Revisiting Homochiral versus Heterochiral Interactions through a Long Detective Story of a Useful Azobis-Nitrile and Puzzling Racemate.

This paper documents and reinvestigates the solid-state and crystal structures of 4,4'-azobis-4-cyanopentanoic acid (ACPA), a water-soluble azobis-nitrile of immense utility as a radical initiator in living polymerizations and a labile mechanophore that can be embedded within long polymer chains to undergo selective scission under mechanical activation. Surprisingly, for such applications, both the commercially available reagent and their derivatives are used as "single initiators" when this azonitrile is actually a mixture of stereoisomers. Although the racemate and meso compounds were identified more than half a century ago and their enantiomers were separated by classical resolution, there have been confusing narratives dealing with their characterization, the existence of a conglomeratic phase, and fractional crystallization. Our results report on the X-ray crystal structures of all stereoisomers for the first time, along with further details on enantiodiscrimination and the always intriguing arguments accounting for the stability of homochiral versus heterochiral crystal aggregates. To this end, metadynamic (MTD) simulations on stereoisomer molecular aggregates were performed to capture the incipient nucleation events at the picosecond time scale. This analysis sheds light on the driving homochiral aggregation of ACPA enantiomers.

On the Origin of Sugar Handedness: Facts, Hypotheses and Missing Links-A Review.

By paraphrasing one of Kipling's most amazing short stories (How the Leopard Got His Spots), this article could be entitled "How Sugars Became Homochiral". Obviously, we have no answer to this still unsolved mystery, and this perspective simply brings recent models, experiments and hypotheses into the homochiral homogeneity of sugars on earth. We shall revisit the past and current understanding of sugar chirality in the context of prebiotic chemistry, with attention to recent developments and insights. Different scenarios and pathways will be discussed, from the widely known formose-type processes to less familiar ones, often viewed as unorthodox chemical routes. In particular, problems associated with the spontaneous generation of enantiomeric imbalances and the transfer of chirality will be tackled. As carbohydrates are essential components of all cellular systems, astrochemical and terrestrial observations suggest that saccharides originated from environmentally available feedstocks. Such substances would have been capable of sustaining autotrophic and heterotrophic mechanisms integrating nutrients, metabolism and the genome after compartmentalization. Recent findings likewise indicate that sugars' enantiomeric bias may have emerged by a transfer of chirality mechanisms, rather than by deracemization of sugar backbones, yet providing an evolutionary advantage that fueled the cellular machinery.

Pasteur made simple - mechanochemical transformation of racemic amino acid crystals into racemic conglomerate crystals.

Conglomerate crystallization is required for many deracemization or enantioenrichment protocols. Here, we report the metal-mediated mechanochemical transformation of racemic compounds of some proteinogenic amino acids - valine, leucine and isoleucine - into their corresponding conglomerates. Specifically, ZnO has the ability to promote and stabilize the conglomerate phase of these amino acids to an extent where the racemic compound is not observed.

Oriented attachment by enantioselective facet recognition in millimeter-sized gypsum crystals.

Crystal growth by oriented attachment involves the spontaneous self-assembly of adjoining crystals with common crystallographic orientations. Herein, we report the oriented attachment of gypsum crystals on agitation to form stereoselective mesoscale aggregates.

Enantiomer-specific oriented attachment: formation of macroscopic homochiral crystal aggregates from a racemic system.

Let's get together: Racemic samples of d- and l-enantiomorphous NaBrO3 (or NaClO3) crystals aggregate with nearly complete enantioselection. Centimeter-sized enantiopure megacrystals are often produced, and these can be sorted easily.

Food marketing towards children: brand logo recognition, food-related behavior and BMI among 3-13-year-olds in a south Indian town.

OBJECTIVES: To assess exposure to marketing of unhealthy food products and its relation to food related behavior and BMI in children aged 3-13, from different socioeconomic backgrounds in a south Indian town. METHODS: Child-parent pairs (n=306) were recruited at pediatric clinics. Exposure to food marketing was assessed by a digital logo recognition test. Children matched 18 logos of unhealthy food (high in fat/sugar/salt) featured in promotion material from the food industry to pictures of corresponding products. Children's nutritional knowledge, food preferences, purchase requests, eating behavior and socioeconomic characteristics were assessed by a digital game and parental questionnaires. Anthropometric measurements were recorded. RESULTS: Recognition rates for the brand logos ranged from 30% to 80%. Logo recognition ability increased with age (p<0.001) and socioeconomic level (p<0.001 comparing children in the highest and lowest of three socioeconomic groups). Adjusted for gender, age and socioeconomic group, logo recognition was associated with higher BMI (p=0.022) and nutritional knowledge (p<0.001) but not to unhealthy food preferences or purchase requests. CONCLUSIONS: Children from higher socioeconomic groups in the region had higher brand logo recognition ability and are possibly exposed to more food marketing. The study did not lend support to a link between exposure to marketing and poor eating behavior, distorted nutritional knowledge or increased purchase requests. The correlation between logo recognition and BMI warrants further investigation on food marketing towards children and its potential role in the increasing burden of non-communicable diseases in this part of India.

Pasteur's tweezers revisited: on the mechanism of attrition-enhanced deracemization and resolution of chiral conglomerate solids.

