Demonstration of spontaneous chiral symmetry breaking in asymmetric Mannich and Aldol reactions

Spontaneous symmetry breaking in reactive systems, known as a rare physical phenomenon and for the Soai autocatalytic irreversible reaction, might in principle also occur in other, more common asymmetric reactions when the chiral product is capable to promote its formation and an element of "nonlinearity" is involved in the reaction scheme. Such phenomena are long sought after in chemistry as a possible explanation for the biological homochirality of biomolecules. We have investigated homogeneous organic stereoselective Mannich and Aldol reactions, in which the product is capable to form H-bridged complexes with the prochiral educt, and found by applying NMR spectroscopy, HPLC analysis, and optical rotation measurements 0.3-50.8% of random product enantiomeric excess under essentially achiral reaction conditions. These findings imply a hitherto overlooked mechanism for spontaneous symmetry breaking and, hence, a novel approach to the problem of absolute asymmetric synthesis and could have also potential significance for the conundrum of homochirality.     

Studies in chiral symmetry breaking crystallization I: The effects of stirring and evaporation rates

Chiral symmetry breaking can be realized in stirred crystallization of Na-ClO₃. We present experimental and theoretical studies of the random distribution of crystal enantiomeric excess (cee) for various stirring and solvent evaporation rates. For a fixed solvent evaporation rate, as the stirring RPM is increased, the probability distribution of cee initially broadens and subsequently develops a sharp peak close to cee = 1. On further increase of stirring rate, the probability distribution once again broadens. This broad probability distribution becomes narrow, with a sharp peak near cee = 1, if the solvent evaporation rate is decreased. Thus we show some ways in which the probability distribution of cee can be controlled in stirred crystallization. In particular, our study shows that the stirring rate and the solvent evaporation rate can be adjusted to maximize crystal enantiomeric excess. © 1995 Wiley-Liss, Inc.     

Chiral symmetry breaking during the self-assembly of monolayers from achiral purine molecules

Scanning tunneling microscopy was used to investigate the structure of the two-dimensional adsorbate formed by molecular self-assembly of the purine base, adenine, on the surfaces of the naturally occurring mineral molybdenite and the synthetic crystal highly oriented pyrolytic graphite. Although formed from adenine, which is achiral, the observed adsorbate surface structures were enantiomorphic on molybdenite. This phenomenon suggests a mechanism for the introduction of a localized chiral symmetry break by the spontaneous crystallization of these prebiotically available molecules on inorganic surfaces and may have some role in the origin of biomolecular optical asymmetry. The possibility that purine-pyrimidine arrays assembled on naturally occurring mineral surfaces might act as possible templates for biomolecular assembly is discussed. Correspondence to: G.B. Petersen     

Generation of molecular chiral asymmetry through stirred crystallization

In our earlier work we established that stirred crystallization of achiral compounds that crystallize in enantiomeric forms result in spontaneous chiral symmetry breaking. The asymmetry thus spontaneously generated is confined to the solid state. In this article, we present a case in which the crystal enantiomeric excess (CEE) can be converted to molecular enantiomeric excess (EE) through a solid state reaction which relates the enantiomeric form of the crystal to the enantiomeric form of the product. Such a process not only provides a means of detecting the CEE generated in stirred crystallization but it is also a means through which chiral asymmetry generated spontaneously is "propagated" to generate chiral compounds with enantiomeric excess.     

Chiral sign selection on the J-aggregates of diprotonated tetrakis-(4-sulfonatophenyl)porphyrin by traces of unidentified chiral contaminants present in the ultra-pure water used as solvent

Traces of biological contaminants that cannot be detected, but are expected to be present, in ultra-pure water suffice to select the emerging chiral sign in the spontaneous mirror symmetry breaking that takes place during the formation of the J-aggregates of the amphiphilic diprotonated tetrakis-(4-sulfonatophenyl)porphyrin (H(4)TPPS(4)(2-)). This is demonstrated by competition experiments with a chiral cationic surfactant. The sensitivity of the detection depends on the hierarchical control of the H(4)TPPS(4)(2-) self-aggregation.     

The search for a deterministic origin for the presence of nonracemic amino-acids in meteorites: a computational approach

Amino-acid enantiomeric excesses (ee's) have been detected in different types of carbonaceous chondrites, all in favor of the L enantiomer. In this article, we discuss possible deterministic causes to the presence of these amino-acid ee's in meteorites and evaluate in particular enantioselective photolysis by circularly polarized light (CPL). The electronic circular dichroism spectra of a set of amino- and hydroxy-acids, all detected in chondritic matter but some with ee's and others without ee's, were calculated and compared. The spectra were calculated for the most stable conformation(s) of the considered molecules using quantum mechanical methods (density functional theory). Our results suggest that CPL photolysis in the gas phase was perhaps not at the origin of the presence of ee's in meteorites and that the search for another, but still unknown, deterministic cause must be seriously undertaken.     

