Chirality transfer from a 3D macro shape to the molecular level by controlling asymmetric secondary flows.

Homochirality is a fundamental feature of living systems, and its origin is still an unsolved mystery. Previous investigations showed that external physical forces can bias a spontaneous symmetry breaking process towards deterministic enantioselection. But can the macroscopic shape of a reactor play a role in chiral symmetry breaking processes? Here we show an example of chirality transfer from the chiral shape of a 3D helical channel to the chirality of supramolecular aggregates, with the handedness of the helical channel dictating the direction of enantioselection in the assembly of an achiral molecule. By combining numerical simulations of fluid flow and mass transport with experimental data, we demonstrated that the chiral information is transferred top-down thanks to the interplay between the hydrodynamics of asymmetric secondary flows and the precise spatiotemporal control of reagent concentration fronts. This result shows the possibility of controlling enantioselectively molecular processes at the nanometer scale by modulating the geometry and the operating conditions of fluidic reactors.

Spontaneous mirror-symmetry breaking coupled to top-bottom chirality transfer: from porphyrin self-assembly to scalemic Diels-Alder adducts.

This report shows how the net supramolecular chirality that emerged by spontaneous mirror-symmetry breaking (SMSB) at the mesoscale level can be transferred towards asymmetric solution chemistry. The J-aggregates obtained by self-assembly of an achiral porphyrin act as chiral counteranions in an iminium-promoted Diels-Alder reaction, leading to enantiomeric imbalances in the final adducts.

Diastereoisomerism, Stability, and Morphology of Substituted meso-4-Sulfonatophenylporphyrin J-Aggregates.

The comparison between nanoparticle morphologies of the J-aggregates of different meso-4-sulfonatophenylporphyrins showing non-sulfonato groups at some of the meso-positions constitutes an ultimate proof of the 2D crystal-like character of the basic self-assembly motif of this family of J-aggregates. Diastereoisomerism stemming from the tacticity of the relative configurations in relation to the J-aggregate bidimensional sheet is the key factor that determines both the striking monolayer in solution and also the hierarchical pathways leading to different nanoparticle morphologies upon further growth. The unexpected stability of such large monolayered sheets made up of porphyrin units is probably caused by the support originated at both surface faces by the double layer potentials of the peripheral ionic substituents. These double layer potentials play a driving role in the subsequent 3D growth of the monolayers, as deduced herein from the determining role of tacticity both in the stability of the J-aggregate sheet and in its evolution either to monolayered or to bilayered nanoparticles. The stabilizing role of the forces at the electrical double layer of the particle suggests a relationship between these forces and the previously reported detection of racemic biases when shear hydrodynamic forces are in action during the aggregation process.

Snapshot circular dichroism measurements.

Two coherent waves carrying orthogonal polarizations do not interfere when they superpose, but an interference pattern is generated when the two waves share a common polarization. This well-known principle of coherence and polarization is exploited for the experimental demonstration of a novel method for performing circular dichroism measurements whereby the visibility of the interference fringes is proportional to the circular dichroism of the sample. Our proof-of-concept experiment is based upon an analog of Young's double-slit experiment that continuously modulates the polarization of the probing beam in space, unlike the time modulation used in common circular dichroism measurement techniques. The method demonstrates an accurate and sensitive circular dichroism measurement from a single camera snapshot, making it compatible with real-time spectroscopy.

5-Phenyl-10,15,20-Tris(4-sulfonatophenyl)porphyrin: Synthesis, Catalysis, and Structural Studies.

A convenient protocol for the preparation of 5-phenyl-10,15,20-tris(4-sulfonatophenyl)porphyrin, a water-soluble porphyrin with unique aggregation properties, is described. The procedure relies on the one-pot reductive deamination of 5-(4-aminophenyl)-10,15,20-tris(4-sulfonatophenyl)porphyrin, that can be in turn easily obtained from 5,10,15,20-tetraphenylporphyrin by a known three-step sequence involving mononitration, nitro to amine reduction and sulfonation of the phenyl groups. This method provides the title porphyrin in gram scale, and compares very favorably with the up to now only described procedure based on the partial sulfonation of TPP, that involves a long and tedious chromatographic enrichment of the final compound. This has allowed us to study for the first time both the use of its zwitterionic aggregate as a supramolecular catalyst of the aqueous Diels⁻Alder reaction, and the morphology of the aggregates obtained under optimized experimental conditions by atomic force microscopy and also by transmission electron cryomicroscopy.

