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The Chain of Chirality Transfer as Determinant of Brain Functional Laterality

Breaking the Chirality Silence: Search for New Generation of Biomarkers; Relevance to Neurodegenerative Diseases, Cognitive Psychology, and Nutrition Science

Neurology and Neuroscience Research. 2017;1(1):2
DOI: 10.24983/scitemed.nnr.2017.00028
Article Type: Review Article


Biomolecules are the products of an evolutionary history. As a result, the phenomenon of molecular chirality is relevant to protein folding, neuronal proliferation, brain functional laterality, as well as the nature of cognition, consciousness, behavior, and psychiatry. Molecular chirality, discovered by Faraday (1846) and Pasteur (1848), helped to reveal that the biochemistry of the living beings has a prevalent chirality. At present, the essence of biochirality is widely recognized, appreciated, and exploited in neuroscience and psychology. In a more general sense, molecular chirality is recognized as the universal “Force of Nature.” From the formal geometrical perspective, a chain of chiral bifurcations is the chain of the chirality transfer between the molecular micro-, meso-, and macro-scales. Consequently, the symmetry is considered as a critical issue in the brain information processing. The fundamental laws of information theory reflect the relationship between entropy, symmetry and information. At the cellular level, signal transduction mechanism involves the wave of chiral transformations in the process of protein-protein, protein-phospholipids, and protein-DNA interactions. The symmetry dynamics at the molecular and cellular levels are considered in connection to the laterality of cognitive functions. The abnormal symmetry dynamics viewed as a primary reason of an aggregation of mis-folded proteins in the neurodegenerative diseases and psychiatric disorders. The molecular basis of the “symmetry evolution” in the biological systems is a question of interest. In this short review, we briefly summarize advances in the broad field of biochirality connecting two poles of the phenomena: the atomic orbitals and the brain’s cognitive function. Analysis of current results allows introducing the new generation of entangled biomarkers ranging from the molecular chirality to laterality of cognitive and executive functions.


  • Stereochemistry; molecular biology, nonequilibrium biochemistry, phase transition, chirality transfer, chiral catalysis, protein folding, protein aggregation, neuronal cell, information processing, cognitive laterality; cognitive association.


The essence of biochiralityis widely recognized, appreciated and exploited. Partially it is illustrated by chronologically sequencing citations from the publications in the diverse branches of the science. "Almost every biochemical process occurring in the cell of all living organisms is based on some specific, stereoselective interaction between reacting molecules” [1]. "From a chemical point of view, proteins are by far the most structurally complex and functionally sophisticated molecules known” [2]. "Stereospecificity is one of the hallmarks of enzyme catalysis” [3]. "One of the most dramatic aspects of biological systems involving proton transfer is their high stereoselectivity” [4]. "Chirality plays a fundamental role in the activity of biological molecules and broad classes of chemical reactions” [5]. "Controlled mirror symmetry breaking arising from chemical and physical origin is currently one of the hottest issues in the field of supramolecular chirality” [6]. "Chiral recognition is the fundamental property of many biological molecules” [7]. "Chiral compounds…pose the significant impact on the understanding of the origin of life and all processes that occur in living organisms” [7]. "Cell chirality may be a general property of eukaryotic cells” [8]. "Chirality is one of the ubiquitous phenomena in biological systems” [9]. "Consistent left-right (LR) asymmetry is a fundamental aspect of the bodyplan across phyla” [10]. "Among the most readily observed topological features in natural structures are chirality, hierarchy, and hierarchy of chirality” [11]. "Chirality is a fundamental property and vital to chemistry, biology, physics and materials science" [12]. In most general sense, molecular chirality is appreciated as the universal “force of nature” [13]. "How chirality at one length scale can be translated to asymmetry at a different scale is largely not well understood” [12].

In such situation, it is reasonable to view the enormous amount of facts of biochirality as the hierarchical system unifying by the common underlying mechanism.

Stereospecific Phenomena

The chiral, spiral and helical structures and shapes are seen in the morphology of many physical [15] and biological [16] systems including the spiraling of plants [17] the shape of the mammalian cochlea [18], and the shape of human brain [8]. In any organism, the geometrical patterns are seen in a position of the heart and visceral organs [10], and in the spatial distribution of brain activity [19]. Left-right asymmetry recognized as a fundamental property of the brain, evident at all levels of an organization, including molecular, cellular, morphological, and functional [20-23]. At the same time, it is well known that the majority of biologically active molecules such as amino acids [22], proteins [23], carbohydrates,II and phospholipids [24] are chiral. The ability of proteins to fold into the chiral secondary, tertiary, and higher-ordered structures assumed to be responsible for their prominent role in the chirality transformation events. The members of protein family known for chirality related functions include enzymesIII [25], cytoskeleton molecular complex [26], amylogenic proteins [27,28], trans-membrane proteins – ligand complex [29], drugsIV [30,31], and antibioticsV [32,33]. For the purpose of our review we will restrict our attention mostly to the proteins and phospholipids.

Chirality Prevalence (Amino Acids, Sugars, Phospholipids, Water)
Most of the bio-compounds have prevalent chirality (phenomenon of homochirality).VI

AMINO ACIDS/PROTEINS. Among more than 700 naturally occurring amino acids only 20 are involved in the proteins synthesize. All of the alpha-amino acids are chiral (exept glicine). The essential chiral amino acids are L-configurationsVII (“left-handed”). The amino acids stereo-chemistry is the major determinant of protein chirality. It is meaningful that the spatial configuration of amino acids in the organic world, as a rule, is governed by enzymes (i.e. proteins) [25]. The evolution known plays a pivotal role in the mechanism of protein folding. Chiral proteins, as the principal constituents of neuronal cells, provide molecular machinery for the lateralized brain cognitive functions.

SUGARS. The sugars are D-configurations (“right-handed”).

PHOSPHOLIPIDS. The majority of the membrane phospholipidsVIII is right-handed, but in the archaea (single-celled organisms) membrane they are left-handed [24,34]. Furthermore, the membrane phospholipids are right-handed [24,34] but in an archaea (single-celled organism)IX membrane, they are left-handed.

WATER. The water molecules (H2O) as the main constituent of the living organism are in the scope of our consideration. In a homogeneous, achiral environment, the H2O molecules possess neither a chiral center nor a helical conformation that can cause spontaneous chirality effects. Accordingly, many assume (at first glance) that water falls apart from phenomenon bio-chirality. However, this view was challenged by studies that devote more close attention to the dynamics of water structure in the chiral environment (proteins, phospholipids, polysaccharides) and dynamics of chirality. In the variety of the “inhomogeneous” situations, water molecules dynamically participate in chirality-related effects. Among such conditions, we can point on the aggregation of water molecules into clusters [38], interaction with magnetic bio-proteins [39], contact with the solid/gel/liquid surface [40], interaction with the chiral solutes [41,42], and dehydration synthesis of proteins (via covalent bonds of amino-acids). In particular, it was shown that structured water exhibits a chirality adapted from DNA [43]. The presence of hydrophobic, hydrophilic, and intermediate groups in the amino acids and phospholipids contributes to the variety pathways of spatial arrangement. The body of accumulated evidence (despite the variety of distinct pathways) suggests some common causal agent in the chain of events from the molecular chirality to the origin of body/brain morphology and function. This "universal agent" is the spatial relationships between the objects linked to the fundamental geometrical patterns of space and force fields.

Biological Evolution as a Chain of Chiral Bifurcations
The pathway of life can be perceived as an “increasing chemical and physical complexity” [44,45]. In a more particular sense, the biological evolution considered as the chain of chiral bifurcations [46].

The symmetry effects propagate from the level of molecular spatial transformations, intracellular /cross-membrane molecular transport, cell motility, to the higher hierarchical level of the spatial organization such as the cell proliferation [47], immune defense, environmental chemistry [49], motor behavior, brain cognitive functions, human psychology [50], psychiatry [48,51-53]. The symmetry effects play a critical role in food preparation [54,55], pharmaceutical industry [56,57], design of molecular devices (biosensors and information processing units. Symmetry is considered the critical issue in the theory of information processing and the design of artificial intellectX [58]. The hierarchy of biological structural organization arms an organism with the abilities of adequate response to environmental challenges of differential time-space ranks.

Origin of Biological Homochirality
The homochirality is usually associated with bio-molecular objects (distinct from non-biological objects). There is an objective reason for this specificity. The biological homochirality known to be essential for the molecular recognition, protein replication, post-translational modification, and degradation processes.

The origin of homochirality in biology is the subject of much debate. The emotional view on bio-chirality is frequently associated with an expression such as a symmetry breaking,XI enigma, puzzle, or mystery. More rational scientific approaches exhibit some degree of uncertainty, but always are ready to move forward along with the newly-coming objective evidence. After works of Prelog, the discussion of an origin and maintenance of homochirality was shifted from the intuitive, emotional domain to the ground of scientific facts [59]. The cumulative advance in chiral physics, chemistry, and mathematics sheds light on the phenomenon of chirality in general and on biological homochirality in particular. Several decades ago Frank developed the mathematical modelXII for the spontaneous autocatalytic reaction as the mechanism for the evolution of homochirality [60,61]. Recently it was shown that the origin of molecular homochirality could be attributed to the non-equilibrium state of biological systems. The Vester-Ulbricht hypothesis, based on the interaction of the left-handed electrons (present in beta-radiation) with biological materials which preferentially destroyed one of the two enantiomer, was the first step in the right direction [62,63]. This hypothesis was successfully tested experimentally [64]. The sensitivity of molecular chirality to external determinants becomes one of the most productive ideas. The classic experiment of Viedma reveals that the bulk and dispersed solid state crystals show different dynamics of solid-liquid phase transition, which, under certain conditions, can be utilized to achieve an enantiomeric preference [65]. The following studies of the chirality dynamics in the solid-liquid phase system leads to several models presumably providing the mechanism implicating for the origin of biochirality. Among them is the model based on the different solubility of homochiral and heterochiral crystals [66] and “chiral amnesia” model [67,68]. The review of current hypothesizes on the biological homochirality in connection with the recent discovery of the interstellar chiral molecule can be found in multiple sources [10,44,69-71]. The new finding reveals the fundamental significance of the symmetry transfer (1) and symmetry-associated phase transitions (2) in resolving the origin of biological homochirality [44,70,72]. Among them are the chiral recognition/selection during the self-assembly of protein-mimic macro-anions [73], chiral recognition in the transmitter-receptor interactions [74], the chirality-induced conformation of the cell membrane lipid raftsXIII [75,76], and the phase-transfer chiral catalysisXIV [77]. The chiral catalysis is productively utilized for symmetry-asymmetry transformations in biochemistry [78]. The phenomenon of chirality is common to all aspects of animal life and body/brain morphology, including the internal organs, the sensory systems, the central nervous system, and behavior. In particular, it pertains to sensory perception [79], motor-behavior [80], and food consumption [54]. All of the arguments related to the origin of the biological homochirality, including terrestrial [44] and extraterrestrial [81,82] are based on the common and experimentally proved effects. The sensitivity of chiral molecules to the internal, external, and mutual (internal-external) physical (objective) parameters [83]. While you can find discussions of the many particular local physical parameters, in the majority of current reviews, you will almost never find discussions about of the global parameters, such as the chirality of space-time evident in the physical systems [83,84].

Transformation of Bio-Chirality
Symmetry transformation is traditionally considered to be the spontaneous processes accompanying all of the molecular interactions (phase separation and phase transition), including symmetry breaking and molecular folding in relation to information minimization or symmetry maximization [86]. The symmetry dynamics at the molecular level are frequently considered to be the mechanism responsible for the laterality of cognitive functions. Thus, the laterality and hemispheric asymmetry should be regarded as the indispensable attributes of the brain. The molecular basis of the symmetry evolution in biological systems is the question of interest. Current evidence suggests that integration of the internal and external determinants [84], as well as global and local signaling pathways, is necessary for orienting the diverse levels of structure with respect to the body/brain axes [87-89]. In particular, the integration is evident in the hierarchical chirality transformation accompanying the planar cell polarityXV in the epithelium, sensory organs [90],XVI and the brain morphology [89]. 

