S S symmetry Concept Paper Mirror Symmetry Breaking in Liquids and Their Impact on the Development of Homochirality in Abiogenesis: Emerging Proto-RNA as Source of Biochirality? Carsten Tschierske * and Christian Dressel Martin Luther University Halle-Wittenberg, Institute of Chemistry, Kurt-Mothes Str. 2, 06120 Halle, Germany; [email protected] * Correspondence: [email protected] Received: 30 May 2020; Accepted: 15 June 2020; Published: 2 July 2020 Abstract: Recent progress in mirror symmetry breaking and chirality amplification in isotropic liquids and liquid crystalline cubic phases of achiral molecule is reviewed and discussed with respect to its implications for the hypothesis of emergence of biological chirality. It is shown that mirror symmetry breaking takes place in fluid systems where homochiral interactions are preferred over heterochiral and a dynamic network structure leads to chirality synchronization if the enantiomerization barrier is sufficiently low, i.e., that racemization drives the development of uniform chirality. Local mirror symmetry breaking leads to conglomerate formation. Total mirror symmetry breaking requires either a proper phase transitions kinetics or minor chiral fields, leading to stochastic and deterministic homochirality, respectively, associated with an extreme chirality amplification power close to the bifurcation point. These mirror symmetry broken liquids are thermodynamically stable states and considered as possible systems in which uniform biochirality could have emerged. A model is hypothesized, which assumes the emergence of uniform chirality by chirality synchronization in dynamic “helical network fluids” followed by polymerization, fixing the chirality and leading to proto-RNA formation in a single process. Keywords: mirror symmetry breaking; biological chirality; liquid crystals; proto-RNA; networks; compartmentalization; chiral liquids; cubic phases; prebiotic chemistry; chirality amplification; helical self-assembly 1. Introduction-Homochirality and Life Ever since Pasteur revealed the molecular asymmetry of organic compounds in 1848 [1], the origin of the homochirality of biologically relevant molecules has attracted considerable attention. The chirality of organic compounds is due to the tetrahedral structure of carbon with a valence of four bondings to adjacent atoms. Only if all four substituents are different, is the compound chiral and existing as two stereoisomers representing mirror images of each other, differing in their configuration, being either d or l. It is well known that in all existing organisms the carbohydrates exist in the d-form and the amino acids in the l-form (see Figure1; there are also l-sugars and d-amino acids in biological systems, but if they are involved, they fulfill specific functions, see [2]). This homochirality is considered as a signature of life. In the 4.5 billion years (Ga) of the history of Earth, by 4.2–4.3 Ga Earth has cooled sufficiently to be covered by liquid water. Already by 3.95 Ga, the first signatures of life appear as carbon isotope signatures. In this astonishing narrow window of only about 200–300 million years (0.2–0.3 Ga), the first cells came to existence, meaning that mirror symmetry must have been broken and the genetic code developed during this, on a geological time scale, amazingly short period Symmetry 2020, 12, 1098; doi:10.3390/sym12071098 www.mdpi.com/journal/symmetry Symmetry 2020, 12, 1098 2 of 30 Symmetry 2020, 12, x FOR PEER REVIEW 2 of 30 oflife abiogenesis and the mechanism [3]. The origin of the of thechirogenesis homochirality remain of the an molecules unsolved of problem life and thein the mechanism hypotheses of the of chirogenesisdevelopment remain of life an [4–7]. unsolved The focus problem of chirogenesis in the hypotheses was most of developmently on the carbohydrates of life [4–7]. The and focus amino of chirogenesisacids being wasintrinsically mostly on chiral, the carbohydrates as described and in amino numerous acids being contributions intrinsically and chiral, reviews as described [8–23]; inamphiphiles numerous contributionswere also considered and reviews [24]. [However,8–23]; amphiphiles there are werealso biologically also considered relevant [24]. molecules, However, there or at areleast also building biologically blocks relevant of such molecules, molecules, or which at least are building achiral, blocks because of suchthey molecules,are built up which of carbons are achiral, with becauseonly three they substituents, are built up ofand carbons these withcompounds only three wi substituents,th trigonal carbons and these are compounds flat. Among with them, trigonal the carbonspyrimidine are und flat. purine Among bases them, (N the-heterocycles) pyrimidine involved und