Spontaneous mirror symmetry breaking and origin of biological homochirality.

Recent reports on both theoretical simulations and on the physical chemistry basis of spontaneous mirror symmetry breaking (SMSB), that is, asymmetric synthesis in the absence of any chiral polarizations other than those arising from the chiral recognition between enantiomers, strongly suggest that the same nonlinear dynamics acting during the crucial stages of abiotic chemical evolution leading to the formation and selection of instructed polymers and replicators, would have led to the homochirality of instructed polymers. We review, in the first instance, which reaction networks lead to the nonlinear kinetics necessary for SMSB, and the thermodynamic features of the systems where this potentiality may be realized. This could aid not only in the understanding of SMSB, but also the design of reliable scenarios in abiotic evolution where biological homochirality could have taken place. Furthermore, when the emergence of biological chirality is assumed to occur during the stages of chemical evolution leading to the selection of polymeric species, one may hypothesize on a tandem track of the decrease of symmetry order towards biological homochirality, and the transition from the simple chemistry of astrophysical scenarios to the complexity of systems chemistry yielding Darwinian evolution.

Spontaneous mirror symmetry breaking in heterocatalytically coupled enantioselective replicators.

Chiral hypercycle replicators (first-order autocatalysis together with mutual cross-catalysis) formed from achiral or racemizing resources may lead to spontaneous mirror symmetry breaking (SMSB) without the need for additional heterochiral inhibition reactions, such as those of the Frank-like models, which are an obstacle for the emergence of evolutionary selection properties. The results indicate that the chemical models for the emergence of primordial autocatalytic self-reproducing systems, of and by themselves, can also explain naturally the emergence of biological homochirality.

Hydrodynamic Effects in Soft-matter Self-assembly: The Case of J-Aggregates of Amphiphilic Porphyrins.

Chiral J-aggregates of achiral amphiphilic porphyrins (4-sulfonatophenyl and aryl meso-substituted porphyrins) show several effects under the hydrodynamic forces of common stirring. These effects can be classified as pure mechanic (e. g. elasticity, plasticity and breaking of the self-assembly non-covalent bonding) and chemically selective as detected in the formation/growth of the nanoparticles. Diastereoselective, enantioselective and, depending on the sign of chiral shear forces, even enantiospecific selections have been described. Some types of these effects have been reported in other type of J-aggregates. Reversible and irreversible structural effects have been studied by atomic force imaging. The determination of the optical polarization properties (linear and circular) of their solutions is best done using Mueller matrix polarimetry methods.

Reversible and irreversible emergence of chiroptical signals in J-aggregates of achiral 4-sulfonatophenyl substituted porphyrins: intrinsic chirality vs. chiral ordering in the solution.

Mueller matrix polarimetry distinguishes the different origins of the reversible and irreversible chiroptical effects emerging in stirred solutions of J-aggregate nanoparticles: the reversible effect is due to an anisotropic ordering in the solution and the irreversible one is due to a bias from the racemic composition of intrinsically chiral structures.

Effect of Hydrodynamic Forces on meso-(4-Sulfonatophenyl)-Substituted Porphyrin J-Aggregate Nanoparticles: Elasticity, Plasticity and Breaking.

The J aggregates of 4-sulfonatophenyl meso-substituted porphyrins are non-covalent polymers obtained by self-assembly that form nanoparticles of different morphologies. In the case of high aspect-ratio nanoparticles (bilayered ribbons and monolayered nanotubes), shear hydrodynamic forces may modify their shape and size, as observed by peak force microscopy, transmission electron microscopy of frozen solutions, small-angle X-ray scattering measurements in a disk-plate rotational cell, and cone-plate rotational viscometry. These nanoparticles either show elastic or plastic behaviour: there is plasticity in the ribbons obtained upon nanotube collapse on solid/air interfaces and in viscous concentrated nanotube solutions, whereas elasticity occurs in the case of dilute nanotube solutions. Sonication and strong shear hydrodynamic forces lead to the breaking of the monolayered nanotubes into small particles, which then associate into large colloidal particles.

Structure vs. excitonic transitions in self-assembled porphyrin nanotubes and their effect on light absorption and scattering.