Dynamic Organic Reactions
The spatial interpretation of molecular structures was advanced (1874) by the concepts of the tetrahedral orientation of carbon's four bonds by Van’t Hoff and optical isomerism by Le Bel [91,92]. These ideas, in turn, gave rise to the stereochemistry of chiral stereoisomers. It was realized that the spatial orientation of different functional groups governs the patterns of specificity in chemical reactivity [93]. The interaction between the chiral and achiral components was widely studied in the biological organic reactions. The dynamics of organic reactions (in particular those that take place within the spatially ordered environment of an enzyme protein interaction) exhibit stereoselectivity and stereospecificity. The excellent review of the stereo-dynamic of chiral objects, including natural molecular structures and artificial molecular devices, can be found in [94]. It is notable, that both the stereoselectivity and stereospecificity are based on the recognition of the symmetry-related characters (such as polarity, chirality, and helicity). Thus, a conclusion such as “chiral recognition is the fundamental property of many biological molecules” is not surprising [7].

Diversity of Stereospecific Phenomena
The diversity of stereospecific (chiral) phenomena was observed in molecular structures including chirality recognition/sensing [95,96], chirality transfer [97], chirality/helicity induction [98-101], chirality amplification [102-104], chirality breaking [61,105], chirality conflict [106,107], helicity inversion [108-110], and chiral phase transitionsXVII [111-114,116]. Progress in the studies of molecular chirality transformation is helpful in resolving three questions. First, what kind of determinants can provide a favor in the production of one enantiomer over the other? Second, what is the mechanism of intermolecular propagation and preservation of chirality? And third, what is the mechanism of chirality propagation from the molecular level to a higher degree of biological organization?

Chiral Phase Transitions in Relation to Chirality Transfer
Physical System
Among the variety of the topological phase transitions [120-123] several sub-categories, including the order–disorder [118], chirality-related [119] and geometry-induced [120,123] transitions, were discovered. In condensed matter physics, phase transitions exhibit sensitivity to external physical parameters (pressure, fields, electro-magnetic radiation, sonication,XVIII and doping). The systematic study of these phenomena has revealed a new class of phase transitions, called “quantum phase transition (QFT)”. Spontaneous QFTs take place at the mesoscopic level at zero temperature and are driven by the quantum fluctuationsXIX (according to Heisenberg's uncertainty principle). For the two above facts, the sensitivity to external physical parameters and the concept of the spontaneous phase transitions are of great importance.

Biological Systems
In relation to the biological systems, the chirality of the sub-cellular structures (such as hair bundles) was observed in auditory and vestibular sensory neurons of vertebrates [87,118]. The phase transitions are the common effects, observed in the chiral molecules with pyramidal atomic centers such carbon and nitrogen. The frequency of a pyramidal inversion (tunnel quantum-mechanical effect) depends on the value of the energy barrier and set of external physicochemical factors. Chirality transfer from molecular to morphological level is observable in a diversity of physical objects as well as biochemical and synthetic materials [124,125]. The hierarchical propagation of chirality was found between the objects of different size, shape, and dimensionality [126]. The chirality breaking in the nonequilibrium systems (Bloch walls) was studied in magnetic materials [127]. Recent progress in the development the concept of “active fluids” reveals the chiral behavior of a class of nonequilibrium systems, which include bacterial suspensions of a bacteria, cytoskeleton proteins, and biological tissues. Even relatively simple combination of chiral and achiral stresses, leads to an “unprecedented range of complex motilities, including oscillatory swimming, helical swimming, and run-and-tumble motion” [128].

Chirality Transfer

Variety of Spatially Related Events
Among the variety of spatially related events, the phase transitions and the symmetry transformations are known as the most closely associated. We will focus mostly on the phenomena of the chirality transfer. The chirality transfer from the molecular to morphological scales was documented in nano-materials [124] and polymers [125]. The studies of the plant's growth reveal the “hierarchy of chirality” which transfers from the molecular (lower) levels to the macro-morphological (higher) level [130]. In our review, we explore what is currently known about how the molecular chirality is transformed into to the laterality of cognitive functions.

Sensitivity of Chirality Transfer to Internal, External, Local and Global Conditions
Symmetry transformation arising from chemical and physical origin is one of the hottest issues in the field of molecular chirality [5-8]. Before the further consideration it is essential to emphasize that hypothesis about the distinction between internal and external determinates in the living organism being very productive could become irrational in the form of an absolute opposition. The most convincing example of the link between external and internal factors is the function of a digestive system, which permanently transforms the external factors into the very internal. Pasteur (1861-1887) was the first who introduced an idea regarding an interaction between the polar physical fields (electrical, magnetic, electromagnetic, gravitational/mechanical) with atomic/molecular chirality [131]. He was also the first who realize the fact of the chirality transfer from the molecular level to the level of macroscopic solid crystal [132]. The ideas were great, but the success was limited. Much later the empirical evidence of the role of the forces of nature on the chiral compounds was obtained. The early idea of Pasteur was supported by modern experimental capabilities [133,134]. Two essential facts were observed: the effect of magnetic field on the molecular chirality [135] and increased enzyme stereo specificity in the course of an enzyme/protein evolution [136,137]. Both results, accompanied by the discovery of the spontaneous [138] and induced chirality provided the tools to disclose the previously mysterious homochirality of life [139]. In particular an essential result was derived by Barron [140]. He demonstrated that supramolecular helices formed from achiral monomers have been controlled by applying the combination of the gravitational and rotational forces [140]. The transfer of stereochemical information (in the form of chirality and helicity) was observed between chiral and achiral constituents of the molecular complexes in general and of biological systems in particular [141-144]. The transfer of chirality from protein to the cellular and embryonic level was suggested in several studies [145,146]. The critical role of a molecular and cellular chirality as the determinants of LR asymmetric in the animal body, and functions has gradually emerged [8]. The explosive advance in the study of asymmetric catalysis over the last four decades has dramatically altered the view on the biomolecular chirality dynamics [147,148]. Before the era of chiral catalysis, the most common characteristic of the enantiomers was the absence or little difference in the chemical and physical properties. At present at the majority of publications related to chiral catalysis we can meet the statements like “enantiomers have different properties”. Resent progress in the synthesis of the chiral compound associated with the study of the catalytic asymmetric reactions of carbonyl compounds, allow an understanding of the principles governing the dynamics of structural conformations in the amino acids and proteins of the living organisms [149]. Molecular chirality and correspondently a chirality transfer are recognized as sensitive to the broad range of modulators including the internal, external, localized, and diffused determinants. It is notable that molecular chirality exhibits sensitivity to all types of the chemical binding including ionic, covalent, and not-covalent [58].

The generation of chiral imbalance in the chiral molecular systems can occur spontaneously, due to intrinsic instability or induced by external factors [102]. In accordance with this instability, the chiral self-organization of molecular complexes is sensitive to the impact of many external factors including electrical (metal ions), magnetic, electromagnetic (photon), mechanical, and gravity force fields. The discovery of magnetically induced optical activity by Faraday was the first demonstration of the sensitivity of a molecular chirality to the physical parameters of an environmentXX [150]. Since then, the sensitivity of the chiral objects to the environmental parameters has been explored at cosmological [151], molecular [152], atomic [57], and elementary particles levels [153]. Thus, it is reasonable to be aware that different molecular structure can have the same or different physical properties depending on the nature of the physical effect and chemical environment.XXI In the specific case of the stereoisomers interaction with an electromagnetic field, we have at last three different situations depending on the energy diapason (such as IR, UV and NMR spectra), and method used (such as the circular dichroism) [40]. The photons (chiral object itself) of different energy interact with the chiral components of the molecular complex (such as electron or proton) compromising its equilibrium spatial configuration. The recent discovery of the quantum chiral light–matter interaction offers fundamentally new functionalities for the charity transfer of the bio-molecular structure related to brain quantum information-processing capability [160]. The chiral molecules reveal the capability of the self-organization of the helical superstructures. The intermolecular interactions related to the modulation of chirality are the part of the supramolecular chemistry [161-165] and interfacial sciences [166,167]. The chiral sensing based on the concept of chirality transfer is of great importance.

Chain of Cirality Transfer
Several relatively new fields of science provide the bridge between dynamic chirality in solid matter physics and bio-chirality. The chirality transfer (or the transfer of handedness) is observed between organic and inorganic molecular structure [168]. The central point of these studies is the chirality transfer in the variety of forms.XXII Among them, we can mention the stereo-physics of liquid crystals [126] and chiral catalysis [169]. The modeling macroscopic chirality emerged from the chiral molecular elements is a challenge for theory, computations, and experiments [126]. Numerous experimental results demonstrate the transfer of chirality among different length scales ranging from dimensions of the elementary particles to the macro-scale (the length of the axon) [124]. In particular, it was shown that the chirality at the molecular scale (amino, acids, proteins, and polysaccharides) could be transferred to the macroscopic and macro- level (neurofilaments and inorganic crystals) as shown in [168]. The issue of dimensionality in the chirality transfer effects is critical for brain information processing in the brain and artificial intelligence devices.XXIII The examples of macroscopic chirality are found in the plant kingdom, animal kingdom and all other groups of organisms.

Physical Systems
In the quantum spin systems, the symmetry-related phase transitions [78,154,155] and the transfer of the stereospecific (symmetry) characters XXIV [97,156] are well-known phenomena. The recent advance in the experimental and theoretical areas of many disciplines related to stereochemistry revealed the chirality-induction effects in the various inorganic materials with mono-chiral and hybrid-chirality structures including plasmonic, semiconducting, metal oxide and silica-based compounds [170]. The most prominent among the field-induced chirality effects are the following: Coulomb (near-field, dipolar), electromagnetic, and plasmonic mechanisms [171]. The chirality transfer from the spin-quantum system of elementary particles to the atomic structure level is an essential element of basic knowledge and serves as the necessary introduction to the understanding of the chemistry and biochemistry. The nuclei of atoms and associated electron system have an innate chirality. The chemical phenomena are viewed as associated with the chirality of electron system and nuclearXXV constituents [172]. The molecular chirality is the consequence of the chirality transfer from the dynamic complex of elementary particles. The transfer of molecular chirality from monomers to polymeric structures has been widely explored and utilized [173]. The advanced field of chiral photon–electron /proton interaction reveals the sensitivity of chiral objects to the physical environment. As a result of such sensitivity, chiral photonelectron/proton interaction offers fundamentally new functional opportunities for information transfer technology and info-processing systems. In particular, the non-reciprocal single-photon devices allow utilizing the quantum information processing based on the superposition of two operational states in chiral spin–photon system [160]. Thus, the stereo-specific effects, including the chirality transfer, are not the unique properties of the organic world.XXVI Quit contrary stereospecific effects are the universal and fundamental character of both organic and inorganic materials.

Biological Systems: Basic Set of the Chirality Transfer Levels
From the physical world chiral events diversity and complexity point of view our primary concern is the chain of the chirality transfer in biological systems. The very essential prediction of the sequential chain of chital events in the organism was done long before the modern progress in biostereochemistry [174]. Taking the review of newly discovered facts as a basis, we will clarify the natures of elements in this chain and the hierarchy of these elements within the chain. Referring to the hierarchy of a chirality transfer, we will assume (based on the review of current publications) that it consists of several distinct levels. The basic set of these levels includes the transfer of following types:

  • From the elementary particles to the atomic orbital level
  • From the atomic orbital to the molecular levelXXVII
  • From molecular to macro- and supra-molecular level
  • From the molecular level to the cellular level
  • From the cellular level to neuronal circuits level
  • From the cellular to morphological level
  • From the morphological to cognitive level
  • From the cognitive to the behavioral level

After reviewing the elements of the chiral hierarchy, we will examine what is currently known about the sensitivity of each of the hierarchical levels of chirality to the internal and external determinants. The chirality transfer occurs under the influence of physical and chemical determinants which play a role of the “chirality directing force.” The stochastic fluctuations in parameters of an environment could result in the transient fluctuations in the relative prevalence of enantiomers [178], while long-term fluctuations will lead to permanent effects giving a chance for amplification and preservation mechanisms. Several reviews provide information about the range of chirality related events [44,45]. Finally, the degree of “stereo-sensitivity” will reveal the multi-variable pathway contributing to the evolution of the brain cognitive functions.

From Elementary Particles to Atomic Level
The chirality transfer from the elementary particles to the arrangement of atomic orbital was considered in the previous paragraphs. The energy difference (parity violation) between the ground and excited states of molecular enantiomers in the presence of weak nuclear force is predicted by theory and proved experimentally [179,180].

From Atomic Orbitals to Molecular Level
The wavefunctions of electron orbitals are traditionally considered to be the determinants of the molecular chirality [14]. Consequently, in the stereochemistry, the spatial arrangement of the atomic orbital is the primary determinant of the chiral center's function in bio-molecules, including the amino acids, sugars, and phospholipids. At present, it is a common recognition that the electronic orbitals of the carbon atom constitute the root contributing to the molecular chiralityXXVIII [181,182].