purine in basesthe nucleic (N-heterocycles) acids form involvedthe basis inof thethe nucleicgenetic acidscode formof RNA/DNA, the basis of thewhich genetic developed code of RNAduring/DNA, abiogenesis. which developed Helical duringself-assembly abiogenesis. (for Helicalexample, self-assembly predominately (for single example, helices predominately for RNA and single double helices helices for RNA for DNA) and double is an helicesimportant for DNA)consequence is an important of molecular consequence chirality and of molecular simultaneously chirality provides and simultaneously a source of homochirality. provides a source It does of homochirality.not require molecular It does not chirality, require and molecular therefore chirality, it can and also therefore be formed it can under also beachiral formed conditions under achiral with conditionsachiral molecules with achiral [25–30]. molecules Helical [ 25superstructures–30]. Helical superstructures are not only formed are not onlyas crystalline formed as assemblies, crystalline assemblies,fibers and gels fibers [31–38], and gels they [31 are–38 also], they common are also in common soft matter in soft systems matter and systems fluids, and where fluids, they where can occur they canspontaneously occur spontaneously [25,26,39–42] [25,26 or,39 induced–42] or inducedby an intern by anal internal or external or external source source of chirality of chirality [43–45]. [43 –Soft45]. Softself-assembly self-assembly in fluids in fluids is of special is of special interest interest for chirogenesis, for chirogenesis, as life most as life likely most developed likely developed in aqueous in aqueousfluids. fluids. Figure 1.1. Biologically relevant chiral and achiral moleculesmolecules andand structures.structures. Herein,Herein, thethe recentlyrecently discovereddiscovered spontaneousspontaneous mirrormirror symmetrysymmetry breakingbreaking inin isotropicisotropic liquidsliquids [[25]25] andand inin liquidliquid crystallinecrystalline (LC) (LC) cubic cubic phases phases [26 [26]] is is discussed discussed under under the the aspect aspect of theirof their relevance relevance for thefor emergencethe emergence of biochirality of biochirality during during abiogenesis. abiogenesis. It is postulated It is postulated that biochirality that biochirality could havecould arisen have byarisen the spontaneousby the spontaneous helical self-assembly helical self-assembly of achiral moleculesof achiral in molecules the liquid state,in the and liquid that synchronizationstate, and that ofsynchronization the helicity of self-assembledof the helicity achiralof self-assembl heteroaromaticed achiral amphiphiles heteroaromatic by the formation amphiphiles of dynamic by the networksformation could of dynamic have been networks the source could of the have developing been the biochirality. source of Itthe is hypothesizeddeveloping biochirality. that early forms It is ofhypothesized RNA could notthat only early have forms acted of RNA as the could first information not only have carrier acted and as catalystthe first in information abiogenesis, carrier but could and alsocatalyst provided in abiogenesis, the biochirality. but could also provided the biochirality. 2. Emergence of Homochirality in Non-Biological Systems-Artificial Chirogenesis 2. Emergence of Homochirality in Non-Biological Systems-Artificial Chirogenesis 2.1. Racemates vs. Conglomerates 2.1. Racemates vs. Conglomerates Based on the fundamentals of stereochemistry, under achiral conditions, chiral molecules are alwaysBased formed on fromthe fundamentals achiral (prochiral) of stereochemistry, substrates as racemic under mixtures achiral conditions, of the two enantiomeric chiral molecules forms are in always formed from achiral (prochiral) substrates as racemic mixtures of the two enantiomeric forms in 1:1 ratio [46]. In these racemic forms, there are intermolecular interactions between the like Symmetry 2020, 12, x; doi: FOR PEER REVIEW www.mdpi.com/journal/symmetry Symmetry 2020, 12, 1098 3 of 30 1:1Symmetry ratio [46 2020]. In, 12 these, x FOR racemic PEER REVIEW forms, there are intermolecular interactions between the like enantiomers3 of 30 (d/d and l/l) as well as between unlike pairs (d/l) with different energies. Two different situations can beenantiomers distinguished (D/ dependingD and L/L) onas thewell strength as between of the unlike attractive pairs intermolecular (D/L) with different interactions energies. between Two the likedifferent (d/d and situationsl/l) and can unlike be distin (d/l)guished pairs. depending on the strength of the attractive intermolecular interactions between the like (D/D and L/L) and unlike (D/L) pairs. As shown in Figure2a,b, the attractive interactions can be either stronger between the