The optical properties of diprotonated meso-tetrakis(4-sulphonatophenyl)porphyrin (TPPS(4)) J-aggregates of elongated thin particles (nanotubes in solution and ribbons when deposited on solid interfaces) are studied by different polarimetric techniques. The selective light extinction in these structures, which depends on the alignment of the nanoparticle with respect to the polarization of light, is contributed by excitonic absorption bands and by resonance light scattering. The optical response as a function of the polarization of light is complex because, although the quasi-one-dimensional structure confines the local fields along the nanotube axis, there are two orthogonal excitonic bands, of H- and J-character, that can work in favor of or against the field confinement. Results suggest that resonance light scattering is the dominant effect in solid state preparations, i.e. in collective groups (bundles) of ribbons but in diluted solutions, i.e. with isolated nanotubes, the absorption at the excitonic transitions remains dominant and linear dichroism spectra can be a direct probe of the exciton orientations. Therefore, by analyzing scattering and absorption data we can determine the alignment of the excitonic bands within the nanoparticle, i.e. of the orientation of the basic 2D porphyrin architecture in the nanoparticle. This is a necessary first step for understanding the directions of energy transport, charge polarization and non-linear optical properties in these materials.

Absolute asymmetric synthesis in enantioselective autocatalytic reaction networks: theoretical games, speculations on chemical evolution and perhaps a synthetic option.

The Soai reaction and the Viedma deracemization of racemic conglomerate crystal mixtures are experimental pieces of evidence of the ability of enantioselective autocatalytic coupled networks to yield absolute asymmetric synthesis. Thermodynamically open systems or systems with non-uniform energy distributions may lead to chiral final states and, in systems able to come into thermodynamic equilibrium with their surroundings, to kinetically controlled absolute asymmetric synthesis. The understanding of network parameters and of the thermodynamic scenarios that may lead to spontaneous mirror symmetry breaking (SMSB) could assist in the development of new methods for asymmetric synthesis and enantioselective polymerizations (e.g., replicators), and to frame reasonable speculations on the origin of biological homochirality.

The Viedma deracemization of racemic conglomerate mixtures as a paradigm of spontaneous mirror symmetry breaking in aggregation and polymerization.

Simulations of a chemical kinetics model, based on the free-energy relationships of classical primary nucleation theory, show that the deracemization phenomenon in systems of achiral or fast racemizing compounds yielding enantiopure crystals as the more stable solid phase is a true spontaneous mirror symmetry breaking process (SMSB). That is, the achievement of a stationary chiral state is more stable than the racemic one. The model translates the free-energy relationships determined by the existence of a critical size cluster to a chemical kinetics model, in which the consideration of forward and backward reaction rate constants avoids the misuse of network parameters that violate thermodynamic constraints (microreversibility principle), which would lead to apparent in silico SMSB. The model provides qualitative agreement for deracemizations by mechanical attrition of visible crystals, as well as for those obtained under temperature gradients. The analysis of the effect of the system parameters to obtain a SMSB scenario shows that the network possesses the principal characteristics of SMSB networks: 1) an enantioselective autocatalytic stage, corresponding to the non-linear kinetics of enantioselective (homochiral) cluster-to-cluster growth, and 2) the mutual inhibition step originating in the backward flow of chiral clusters towards smaller achiral clusters, or even to a racemizing monomer. The application of such a SMSB kinetic model to enantioselective polymerizations and to chiral biopolymers is discussed.

Electron cryo-microscopy of TPPS4⋠2HCl tubes reveals a helical organisation explaining the origin of their chirality.

A widely studied achiral porphyrin, which is highly soluble in aqueous solutions (TPPS4), is shown to self-assemble into helical nanotubes. These were imaged by electron cryo-microscopy and a state-of-the-art image analysis allows building a map at ∼5 Šresolution, one of the highest obtained so far for molecular materials. The authors were able to trace the apparent symmetry breaking to existing nuclei in the "as received samples", while carefully purified samples show that both handnesses occur in equal amounts.

Spontaneous emergence of chirality in the limited enantioselectivity model: autocatalytic cycle driven by an external reagent.

