Homochiral Interactions Research Articles

Self-Assembly of N-Rich Triimidazoles on Ag(111): Mixing the Pleasures and Pains of Epitaxy and Strain.

In the present report, homochiral hydrogen-bonded assemblies of heavily N-doped (C9H6N6) heterocyclic triimidazole (TT) molecules on an Ag(111) substrate were investigated using scanning tunneling microscopy (STM) and low energy electron diffraction (LEED) techniques. The planar and prochiral TT molecules, which exhibit a threefold rotation symmetry and lack mirror symmetry when assembled on the substrate, carry multiple hydrogen-bonding donor and acceptor functionalities, inevitably leading to the formation of hexameric two-dimensionally extended assemblies that can be either homo- (RR/SS) or heterochiral (RS). Experimental STM data showing well-ordered homochiral domains and experimental LEED data are consistent with simulations assuming the R19.1° overlayer on the Ag(111) lattice. Importantly, we report the unexpected coincidence of spontaneous resolution with the condensation of neighboring islands in adjacent "Janus pairs". The islands are connected by a characteristic fault zone, an observation that we discuss in the context of the fairly symmetric molecule and its propensity to compromise and benefit from interisland bonding at the expense of lattice mismatches and strain in the defect zone. We relate this to the close to triangular shape and the substantial but weak bonding scheme beyond van der Waals (vdW) of the TT molecules, which is due to the three N-containing five-membered imidazole rings. Density functional theory (DFT) calculations show clear energetic differences between homochiral and heterochiral pairwise interactions, clearly supporting the experimental results.

Fluid-fluid phase transitions in a chiral molecular model.

Molecular chirality is a fundamental phenomenon, underlying both life as we know it and industrial pharmaceutical syntheses. Understanding the symmetry breaking phase transitions exhibited by many chiral molecular substances provides basic insights for topics ranging from the origin of life to the rational design of drug manufacturing processes. In this work, we have performed molecular dynamics simulations to investigate the fluid-fluid phase transitions of a flexible three-dimensional four-site chiral molecular model developed by Latinwo et al. [J. Chem. Phys. 145, 154503 (2016)] and Petsev et al. [J. Chem. Phys. 155, 084105 (2021)]. By introducing a bias favoring local homochiral vs heterochiral interactions, the system exhibits a phase transition from a single achiral phase to a single chiral phase that undergoes infrequent interconversion between the two thermodynamically identical chiral states: the L-rich and D-rich phases. According to the phase rule, this reactive binary system has two independent degrees of freedom and exhibits a density-dependent critical locus. Below the liquid-liquid critical locus, there exists a first-order vapor-liquid coexistence region with a single independent degree of freedom. Our results provide basic thermodynamic and kinetic insights for understanding many-body chiral symmetry breaking phenomena.

Influence of Stereochemistry on the Monolayer Characteristics of N-alkanoyl-Substituted Threonine and Serine Amphiphiles at the Air-Water Interface.

Thermodynamic and structural properties of the N-alkanoyl-substituted α-amino acids threonine and serine, differing only by one CH3 group in the head group, are determined and compared. Detailed characterization of the influence of stereochemistry proves that all enantiomers form an oblique monolayer lattice structure whereas the corresponding racemates build orthorhombic lattice structures due to dominating heterochiral interactions, except N-C16-dl-serine-ME as first example of dominating homochiral interactions in a racemic mixture of N-alkanoyl-substituted α-amino acids. In all cases, the liquid expanded–liquid condensed (LE/LC) transition pressure of the racemic mixtures is above that of the corresponding enantiomers. Phase diagrams are proposed. Using the program Hardpack to predict tilt angles and cross-sectional area of the alkyl chains shows reasonable agreement with the experimental grazing incidence X-ray diffraction (GIXD) data.

Persistent Organic Room-Temperature Phosphorescence in Cyclohexane-trans-1,2-Bisphthalimide Derivatives: The Dramatic Impact of Heterochiral vs Homochiral interactions.