From Molecular to Macro-Molecular and Supra-molecular Level
The alterations of brain molecular chirality, represented in particular by the proteins or lipids constituents, are accompanied by the changes in the left/right asymmetry of the synapse (cellular chirality), asymmetry in the regional brain morphology, and laterality of brain functions in many experimental situations. In this sense the molecular chirality, is the principal initiator of the origin of the life. We will review the chirality transfer events in the order of their natural sequence. The transfer of the symmetry patterns (chirality-induced helicity or chirality-helicity transfer) from the amino acids to peptides [179] and proteins [181] is broadly studied. Four main categories of biological-macromolecules, which exhibit chirality, are proteins, lipids, carbohydrates, and nucleic acids [180,183].

PROTEINS. In the human body about 100,000 different proteins introduce the charity phenomenon for all the key physiological, perceptual, cognitive and psychological function of an organism. The chirality transfer from amino acids to proteins secondary and higher order structure is one of the most studied fields in biochemistry. The chirality of protein folding gained attention in condensed matter physics [14,184] and molecular biology [36,185]. The stereo-transformations of proteins are a highly dynamic field of science involving the most advanced analytical capabilities [146,186-196]. The protein’s stereo-transformations is the area of particular interest in the neuroscience due to relevance to proteins aggregation disorders such as Alzheimer's, Parkinson's, and Huntington's disease (AD, PD, HD).

CELL MEMBRANE (PHOSPHOLIPIDS AND CHOLESTEROL). A similar mechanism is responsible for the transfer of molecular-level stereo-specificity (chirality) to the supra-molecular level (helicity) in cell membrane rafts during endocytosis [197]. The establishment of helical handedness can be formed at the macro-molecular level due to the stereo-ordering regularity of constituted chiral entities at the intra-molecular and intermolecular interactions [198]. The chirality transfer from the molecular to the supramolecular level (nanometer and micrometer scale) and the morphological level was observed in the inorganic liquid crystals [115], polymers [198], and bio-polymersXXIX including cellulose, sugars, proteins, RNA, and DNA.

From Molecular to Cellular Level
The origin of cell chirality and its role in the upstream laterality are the subject of many reviews [7]. The review of current studies suggests that “molecular chirality direct whole-cell chirality [8]. The chirality transfer from the molecular (cytoskeleton proteins) to the cellular level (cell wall and cell shape) was demonstrated in the bacterium [199,200,201, 202]. Cellular chirality, in a variety of its forms, is governed by crosstalk of the internal and external determinants.XXX Chirality at the cellular level was first studied mostly in ciliates or single-celled protozoans. These studies reveal that molecular chirality directs whole-cell chiralityXXXI [8]. At the cellular level, signal transduction involves the wave of chiral transformations in the protein-phospholipid interactions [204-206].

From Cellular to Morphological Level
The chirality of the biomolecules and the intrinsic cell chirality observed in various organisms appear to be a causal event for the left–right (LR) asymmetric of morphogenesis [8,130]. The multiple pathways of chirality transfer from the molecular cytoskeleton dynamics to the cellular behavior, and to organ asymmetry were found [10]. As was mentioned above, the cell-shape chirality (cell chirality) is found to be driven by an intrinsic molecular mechanism comprising from the family of chiral cytoskeleton proteins [203]. In turn, the chirality transfer from the “chiral cells” to an organ occurs by the process of “planar cell chirality” (PCC). According to the early observation of Brown and Wolpert “the spiral asymmetry, as seen in spiral cleavage and ciliates, involves the conversion of molecular asymmetry to the cellular and multicellular level” [174]. In particular, it includes climbing plants tendrils [207,208], flower petals [209], and shells [210]. In the literature, the cellular and morphological hierarchical levels of chirality transfer are frequently considered together. It is notable, that chiral morphology exhibits the prevalence of the handedness [211]. The coherent and quasi-independent role of the intracellular (gene expression and cytoskeleton dynamics) and extracellular (cilia) determinants in the initiation of the embryonic asymmetry were studied in Caenorhabditis elegans, Xenopus, snails, Drosophila,XXXII frogs, chicks, and mice [8,212]. The interaction of proteins and phospholipids chirality at cellular level finally result in the asymmetrical distribution of major CNS receptorsXXXIII between left and right cerebral cortex [213].

From the Morphological to Cognitive Level
The chiral, spiral or helical shapes are seen in the morphology of many biological systems, including the spiraling of plants, and shape of the mammalian cochlea [18]. During animal development, chirality transfer repeatedly occurs at the different levels and scales of spatial organization. As we will see later, each lower-level (in the hierarchy of symmetry transformation) generates the higher level of the morphological and functional specialization. The functional specialization of the nervous system at the molecular (intracellular) level is always under impact of the extracellular events. The functions on the cellular and organ (brain) level, in turn, are always under the acute influence of evolutionary preserved behavioral paradigms. The studies of the association of brain function with the body’s reflexive reactions and goal-oriented movement were initiated by works of Pavlov in relation to the conditioned and unconditioned reflexes [214]. The ideas of Pavlov resonate with the earliest thoughts of Plate and Aristotle regarding the succession of memory events and modern theories of cognitive association. Brain asymmetry at the structural level begins to be apparent in the fetal brain in humans and nonhuman primates [215]. Brain laterality at the functional level is considered to be a result of morphological laterality [216]. The higher-order cognitive functions are associated with the spatially distributed activity of cerebral cortex. The anatomical asymmetry of the human cerebral cortex is exhibiting a three-partial differentiation. First-the torque {right frontal and left occipital areas are more prominent in size} [217]. Second-the leftward volumetric dominance in language-related areas [218,219]. Third-the left-right asymmetry in cortical thickness (right biased in frontal and left biased in parietal regions [220-222].

The discrimination between sleep and evoke brain activity with fMRI and EEG techniques demonstrates objective (and now trivial) link of the quantum dynamics of proton and electron with the faculties of space perception,XXXIV and consciousness [223,224]. The chirality transfer from the morphological level to functional brain laterality is considered in the plenty of the articles, reviews, and monographs [44,224-226].

From Cognitive to Behavioral Level
Chiral information is used for social communication in the variety of species from insectXXXV to humanXXXVI {face expression and perception} [228,229]. Diverse explanations have been proposed for the origin of the behavioral laterality including space constraints [230], as well as genetic, and ecological determinants. The link between the molecular, functional, and behavioral laterality is the focus of many studies. It is known that lateralized expression of the neuro-receptors serves as internal positional markers (compass) to distinguish the left and right hemisphere. Long time ego these markers were hypothesized to be necessary during ontogenesis for bilaterally-symmetrical brain formation and performance the hemisphere-specific perceptual and cognitive functions [231]. In particular, it was shown that the circle rotation of animal, which is mediated by several neurotransmitting systems, significantly contributed by an asymmetric expression of the hypothalamic neurohormones (such as somatostatin, substance P, and others [232]. Thus behavioral studies support the idea of a hierarchical chain of the chirality transfer.

Biological Transport, Information Processing, and Cognitive Systems

It is reasonable to mention here that the chirality transfer is relevant to three essential issues associated with space topology: the biological transport, information processing, and principle of cognition. A wide range of the coordinated motions, including the locomotion of organisms, spatial displacements at morphological (muscle fibers), cellular (flagella, cilia, synaptic spine) and molecular levels (protein fold, lipid chirality) are based on the principles of the chiral dynamics [91]. It has become clear that the evolutionary design of biological molecular motors acts upon the chirality transfer from the amino acids to the helical chirality of proteins. The biological molecular transport systems consist of two major parts: the cytoskeleton and motor proteins [233,234]. The functions of intracellular motor-proteins inspired the engineering molecular motors [235,236]. The advance in the design of artificial molecular motors promotes the understanding of the mechanism of intracellular transport [112,202,237, 238]. Thus not only the lower level biological features like the molecular transport, neuronal signaling, but also the higher level features such as sensory perception, brain information processing, and cognitive functions in general are related to the modality of chirality transfers.


Noether's Theorem
Noether's theorem states that each conservation lawXXXVII is associated with symmetry in the underlying physics [239]. The universal role of symmetry principles in the stereochemical configuration traditionally discussed in relations to the fundumental theorems of Noether, Ruch, and Gödel (240,241). From the platform of modern science, each of the conservation and violation laws is fundamentally associated with the preservation or alteration of the symmetry-related parameters. These universal laws are not only relevant to both nonbiological and biological objects but also are the fundamental determinants of an interaction between them. The symmetry patterns are persistently transferred between any combinations of the objects of similar or different nature. 

Our Hypothesis
Utilizing the application of universal space time topology principles to the biological world, our hypothesisXXXVIII state that the link between molecular chirality and laterality of the cognitive function is based on the universal law of symmetry. Refraining known sentence “space and time are the primary forms of existence” we can say that the dynamic symmetry is the form of existence for the entire variety of the biological objects.

Biological molecules reveal the chirality (handedness) in a variety of fashions many of which are critical for the healthy functions of human body, brain, and mind. The observation of the sign-alternating hierarchies for DNA and proteins contribute to the structure-function link in biochemistry, neuroscience, and psychology [242]. The striking similarity in the chirality-related effects within a broad class of molecular, cellular, and morphological structures inspired researchers in many fields of stereochemistry and neuroscience. The advance in the current results reveals the fundamental significance of molecular chirality in the broad range of inter-related disciplines including an intracellular transport, neuro-development, sensory perception, motor behavior, brain cognitive functions, human psychology, and psychiatry. The helical structures of the proteins are known to be the consequence of amino acid chirality. The helicity of proteins, in turn, provides an opportunity for chiral biological macromolecular systems with higher hierarchical levels of symmetry and yet unknown functions [46,242,243]. The hierarchy in the chain of the chirality transfer, evident particularly from the current review, possesses several not trivial features. Each of the consequently following hierarchical levels is contributed to from the cumulative power of all lower and higher levels. Each level has its own quasi-independent internal and external determinants. The majority of the external determinants (including environmental) exhibit a chiral nature. As such, the chirality of external determinants is a critical factor in the evolution and development of the organism. The chirality is naturally imposed to the brain structure and function from the two seemingly opposite but fundamentally linked to each other sides: the nature of bio-molecular structures and from the geometry of the environment. The fundamental nature of the chirality transfer should be considered in the experimental design strategy in neuroscience, cognitive science, psychology, and pharmacology. In particular, the molecular chirality is a sensitive indicator of both: the proper protein folding and pathological aggregation. Accordingly, the chirality patterns (raging from molecular chirality to the laterality of brain function) should be considered as a new generation of the biomarkers in the spectrum of the disease conditions including neurodegenerative and psychiatric disorders [22,244]

Several recently published essential papers provide the broad review of the previous and current hypothesis of a perceptual and cognitive development in health [245], and pathology [246]. Referring to the limited progress in the current models, and the low efficiency of drug treatment, authors frequently appeal to the necessity of a new approach in the research of the cognitive functions mechanism. Notably that none of the above-mentioned review are focused on the issues of stereochemistry, and brain asymmetry which are a central point for the study of links between protein folding and brain functions. [247-249]. Even the reviews devoted to structure, function, and assembly of the visual system (which is lateralized and well-studied as one of the most asymmetrical) do not focused on the molecular substrate of sensory functions. The explosive attention to protein-brain topology demonstrated in this year’s publications can be considered as a response to the “necessity calls’’ [250,245,251, 252].

Our review aims to contribute toward attention to the unifying direction for the studies of development, function, and decline of human perception, cognitive function, and action [252,253].


IWe assume that the readers are familiar with the basic concept of the chirality in relation to the theory of symmetry groups, quantum electrodynamics, and stereochemistry [14].

IICarbohydrates contain multiple stereocenters, allowing many forms of isomers including enantiomers, diastereoisomers, and epimers.

IIIThe enzymes determine the crystallization of chiral amino acids [25] and the "handedness" (chirality) of the proteins during catalytic synthesis.

IVThe enantiomers of a drug, as a rule, are differing in potency, toxicity, and behavior in biological systems.

VThe advance in enantio-separation of the antibiotics reveals the significance of chirality in their biological activity [32,33].

VIPhospholipids and cholesterol both contain chiral carbon atoms and could themselves mediate stereoselective effects [35].

VIIBrain tightly regulates the balance between the levels of right- and left-handed amino acids for proper structure of functional proteins [22,36,37]. 

VIIIIt is essential to know that homochirality is always relative (not absolute). There are many examples in nature where polypeptide topologies use both: L- and D-amino acids [36,37].