The model of limited enantioselectivity (LES) in closed systems, and under experimental conditions able to achieve chemical equilibrium, can give rise to neither spontaneous mirror symmetry breaking (SMSB) nor kinetic chiral amplifications. However, it has been recently shown that it is able to lead to SMSB, as a stationary final state, in thermodynamic scenarios involving nonuniform temperature distributions and for compartmentalized separation between the two autocatalytic reactions. Herein, it is demonstrated how SMSB may occur in LES in a cyclic network with uniform temperature distribution if the reverse reaction of the nonenantioselective autocatalysis, which gives limited inhibition on the racemic mixture, is driven by an external reagent, that is, in conditions that keep the system out of chemical equilibrium. The exact stability analysis of the racemic and chiral final outcomes and the study of the reaction parameters leading to SMSB are resolved analytically. Numerical simulations, using chemical kinetics equations, show that SMSB may occur for chemically reasonable parameters. Numerical simulations on SMSB are also presented for speculative, but reasonable, scenarios implying reactions common in amino acid chemistry.

Achiral-to-chiral transition in benzil solidification: analogies with racemic conglomerates systems showing deracemization.

Experimental results show that benzil (1,2-diphenyl-1,2-ethanedione), an achiral compound that crystallizes as a racemic conglomerate, yields by solidification polycrystalline scalemic mixtures of high enantiomeric excesses. These results are related to those previously reported in this type of compounds on deracemizations of racemic mixtures of crystal enantiomorphs obtained by wet grinding. However, the present results strongly suggest that these experiments cannot be explained without taking into account chiral recognition interactions at the level of precritical clusters. The conditions that would define a general thermodynamic scenario for such deracemizations are discussed.

Spontaneous mirror symmetry breaking in the limited enantioselective autocatalysis model: abyssal hydrothermal vents as scenario for the emergence of chirality in prebiotic chemistry.

The emergence of chirality in enantioselective autocatalysis for compounds unable to transform according to the Frank-like reaction network is discussed with respect to the controversial limited enantioselectivity (LES) model composed of coupled enantioselective and non-enantioselective autocatalyses. The LES model cannot lead to spontaneous mirror symmetry breaking (SMSB) either in closed systems with a homogeneous temperature distribution or in closed systems with a stationary non-uniform temperature distribution. However, simulations of chemical kinetics in a two-compartment model demonstrate that SMSB may occur if both autocatalytic reactions are spatially separated at different temperatures in different compartments but coupled under the action of a continuous internal flow. In such conditions, the system can evolve, for certain reaction and system parameters, toward a chiral stationary state; that is, the system is able to reach a bifurcation point leading to SMSB. Numerical simulations in which reasonable chemical parameters have been used suggest that an adequate scenario for such a SMSB would be that of abyssal hydrothermal vents, by virtue of the typical temperature gradients found there and the role of inorganic solids mediating chemical reactions in an enzyme-like role.

Mirror symmetry breaking with limited enantioselective autocatalysis and temperature gradients: a stability survey.

We analyze limited enantioselective (LES) autocatalysis in a temperature gradient and with internal flow/recycling of hot and cold material. Microreversibility forbids broken mirror symmetry for LES in the presence of a temperature gradient alone. This symmetry can be broken however when the auto-catalysis and limited enantioselective catalysis are each localized within the regions of low and high temperature, respectively. This scheme has been recently proposed as a plausible model for spontaneous emergence of chirality in abyssal hydrothermal vents. Regions in chemical parameter space are mapped out in which the racemic state is unstable and bifurcates to chiral solutions.

Kinetic control of the supramolecular chirality of porphyrin J-aggregates.

The aggregation of achiral sulfonatophenyl- and phenyl-meso-substituted diprotonated porphyrins to chiral J-aggregates is a hierarchical noncovalent polymerization process preceded by a critical nucleation stage. This allows significant enantiomeric excesses by the formation of a few primary nuclei and the control of their growth by the effect that flows (imperfect mixing) have on the secondary nucleation of the J-aggregate particles. In addition, the results strongly suggest that when only one species of aggregate predominates, the CD signals of the three excitonic bands in the visible region (around 420, 490, and 700 nm) show the same sign. Thus, differences on their relative sign would be due to the presence of different species.

Effects of flow-selectivity on self-assembly and auto-organization processes: an example.

The homoassociation of H(4)TPPF(5)S(3) leads to different J-aggregates depending on whether solutions are shaken (homogenization) or stirred magnetically (square-section flask). Vortex stirring due to the generation of laminar flows decreases lateral diffusion therefore it inhibits cluster-to-cluster aggregation mechanisms.