Synthesis, Characterization, X-ray Molecular Structure, Antioxidant, Antifungal, and Allelopathic Activity of a New Isonicotinate-Derived meso-Tetraarylporphyrin.

The present article describes the synthesis of an isonicotinate-derived meso-arylporphyrin, that has been fully characterized by spectroscopic methods (including fluorescence spectroscopy), as well as elemental analysis and HR-MS. The structure of an n-hexane monosolvate has been determined by single-crystal X-ray diffraction analysis. The radical scavenging activity of this new porphyrin against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical has been measured. Its antifungal activity against three yeast strains (C. albicans ATCC 90028, C. glabrata ATCC 64677, and C. tropicalis ATCC 64677) has been tested using the disk diffusion and microdilution methods. Whereas the measured antioxidant activity was low, the porphyrin showed moderate but encouraging antifungal activity. Finally, a study of its effect on the germination of lentil seeds revealed interesting allelopathic properties.

Spontaneous Deracemizations.

Spontaneous deracemizations is a challenging, multidisciplinary subject in current chirality research. In the absence of any chiral inductors, an achiral substance or a racemic composition is driven into an enantioenriched or even homochiral state through a selective energy input, e.g., chemical potential, photoirradiation, mechanical grinding, ultrasound waves, thermal gradients, etc. The most prominent examples of such transformations are the Soai reaction and the Viedma deracemization. In this review, we track the most recent developments in this topic and recall that many other deracemizations have been reported for solutions from mesophases to conglomerate crystallizations. A compiled set of simply available achiral organic, inorganic, organometallic, and MOF compounds, yielding conglomerate crystals, should give the impetus to realize new experiments on spontaneous deracemizations. Taking into account thermodynamic constraints, modeling efforts have shown that structural features alone are not sufficient to describe spontaneous deracemizations. As a guideline of this review, particular attention is paid to the physicochemical origin and symmetry requirements of such processes.

Synthesis of New Amino-Functionalized Porphyrins:Preliminary Study of Their Organophotocatalytic Activity.

The design, synthesis, and initial study of amino-functionalized porphyrins as a new class of bifunctional catalysts for asymmetric organophotocatalysis is described. Two new types of amine-porphyrin hybrids derived from 5,10,15,20-tetraphenylporphyrin (TPPH2), in which a cyclic secondary amine moiety is covalently linked either to a ß-pyrrolic position (Type A) or to the p-position of one of the meso phenyl groups (Type B), were prepared by condensation, reductive amination, or amidation reactions from the suitable porphyrins (either formyl or methanamine derivatives) with readily available chiral amines. A preliminary study of the possible use of Type A amine-porphyrin hybrids as asymmetric, bifunctional organophotocatalysts was performed using the chiral, imidazolidinone-catalyzed Diels-Alder cycloaddition between cyclopentadiene 28 and trans-cinnamaldehyde 29 as a benchmark reaction. The yield and the stereochemical outcome of this process, obtained under purely organocatalytic conditions, under dual organophocatalysis, and under bifunctional organophotocatalysis, were compared.

Chiral Amphiphilic Secondary Amine-Porphyrin Hybrids for Aqueous Organocatalysis.

Two chiral proline-derived amphiphilic 5-substituted-10,15,20-tris(4-sulfonatophenyl)porphyrins were prepared, and their pH-dependent supramolecular behavior was studied. In neutral aqueous solutions, the free-base form of the hybrids is highly soluble, allowing enamine-based organocatalysis to take place, whereas under acidic conditions, the porphyrinic protonated core of the hybrid leads to the formation of self-assembled structures, so that the hybrids flocculate and their catalytic activity is fully suppressed. The low degree of chirality transfer observed for aqueous Michael and aldol reactions strongly suggests that these reactions take place under true "in water" organocatalytic conditions. The highly insoluble catalyst aggregates can easily be separated from the reaction products by centrifugation of the acidic reaction mixtures, and after neutralization and desalting, the sodium salts of the sulfonated amine-porphyrin hybrids, retaining their full catalytic activity, can be recovered in high yield.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Chirality generated by flows in pseudocyanine dye J-aggregates: revisiting 40 years old reports.