IXArchaea are classified as microbes (single-celled prokaryotes).

XIt is notable that the design of an intelligent human-made sensing system is based on the discrimination of the   object chirality and the use of chiral shape-defined polymers such as the dynamic helical polymers [58].

XIAt the molecular level, the term “symmetry breaking” refers to the imbalance between two enantiomers.

XIIThe main idea is that a substance acts as a catalyst in its own self-production and at the same time acts to suppress synthesis of its enantiomer.

XIIIIt has been suggested that the chiral nature of cholesterol plays a role in the process of the bud formation [85].

XIVThe variety of intracellular chemical reactions is mediated by seospecific enzymes. Many catalytic mechanisms require stereospecific deprotonation and reprotonation steps [77]. The L-amino acid active center is the primary determinant of catalytic activity. Thus, L-amino acid actively transfer chirality to the stereospecific enzyme activities [77].

XVPlanar cell polarity (PCP) “is driven by multiple global cues, including gradients of gene expression, gradients of secreted ligands, and anisotropic tissue strain” [117].

XVIThe chirality of the sub-cellular structures (such as hair bundles) was observed in auditory and vestibular sensory neurons of vertebrates [87,118].

XVIIThe formation of supramolecular helicity is associated with the occurrence of new thermodynamic phases. The chirality related effects in thermotropic and lyotropic liquid crystals were demonstrated through the ferroelectricity [115]. The phase transitions were shown to be implicated in the effects of the chirality transformation and mono-chirality observed in the amino acids and proteins [119].

XVIIIThe sonication-induced chiral symmetry breaking events were observed during sol-gel phase transition [129].

XIXThe quantum fluctuations are associated with Heisenberg's uncertainty principle.

XXFollowing Faraday’s discovery [150], Pasteur tried to grow chiral crystals in the presence of magnetic field [157].

XXIThe NMR spectra of two stereoisomers can be identical or differ depending on the chirality of an environment (solvent).

XXIIThe effect of chirality transfer is routinely used in nuclear magnetic resonance spectroscopy for the discrimination of the molecular stereoisomers absolute configurations [158].

XXIIIThe chirality transfer from monomers to a polymer is widely used in plastic engineering [159].

XXIVThe process is frequently referred to as the chirality transfer.

XXV“All nuclei are innately chiral and, because electrons can penetrate nuclei, all atoms and molecules are likewise chiral” [172].

XXVIIt is notable for the sake of our review that the spiral galaxies are the objects showing preferred chirality analogous to amino acids and sugars [175]. According to a contemporary view, the origins of the elementary particles and chemical elements are associated with the physical events at the galactic scale [176].

XXVIIDue to the topic of our review, we discussed very briefly (just mentioned) the two polar elements in the chain of the chirality transfer: the physic of elementary particles and space-time chirality of an environment. Actually these two elements are seemingly-polar only within our “hierarchical chain”. In the nature they are inherently linked to each other by concept of space-time symmetry. Thus the linear sequence of chiral events, in this consideration, becomes a natural circle of the chiral transformations. For those who are interested in the quantum aspects of the chirality transfer we recommend to explore the “chiral effective field theory” [177].

XXVIIIMolecular level of the chirality transfer cover the broad range of molecular structures from small molecules (such the amino acids) to the large complexes including polymers (such as proteins) and globular molecules.

XXIXAmong the biopolymers, we will mostly concentrate on the proteins.

XXXSupport of this statement speaks to the fact that the cells isolated from developing organism undergo the symmetry transformation even in the absence of the external signals [8].

XXXISeveral chiral compounds exhibit capability to block cell proliferation suggesting their relation to issue of the cancer treatment [47].

XXXIIIn Drosophila, intrinsic cell chirality is observed in various left–right (LR) asymmetric tissues, and appears to be responsible for their LR asymmetric morphogenesis. It is notable that the cell chirality can drive the LR asymmetric development of individual organs without establishing the LR axis of the whole embryo [8].

XXXIIIThe muscarinic acetylcholine receptors (mAChR), the prevalent receptors in the central nervous system, are asymmetrically distributed between left and right cerebral cortex with the right-side dominance [213].

XXXIVIn Kant’s view, space and time are a priory forms of sensibility, providing two windows’ for empirical intuition.

XXXVThe insects and many other animals use molecular chirality for olfactory perception. Insects, which use chiral pheromones, typically produce and respond to either a single stereoisomer or to species-specific blend of only some of the possible stereoisomers [227].

XXXVIThe face expression and perception, which play a significant role in human social communication, both are the chirality related functions.

XXXVIIConservation Laws: Conservation of the Linear Momentum, Angular Momentum, and Energy.

XXXVIIIMeaning that the hypothesis is based on the universal nature of Noether’s theorem and is generated by the review of contemporary experimental facts and theoretical models.


