First Results of the RAMBAS Experiment on Investigation of the Radiation Mechanism of Chiral Influence

The first results of the RAdiation Mechanism of Biomolecular ASymmetry (RAMBAS) experiment on investigation of the radiation mechanism of the influence on chiral molecules, as a factor leading to origination of chiral asymmetry are presented. It was found that irradiation of simple achiral materials by a flux of electrons from radioactive source initiated the synthesis of amino acids, and it resulted in asymmetric degradation and chiral asymmetry in a racemic mixture of amino acids. The results obtained can be important for the solution of the origin-of-life and biological homochirality problems.     

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.     

Results of the Second Stage of the Investigation of the Radiation Mechanism of Chiral Influence (RAMBAS-2 Experiment)

Results of the second stage of the RAMBAS (RAdiation Mechanism of Biomolecular ASymmetry) experiment on investigation of the radiation mechanism of the influence on chiral molecules are presented. Optical activity of samples of racemic mixtures of amino acids with heavy metals was compared prior to and after irradiation by electron flux from a radioactive source. It is found that the irradiation results in asymmetric degradation of both complexes and amino acids and in production of chiral asymmetry of the samples under study. These results confirm the conclusions inferred from the first stage of the RAMBAS experiment and could be important for the solution of the origin-of-life and biological homochirality problems.     

Understanding Photochirogenesis: Solvent Effects on Circular Dichroism and Anisotropy Spectroscopy

The basic units that constitute essential biopolymers (proteins and nucleic acids) are enantiomerically biased. Proteins are constructed from L‐amino acids and nucleic acids possess a backbone composed exclusively of D‐sugars. Photochirogenesis has been postulated to be the source of this homochirality of biomolecules: Asymmetric photochemical reactions were catalyzed by circularly polarized light (cpl) in interstellar environments and generated the first chiral prebiotic precursors. Enantiomers absorb cpl differently and this difference can dictate the kinetics of asymmetric photochemical reactions. These differences in absorption can be studied using circular dichroism (CD) and anisotropy spectroscopy. Rather than measuring the CD spectrum alone, the anisotropy factor g is recorded (CD divided by absorption). This factor g is directly related to the maximum achievable enantiomeric excess. We now report on the substantial influence of solvent and molecular surroundings on CD and anisotropy spectroscopy. This shows for the first time that CD and anisotropy signals depend just as much on the molecular surroundings of a molecule as on the nature of the molecule itself. CD and g spectra of amino acids in different solvents and in the solid state are presented here and the influence of these different surroundings on the spectra is discussed. Chirality 26:373–378, 2014. © 2014 Wiley Periodicals, Inc.     

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.     

UV Circular Polarisation in Star Formation Regions: The Origin of Homochirality?

Ultraviolet circularly polarised light has been suggested as the initial cause of the homochirality of organic molecules in terrestrial organisms, via enantiomeric selection of prebiotic molecules by asymmetric photolysis. We present a theoretical investigation of mechanisms by which ultraviolet circular polarisation may be produced in star formation regions. In the scenarios considered here, light scattering produces only a small percentage of net circular polarisation at any point in space, due to the forward throwing nature of the phase function in the ultraviolet. By contrast, dichroic extinction can produce a fairly high percentage of net circular polarisation (10%) and may therefore play a key role in producing an enantiomeric excess.     

氨基酸的手性与蛋白质生物合成

生命体中行使生物学功能的重要大分子蛋白质,由其基本单位氨基酸组成. 除甘氨酸外,其余19种常见氨基酸均具有手性,且均为L-构型,称为氨基酸的纯手性（homochirality,或称同手性）.这个现象长久以来困扰着科学家们. 本文简要综述了目前对纯手性起源的一些假说,D-氨基酸在生命体中的存在和可能的作用,以及D-氨基酸在蛋白质合成这个重要过程中的特性,包括D-氨基酸的氨酰化和在新生肽链的掺入. D-氨基酸的研究,让人们对生命有了更深入的认识,为疾病、制药等领域提供了新的思路,也为生命科学的基础研究提供了新的理论支撑和研究方向.     

Extraterrestrial Handedness: A Reply

Recent investigations of stable isotope ratios of amino acids from the Murchison meteorite have shown them to be of unambiguous extraterrestrial origin, and examinations of their enantiomeric compositions, where terrestrial contamination can be excluded, have found a consistent excess of L-enantiomers. One explanation for this observation has been the asymmetric photolysis of racemic extraterrestrial amino acids by circularly polarized light (CPL) in the synchrotron radiation from orbiting electrons around the pulsar remnants of supernovae. Mason (1997) has attempted to discredit this mechanism on the grounds that circular dichroism (CD) bands for optically active molecules alternate in sign and sum to zero over the entire spectrum, and hence enantioselective photochemical reactions cannot be induced by broad band CPL. We submit arguments disputing this conclusion and present reasons for expecting that broad band CPL synchrotron radiation would be quite capable of inducing asymmetric photolysis, particularly in aliphatic amino acids.     