Persistent metal-free room-temperature phosphorescence (RTP) materials attract significant interest owing to the production of long-lived triplet excited states. Although several organic designs show RTP, the impact of intermolecular interactions on the triplet excitons stabilization and migrations remains hardly understood because obtaining different ordered intermolecular interactions while conserving identical molecular electronic properties is very challenging. We propose here a new strategy to circumvent this problem by taking advantage of the distinct molecular packing that can be found between enantiomer and racemic forms of a chiral molecule. Structural, photophysical, and chiroptical investigations of chiral cyclohexane bisphthalimide derivatives showed that heterochiral and homochiral dimer interactions play a crucial role on the triplet excited state stabilization, resulting in higher RTP efficiency for enantiopure systems than for racemic one. This study paves the way to the use of molecular chirality to rationalize supramolecular properties arising from subtle intermolecular interactions.

Mirror Symmetry Breaking in Liquids and Their Impact on the Development of Homochirality in Abiogenesis: Emerging Proto-RNA as Source of Biochirality?

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.

Enantiomeric Recognition and Separation by Chiral Nanoparticles.

Chiral molecules are stereoselective with regard to specific biological functions. Enantiomers differ considerably in their physiological reactions with the human body. Safeguarding the quality and safety of drugs requires an efficient analytical platform by which to selectively probe chiral compounds to ensure the extraction of single enantiomers. Asymmetric synthesis is a mature approach to the production of single enantiomers; however, it is poorly suited to mass production and allows for only specific enantioselective reactions. Furthermore, it is too expensive and time-consuming for the evaluation of therapeutic drugs in the early stages of development. These limitations have prompted the development of surface-modified nanoparticles using amino acids, chiral organic ligands, or functional groups as chiral selectors applicable to a racemic mixture of chiral molecules. The fact that these combinations can be optimized in terms of sensitivity, specificity, and enantioselectivity makes them ideal for enantiomeric recognition and separation. In chiral resolution, molecules bond selectively to particle surfaces according to homochiral interactions, whereupon an enantiopure compound is extracted from the solution through a simple filtration process. In this review article, we discuss the fabrication of chiral nanoparticles and look at the ways their distinctive surface properties have been adopted in enantiomeric recognition and separation.

Energy transfer in turbulence under rotation

It is known that rapidly rotating turbulent flows are characterized by the emergence of simultaneous upscale and downscale energy transfer. Indeed, both numerics and experiments show the formation of large-scale anisotropic vortices together with the development of small-scale dissipative structures. However the organization of interactions leading to this complex dynamics remains unclear. Two different mechanisms are known to be able to transfer energy upscale in a turbulent flow. The first is characterized by two-dimensional interactions among triads lying on the two-dimensional, three-component (2D3C) manifold, namely on the Fourier plane perpendicular to the rotation axis. The second mechanism is three-dimensional and consists of interactions between triads with the same sign of helicity (homochiral). Here, we present a detailed numerical study of rotating flows using a suite of high Reynolds number direct numerical simulations within different parameter regimes to analyze both upscale and downscale cascade ranges. We find that the upscale cascade at wave numbers close to the forcing scale is generated by increasingly dominant homochiral interactions which couple the three-dimensional bulk and the 2D3C plane. This coupling produces an accumulation of energy in the 2D3C plane, which then transfers energy to smaller wave numbers thanks to the two-dimensional mechanism. In the forward cascade range, we find that the energy transfer is dominated by heterochiral triads and is dominated primarily by interaction within the fast manifold where $k_z\ne0$. We further analyze the energy transfer in different regions in the real-space domain. In particular, we distinguish high-strain from high-vorticity regions and we uncover that while the mean transfer is produced inside regions of strain, the rare but extreme events of energy transfer occur primarily inside the large-scale column vortices.

Temperature Dependences and Enthalpic Discrimination of Homochiral Pairwise Interactions of Six α-Amino Acid Enantiomers in Pure Water

Dilution enthalpies of six α-amino acid enantiomers (l-alanine vs d-alanine, l-serine vs d-serine, and l-proline vs d-proline) in pure water were determined at T = (288.15 to 323.15) K by isothermal titration calorimetry (ITC). Homochiral enthalpic pairwise interaction coefficients (hxx) at each temperature were evaluated according to the McMillan–Mayer theory. The hxx values of α-alanine and α-proline enantiomers are all positive (hLL > hDD > 0), while those of α-serine enantiomers are all negative (hLL < hDD < 0). In both cases, the hxx values increase uniformly and gradually with elevating temperatures. A slight but significant enthalpic discrimination effect is found in the homochiral pairwise interactions of these α-amino acid enantiomers. The positive growth of hxx values indicates that increasing temperature promotes the predominance of hydrophobic interactions in the binary aqueous solutions studied.