  1. Dzygiel P & Wieczorek P. Stereo-selective Transport of Amino Acids and Peptides through Liquid Membranes. Chemical Papers  2002; 56:24-31. [view article
  2. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. PMCID: PMC4244961; DOI: 10.1093/aob/mcg023
  3. St-Jean M and Sygusch J. Stereospecific Proton Transfer by a Mobile Catalyst in Mammalian Fructose-1, 6-bisphosphate Aldolase. The Journal of Biological Chemistry 2007;282:31028-31037. DOI: 10.1074/jbc.M704968200 [view article]
  4. Solntsev KM, Bartolo EA, Pan G, et al. Excited-State Proton Transfer in Chiral Environments: Photo-racemization of BINOLs1. Israel journal of chemistry 2009;49:27–233. PMCID: PMC2756819; DOI: 10.1560/IJC.49.2.227
  5. Pattersona D and Schnell M. New studies on molecular chirality in the gas phase: enantiomer differentiation and determination of enantiomeric excess. Physical Chemistry Chemical Physics 2014;23. [view article]
  6. Fujiki M. Review. Supramolecular Chirality: Solvent Chirality Transfer in Molecular Chemistry and Polymer Chemistry. Symmetry 2014;6:677-703. DOI: 10.3390/sym6030677
  7. Tiwari MP and Prasad A. Molecularly imprinted polymer based enantioselective sensing devices: a review. Analytica chimica acta 2015;853:1-18. PMID: 25467446; DOI: 10.1016/j.aca.2014.06.011
  8. Inaki M, Liu J and Matsuno K. Cell chirality: its origin and roles in left–right asymmetric development. Philosophical Transactions of the Royal Society B 2016;371:1710. DOI: 10.1098/rstb.2015.0403
  9. Deng L, Wu S, Yao M and Gao C. Surface-anchored poly (acryloyl-L (D)-valine) with enhanced chirality-selective effect on cellular uptake of gold nanoparticles.Scientific Reports 2016;6:31595. DOI: 10.1038/srep31595.
  10. McDowell G, Rajadurai S and Levin M. From cytoskeletal dynamics to organ asymmetry: a nonlinear, regulative pathway underlies left-right patterning. Philosophical Transactions B 2016;371:1710. PMID: 27821521; PMCID: PMC5104508; DOI: 10.1098/rstb.2015.0409
  11. Mousanezhada D, Haghpanaha B, Ghosha R, et al. Elastic properties of chiral, anti-chiral, and hierarchical honeycombs: A simple energy-based approach. Theoretical and Applied Mechanics Letters 2016;6:81–96. DOI: 10.1016/j.taml.2016.02.004
  12. Morrow SM, Bissette AJ and Fletcher SP. Transmission of chirality through space and across length scales. Nature Nanotechnology 2017;12:410–419. DOI:10.1038/nnano.2017.62
  13. Noyori R. Nobel lecture. Asymmetric Catalysis; science and opportunities 2001. [view article]
  14. Le Guennec P. On the concept of chirality. Journal of Mathematical Chemistry 1998;23:429–439.  DOI: 10.1023/A: 1019197930712
  15. Ni J, Wang C, Zhang C, Hu Y, et al. Three-dimensional chiral microstructures fabricated by structured optical vortices in isotropic material. Cornel Univ. Library (205). ArXiv: 1608.01220 [physics.optics]. [view article]
  16. Book by Nandi N. Chirality in Biological Nanospaces: Reactions in Active Sites. CRC Press. Taylor & Fransis Group 2012.  [view article]
  17. Piconese S, Tronelli G, Pippia P and Migliacco F. Chiral and non-chiral nutations in Arabidopsis roots growth on the random positioning machine. Journal of Experimental Botany 2003;54:1909-1918.  DOI:
  18. Cai H, Manoussaki D and Chadwick R. Effects of coiling on the micromechanics of the mammalian cochlea. J R Soc Interface 2005; 2: 341–348.   PMCID: PMC1578277; DOI: 10.1098/rsif.2005.0049
  19. Shannahoff-Khalsa D. Review. Lateralized rhythm of the central and autonomic nervous systems. International Journal of Psychopathology 1991;11:225-251.  [view article]
  20. Novoselova NY and Sapronov NS. Role of inversion of interhemispheric asymmetry of phospholipid content in rat brain synaptosomes under stress conditions. Doklady Biological Sciences 2012; 442:7-10.  PMID: 22427212; DOI: 10.1134/S0012496612010085
  21. Novoselova NY, Sapronov NS, Reichardt BA. Phospholipids of synaptosomes from rat brain hemispheres in dynamics of experimental myocardial infarction. Key role of right hemisphere in pathogenesis of depression associated with myocardial infarction (hypothesis). Journal of Asymmetry 2014;8:34-43.  [view article]
  22. Weatherly CA, Du S, Parpia C, Santos PT, Hartman AL and Armstrong DW. d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study. ACS Chemical Neuroscience 2017;8:1251-1261.  DOI: 10.1021/acschemneuro.6b00398
  23. GM, Mao B and Cho KC. Chiral Features of Proteins. In the book by Paul G. Mezey: New Developments in Molecular Chirality 1991.  [view article]
  24. Tan HH, Makino A, Sudesh K, Greimel P and Kobayashi T. Spectroscopic evidence for the unusual stereochemical configuration of an endosome-specific lipid. Angewandte Chemie International Edition 2012;51:533–535.  DOI: 10.1002/anie.201106470
  25. Book by Würges K. Enzyme Supported Crystallization of Chiral Amino Acids. Forschungszentrum Juilich 2011.  [view article]
  26. Satir P. Chirality of the cytoskeleton in the origins of cellular asymmetry. Philosophical Transactions of the Royal Society B 2016;371. PMID: 27821520
  27. Li M, Zhao C, Ren J and Qu X. Chiral Metallo-Supramolecular Complex Directed Enantioselective Self-Assembly of β-Sheet Breaker Peptide for Amyloid Inhibition. Small 2015;11:4651–4655. DOI: 10.1002/smll.20150132
  28. Scala CD, Yahi N, Boutemeur S, et al. Common molecular mechanism of amyloid pore formation by Alzheimer's ă beta-amyloid peptide and alpha-synuclein. Scientific Reports 2016;6:28781.  DOI: 10.1038/srep28781
  29. Thakur GA, Palmer SL, Harrington PE, et al. Enantiomeric resolution of a novel chiral cannabinoid receptor ligand. Journal of Biochemical and Biophysical Methods 2002; 54:415-422.  PMID:12543516; DOI: 10.1016/S0165-022X(02)00144-6
  30. Book edited by Eichelbaum MF, Testa B and Somogyi A. Stereochemical Aspects of Drug Action and Dispositio. Springer-Verlag Berlin Heidelberg (2003).  [view article]
  31. Nguyen LA, He H and Pham-Huy C. Chiral Drugs: An Overview. International journal of biomedical science 2006;2:85–100. PMCID: PMC3614593
  32. Hutt AJ and O’Grady J. Drug chirality: a consideration of the significance of the stereochemistry of antimicrobial agents. Journal of Antimicrobial Chemotherapy 1996;37:7-32.  PMID: 8647776
  33. Dixit S and Hag Park J. Application of antibiotics as chiral selectors for capillary electrophoretic enantioseparation of pharmaceuticals: a review. Biomedical Chromatography 2014;28:10–26. DOI: 10.1002/bmc.2950
  34. Wächtershäuser G. From pre-cells to Eukarya – a tale of two lipids. Molecular microbiology 2003;47:13-22.  PMID: 12492850
  35. Weiskopf RB, Nau C and Strichartz GR. Drug Chirality in Anesthesia. Anesthesiology 2002;97:497-502.  [view article]
  36. Nanda V, Andrianarijaona A and Narayanan C. The role of protein homochirality in shaping the energy landscape of folding. Protein science : a publication of the Protein Society 2007;8:1667–1675.  PMCID: PMC2203351; DOI: 10.1110/ps.072867007
  37. Ali HS, Alhaj OA, Al-Khalifa AS and Brückner H. Determination and stereochemistry of proteinogenic and non-proteinogenic amino acids in Saudi Arabian date fruits. Amino Acids 2014;46:2241-2257.  PMID: 24938763; DOI: 10.1007/s00726-014-1770-7
  38. Drechsel-Grau C and Marx D. Tunnelling in chiral water clusters: Protons in concert. Nature Physics 2015;11:216–218. DOI: 10.1038/nphys3269
  39. Matsumoto Y, Chen R, Anikeeva P and Jasanoff A. Engineering intracellular biomineralization and biosensing by a magnetic protein. Nature Communications 2015;6:8721.  DOI: 10.1038/ncomms9721
  40. Spector MS, Easwaran KRK, Jyothi G, et al. Chiral molecular self-assembly of phospholipid tubules: A circular dichroism study. Proceedings of the National Academy of Sciences of the United States of America 1996;93:12943–12946.  PMCID: PMC24025
  41. S. Bisht S, Pandey P, Bhargava B, et al. Bioremediation polyaromatic hydrocarbons (PAHs) using rhizosphere technology. Brazilian journal of microbiology 2015;46:7-21.  PMID: 26221084; PMCID: PMC4512045; DOI: 10.1590/S1517-838246120131354
  42. Kessler D, Kallenbach M, Diezel C, et al.. How scent and nectar influence floral antagonists and mutualists. eLife 2015;4:e07641.  DOI:
  43. Petersen P. I. Speaker. Water at surfaces with tunable surface chemistries and the chiral imprint of water around DNA. APS March Meeting 2016.Vol. 61, Number 2. Monday–Friday, March 14–18, 2016; Baltimore, Maryland. Session P31: Water at Interfaces: From Spectroscopy Techniques to Computer Simulations. P31.00001 (March 16, 2016). [view article]
  44. Hazen RM. Mineral surfaces, geochemical complexities, and the origin of life. Cold Spring Harbor perspectives in biology 2010;2: a002162.  PMCID: PMC2857174
  45. Blackmond DG. The origin of biological homochirality. Cold Spring Harbor perspectives in biology Labor. Press. 2010.  PMCID: PMC2857173; DOI: 10.1101/cshperspect.a002147
  46. Malyshko EV and Tverdislov VA. Chirality as a physical aspect of structure formation in biological macromolecular systems. Journal of Physics: Conference Series 2016;741:1.   DOI: 20.1088/1742-6596/741/1/012065
  47. Chhabra SR, Harty C, Hooi DS, Daykin M, et al. Synthetic analogues of the bacterial signal (quorum sensing) molecule N-(3-oxododecanoyl)-L-homoserine lactone as immune modulators. Journal of medicinal chemistry 2003;46:97-104.   PMID: 12502363; DOI: 10.1021/jm020909n
  48. Yan ECY, Fu L, Wang Z and Liu W. Review. Biological Macromolecules at Interfaces Probed by Chiral Vibrational Sum Frequency Generation Spectroscopy. Chemical Reviews 2014;114:8471–8498.  DOI: 10.1021/cr4006044
  49. Book edited by Lichtfouse E, Schwarzbauer J and Robert D. Environmental Chemistry for a Sustainable World: Volume 2: Remediation of Air and Water Pollutions. Springer Sc. +Bus. Media B.V. 2012.  [view article]
  50. Martin M and Jones GV. Motor imagery theory of contralateral handedness effect in recognition memory: toward a chiral psychology of cognition. Journal of Experimental Psychology, General. 1999;128: 265-282.   DOI:
  51. Burke WJ and Kratochvil ChJ. Stereoisomers in psychiatry: the case of escitalopram. Journal of clinical psychiatry 2002;4:20-24. PMID: 15014731; PMCID: PMC314378
  52. Baker GB, Prior TI, and Coutts RT. Chirality and drugs used to treat psychiatric disorders. Journal of psychiatry and neuroscience 2002;6:401–403.  PMCID: PMC161712
  53. Patocka J and Dvorak A. Biomedical aspects of chiral molecules. Journal of Applied Biomedicine 2004;2:95-100.   [view article]
  54. Zawirska-Wojtasiak R. Chirality and the Nature of Food Authenticity of Aroma. Acta Scientiarum Polonorum, Technologia Alimentaria 2006;5: 21-36. [view article]
  55. Carlavilla D, Victoria Moreno-Arribas M, Fanali S, Cifuentes A. Chiral MEKC-LIF of amino acids in foods: Analysis of vinegars. Electrophoresis 2006;27:2551–2557.  DOI: 10.1002/elps.200500909
  56. Li B and Haynie DT. Chiral Drug Separation. In the book edited by Sunggyu Lee. Encyclopedia of Chemical Processing 2006;1.  [view article]
  57. Wang P, Yu SJ, Govorov AO and Ouyang M. Cooperative expression of atomic chirality in inorganic nanostructures. Nature Communications 2017.  DOI: 10.1038 /ncomms14312
  58. Ariga K, Richards GJ, Ishihara S, Izawa H and Hill JP. Review. Intelligent Chiral Sensing Based on Supramolecular and Interfacial Concepts. Sensors 2010;10:6796-6820.   DOI: 10.3390/s100706796
  59. Prelog V. Chirality in Chemistry. Nobel Lecture, December 12, 1975. The Nobel Foundation (1975). From Nobel Lectures, Chemistry 1971-1980, Editor-in-Charge Tore Frängsmyr, Editor Sture Forsén, World Scientific Publishing Co., Singapore, 1993. [view article]
  60. Frank. On spontaneous asymmetric synthesis. Biochimica et biophysica acta 1953;4:459-63. PMID: 13105666
  61. Jafarpour F, Biancalani T, Goldenfeld N. Noise-induced symmetry breaking far from equilibrium and the emergence of biological homochirality. Physical Review E 2017;95(3-1):032407.  DOI: 10.1103/PhysRevE.95.032407
  62. Ulbricht TLV and Vester F. Attempts to induce optical activity with polarized β -radiation. Tetrahedron 1962;18:629-637. DOI: 10.1016/S0040-4020(01)92714-0
  63. Dreiling JM and Gay TJ. Chirality Sensitive Electron-Induced Molecular breaking and the Vester-Ulbricht Hypothesis. Physical Review Letters 2014;113:118103.  DOI: 10.1103/PhysRevLett.113.118103
  64. Dreiling and Joan. Chiral Sensitivity in Electron-Molecular Interactions. APS Gaseous Electronics Conference 2015, abstract #IW4.001The Smithsonian/NASA Astrophysics Data System.  [view article]
  65. Viedma C. Chiral symmetry breaking crystallization: complete chiral purity induced by nonlinear autocatalysis recycling. Physical Review Letters 2005;94:065504.   DOI: 10.1103/PhysRevLett.94.065504
  66. Klussmann M, Iwamura H, Mathew SP, Wells DH, et al. Thermodynamic control of asymmetric amplification in amino acid catalysis. Nature 2006;441:621–623.   DOI: 10.1038/nature04780
  67. Blackmond DG. Chiral amnesia as a driving force for solid-phase homochirality. Chemistry European. Journal. 2007;13:3290-3295.  DOI: 10.1002/chem.200601463
  68. Viedma C. Chiral symmetry breaking and complete chiral purity in thermodynamic-kinetic feedback near equilibrium: implication for the origin of biochirality. Astrobiology 2007;7:312-319.  DOI: 10.1089/ast.20060099
  69. Cronin J and Reisse J. Chirality and the Origin of Homochirality. Ch. 3 in the Book edited by Muriel Gargaud, Bernard Barbier, Hervé Martin, Jacques Reisse. Lectures in Astrobiology. 1:473. Edited by Muriel Gargaud, Bernard Barbier, Hervé Martin and Jacques Reisse. [view article]
  70. Blackmond DG. The origin of biological homochirality. Cold Spring Harbor perspectives in biology 2010;2:a002147. DOI: 10.1101/cshperspect.a002147
  71. McGuire BA, Carroll PB, Loomis RA, et al. Discovery of the Interstellar Chiral Molecule Propylene Oxide (CH3CHCH2O). Science 2016;352:1449-1452.  PMID: 27303055; DOI: 10.1126/ science.aae0328.
  72. Hein JE and Blackmond DG. On the origin of single chirality of amino acids and sugars in biogenesis. Accounts of chemical research. 2012;45:2045–2054.   PMID: 22353168; DOI: 10.1021/ar200316n
  73. Yin P, Zhang ZM, Lv H, et al. Chiral Recognition and Selection during the Self-Assembly Process of Protein-Mimic Macroanions. Nature Communications 2015;6:6475.  PMID: 25756393; Doi: 10.1038/ncomms7475
  74. Bouvier M. Review. Oligomerization of G-protein-coupled transmitter receptors. Nature Reviews Neuroscience 2012;2:274-286.  DOI: 10.1038/35067575
  75. Turner NJ. Controlling chirality. Current Opinion in Biotechnology 2003;14:401-416. PMID: 12943849; DOI: 10.1016/S0958-1669(03)00093-4
  76. Kanga L and Lubenskya TC. Chiral twist drives raft formation and organization in membranes composed of rod-like particles. Proceedings of the National Academy of Sciences of the United States of America 2017;114:E19–E27.  PMCID: PMC5224397; DOI: 10.1073/pnas.1613732114
  77. Pemberton TA and Christianson DW. Review. Genera base-general acid catalysis by terpenoid cyclases. The Journal of Antibiotics 2016;69:486–493.  PMID: 27072285; PMCID: PMC4963284; DOI: 10.1038/ja.2016.39
  78. Shiho K, Kumatabara Y and Shirakawa S. A new generation of chiral phase-transfer catalysts. Organic and Biomolecular Chemistry 2016;14:5367-5376.   DOI:10.1039/C5OB02446C
  79. Stamatopoulos P , Brohan E, Prevost C, et al. Influence of Chirality of Lactones on the Perception of Some Typical Fruity Notes through Perceptual Interaction Phenomena in Bordeaux Dessert Wines. Journal of agricultural and food chemistry 2016;64:8160-8167.  PMID: 27717288; DOI: 10.1021/acs.jafc.6b03117
  80. Book edited by Stamenov M and Gallese V. Mirror Neurons and the Evolution of Brain and Language. John Benjamines B.V. 2002.  DOI: 10.1075/aicr.42
  81. Pizzarello S. The chemistry of life's origin: A carbonaceous meteorite perspective. Accounts of Chemical Research 2006;39:231-237.  DOI: 10.1021/ar050049f