长江流域的生物多样性及其与经济协调发展的对策

长江流域的生物多样性及其与经济协调发展的对策陈家宽李博（武汉大学生命科学学院,武汉４３００７２）吴千红（复旦大学生命科学学院,上海２００４３３）众所周知,生物多样性（ｂｉｏｄｉｖｅｒｓｉｔｙ）是当代国际社会日益关注的重大问题之一。生物多样性是人类赖以...     

Actin polymerization or myosin contraction: two ways to build up cortical tension for symmetry breaking

Cells use complex biochemical pathways to drive shape changes for polarization and movement. One of these pathways is the self-assembly of actin filaments and myosin motors that together produce the forces and tensions that drive cell shape changes. Whereas the role of actin and myosin motors in cell polarization is clear, the exact mechanism of how the cortex, a thin shell of actin that is underneath the plasma membrane, can drive cell shape changes is still an open question. Here, we address this issue using biomimetic systems: the actin cortex is reconstituted on liposome membranes, in an ‘outside geometry’. The actin shell is either grown from an activator of actin polymerization immobilized at the membrane by a biotin–streptavidin link, or built by simple adsorption of biotinylated actin filaments to the membrane, in the presence or absence of myosin motors. We show that tension in the actin network can be induced either by active actin polymerization on the membrane via the Arp2/3 complex or by myosin II filament pulling activity. Symmetry breaking and spontaneous polarization occur above a critical tension that opens up a crack in the actin shell. We show that this critical tension is reached by growing branched networks, nucleated by the Arp2/3 complex, in a concentration window of capping protein that limits actin filament growth and by a sufficient number of motors that pull on actin filaments. Our study provides the groundwork to understanding the physical mechanisms at work during polarization prior to cell shape modifications.     

Chiral nanotechnology

A review of chiral, nanoscale science and technology is presented, with the subject divided into two topics. The first discusses nanotechnology in the service of asymmetric synthesis, chiral separations, and analysis. The second topic concerns broader research in the nanotechnology realm, where molecular chirality plays a role in the properties of materials, including molecular devices, chiral supramolecules, chiral nanotubes, chiral fullerenes, and DNA nanotechnology.     

A rate distortion approach to protein symmetry

A spontaneous symmetry breaking argument is applied to the problem of protein folding, via a rate distortion analysis of the relation between genome coding and the final condensation of the protein molten globule that is, in spirit, analogous to Tlusty’s (2007) exploration of the evolution of the genetic code. In the ‘energy’ picture, the average distortion between codon message and final protein structure, under constraints driven by evolutionary selection, serves as a temperature analog, so that low values limit the possible distribution of protein forms, producing the canonical folding funnel. A dual ‘developmental’ perspective sees the rate distortion function itself as the temperature analog, and permits incorporation of chaperons or toxic exposures as catalysts, driving the system to different possible outcomes or affecting the rate of convergence. The rate distortion function appears constrained by the availability of metabolic free energy, with implications for prebiotic evolution, and a nonequilibrium empirical Onsager treatment provides an adaptable statistical model that can be fitted to data, in the same manner as a regression equation. In sum, mechanistic models of protein folding fail to account for the observed spectrum of protein folding and aggregation disorders, suggesting that a biologically based cognitive paradigm describing folding will be needed for understanding the etiology, prevention, and treatment of these diseases. The developmental formalism introduced here may contribute substantially to such a paradigm.     

Chiroptical properties of diamino carboxylic acids

Diamino carboxylic acids have recently come to the attention of scientists working in the field of early life and its development. These are the monomers of a hypothetic early form of genetic material, the so-called Peptide Nucleic Acid (PNA) (Nielson et al., Proc Natl Acad Sci USA 2000;97:3868-3871). Since all biopolymers rely on a specific handedness of their building blocks, the question of symmetry breaking occurs in diamino acids and PNA in the same way as in amino acids and proteins. One possible mechanism for triggering this, is asymmetric photochemistry in interstellar/circumstellar matter by means of circularly polarized light (Bailey et al., Science 2005;281:672-674; Bailey, Orig Life Evol Biosphere 2001;21:167-183; Buscherm?hle, Astrophys J 2005;624:821-826; Meierhenrich, Angew Chem Int Ed Engl 2005;44:5630-5634). Here we have measured the CD-spectra of four chiral diamino carboxylic acids, three of which were found in the Murchison meteorite (Meierhenrich, Proc Natl Acad Sci USA 2004;101:9182-9186). The spectra show a uniform peak at 200 nm. These results and additional quantum mechanical calculations of the involved molecular orbitals support the assumption that the process of symmetry breaking in diamino acids does not depend significantly on the length of the side chain. This means that one process alone could suffice to lead to symmetry breaking in all four measured diamino carboxylic acids and might even to some extent be transferable to monoamino acids, the monomers of proteins.     