Insights into the mechanism of attrition-enhanced deracemization and resolution of solid enantiomorphic chiral compounds are obtained by crystal size and solubility measurements and by isotopic labeling experiments. Together these results help to deconvolute the various chemical and physical rate processes contributing to the phenomenon. Crystal size measurements highlight a distinct correlation between the stochastic, transient growth of crystals and the emergence of a single solid enantiomorph under attrition conditions. The rapid mass transfer of molecules between the solution and solid phases under attrition is demonstrated, and the concept of a crystal-size-induced solubility driving force is exploited to overcome the stochastic nature of the crystal growth and dissolution processes. Extension to non-racemizing conditions provides a novel methodology for chiral resolution. Implications both for practical chiral separations and for the origin of biological homochirality are discussed.

On the physical basis of asymmetry and homochirality.

Mirror symmetry breaking is ubiquitous in our visible universe taking place in elementary particles, atoms, and molecules. Molecular chirality is not biogenic in itself, although its detection is often considered a biosignature, a conjecture inferred from the fact that we do not know life devoid of homochirality. The question of whether there is a connection between the cosmic preference for one enantiomer, as imposed by the weak force, and the single chirality displayed on Earth is vividly debated. This article gives a glimpse on the origin of asymmetry from a cosmological perspective and on physical transformations that lead to an enantiomeric imbalance, leaving chemical reactions essentially aside. These processes are more plausible as sources of prebiotic chirality than asymmetric amplifications requiring unnatural substrates and conditions and fighting against racemization. The latter may actually be a friend, not foe, and a driving force for enantioselection.

Enantioenrichment in sublimed amino acid mixtures.

A real amplification of an initial enantiomeric excess can be detected when two amino acids are sublimed at high temperature, even if one of the components is a racemic compound that does not convert into a conglomerate by sublimation.

Homochirality beyond grinding: deracemizing chiral crystals by temperature gradient under boiling.

A single-chirality solid phase can be obtained in boiling solutions containing a racemic mixture of left- and right-handed enantiomorphous crystals due to dissolution-crystallization cycles induced by a temperature gradient. This phenomenon provides further insights into asymmetric amplification mechanisms under presumably prebiotic conditions.

Asymmetric amplification in amino acid sublimation involving racemic compound to conglomerate conversion.

A straightforward unprecedented sublimation protocol that reveals both conversion of a racemic compound into a racemic conglomerate and subsequent enantioenrichment has been developed for the proteinogenic amino acid valine. The phenomenon has been observed in closed and open systems, providing insight into asymmetric amplification mechanisms under presumably prebiotic conditions.

Solution-phase racemization in the presence of an enantiopure solid phase.

Solution-phase racemization drives the evolution of single chirality in the solid phase by the "chiral amnesia" process first described by Viedma. The current investigations lay the basis for a better understanding of the mechanism of the solid-phase deracemization by uncoupling the chemical rate processes associated with the interconversion of enantiomers in the solution phase from the physical processes associated with solution-solid phase transfer via dissolution and reaccretion of molecules onto crystals. In addition, the enantiomer concentration profiles presented in this work, together with an analytical treatment of the racemization process in the presence of excess enantiopure solid, unequivocally reconfirm the validity of the Meyerhoffer double solubility rule for systems under solution racemization conditions.

Evolution of solid phase homochirality for a proteinogenic amino acid.

The inexorable evolution of solid-phase single chirality is demonstrated for the first time for a proteinogenic amino acid. Enantioenrichment is observed both under attrition-enhanced conditions and without the aid of particle grinding. Differences in the form of the conversion profiles for the process under the two sets of conditions provide suggestions concerning the mechanism of the transformation.

Chiral symmetry breaking and complete chiral purity by thermodynamic-kinetic feedback near equilibrium: implications for the origin of biochirality.

Chiral symmetry breaking occurs when a physical or chemical process spontaneously generates a large excess of one of the two enantiomers--left-handed (L) or right-handed (D)--with no preference as to which of the two enantiomers is produced. From the viewpoint of energy, these two enantiomers can exist with an equal probability, and inorganic processes that involve chiral products commonly yield a racemic mixture of both. The fact that biologically relevant molecules exist only as one of the two enantiomers is a fascinating example of complete symmetry breaking in chirality and has long intrigued the science community. The origin of this selective chirality has remained a fundamental enigma with regard to the origin of life since the time of Pasteur, some 140 years ago. Here, it is shown that two populations of chiral crystals of left and right hand cannot coexist in solution: one of the chiral populations disappears in an irreversible autocatalytic process that nurtures the other one. Final and complete chiral purity seems to be an inexorable fate in the course of the common process of growth-dissolution. This unexpected chiral symmetry breaking can be explained by the feedback between the thermodynamic control of dissolution and the kinetics of the growth process near equilibrium. This "thermodynamic-kinetic feedback near equilibrium" is established as a mechanism to achieve complete chiral purity in solid state from a previously solid racemic medium. The way in which this mechanism could operate in solutions of chiral biomolecules is described. Finally, based on this mechanism, experiments designed to search for chiral purity in a new way are proposed: chiral purity of amino acids or biopolymers is predicted in solid phase from a previously solid racemic medium. This process may have played a key role in the origin of biochirality.

Chiral symmetry breaking during crystallization: complete chiral purity induced by nonlinear autocatalysis and recycling.

We report experimental results that show a large and symmetric population of D and L crystals moving into complete chiral purity, with one of the enantiomers completely disappearing. The results indicate (i) a new symmetry breaking process incompatible with the hypothesis of an initial single chiral phase or "mother crystal," (ii) that total symmetry breaking and complete chiral purity can be achieved from a system that initially includes both enantiomers, and (iii) that this is achieved through a nonlinear autocatalytic-recycling process.