Solid Tryptophan as a Pseudoracemate: Physicochemical and Crystallographic Characterization

The crystalline nature of solid tryptophan has been characterized by X-ray single crystal and powder diffraction analyses, differential scanning calorimetry, as well as measurement of solid-liquid equilibrium in water/isopropanol solution. Both the thermodynamic and crystallographic investigations have demonstrated unambiguously that solid tryptophan crystallizes in the form of a pseudoracemate (i.e., solid solution) with maximum melting over the entire enantiomeric composition range. Comparative single-crystal X-ray studies show that the crystal structures of racemic and enantiomeric tryptophan give very similar solid-state packing geometries dictated by hydrogen bonding interactions. Our results indicate that the insignificant difference between homochiral and heterochiral interactions accounts for the formation of a pseudoracemate for this system.

Conformational space of tetrakis(2-naphthalenyl)ethene: a naphthologous AIE luminogen

The AIE luminogen tetrakis(2-naphthalenyl)ethene (2-NA4E) was synthesized by Barton’s double extrusion diazo-thione coupling method from 2,2′-dinaphthyl thioketone and 2,2′-(diazomethylene)bisnaphthylene in 77 % yield. The structure of 2-NA4E was confirmed by its 1H NMR and 13C NMR spectra with full assignments. 2-NA4E and its parent tetraphenylethene (Ph4E) have been subjected to a comprehensive computational DFT study, in search of their conformational spaces. Seven conformers and two transition states of 2-NA4E have been located. Four conformers and one transition state of Ph4E have been located. The conformers of 2-NA4E and Ph4E are not overcrowded, as indicated by the contact distances in the fjord and cove regions. The relative free energies (ΔG298) of the six most stable conformers of 2-NA4E are in the narrow range of 2.3 kJ/mol; they make comparable contributions (12–29 %) to the equilibrium mixture. The energy barriers for the diastereomerization D2-Z,Z,Z,Z\( \rightleftharpoons \)D2-E,E,E,E via the transition state C1-Z,E,E,Z and for the enantiomerization C2-Z,Z,E,E\( \rightleftharpoons \)C2-E,E,Z,Z via the transition state Ci-Z,E,Z,E are only 29.8 and 29.0 kJ/mol, respectively, indicating very rapid rates of diastereomerization and enantiomerization at room temperature. The values of naphthalenyl torsion angles and ethenic twist angles in 2-NA4E are almost identical to those in the parent Ph4E. The previously proposed “bulkiness” of the naphthalenyl substituents and the validity of the restriction of naphthalenyl rotation are challenged. The analysis of the AIE effect in 2-NA4E should take into account the intermolecular homochiral and heterochiral interactions between the conformers.

Enthalpic discrimination of homochiral pairwise interactions: Enantiomers of proline and hydroxyproline in (dimethyl formamide (DMF) + H2O) and (dimethylsulfoxide (DMSO) + H2O) mixtures at 298.15 K

Dilution enthalpies of two pairs of α-amino acid enantiomers, namely l-proline vsd-proline, and l-hydroxyproline vsd-hydroxyproline, in water-rich regions of dimethyl formamide (DMF)+H2O and dimethylsulfoxide (DMSO)+H2O mixtures (mass fractions of cosolvents wCOS=0 to 0.30) have been determined respectively at 298.15K by isothermal titration calorimetry (ITC). The successive values of dilution enthalpy obtained in a single run of ITC determination were used to calculate homochiral enthalpic pairwise interaction coefficients (hxx) at the corresponding composition of mixed solvents according to the McMillan–Mayer’ statistical thermodynamic approach. The sign and magnitude of hxx were interpreted in terms of solute–solute interactions mediated by solvent and cosolvent molecules, and preferential configurations of homochiral pairwise interactions (l–l or d–d pairs) in aqueous solutions. The variations of hxx with wCOS were considered to be dependent greatly on the competition equilibrium between hydrophobic and hydrophilic interactions, as well as the structural alteration of water caused by the two highly polar aprotic cosolvents (DMF and DMSO). Especially, it was found that when one of the two kinds of interactions (hydrophobic or hydrophilic interactions) preponderates over the other in solutions, enthalpic effect of homochiral pairwise interactions is always remarkable, and is characterized by a large absolute value of hxx, positive or negative, which corresponds respectively to the prevailing interactions of hydrophobicity or hydrophilicity. Interestingly, it was also found that the hxx values of l-enantiomers are generally larger than those of d-enantiomers across the whole studied composition range of mixed solvents, i.e. |hLL|>|hDD|, which is defined as enthalpic discrimination effect and attributed to the influence of preferential configuration on homochiral pairwise interactions in aqueous solutions.