Synthesis and circular dichroism studies of N,N-bis(2-quinolylmethyl)amino acid Cu(II) complexes: determination of absolute configuration and enantiomeric excess by the exciton coupling method

We report a method to determine the absolute configuration of alpha-amino acids by exciton coupled circular dichroism (ECCD). Naturally occurring amino acids were successfully derivatized with 2-bromomethylquinoline. Complexation of these conformationally flexible ligands with Cu(II) salts yielded defined propeller-like structures. The direction of the twist (i.e., the relative orientation of the chromophores to each other) is governed by the asymmetric amino acid carbon center. The transition moments of the chromophores couple and yield a bisignate circular dichroism spectrum, the sign of which corresponds to the absolute configuration of the chiral center of the amino acid. Enantiomeric excess (e.e.) of amino acid derivatives is linearly related to the differential extinction coefficient Delta(epsilon) and can be assessed easily utilizing a standard curve. This efficient, sensitive technique requires low analyte concentrations, offers several advantages over established methods, and could be applied in medicinal, pharmaceutical, or chemical retail and manufacturing industry.     

A search for circular dichroism in the VUV photofragmentation mass spectra of 2-amino-1-butanol

The dissociative photoionization of a single-enantiomer chiral molecule by circularly polarized synchrotron radiation was investigated, for the first time, in the gas phase. Photoion mass spectra were produced by the interaction of (+)-(S)-, (-)-(R)- and rac-2-amino-l-butanol with circularly polarized light. Comparison of these spectra places an upper bound of approximately 2% on circular dichroism in the dissociative photoionization of 2-amino-l-butanol at 21 eV, which may have consequences for the theory that the origin of biological homochirality was predominantly enantioselective photofragmentation by circularly polarized light. We have also identified and elucidated many of the difficulties of performing gas phase CD measurements in crossed beam experiments.     

A novel spectroscopic probe for molecular chirality

Recent advances in developing sum frequency generation (SFG) as a novel spectroscopic probe for molecular chirality are reviewed. The basic principle underlying the technique is briefly described, in comparison with circular dichroism (CD). The significantly better sensitivity of the technique than CD is pointed out, and the reason is discussed. Bi-naphthol (BN) and amino acids are used as representatives for two different types of chiral molecules; the measured chirality in their electronic transitions can be understood by two different molecular models, respectively, that are extensions of models developed earlier for CD. Optically active or chiral SFG from vibrational transitions are weaker, but with the help of electronic-vibrational double resonance, the vibrational spectrum of a monolayer of BN has been obtained. Generally, optically active SFG is sufficiently sensitive to be employed to probe in-situ chirality of chiral monolayers and thin films.     

The Extraterrestrial Origin of the Homochirality of Biomolecules – Rebuttal to a Critique

Having concluded that abiotic terrestrial mechanisms would have been ineffectual for the origin of terrestrial homochirality, we have proposed an alternative extraterrestrial scenario involving stereoselective ultraviolet photolysis of the racemic constituents of interstellar grain mantles by circularly polarized synchrotron radiation from neutron stars, followed by terrestrial accretion of the resulting chiral molecules via cometary impact. Recently L. Keszthelyi (1995) has reviewed a number of our arguments and advanced several erroneous calculations and conclusions purporting to negate them. We offer here points of rebuttal to Keszthelyi's criticisms, and support our inferences with recent data regarding indigenous enantiomeric excesses of L-amino acids in the Murchison meteorite.     

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.     

Photochemical Concepts on the Origin of Biomolecular Asymmetry

Biopolymers like DNA and proteins are strongly selective towards the chirality of their monomer units. The use of homochiral monomers is regarded as essential for the construction and function of biopolymers; the emergence of the molecular asymmetry is therefore considered as a fundamental step in Chemical Evolution. This work focuses on physicochemical mechanisms for the origin of biomolecular asymmetry. Very recently two groups, one from Allamandola at NASA Ames and the other from our Inter-European team, demonstrated simultaneously the spontaneous photoformation of a variety of chiral amino acid structures under simulated interstellar conditions. Since both groups used unpolarized light for the photoreaction the obtained amino acids turned out racemic as expected. The obtained experimental data support the assumption that tiny ice grains can furthermore play host to important asymmetric reactions when irradiated by interstellar circularly polarized ultraviolet light. It is possible that such ice grains could have become incorporated into the early cloud that formed our Solar System and ended up on Earth, assisting life to start. Several lines of evidence suggest that some of the building blocks of life were delivered to the primitive Earth via (micro-) meteoroids and/or comets. These results suggest that asymmetric interstellar photochemistry may have played a significant part in supplying Earth with some of the enantioenriched organic materials needed to trigger life. The search for the origin of biomolecular homochirality leads to a strong interest in the fields of asymmetric photochemistry with special emphasis on absolute asymmetric synthesis. We outline here the theoretical background on asymmetric interstellar ice photochemistry, summarize recent concepts and advances in the field, and discuss briefly its implications. The obtained data are crucial for the design of the enantioselective COSAC GC-MS experiment onboard the ROSETTA spacecraft to a comet to be launched in the very near future.     

