Creation of chiral adsorbed structures using external inputs: results from lattice Monte Carlo simulations

Patterning of solid surfaces with organic molecules has been recognized as a promising method to create functional 2D matrices with tunable structure and properties. In this work we use the lattice Monte Carlo simulations to study chiral pattern formation in adsorbed systems comprising simple molecular building blocks differing in shape. To that end we consider five-membered rigid isomers whose composite segments can occupy vertices of a triangular lattice and interact with short-range (nearest neighbors) forces. Our main focus is on those molecules which are prochiral, that is they can adopt mirror-image planar configurations when adsorbed. Moreover, the effect of orientational in-plane confinement of the molecules, which reflects their coupling with an external directional field, on the structure formation and chiral resolution in 2D is explored. The obtained results demonstrate that the confinement imposed on the surface enantiomers can induce their resolution and formation of extended homochiral domains. However, it is also shown that for certain molecular shapes the confinement can produce mixed racemic crystals instead of the homochiral assemblies. The insights from our simulation studies can be helpful in preliminary screening of molecular libraries to select optimal building blocks able to self-assembly into chiral 2D patterns with predefined architecture.     

Spontaneous segregation on a hybrid chiral surface

Segregation of enantiomers in two-dimensional adsorbed layers is a process that is usually controlled by anisotropic directional interactions between adsorbed molecules. In this contribution, we propose a simple theoretical model in which the chiral segregation occurs even though the lateral interactions are neglected. In particular, we consider a solid surface composed of two domains with different patterns of active sites being mirror images of each other. The domains of opposite handedness represent crystal facets of a composite chiral material which are adjoined to form a heterochiral adsorbing surface. To explore equilibrium properties of the system, we use Canonical Ensemble Monte Carlo method for a square lattice. The influence of factors such as energetic properties of the surface and density of the adsorbed layer on the extent of separation is examined. The obtained results indicate that effective two-dimensional separation on the hybrid chiral surface assumed in our model can be achieved only at sufficiently low adsorbate densities. The results also suggest that the segregation on the hybrid surface would be a promising method of enantiodiscrimination for those chiral molecules which do not exhibit strong lateral interactions.     

Influence of a Change in Helical Twisting Power of Photoresponsive Chiral Dopants on Rotational Manipulation of Micro‐Objects on the Surface of Chiral Nematic Liquid Crystalline Films

Herein we report a group of five planar chiral molecules as photon‐mode chiral switches for the reversible control of the self‐assembled superstructures of doped chiral nematic liquid crystals. The chiral switches are composed of an asymmetrically substituted aromatic moiety and a photoisomerizing azobenzene unit connected in a cyclic manner through methylene spacers of varying lengths. All the molecules show conformational restriction in the rotation of the asymmetrically substituted aromatic moiety in both the E and Z states of the azobenzene units resulting in planar chirality with separable enantiomers. Our newly synthesized compounds in pure enantiomeric form show high helical twisting power (HTP) in addition to an improved change in HTP between the E and Z states. The molecule with a diphenylnaphthalene unit shows the highest ever known initial helical twisting power among chiral dopants with planar chirality. In addition to the reversible tuning of reflection colors, we employed the enantiomers of these five compounds in combination with four nematic liquid crystalline hosts to study their properties as molecular machines; the change in HTP of the chiral dopant upon photoisomerization induces rotation of the texture of the liquid crystal surfaces. Importantly, this study has revealed a linear dependence of the ratio of the difference between HTPs before and after irradiation against the absolute value of the initial HTP, not the absolute value of the change in helical twisting power between two states, on the angle of rotation of micro‐objects on chiral nematic liquid crystalline films. This study has also revealed that a change in irradiation intensity does not affect the maximum angle of rotation, but it does affect the speed of rotational reorganization of the cholesteric helix.     

The chiral recognition of guest molecules in trio-o-thymotide clathrates: A semi-empirical approach. Preliminary communication

The enantiomers of a chiral solvent can be enclathrated to a different extent in a crystal lattice consisting of tri-o-thymotide ( 1 ) molecules of a given handedness. This property affords a mean of studying the stereoselective interaction of a chiral environment with an enclosed chiral component. The general approach to account for the observed differences in stereoselectivity is based on the calculation and comparison of the minimum energies for the respective inclusion of enantiomeric guest molecules within a rigid cage of given chirality. An interpretation of the fair chiral recognition of 2-bromobutane as opposed to the unselective inclusion of 2-butanol is attempted.     

Disappearing Enantiomorphs: Single Handedness in Racemate Crystals

Although crystallization is the most important method for the separation of enantiomers of chiral molecules in the chemical industry, the chiral recognition involved in this process is poorly understood at the molecular level. We report on the initial steps in the formation of layered racemate crystals from a racemic mixture, as observed by STM at submolecular resolution. Grown on a copper single‐crystal surface, the chiral hydrocarbon heptahelicene formed chiral racemic lattice structures within the first layer. In the second layer, enantiomerically pure domains were observed, underneath which the first layer contained exclusively the other enantiomer. Hence, the system changed from a 2D racemate into a 3D racemate with enantiomerically pure layers after exceeding monolayer‐saturation coverage. A chiral bias in form of a small enantiomeric excess suppressed the crystallization of one double‐layer enantiomorph so that the pure minor enantiomer crystallized only in the second layer.     

Low temperature phases of the Andelman-de Gennes model of chiral discrimination: rigorous results

We determine the ordered low temperature phases of the Andelman-de Gennes model of chiral discrimination, using rigorous statistical mechanical methods. The system is considered in the close-packed regime, equivalent to placing the molecules at every site of a honeycomb lattice. If the system contains an equimolar mixture of each of a pair of enantiomers, we prove in general that a heterochiral phase (disfavoring enantiomeric segregation) as well as a homochiral phase (favoring the segregation) is possible, depending on the types of intermolecular interactions. We apply our general results to the specific examples of the interactions considered by Andelman and de Gennes and provide a comparison with their conjectures that were based on two-molecule partition functions.     