Deracemization of amino acids by partial sublimation and via homochiral self-organization.

Deracemization of a 50/50 mixture of enantiomers of aliphatic amino acids (Ala, Leu, Pro, Val) can be achieved by a simple sublimation of a pre-solubilized solid mixture of the racemates with a huge amount of a less-volatile optically active amino acid (Asn, Asp, Glu, Ser, Thr). The choice of chirality correlates with the handedness of the enantiopure amino acids--Asn, Asp, Glu, Ser, and Thr. The deracemization, enantioenrichment and enantiodepletion observed in these experiments clearly demonstrate the preferential homochiral interactions and a tendency of natural amino acids to homochiral self-organization. These data may contribute toward an ultimate understanding of the pathways by which prebiological homochirality might have emerged.

Unconventional preparation of racemic crystals of isopropyl 3,3,3-trifluoro-2-hydroxypropanoate and their unusual crystallographic structure: the ultimate preference for homochiral intermolecular interactions

This work reports the first example of the transformation of conglomerate (R)- and (S)-crystals into racemic crystals via sublimation. Crystallographic analysis of racemic isopropyl 3,3,3-trifluoro-2-hydroxypropanoate did not reveal the highly expected heterochiral dimer indicating that this compound is capable of forming exclusively homochiral oligomers via infinite multi-centred H-bonding networks.

A Series of [MnMo9O32]6– Based Solids: Homochiral Transferred from Adjacent Polyoxoanions to One-, Two-, and Three-Dimensional Frameworks

Five new compounds based on the Waugh-type polyoxoanion [MnMo9O32]6– Na4Mn[MnMo9O32]·11.5H2O (1), KNa3Mn[MnMo9O32]·9H2O (2), Na2Ni2[MnMo9O32]·12H2O (3), l-Mn3[MnMo9O32]·13H2O (4a), d-Mn3[MnMo9O32]·13H2O (4b), and l-Ni3[MnMo9O32]·11.5H2O (5a) have been synthesized. In these compounds, with the changes of Na+/TM (TM = Mn2+, Ni2+) in the crystal, the homochiral interactions were extended from two adjacent [MnMo9O32]6– to one-dimensional (compounds 1 and 2), two-dimensional (compound 3), and three-dimensional (compounds 4 and 5) systems, respectively.

Enantiomeric Segregation in the Gel Phase of Lipid Bilayers

Enantiospecific interactions within a monoglyceride lipid bilayer are investigated using molecular dynamics simulations. Preferential homochiral interactions are observed in the gel phase, whereas no detectable enantiospecificity is seen in the liquid-crystal phase. On the basis of these results and available experimental data, a mechanism is proposed for the formation of the coagel phase of monoglycerides. Enantiomeric segregation in the gel phase is also discussed in terms of its possible implications for prebiological evolution and membrane raft function.

Enthalpies of Dilution of 1,3-Propanediol and Isomers of 2,3-Butanediol in Dimethylsulfoxide + Water Mixtures at 298.15 K

The dilution enthalpies of three isomers of 2,3-butanediol, namely, meso-2,3-butanediol, (2S,3S)-(+)-2,3-butanediol, (2R,3R)-(−)-2,3-butanediol, as well as 1,3-propanediol in dimethylsulfoxide (DMSO) + water mixtures have been determined, respectively, using an isothermal titration calorimeter (ITC) at 298.15 K. On the basis of the McMillan−Mayer theory, the homochiral enthalpic pairwise interaction coefficients (hXX) of the four diols in the DMSO + water mixtures of various mass fractions (w = 0 to 0.3) have been calculated. The results are discussed from the point of view of solute−solute interaction and solute−solvent interaction. It was found that the method of ITC can differentiate the energies of homochiral interactions between different pairs of optical isomers in aqueous solutions. The variations of hXX with w for the four diols depend largely on the competition equilibrium between hydrophobic−hydrophobic, hydrophilic−hydrophilic, and hydrophobic−hydrophilic interactions in DMSO + water mixtures. The five-membered intramolecular hydrogen bonding of vicinal diols plays an important role on homochiral pairwise interactions. The structure of relative rigid ring favors the forming of preferential configuration in molecular pairwise interaction.