Circular dichroism user facility at the National Synchrotron Light Source: estimation of protein secondary structure.

The ultraviolet circular dichroism of a protein can be used to estimate the net fraction of its amino acids in different classes of secondary structure. Recent advances in the accuracy of such calculations have resulted from improved computational techniques, as well as extension of the spectral region analyzed to wavelengths less than 180 nm, a wavelength range beyond the limit of most laboratory-based circular dichroism spectrometers. We describe a spectrometer that uses UV radiation from the National Synchrotron Light Source at the Brookhaven National Laboratory to record circular dichroism spectra of proteins (and other biologically important molecules) in aqueous solution over the optimum wavelength range required for calculation of secondary structures. This instrument is available for use by scientists from academic, commercial and research institutions.     

Amplification of Chirality at Solid Surfaces

Symmetry-breaking phenomena in two-dimensional crystallization at surfaces are reviewed and the potential impact to chiral amplification in three-dimensional systems in connection with the origin of homochirality in the biomolecular world is discussed. Adsorption of prochiral molecules leads to two-dimensional conglomerates, i.e., on a local scale spontaneously to homochiral crystal structures. Small enantiomeric excess or chiral impurities in this environment install homochirality on a global scale, that is, on the entire surface.     

Racemization and the origin of optically active organic compounds in living organisms

The organic compounds synthesized in prebiotic experiments are racemic mixtures. A number of proposals have been offered to explain how asymmetric organic compounds formed on the Earth before life arose, with the influence of chiral weak nuclear interactions being the most frequent proposal. This and other proposed asymmetric syntheses give only slight enantiomeric excess and any slight excess will be degraded by racemization. This applies particularly to amino acids where half-lives of 10(5)-10(6) years are to be expected at temperatures characteristic of the Earth's surface. Since the generation of chiral molecules could not have been a significant process under geological conditions, the origins of this asymmetry must have occurred at the time of the origin of life or shortly thereafter. It is possible that the compounds in the first living organisms were prochiral rather than chiral; this is unlikely for amino acids, but it is possible for the monomers of RNA-like molecules.     

Biocatalytic asymmetric amination of carbonyl functional groups – a synthetic biology approach to organic chemistry

Transaminases catalyze amino transfer reactions from amino donors such as amino acids or amines to keto acids or ketones to give chiral amino acid or amines in optically pure form. α-Amino acid dehydrogenases catalyze the asymmetric reductive amination of α-keto acids using ammonia as amino donor to furnish L -amino acids. The distinct features and synthetic application of these two enzymes are reviewed in an effort to illustrate their promising and challenging aspects in serving as approaches to the direct asymmetric synthesis of optically pure amines from the corresponding keto compounds, a formidable problem in organic chemistry.     

Conformational studies of proteins with aromatic side-chain effects

We present here a brief analysis of ultraviolet isotropic absorption and related circular dichroism of the n–π* and π–π* transitions for the peptide (amide) chromophore in the 185–240 mμ region. Investigations by ultraviolet absorption and circular dichroism techniques on natural amino acids with aromatic chromophores in their side chains are also reported. By taking into account both the peptide and aromatic transitions we discuss the conformational studies of proteins with aromatic side-chain effects. Our attention is largely focused on the optical rotatory dispersion and circular dichroism spectra of these proteins in the near ultraviolet region, where characteristic aromatic side-chain bands occur. The 185–240 mμ region is also discussed when evidence exists of overlapping Cotton effects of aromatic and peptide groups.     

Methods for determining the absolute configurations of marine ladder-shaped polyethers

Marine dinoflagellates produce a unique family of bioactive substances featuring multiple ether rings aligned in a ladder shape. These are large, complex molecules with potent bioactivity. Targeted chiral centers sit on either the skeletal ladders or on the side chains of these compounds. However, the laborious steps of isolation and purification severely diminish the amount of sample available for assigning these chiral centers via structural investigations. Three important methods were used to assign the stereochemistry of the molecules, (a) circular dichroism (CD) spectroscopy, (b) labeling with fluorescent chiral reagents for high-performance liquid chromatography (HPLC) analysis, and (c) derivatization with anisotropic reagents for nuclear magnetic resonance (NMR) analysis. The addition of fluorescent chiral reagents allowed for the use of much less material than typically required. In this review, we present examples of the determination of absolute configurations in ladder-shaped polyethers. The targeted compounds include ciguatoxins (CTXs), gymnocin-B, gambieric acids, prymnesin-2, maitotoxin, yessotoxins, gambierol, brevisamide, and brevisin.