  82. Zahnle K, Schaefer L and Fegley B. Earth's early atmospheres. Cold Spring Harbor perspectives in biology 2010;2:a004895. DOI: 10.1101/cshperspect.a004895
  83. Meinert C. Understanding the Origin of Chiral Molecules in Interstellar Space. Séminaires LLR. Institut de chimie de Nice. (Europe/Paris) 2016. [view article]
  84. Singh D. Neutrino helicity and chirality transitions in Schwarzschild space-time. Physical Review D 2005;71.  DOI: 10.1103/PhysRevD.71.105003
  85. Sarasij RC and Rao M. Tilt texture domains on a membrane and chirality induced budding. Physical Review Letters 2002;88. DOI: 10.1103/PhysRevLett.88.088101
  86. Lin SK. The Nature of the Chemical Process. 1. Symmetry Evolution - Revised Information Theory, Similarity Principle and Ugly Symmetry. International Journal of Molecular Sciences 2001;2:10-39.  [view article]
  87. Wang Y and Nathans J. REVIEWS. Tissue/planar cell polarity in vertebrates: new insights and new questions. Development 2007;134:647-658.  DOI: 10.1242/dev.02772
  88. Lawrence PA, Struhl G and Casal J. Perspective Opinion. Planar cell polarity: one or two pathways? Nature Reviews Genetics 2007;8:555-563.  DOI: 10.1038/nrg2125
  89. Vandenberg LN and Levin M. A unified model for left-right asymmetry? Comparison and synthesis of molecular models of embryonic laterality. Developmental biology 2013;379:1-15.  PMID: 23583583; PMCID: PMC3698617; DOI: 10.1016/j.ydbio.2013.03.021
  90. Axelrod JD. Strabismus comes into focus. Nature Cell Biology 2002;4:E6-E8.  Doi: 10.1038/ncb0102-e6
  91. Le Bel JA. "Sur les relations qui existent entre les formules atomiques des corps organiques et le pouvoir rotatoire de leurs dissolutions" (On the relations that exist between the atomic formulas of organic substances and the rotatory power of their solutions), Bulletin de la Société Chimique de Paris 1874;22:337–347. [view article]
  92. van’t Hoff JH. A suggestion looking to the extension into space of the structural formulas at present used in chemistry. And a note upon the relation between the optical activity and the chemical constitution of organic compounds. Archives neerlandaises des sciences exactes et naturelles 1874; 9: 445-454.  [view article]
  93. Weisberg M, Needham P and Hendry R. Philosophy of Chemistry. Stanford Encyclopedia of Philosophy 2011.  [view article]
  94. Wolf C. Dynamic Stereochemistry of Chiral Compounds: Principles and Applications. Copyright: 2007.  [view article]
  95. Tsukube H and Shinoda S. Lanthanide complexes in molecular recognition and chirality sensing of biological substrates. Chemical Reviews 2002;102:2389–2404.  DOI: 10.1021/cr010450p
  96. SongG and Ren J. Recognition and regulation of unique nucleic acid structures by small molecules. Chemical Communications 2010;46:7283–7294. DOI: 10.1039/C0CC01312A
  97. J. Crassous J. Transfer of chirality from ligands to metal centers: Recent examples. Chemical Communications 2012;48:9684-9692.  [view article]
  98. Kolomiets E, Berl V and Lehn JM. Chirality induction and protonation-induced molecular motions in helical molecular strands. Chemistry A European Journal 2007;13:5466-5479.  DOI: 10.1002/chem.200601826
  99. Eerdun C, Hisanaga S and Setsune J. Single helicates of dipalladium (II) hexapyrroles: Helicity induction and redox tuning of chiroptical properties. Angewandte Chemie International Education 2013;52:929-932. DOI: 10.1002/anie.201207113
  100. Brown RA, Diemer V, Webb SJ, Clayden J. End-to-end conformational communication through a synthetic purinergic receptor by ligand-induced helicity switching. Nature Chemistry 2013;5:853-860.  [view article]
  101. Miyake H. Supramolecular Chirality in Dynamic Coordination Chemistry. Symmetry 2014;6:880-895.  DOI: 10.3390/sym6040880
  102. K. Soai K. Amplification of Chirality. Pg. 73. Topic in Current Chemistry 2008;284. Springer-Verlag Berlin (2008). [view article]
  103. Ito H, Ikeda M, Hasegawa T, Furusho Y and Yashima E. Synthesis of complementary double-stranded helical oligomers through chiral and achiral amidinium-carboxylate salt bridges and chiral amplification in their double-helix formation. Journal of the American Chemical Society 2011;133:3419-3432.  DOI: 10.1021/ja108514t
  104. Yashima E, Ousaka N, Taura D, et al. Supramolecular Helical Systems: Helical Assemblies of Small Molecules, Foldamers, and Polymers with Chiral Amplification and Their Functions. Chemical Reviews 2016;116:13752-13990. DOI: 10.1021/acs.chemrev.6b00354
  105. Kafri R, Markovitch O and Lancet D. Spontaneous chiral symmetry breaking in early molecular networks.Biology Direct 2010;5:38. PMID: 20507625; PMCID: PMC2894767; DOI: 10.1186/1745-6150-5-38
  106. Li Y, Wang M, Li Q, et al. Azoarenes with opposite chiral configuration: light-dravercible handedness inversion in self-organized helical superstructures. Angewandte Chemie International Edition 2013;52:8925-8929.  DOI: 10.1002/anie.201303786
  107. Li Q. Nanoscience with Liquid Crystals: From Self-Organized Nanostructures to Applications. Springer Int. Publish. Switzerland 2014.  [view article]
  108. Jiang X, Lim YK, Zhang BJ, et al. Dendritic molecular switch: Chiral folding and helicity inversion. Journal of the American Chemical Society 2008;130:16812-16822.  DOI: 10.1021/ja806723e
  109. Akine S, Hotate S and Nabeshima T. A molecular leverage for helicity control and helix inversion. Journal of the American Chemical Society 2011;133:13868-13871.  DOI: 10.1021/ja205570z
  110. Miyake H, Ueda M, Murota S, Sugimoto H and Tsukube H. Helicity inversion from left- to right-handed square planar Pd (II) complexes: Synthesis of a diastereomer pair from a single chiral ligand and their structure dynamism. Chemical Communications 2012;48:3721-3723.  DOI: 10.1039/C2CC18154A
  111. Weigelt S, Busse C, Petersen L, et al. Chiral switching by spontaneous conformational change in adsorbed organic molecules. Nature Materials 2006;5:112-117.  DOI: 10.1038/nmat1558
  112. Pijper D, Jongejan MGM, Meetsma A and Feringa BL. Light-controlled supramolecular helicity of a liquid-crystalline phase using a helical polymer functionalized with single chiroptical molecular switch. Journal of the American Chemical Society 2008;130:4541-4552.  DOI: 10.1021/ja711283c
  113. Stillinger FC. Microscopic Kinetic Model Exhibiting Chiral Symmetry Breaking. Bruce Berne Symposium, ACS, Boston, Aug. 22-25, 2010.  [view article]
  114. Hajlaouia F, Yahyaouia S, Nailia H, Mhiria T and Batailleb T. Crystal structure, phase transition and thermal decomposition of a copper (II) sulfate dihydrate containing a chiral organic ammonium cation. Inorganica Chimica Acta 2010;363:691-695. DOI: 10.1016/j.ica.2009.11.024
  115. Dierking I. Chiral Liquid Crystals: Structure, Phases, Effects. Symmetry 2014;6:444-472.  DOI: 10.3390/sym6020444
  116. Smith E and Morowitz HJ. The Origin and Nature of Life on Earth: The Emergence of the Fourth Geosphere. Cambroge University Press 2016.  DOI: 10.1017/CBO9781316348772
  117. Butler MT and John B. Wallingford. Planar cell polarity in development and disease. Nature Reviews Molecular Cell Biology 2017;18:375-388.  DOI: 10.1038/nrm.2017.11
  118. Strutt D and Goodrich LV. Review. Principles of planar polarity in animal development. Development 2011;138:1877-1892. DOI: 10.1242/dev.054080
  119. Chela-Flores J. The origin of chirality in protein amino acids. Chirality 1994;6:165-168.  [view article]
  120. Iachello F. Analytic Description of Critical Point Nuclei in a Spherical-Axially Deformed Shape Phase Transition. Physical Review Letters 2001;87.   DOI: 10.1103/PhysRevLett.87.052502
  121. Alloyeau D, Ricolleau C, Mottet C, et al. Size and shape effects on the order-disorder phase transition in CoPt nanoparticles. Nature Materials 2009;8:940-946.   DOI: 10.1038/nmat2574
  122. Nishiyama I, Yamamoto J, Goodby JW and Yokoyama H. Chiral smectics: Molecular design and superstructures. Molecular Crystals and Liquid Crystals  2005;443:25-41.   DOI: 10.1080/15421400500236485
  123. Callister T, Sammut L, Qiu S, Mandel I and Thrane E. Limits of Astrophysics with Gravitational-Wave Backgrounds. Physical Review X 2016;6.   DOI: 10.1103/PhysRevX.6.031018
  124. Wang JS, Feng XQ, Xu J, Qin QH and Yu SW. Chirality Transfer from Molecular to Morphological Scales in Quasi-One-Dimensional Nano-Materials: A Continuum Model. Journal of Computational and Theoretical Nanoscience 2011;8:1278-1287.  DOI: 10.1166/jctn.2011.1811
  125. Qing G and Sun T. The transformation of chiral signals into macroscopic properties of materials using chirality-responsive polymers. NPG Asia Materials 2012;4:e4.  DOI: 10.1038/am.2012.6
  126. De Michele C, Zanchetta G, Bellini T, Frezza E and Ferrarini A. Hierarchical Propagation of Chirality through Reversible Polymerization: The Cholesteric Phase of DNA Oligomers. ACS Macro Letters 2016;5:208-212.  DOI: 10.1021/acsmacrolett.5b00579
  127. Coullet P, Lega J, Houchmandzadeh B and Lajzerowicz J. Breaking chirality in nonequilibrium systems. Physical Review Letters 1990;65:1352.    DOI: 10.1103/PhysRevLett.65.1352
  128. Tjhunga E, Catesa ME and Marenduzzob Dd. Contractile and chiral activities codetermine the helicity of swimming droplet trajectories. Proceedings of the National Academy of Sciences of the United States of America 2017;18:4631-4636. DOI: 10.1073/pnas.1619960114
  129. Pi-Boleda B, Sans M, Campos M, et al. Studies on Cycloalkane-Based Bisamide Organogelators: A New Example of Stochastic Chiral Symmetry-Breaking Induced by Sonication. A European Journal of Chemistry 2017;23:3357-3365. DOI: 10.1002/chem.201604818
  130. Wang JS, Wang G, Feng XQ, et al. Hierarchical chirality transfer in the growth Towel Gourd tendrils. Scientific Reports 2013;3:3102.  DOI: 10.1038/srep03102
  131. Pasteur L. Sur les corpuscles organizes qui existent dand l’atmosphere: Examen de la doctrine des generations spontaneous. Lecon Professee a la Societe Chimique de Paris. lw. 19 Mai 1861.  [view article]
  132. Gal J. Louis Pasteur, Language, and Molecular Chirality. I. Background and Dissymmetry. Chirality 2011;23:1-16. PMID: 20589938; DOI: 10.1002/chir.20866
  133. Mason SF. Molecular Optical Activity and the Chiral Discriminations. Cambridge University Press. 1982.  [view article]
  134. Bonet JC, Ignés-Mullol J and Sagués F. Chiral selection under swirling: From a concept to its realization in soft-matter self-assembly. Contributions to science 2015;11:199-205. Thematic issue on Non-equilibrium physics.  [view article]
  135. Kozlova SG, Kompankov NB and Zavakhina MS. Activation Parameters of Self-Diffusion of Aromatic Chiral Molecules in External Magnetic Fields. Journal of Physical Chemistry B. 2017;121:6655-6658.  DOI: 10.1021/acs.jpcb.7b05847
  136. Bonner WA. Chirality and life. Origins of Life and Evolution of the Biosphere 1995;25:175-190.  DOI: 10.1007/BF015.81581
  137. Shimada A, Ozaki H, Saito T and Noriko F. Tryptophanase-Catalyzed l-Tryptophan Synthesis from d-Serine in the Presence of Diammonium Hydrogen Phosphate. International journal of molecular sciences 2009;10:2578-2590. PMCID: PMC2705506; DOI: 10.3390/ijms10062578
  138. Jeong J, Aetukuri N, Graf T, et al. Suppression of Metal-Insulator Transition in VO2 by Electric Field-Induced Oxygen Vacancy Formation. Science 2013; 339: 402-1405. PMID: 23520104; DOI: 10.1126/science.1230512
  139. Palyi G, Zucchi C and Caglioti L. Progress in Biological Chirality. Chapter: 26. Shimada A, Fujii N and Saiko T. Tryptophanase on D-Tryptophan. Introduction. Elsevier Ltd (2004).  [view article]
  140. Barron LD. Chirality: spin and gravity give a helping hand. Nature Chemistry 2012;4:150-152. PMID: 22354423; DOI:10.1038/nchem.1278
  141. Ousaka N, Takeyama Y, Iida H and Yashima E. Chiral information harvesting in dendritic metallopeptides. Nature Chemistry 2011;3:856-861.   DOI:10.1038/ nchem.1146
  142. Albrecht M. Let's twist again’—double-stranded, triple-stranded, and circular helicates. Chemical Reviews 2001;101:3457-3498.   DOI: 10.1021/cr0103672
  143. Clayden J. Molecular devices: Communicating chirality. Nature Chemistry 2011;3:842-843.  DOI: 10.1038/nchem.1181.
  144. Palmans ARA and Meijer EW. Amplification of chirality in dynamic supramolecular aggregates. Angewandte Chemie International Edition 2007;46:8948-8968.  DOI: 10.1002/anie.200701285
  145. Aw S, and Levin M. Hypothesis. Is left-right asymmetry a form of planar cell polarity? Development 2009;136:355-366. DOI: 10.1242/dev.015974
  146. Kannan S and Zacharias M. Folding simulations of Trp-cage mini protein in explicit solvent using biasing potential replica-exchange molecular dynamics simulations. Proteins 2009;76:448-460.  DOI: 10.1002/prot.22359
  147. Jacobsen EN, Pfaltz A and Yamamoto H. Comprehensive Asymmetric Catalysis. Springer, Berlin. 1999; I-III. [view article]
  148. Ojima I. Catalytic Asymmetric Synthesis. Wiley, New York, 3rd Edition 2000.  [view article]
  149. Hosamani B, Ribeiro MF, da Silva Júnior EN and Namboothiri NNI. Catalytic asymmetric reactions and synthesis of quinones. Journal of Organic & Biomolecular Chemistry 2016;29: 6913-6931.  DOI: 10.1039/C6OB01119E
  150. Faraday M. Esq. D.C.L. F.R.S. LIV.Thoughts on Ray-vibrations. Philosophical Magazine 1846;28. DOI: 10.1080/14786444608645431
  151. Dvornikov M and Semikoz V. Lepton asymmetry growth in the symmetric phase of an electroweak plasma with hypermagnetic fields versus its washing out by sphalerons. Physical Review 2013. DOI: 10.1103/PhysRevD.87.025023
  152. Woszczyk A and Szabelski P. Enhancing the separation of enantiomers in absorbed overlayers: a Monte Carlo study. Annales Universitatis Mariae Curie-Skłodowska. Lublin - Polonia. 2014;68:133-141. DOI: 10.2478/umcschem-2013-0011
  153. Volovik GE and Krusius M. Viewpoint: Chiral Quantum Textures. Physics 2012;5:130.  [view article]
  154. Kessler EM, Giedke G, Imamoglu A, et al. Dissipative phase transition in a central spin system. Physical Review A 2012;86. DOI: 10.1103/PhysRevA.86.012116
  155. Krokhmalskii T, Baliha V, Derzhko O, Schulenburg J and Richter J. Frustrated honeycomb-lattice bilayer quantum antiferromagnet in a magnetic field: Unconventional phase transitions in a two-dimensional isotropic Heisenberg model. Physical Review B 2017;95.   DOI: 10.1103/PhysRevB.95.094419
  156. Labuta J, et al. NMR Spectroscopic detection of chirality and enantopurity in referenced systems without formation of diastereomers. Nature Communications 2013;4: 2188.  PMCID: PMC3759048; DOI: 10.1038/ncomm3188
  157. Pasteur L. C.r. hebd. Séanc. Acad. Sci. Paris. 1848. 26;535. Oeuvres de Pasteur Vol. 1 (ed. Pasteur Valery-Radot) 61-64 (Masson, Paris, 1922). [view article]
  158. Parker D. NMR determination of enantiomeric purity. Chemical Reviews 1991;91:1441-1457.  DOI: 10.1021/cr00007a009
  159. Park J, Goh M and Akagi K. Helical Nylons and Polyphthalamides Synthesized by Chiral Interfacial Polymerizations between Chiral Nematic Liquid Crystal and Water Layers. Macromolecules 2014;47:2784-2795.  DOI: 10.1021/ma500515s
  160. Lodah P, Mahmoodian S, Stobbe S, et al. Chiral quantum optics. Nature 2017;541:473-480.  DOI: 10.1038/ nature21037
  161. Ariga K, Vinu A, Hill JP, Mori T. Coordination chemistry and supramolecular chemistry in mesoporous nanospace. Coordination Chemistry Reviews 2007;251:2562-2591.  DOI: 10.1016/j.ccr.2007.02.024
  162. Nakanishi T, Michinobu T, Yoshida K, et al. Nanocarbon superhydrophobic surfaces created from fullerene-based hierarchical supramolecular assemblies. Advanced Materials 2008;20:443-446.   DOI: 10.1002/adma.200701537
  163. Nakanishi T, Takahashi H, Michinobu T, et al. Fine-tuning supramolecular assemblies of fullerenes bearing long alkyl chains. Thin Solid Films 2008;516:2401-2406. DOI: 10.1016/j.tsf.2007.04.110
  164. Okamoto K, Chithra P, Richards JG, JP, Ariga K. Self-assembly of optical molecules with supramolecular concepts. International journal of molecular sciences 2009;10:1950-1966. DOI: 10.3390/ijms10051950