Preparation of a New Chiral Stationary Phase Based on Macrocyclic Amide Chiral Selector for the Liquid Chromatographic Chiral Separations

A new chiral stationary phase (CSP) based on macrocyclic amide receptor was prepared starting from (1R,2R)‐1,2‐diphenylethylenediamine. The new CSP was successfully applied to the resolution of various N‐(substituted benzoyl)‐α‐amino amides with reasonably good separation factors and resolutions (α = 1.75 ~ 2.97 and R_S = 2.89 ~ 6.82 for 16 analytes). The new CSP was also applied to the resolution of 3‐substituted 1,4‐benzodiazepin‐2‐ones and some diuretic chiral drugs including bendroflumethiazide and methylchlothiazide and metolazone. The resolution results for 3‐substituted 1,4‐benzodiazepin‐2‐ones and some diuretic chiral drugs were also reasonably good. Chirality 28:253–258, 2016. © 2016 Wiley Periodicals, Inc.     

手性药物分析方法研究进展

综述了近10 年来手性药物分离检测方法的发展,包括高效液相色谱法、气相色谱法、毛细管电泳法,以及超临界流体色谱法等,旨在为该领域的进一步发展提供参考。     

Synthesis and Application of C2 and C3 Symmetric (R)‐Phenylglycinol‐Derived Chiral Stationary Phases

A C3 symmetric (R)‐phenylglycinol N‐1,3,5‐benzenetricarboxylic acid‐derived chiral stationary phase (CSP) and three C2 symmetric (R)‐phenylglycinol CSPs were newly synthesized using o‐, m‐, and p‐phthaloyl dichlorides. © 2016 Wiley Periodicals, Inc. These CSPs were used to compare the resolution of 25 chiral samples using a previously reported 3,5‐dinitrobenzoyl (R)‐phenylglycinol‐derived CSP. Even though all CSPs have the same chiral moiety, the C3 symmetric CSP showed the best resolution. Chirality 28:186–191, 2016.© 2016 Wiley Periodicals, Inc.     

Effect of Cosmological Neutrinos on Discrimination Between the Two Enantiomers of a Chiral Molecule

In the framework of an extraterrestrial origin of biological homochirality, universal mechanisms are of particular interest. In this sense we consider the weak parity-violating neutrino-electron interaction through weak charged currents W ^± between the relic flux of cosmological neutrinos and the electrons of a chiral molecule. We use the known theoretical result of the split in energy of the two helicity sates of an electron in the cosmic neutrino bath, due to weak charged currents. In the case that electrons of a chiral molecule are submitted to a helicoidal potential due to the nuclear conformation, these electrons have opposite helicities for the two enantiomers of the molecule and consequently the mentioned neutrino-electron interaction would produce a splitting in energy between the two enantiomers. An estimation of this energy for the case of a single electron yields a small value of the order of 10⁻²⁶ eV. This value results amplified by the contribution of all the molecular electrons having helicity and other possible mechanisms.     

The Chiral Separation and Enantioselective Degradation of the Chiral Herbicide Napropamide

The chiral pesticide enantiomers often have different toxic effects and environmental behaviors, which suggests that the risk assessments should be on an enantiomeric level. In this work, the chiral separation of the napropamide enantiomers and the stereoselective degradation in tomato, cucumber, rape, cabbage, and soil were investigated. Napropamide enantiomers could be separated absolutely by high‐performance liquid chromatography (HPLC) using a Chiralpak IC column with a resolution factor of 11.75 under the optimized condition. Solid phase extraction (SPE) was used for cleanup of the enantiomers in the vegetable samples. The residue analysis method was validated. Good linearities (R² = 0.9997) and recoveries (71.43% ‐97.64%) were obtained. The limits of detection (LOD) were 0.05 mg/kg in soil and 0.20 mg/kg in vegetables. The results of degradation showed that napropamide dissipated rapidly in vegetables with half‐lives of only 1.13–2.21 days, but much more slowly in soil, with a half‐life of 11.95 d. Slight stereoselective degradation of the two enantiomers was only observed in cabbage, with enantiomeric fraction (EF) = 0.46, and there was no enantioselectivity in the other vegetables. The degradation of napropamide in the five matrixes was fast, and there was no enantioselectivity. Chirality 28:108–113, 2014. © 2014 Wiley Periodicals, Inc.     

Chiral asymmetry in spiral galaxies?

Spiral galaxies are chiral entities when coupled with the direction of their recession velocity. As viewed from the Earth, the S‐shaped and Z‐shaped spiral galaxies are two chiral forms. What is the nature of chiral symmetry in spiral galaxies? In the Carnegie Atlas of Galaxies that lists photographs of a total of 1,168 galaxies, we found 540 galaxies, classified as normal or barred spirals, that are clearly identifiable as S‐ or Z‐ type. The recession velocities for 538 of these galaxies could be obtained from this atlas and other sources. A statistical analysis of this sample reveals no overall asymmetry but there is a significant asymmetry in certain subclasses: dominance of S‐type galaxies in the Sb class of normal spiral galaxies and a dominance of Z‐type in the SBb class of barred spiral galaxies. Both S‐ and Z‐type galaxies seem to have similar velocity distribution, indicating no spatial segregation of the two chiral forms. Chirality 13:351–356, 2001. © 2001 Wiley‐Liss, Inc.