

Deracemization of a 50/50 mixture of enantiomers of aliphatic amino acids (Ala, Leu, Pro, Val) can be achieved by a simple sublimation of a pre-solubilized solid mixture of the racemates with a huge amount of a less-volatile optically active amino acid (Asn, Asp, Glu, Ser, Thr). The choice of chirality correlates with the handedness of the enantiopure amino acids—Asn, Asp, Glu, Ser, and Thr. The deracemization, enantioenrichment and enantiodepletion observed in these experiments clearly demonstrate the preferential homochiral interactions and a tendency of natural amino acids to homochiral self-organization. These data may contribute toward an ultimate understanding of the pathways by which prebiological homochirality might have emerged.     

Conformation inversion of bilirubin formed by reduction of the biliverdin-human serum albumin complex: evidence from circular dichroism.

As shown by circular dichroism spectroscopy, biliverdin preferentially adopts an M-helicity conformation on human serum albumin in aqueous buffer, pH 7.5, whereas biliverdin exhibits only a weak preference for the P-helicity conformation on bovine serum albumin at the same pH. Upon rapid reduction of the complexes with sodium borohydride, P-helicity bilirubin-IX alpha is obtained on the human albumin complex, and M-helicity bilirubin-IX alpha is obtained on the bovine serum albumin complex. Thus, biliverdin in effect undergoes an inversion of chirality upon reduction. Since the reduction did not afford a rubin with the same helicity as that of the verdin, the observations point to a hitherto undetected conformational mobility of albumin-bound bilirubin.