  165. Mandal S, Lee MV, Hill JP, Vinu A and Ariga K. Recent developments in supramolecular approach for nanocomposites. Journal of Nanoscience and Nanotechnology 2010;10:21-33.   DOI: 10.1166/jnn.2010.1503
  166. Pu L. Fluorescence of organic molecules in chiral recognition. Chemical Reviews 2004;104:1687-1716.  DOI: 10.1021/cr030052h
  167. Watarai H and Adachi K. Measuring the optical chirality of molecular aggregates at liquid-liquid interfaces. Analytical and Bioanalytical Chemistry 2009;395:1033-1046. [view article]
  168. Xiao W, Ernst KH, Palotas K, et al. Microscopic origin of chiral shape induction in achiral crystals. Nature Chemistry 2016; 8:326-330.   DOI: 10.1038/NCHEM.2449
  169. Fu W and Tang W. Chiral Monophosphorus Ligands for Asymmetric Catalytic Reactions. ACS Catalasis 2016;6: 4814-4858.  DOI: 10.1021/acscatal.6b01001
  170. Govana J and Gun'ko YK. Recent progress in chiral inorganic nanostructures. Nanoscience 2016;3:1-30. DOI: 10.1039/9781782623717-00001
  171. Ben-Moshe A, Maoz BM, Govorov AO and Markovich G. Chirality and chiroptical effects in inorganic nanocrystal systems with plasmon and exciton resonances. Chemical Society Reviews. 2013;42:7028-7041. DOI: 10.1039/C3CS60139K
  172. Pagni RM. The weak nuclear force, the chirality of atoms, and the origin of optically active molecules. Foundations of Chemistry 2009;11:105-122.  [view article]
  173. Kawagoe Y, Fujiki M and Nakanoa Y. Limonene magic: noncovalent molecular chirality transfer leading to ambidextrous circularly polarised luminescent π-conjugated polymers. New Journal of Chemistry 2010;34:637-647.  DOI: 10.1039/B9NJ00733D
  174. Brown NA and Wolpert L. The development of handedness in left/right asymmetry. Development 1990;109:1-9. PMID: 2209459
  175. Capozziello S and Lattanzi A. Spiral galaxies as enantiomers: Chirality, an underlying feature in chemistry and astrophysics. Chirality 2006;18:17-23.   [view article]
  176. Boyd R. ChiralStardust, Supernovae and the Molecules of Life: Might We All Be Aliens? Springer Science+Business Media. 2012. [view article]
  177. Machleidt R and Entem DR. Chiral effective field theory and nuclear forces. Physics Reports 2011;503:1-75. DOI: 10.1016/j.physrep.2011.02.001 
  178. Vasseur DA and Fox JW. Phase-locking and environmental fluctuations generate synchrony in a predator-prey community. Letter Nature 2009;460:1007-1010.  DOI: 10.1038/nature08208
  179. Lin H, Jiang Y, Zhang Q, Hua K and Li Z. An in-tether sulfilimine chiral center induces helicity in short peptides. Chemical Communications 2016;52:10389-10391. DOI: 10.1039/C6CC04508A
  180. Letokhov VS. On difference of energy levels of left and right molecules due to weak interactions. Physics Letters A 1975;53:275-276. DOI: 10.1016/0375-9601(75)90064-X
  181. Quick M. How important is parity violation for molecular and bimolecular chirality? Angewandte Chemie International Edition 2002;41:4618-4630.  [view article]
  182. Xu K. Anisotropic 2s2p Orbitals as Simple Descriptors of the Chirality of Carbon Centres. Australian Journal of Chemistry 2016;69:775-784.  DOI: 10.1071/CH15568
  183. Jackson G. Types of Biological Macromolecules.   [view article]
  184. Kwiecińska J and Cieplak M. Chirality and protein folding. Journal of Physics: Condensed Matter 2005;17. DOI: 10.1088/0953-8984/17/18/013
  185. Stefani M. Protein Folding and Misfolding on Surfaces. International Journal of Molecular Sciences 2009;9:2515-2542. DOI: 10.3390/ijms9122515
  186. Onuchic JN, Luthey-Schulten Z and Wolynes PG. Theory of protein folding: the energy landscape perspective. Annual Review of Physical Chemistry 1997;48:545-600. PMID: 9348663; DOI: 10.1146/annurev.physchem.48.1.545
  187. Duan Y and Kollman PA. Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution. Science 1998;282:740-744. PMID: 9784131
  188. Daggett V and Fersht A. The present view of the mechanism of protein folding. Nature Reviews Molecular Cell Biology 2003;4:497-502. PMID: 12778129; DOI: 10.1038/nrm1126
  189. Kubelka J, Hofrichter J and Eaton WA. The protein folding ‘speed limit’. Current Opinion in Structural Biology 2004;14:76-88.  PMID: 15102453; DOI: 10.1016/
  190. Seibert MM, Patriksson A, Hess B and van der Spoel D. Reproducible polypeptide folding and structure prediction using molecular dynamics simulations. Journal of Molecular Biology 2005;354:173-183.  PMID: 16236315; DOI: 10.1016/j.jmb.2005.09.030
  191. Scheraga HA, Khalili M and Liwo A. Protein-folding dynamics: Overview of molecular simulation techniques. Annual Review of Physical Chemistry 2007;58:57-83.  DOI: 10.1146/annurev.physchem.58.032806.104614
  192. Dill KA, Ozkan SB, Weikl TR, Chodera JD and Voelz VA. The protein folding problem: When will it be solved? Current Opinion in Structural Biology 2007;17:342-346. DOI: 10.1016/
  193. Ensign DL, Kasson PM and Pande VS . Heterogeneity even at the speed limit of folding: Large-scale molecular dynamics study of a fast-folding variant of the villin headpiece. Journal of Molecular Biology 2007;374:806-816.  PMID: 17950314; PMCID: PMC3689540 DOI: 10.1016/j.jmb.2007.09.069
  194. Juraszek J, Bolhuis PG. Rate constant and reaction coordinate of Trp-cage folding in explicit water. Biophysical Journal 2008;95:4246-4257. PMCID: PMC2567936; DOI: 10.1529/biophysj.108.136267
  195. Freddolino PL and Schulten K. Common structural transitions in explicit-solvent simulations of villin headpiece folding. Biophysical Journal 2009;97:2338-2347. PMCID: PMC2764099; DOI: 10.1016/j.bpj.2009.08.012
  196. Zhanga C and Maa J. Folding helical proteins in explicit solvent using dihedral-biased tempering. Proceedings of the National Academy of Sciences of the United States of America 2012;109:8139-8144. DOI: 10.1073/pnas.1112143109
  197. Sarasij RC, Mayor S and Rao M. Chirality-Induced Budding: A Raft-Mediated Mechanism for Endocytosis and Morphology of Caveolae? BioPhysical Journal 2007;92:3140-3158.  PMCID: PMC1852369; DOI: 10.1529/biophysj.106.085662
  198. Ho RM, Wang HF and Li MC. Chirality Transfer in Chiral Polymers and Block Copolymers. Encyclopedia of Polymer Science and Technology 2014.   DOI: 10.1002/0471440264.pst625
  199. Cabeen MT and Jacobs-Wagner C. Bacterial cell shape. Nature Reviews Microbiology 2005;3:601-610. PMID: 16012516; DOI: 10.1038/nrmicro1205
  200. Gitai Z. The new bacterial cell biology: Moving parts and subcellular architecture. Cell 2005;120:577-586. PMID: 15766522; DOI: 10.1016/j.cell.2005.02.026
  201. Gaballah A, Kloeckner A, Otten C, Sahl HG and Henrichfreise B. Functional Analysis of the Cytoskeleton Protein MreB from Chlamydophila pneumoniae. PLoS ONE 2011;6:e25129. DOI: 10.1371/journal.pone.0025129
  202. Wang S, Furchtgott L, Huang KC and Shaevitza JW. Helical insertion of peptidoglycan produces chiral ordering of the bacterial cell wall. Proceedings of the National Academy of Sciences of the United States of America 2012;109(10): E595-E604. DOI: 10.1073/pnas.1117132109
  203. Hatori R, Ando T, Sasamura T, et al. Left-right asymmetry is formed in individual cells by intrinsic cell chirality. Mechanisms of Development 2014;133:146-62.  PMID: 24800645; DOI: 10.1016/j.mod.2014.04.002
  204. Zhong-can OY and Jixing L. Theory of helical structures of tilted chiral lipid bilayers. Physical Review A 1991;43:6826-6836. DOI: 10.1103/PhysRevA.43.6826
  205. Eghiaian F. Lipid Chirality Revisited: A Change in Lipid Configuration Transforms Membrane-Bound Protein Domains. Biophysical Journal 2015;108:2757-2758.  PMID: 26083912; PMCID: PMC4472042; DOI: 10.1016/j.bpj.2015.05.018
  206. Lister FGA, Le Bailly BAF, Webb SJ and Jonathan C. Ligand-modulated conformational switching in a fully synthetic membrane-bound receptor. Nature Chemistry 2017;9:420-425. DOI: 10.1038/nchem.2736
  207. Darwin C. On the movement and habits of climbing plants. John Murray. London. 1865. DOI: 10.1111/j.1095-8339.1865.tb00011.x
  208. Isnard S and Silk WK. Moving with climbing plants from Charles Darwin’s time into 21st century. American Journal Botany 2009;96:1205-1221. DOI: 10.3732/ajb.0900045
  209. Ye HM, et al. Surface stress effects on the bending direction and twisting chirality of lammelar crystals of chiral polymer. Macromolecules 2010;43:5762-5770.  DOI: 10.1021/ma100920u
  210. Grande C & Patel NH. Nodal signaling is involved in left-right asymmetry in snails. Nature 2009;475:1007-1011. PMCID: PMC2661027; DOI: 10.1038/nature07603
  211. Lough WJ and Wainer IW. Chirality in mature and applied science. Blacjwel Science, Oxford 2002.  [view article]
  212. Qiu D, Cheng SM, Wozniak L, et al. Localization and loss-of-function implicate ciliary proteins in early, cytoplasmic LR asymmetry. Developmental Dynamics 2005;234:176-189.  DOI: 10.1002/dvdy.20509
  213. Pediconi MF, de Fernández AMR and Barrantes FJ. Asymmetric distribution and down-regulation of the muscarinic acetylcholine receptor in rat cerebral cortex. Neurochemical research 1993;18:565-72.  PMID: 8474575
  214. Pavlov IP. Conditional Reflexes. 1927/1960.  [view article]
  215. Galaburda AM, LeMay M, Kemper TL and Geschwind N. Right-left asymmetries in the brain. Science 1978;199:852-856. PMID: 341314
  216. Toga AW and Thompson PM. Mapping brain asymmetry. Nature Reviews Neuroscience 2003;4:37-48.  PMID: 12511860; DOI: 10.1038/nrn1009
  217. Kertesz A, Polk M, Black SE and Howell J. Sex, handedness, and the morphometry of cerebral asymmetries on magnetic resonance imaging. Brain research 1990;530:40-48. PMID: 2271951
  218. Good CD, Johnsrude I, Ashburner J, et al. Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains. Neuroimage 2001;14:685-700. PMID: 11506541; DOI: 10.1006/nimg.2001.0857
  219. Watkins KE, Paus T, Lerch JP, et al. Structural asymmetries in the human brain: a voxel-based statistical analysis of 142 MRI scans. Cerebral Cortex 2001;11:868-877.  PMID: 11532891
  220. Shaw P, Lalonde F, Lepage C, et al. Development of cortical asymmetry in typically developing children and its disruption in attention-deficit/hyperactivity disorder. Archives of General Psychiatry 2009;66:888-896.  PMID: 19652128; PMCID: PMC2948210; DOI: 10.1001/archgenpsychiatry.2009.103
  221. Zhou D, Lebel C, Evans A and Beaulieu C. Cortical thickness asymmetry from childhood to older adulthood. Neuroimage 2013;83:66-74.  PMID: 23827331; DOI: 10.1016/j.neuroimage.2013.06.073
  222. Lin A, Clasen L, Lee NR, et al. Mapping the Stability of Human Brain Asymmetry across Five Sex-Chromosome Aneuploidies. Journal of Neuroscience 2015;35:140-145. DOI: 10.1523/JNEUROSCI.3489-14.2015
  223. Duyn JH. EEG-fMRI Methods for the Study of Brain Networks during Sleep. Frontiers in Neurology 2012;3:100. PMCID: PMC3387650; DOI: 10.3389/fneur.2012.00100
  224. Hughahl K and Davidson RJ. The Asymmetrical Bran. The MIT Press. 2003. [view article]
  225. Hugdahl K and Westerhausen R. The Two Halves of the Brain. MIT Press. 2010. DOI: 10.7551/mitpress/9780262014137.001.0001
  226. Bryden M. Laterality Functional Asymmetry in the Intact Brain.  [view article]
  227. Mori K. Significance of chirality in pheromone science. Bioorganic & Medicinal Chemistry 2007;15:7505-7523.  PMID:17855097; DOI: 10.1016/j.bmc.2007.08.040
  228. Wyatt TD. Pheromones and Animal Behavior: Chemical Signals and Signatures. 2nd Edition Cambr. Univ. Press 2014.   DOI: 10.1017/CBO9781139030748
  229. de Moraes Júnior R, de Sousa BM and Fukusima S. Hemispheric specialization in face recognition: from spatial frequencies to holistic/analytic cognitive processing. Psychology and Neuroscience 2014;7:503-511.  DOI: 10.3922/j.psns. 2014.4.09
  230. Huber BA. Mating positions and the evolution of asymmetric insect genitalia. Genetica 2010;138:19-25.  PMID: 19089587; DOI: 10.1007/s10709-008-9339-6
  231. Bakalkin GYa. Review Article. Neuropeptides induce directional asymmetry in brain and spinal cord: facts and hypotheses. The International journal of neuroscience 1989;48:105-124. PMID: 2684885
  232. Dubovy SR, Fernandez MP, Echegaray JJ, et al. Expression of hypothalamic neurohormones and their receptors in the human eye. Oncotarget 2017. DOI: 10.18632/oncotarget.18358.   [view article]
  233. Wang J and Feringa BL. Dynamic control of chiral space in a catalytic asymmetric reaction using a molecular motor. Science 2011;331:1429-1432.   PMID: 21310964; DOI: 10.1126/science.1199844
  234. Kistemaker JCM, Štacko P, Visser J and Feringa BL. Unidirectional rotary motion in achiral molecular motors. Nature Chemistry 2015;7:890-896. DOI: 10.1038/nchem.2362
  235. Silvi S, Venturia M and Credi A. Artificial molecular shuttles: from concepts to devices. Journal of Materials Chemistry 2009;19:2279-2294.  DOI: 10.1039/B818609J
  236. Zhu K, O'Keefe CA, Vukotic VN, Schurko RW and Loeb SJ. A molecular shuttle that operates inside a metal-organic framework. Nature Chemistry 2015;7:514-519.  DOI: 10.1038/nchem.2258
  237. Yamaki M, Nakayama S, Hoki K, Kono H and Fujimura Y. Quantum dynamics of light-driven chiral molecular motors. Physical Chemistry Chemical Physics 2009;11:1662-1678.  PMID: 19290336; DOI: 10.1039/b815047h
  238. von Deliusa M and Leigh DA. Walking molecules. Chemical Society Reviews 2011;40:3656-3676. DOI: 10.1039/C1CS15005G
  239. Noether E; Tavel M (translator). Invariant Variation Problems. Transport Theory and Statistical Physics 1971;1:186-207. DOI: 10.1080/00411457108231446
  240. Sokolov VI. Concept of a Stereochemical System. Russian Journal of Organic Chemistry 2002;38:1553-1563.  [view article]
  241. István Hargittai I. Symmetry: Unifying Human Understanding. Pergamon Press 1986.  [view article]
  242. TverdislovVA, Yakovenko LV and Zhavoronko AA, Chirality as a problem of biochemical physics. Russian Journal of General Chemistry 2007;77:1994-2005.  DOI: 10.1134/S1070363207110291
  243. Tverdislov VA. Chirality as an Instrument of Stratification of Hierarchical Systems in Animate and Inanimate Nature. Cornell University Library 2012.  [view article].
  244. Kimura T, Hamase K, Miyoshi Y, et al. Chiral amino acid metabolomic for novel biomarker screening in the prognosis of chronic kidney disease. Scientific Reports 2016;6:26137.  DOI: 10.1038/srep26137
  245. Gunturkun O and Ocklenburg S. Ontogenesis of Lateralization. Neuron 2017;94:249-263. PMID: 28426959; DOI: 10.1016/j.neuron.2017.02.045
  246. Celeman PD and Mastroeni D. A Call for new approaches to Alzheimer’s disease research. Neuro-Biology of Aging 2017;57:iii-iv.  DOI: 10.1016/j.neurobiolaging.2017.04.027
  247. Rothschild G and Mizrahi A. Global Order and Local Disorder in Brain Maps. Annual Review of Neuroscience 2015;38:247-268.  DOI: 10.1146/annurev-neuro-071013-014038
  248. Niell CM. Cell Types, Circuits, and Receptive Fields in the Mouse Visual Cortex. Annual Review of Neuroscience 2015;38:413-431. DOI: 10.1146/annurev-neuro-071714-033807
  249. Seabrook TA, Burbridge TJ, Crair MC and Huberman AD. Architecture, Function, and Assembly of the Mouse Visual System. Annual Review of Neuroscience 2017;40:499-538.  PMID: 28772103; DOI: 10.1146/annurev-neuro-071714-033842
  250. Kaplan G. Audition and Hemispheric Specialization in Songbirds and New Evidence from Australian Magpies. Symmetry 2017;9:99. DOI: 10.3390/sym9070099
  251. Schmitz J, Lor S, Klose R, Güntürkün O and Ocklenburg S. The Functional Genetics of Handedness and Language Lateralization: Insights from Gene Ontology, Pathway and Disease Association Analyses. Frontiers in Psychology 2017;8:1144.  PMID: 28729848; PMCID: PMC5498560; DOI: 10.3389/fpsyg.2017.01144
  252. Ocklenburg S, Schmitz J, Moinfar Z, et al. Epigenetic regulation of lateralized feta spinal gene expression underliehemispheric asymmetries. eLIFE 2017;6:e22784.  DOI: 10.7554/eLife.22784.001
  253. Towse CL, Hopping G, Vulovic I and Daggett V. Nature versus design: the conformational propensities of D-amino acids and the importance of side chain chirality. Protein Engineering, Design and Selection 2014;27:447-455.  PMID: 25233851; PMCID: PMC4204638; DOI: 10.1093/protein/gzu03