Spontaneous symmetry breaking in J-aggregates of cyanine dyes has a long history in chemical literature. In 1976, Honda and Hada claimed that they had achieved chiral induction (CD) by stirring J-aggregates of pseudocyanine. However, this report is controversial, as the combinations of linear dichroism and birefringence can lead to artifactual circular dichroic signals that are unrelated to molecular chirality. A Mueller matrix spectroscopy study, with an approach for the application of a gradient of the shear rate (solution layer between a rotating and a fixed disk) that differs from the simple vortex stirring used in the original report, shows that true CD can be induced in the sample. The phenomenon is discussed, taking into account the flow dynamics that allows the alignment of the aggregate particles and the gradient of shear rates that determines their folding/torsion, which leads to a chiral excitonic transition.

Hydrodynamic effects on chiral induction.

There are few unambiguous reports describing the transfer of chirality from stirring vortices down to the level of electronic transitions. In this tutorial review the methods reported are discussed as well as the structural trends that seem to be necessary conditions in order to detect this phenomenon.

Emergence of supramolecular chirality by flows.

Hydrodynamic forces in stirred solutions induce chirality in some supramolecular species of J-aggregates, as detected at the level of the electronic transition. However, the mechanism that explains the phenomenon remains to be elucidated, although the basic effect of hydrodynamic gradients of the shear rate is most probably the folding or bending of the nanoparticles in solution. Herein, we demonstrate a correlation between chiral flows in different regions of circular and square stirred cuvettes and the emergence of true circular dichroism (CD). The results show that chaotic flows lead to a racemic mixture of chiral shaped supramolecular species, and vortical flows to scalemic mixtures. In a magnetically stirred flask the descending and ascending flows are of different chiral sign and the CD reading depends on the weighting of these two flows of inverse chiral sign. The effect of the gradient of shear rates of the flows leading to chiral shape objects depends on the shape of the cuvette, which suggests that the flask shape and the controlled addition of reagents in defined regions of the stirred solutions may exert a control in self-assembly processes.

Chiral biases in solids by effect of shear gradients: a speculation on the deterministic origin of biological homochirality.

We present an experimental approach to the study of the chirality of three CM2 meteorite solid samples by direct measurement of the optical activity (circular birefringence; CB). The measurements are based on transmission two modulator generalized ellipsometry in conjuction with microscope optics to map the CB of the samples. In spite of the complexity of such optical analysis, these first results indicate the presence of optically active areas in the meteorite solid matrix. In the case of the Murchison sample the statistics of the CB mapping shows a bimodal distribution with a bias to negative CB values. The composition of the active areas probably corresponds to serpentines and other poorly identified phyllosilicate phases. The results are compatible with the hypothesis that in a mineral-based scenario for the origin of life a CB sign bias in the chiral fractures originated by mechanical and flow shear gradients on clays could be later transferred to the reactions of the absorbed organic compounds.

Frank model and spontaneous emergence of chirality in closed systems.

In a closed system an irreversible enantioselective autocatalysis coupled to a mutual inhibition reaction, corresponding to a fast and low exergonic formation of the heterochiral dimer which reverts to the monomers in the final reaction work-up, yields absolute asymmetric synthesis even in the absence of chiral polarizations. This is due to the very high chiral amplifications of the initial small statistical deviations from the ideal racemic composition. Moreover, this system is sensitive to very small chiral polarizations (energy differences between transition states below the mJ mol(-1) range). This behaviour can also be observed in reversible exergonic reactions, because the racemization time scale is substantially longer than that of the transformation of the initial reagents. The effect of the presence of other reactions likely to occur (i.e. non-catalytic transformations, non-enantioselective catalysis and homodimer formation) is discussed. Even if these decrease the sensitivity of the network in several chemical scenarios, the emergence of kinetically controlled spontaneous symmetry breaking is not hindered. These features, together with the response of the system to a sequential reaction procedure, suggest that a similar type of network is at the heart of the Soai reaction.

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

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

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.