Stereochemical aspects of the molecular pharmaceutics of ibuprofen.

Thermal analysis, thermodynamics of solution and molecular modelling of (+)-ibuprofen and (+/-)-ibuprofen gave information on how heterochiral or homochiral interactions would affect the processing of ibuprofen. The study confirmed that (+/-)-ibuprofen exists as a true racemate with a 10% eutectic pure enantiomer composition. Both the racemate and the (+)-isomer crystal unit cells include four molecules and crystallize in the P2(1/c) and P2(1) space groups, respectively. Thus the intermolecular forces were different in each crystal. As a consequence the (+)-enantiomer lattice was more fragile but only slightly more soluble than the racemate in aqueous media. The solid-state structure contributions to solubility were different for the two crystals (delta H (+) = 51.1 and delta H(+/-) = 32.2 kJ mol-1) but the standard free energies of the solutions were comparable for both compounds.

Stabilization of chiral molecules by decoherence and environment interactions in the gas phase

We study the tunnel dynamics of a chiral molecule between its left (L) and right (R) conformations, under the global effect of collisional decoherence together with the effect of a mean-field generated by the environment where an energetic difference, K, between homochiral and heterochiral interactions is assumed. We show that this decoherence leads unavoidably to equal populations of the L and R chiral conformations even for a high enough value of K which tends to keep localized an initial chiral state. However, we also show that K contributes to the stabilization of an initial L or R state for times that could be many orders of magnitude larger than the tunneling time, in the case the decoherence rate is much greater than the tunneling rate. In this case, an estimation of this stabilization time and a critical tunneling time is made. Even in the case in which the tunneling rate is greater than the decoherence rate, the effect of K is to keep localized the initial chiral state for times greater than the tunneling time. A possible slight chiral asymmetry is also considered.

Ab initio and DFT calculations of three-body interactions in chiral mixtures

In order to elucidate the enthalpic stabilization of a 2-methyl-1,4-butanediol system (2M14BD) and a 3-chloro-1,2-propanediol (3C12PDO) system by mixing of each (R)- and (S)-enantiomers, three-body interaction energies are obtained by PW91/6-311G** and MP2/6-311G** level calculations. The differences between homochiral interactions and heterochiral interactions in a 3C12PDO system are found. On the other hand, in 2M14BD systems, very slight differences can be observed between the three-body interaction energies of the three ternary systems. Further, the relationship between excess enthalpies and chiral interactions is discussed.

Interparticle Chiral Recognition of Enantiomers: A Nanoparticle-Based Regulation Strategy

The ability to regulate how molecular chirality of enantiomeric amino acids operates in biological systems constitutes the basis of drug design for specific targeting. We report herein a nanoparticle-based strategy to regulate interparticle chiral recognition of enantiomers using enantiomeric cysteines (l and d) and gold nanoparticles as a model system. A key element of this strategy is the creation of a nanoscale environment either favoring or not favoring the preferential configuration of the pairwise zwitterionic dimerization of the enantiomeric cysteines adsorbed on gold nanoparticles as a footprint for interparticle chiral recognition. This recognition leads to interparticle assembly of the nanoparticles which is determined by the change in the nanoparticle surface plasmonic resonance. While the surface density and functionality of cysteines on gold nanoparticles are independent of chirality, the interparticle chiral recognition is evidenced by the sharp contrast between the interparticle homochiral and heterochiral assembly rates based on a first-order kinetic model. The structural properties for the homochiral and heterochiral assemblies of nanoparticles depend on the particle size, the cysteine chirality, and other interparticle binding conditions. The structural and thermodynamic differences between the homochiral and heterochiral interactions for the interparticle assemblies of nanoparticles were not only substantiated by spectroscopic characterizations of the adsorbed cysteine species but also supported by structures and enthalpies obtained from preliminary density functional theory calculations. The experimental-theoretical correlation between the interparticle reactivity and the enantiomeric ratio reveals that the chiral recognition is tunable by the nanoscale environment, which is a key feature of the nanoparticle-regulation strategy for the interparticle chiral recognition.