Editorial Information

Publication history

Received date: May 31, 2017
Accepted date: August 17, 2017
Published date: September 19, 2017


© 2017 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY).

The Nathan S. Kline Institute for Psychiatric Research, New York State Office of Mental Health, USA
Targeted therapeutics Oncology Research Unit, Pfizer, USA
Child, Adolescent and Young Adult Psychiatry, Columbia University Medical Center, USA
Phelps Hospital, Northwell Health, Baby-Friendly Hospital Initiative, USA
The Nathan S. Kline Institute for Psychiatric Research, New York State Office of Mental Health, USA
The Nathan S. Kline Institute for Psychiatric Research, New York State Office of Mental Health, USA

Reviewer 1 Comments

  1. In this review, the authors systematically summarize biochirality, a widely recognized phenomenon in current biology, especially neurology, on different and gradual scales. From microscopic to macroscopic levels, they successively state the concept of chirality on atomic orbital, molecular, supramolecular, macromolecular, cellular, morphological, functional, and behavioral levels. Through such progressive elucidation, they successfully and clearly connect two phenomena on the poles, which are the symmetry of atomic orbitals and the laterality of brain’s cognitive function, respectively. Generally, I think it’s a good review with an explicit topic. In conclusion, I recommend its publication in Neurology and Neuroscience Research. A small suggestion: some description about the optical properties resulting from the chirality, such as circular dichroism, may be added when referring to chirality on the macromolecular and supramolecular levels, since they are quite significant optical phenomena for the characterization of chiral biomacromolecules like nucleic acids and proteins.
    ResponseReference to the circular dichroism has been added to the text as well as the list of references: 40. (Mark et al 1996) M. S. Spector, K. R. K. Easwaran, G. Jyothi et al. Chiral molecular self-assembly of phospholipid tubules: A circular dichroism study. Proc Nat. Acad. Sci. U S A. 1996;93:12943–12946. PMCID: PMC24025. Location in the manuscript: II.2. Sensitivity of Chirality Transfer to Internal, External, Local and Global Conditions.

Reviewer 2 Comments

  1. This is a good review and I approve it for publication. I find no error in the manuscript. The review is well supported by different scientists and is well cited with the supporting references. The review discloses significant research and is unique. It will certainly have a good impact in the neuroscience research.
    Response Thanks for the reviewer’s comments.