Effect of molecular structure of tartrates on chiral recognition of tartrate–boric acid complex chiral selectors in chiral microemulsion electrokinetic chromatography

Eight l-tartrates and a d-tartrate with different alcohol moieties were used as chiral oils to prepare chiral microemulsions, which were utilized in conjunction with borate buffer to separate the enantiomers of β-blockers or structurally related compounds by the chiral microemulsion electrokinetic chromatography (MEEKC) method. Among them, six were found to have a relatively good chiral separation performance and their chiral recognition effect in terms of both enantioselectivity and resolution increases linearly with the number of carbon atoms in the alkyl group of alcohol moiety. The tartrates containing alkyl groups of different structures but the same number of carbon atoms, i.e. one of straight chain and one of branched chain, provide similar enantioseparations. The trend was elucidated according to the changes in the difference of the steric matching between the molecules of two enantiomers and chiral selector. Furthermore, it was demonstrated for the first time that a water insoluble solid compound, di-i-butyl l-tartrate (mp. 73.5 °C), can be used as an oil to prepare a stable microemulsion to be used in the chiral MEEKC successfully. And a critical effect of the microemulsion for chiral separation, which has never been reported before, was found in this experiment, namely providing a hydrophobic environment to strengthen the interactions between the chiral selector and enantiomers.     

Enantiodiscrimination in deuterium NMR spectra of flexible chiral molecules with average axial symmetry dissolved in chiral liquid crystals: the case of tridioxyethylenetriphenylene

Flexible chiral molecules undergoing fast interconversion (on the NMR time scale) between different conformational enantiomers may yield "average" axial species with enantiotopically related sites. Contrary to the situation observed for rigid axial molecules, signals from these enantiotopic sites in NMR spectra recorded in chiral liquid-crystalline solvents can be resolved. In the present work, we studied the deuterium NMR spectra of tridioxyethylenetriphenylene (compound 4) statistically deuterated to 10% in the flexible side chains and dissolved in chiral and achiral lyotropic liquid crystals based on poly(gamma-benzylglutamate). The fast chair-chair flipping of the side chains in 4 on average renders the molecule axially symmetric ( D 3 h ) with pairs of enantiotopic ethylene deuterons. These deuterons exhibit unusually large enantiodiscrimination. To explain this observation, we first describe how the average symmetry of flexible molecules can be derived from the symmetry of the "frozen" conformers and the nature of the averaging process. The procedure is then applied to 4 and used to analyze the NMR results. It is shown that the large enantiodiscrimination in the present case reflects a large difference in the orientational ordering of the conformational enantiomers participating in the interconversion processes as well as a large geometrical factor due to the special shape of the dioxyethylene side groups. (1)H and (13)C NMR spectra of 4 in the same lyotropic liquid crystalline solvent are analyzed to determine its ordering characteristics. Several related cases are also discussed.     

Chiral separation: mechanism modeling in two-dimensional systems

Fluid phase separations of racemates are difficult because the subtle, short-ranged differences in intermolecular interactions of like and unlike pairs of chiral molecules are typically smaller than the thermal energy. A surface restricts the configurational space available to the pair of interacting molecules, thus changing the effective interactions between them. Because of this restriction, a surface can promote chiral separation of mixtures that are racemic in bulk. In this paper, we investigate chiral symmetry breaking induced by an achiral surface in a racemate. A parallel tempering Monte Carlo algorithm with tempering over the temperature domain is used to examine the interplay between molecular geometry and energetics in promoting chiral separations. The system is restricted to evolve in two dimensions. By controlling the balance between electrostatic and steric interactions, one can direct the surface assembly of the chiral molecules toward formation of small clusters of identical molecules. When molecular shape asymmetry is complemented by dipolar alignment, chiral micellar clusters of like molecules are assembled on the surface. We examine the case of small model molecules for which the two-dimensional restriction of the pair potential is sufficient to induce chiral segregation. An increase in molecular complexity can change the balance of intermolecular interactions to the point that heterochiral pairs are energetically more favored. In this case, we find conditions in which formation of homochiral micelles is still achieved, due to a combination of multibody and entropic effects. In such systems, an examination of the pair potential alone is insufficient to predict whether the multimolecular racemate will or will not segregate.     

奥美拉唑、兰索拉唑对映体及相关物质在不同手性柱的分离比较

考察了奥美拉唑、兰索拉唑对映体及其拆分剂联二萘酚在4种手性柱（chiralcel OD、chiralpak AD、kromasil CHI-TBB和chiral-AGP)上的色谱行为。实验结果表明：Chiralpak AD、 Chiral-AGP柱分离度大，柱效稳定，并且这两种柱子的配合使用实现了对包结拆分的全过程监控。此外，本文根据对映体在不同手性柱的出峰顺序进行了讨论。     

Chiral ordering and conformational dynamics for a class of oligo-phenylene-ethynylenes on Au(111)

Adsorption structures formed from a class of planar organic molecules on the Au(111) surface under ultrahigh vacuum conditions have been characterized using scanning tunneling microscopy (STM). The molecules have different geometries, linear, bent, or three-spoke, but all consist of a conjugated aromatic backbone formed from three or four benzene rings connected by ethynylene spokes and functionalized at all ends with an aldehyde, a hydroxyl, and a bulky tert-butyl group. Upon adsorption, the molecules adopt different surface conformations some of which are chiral. For the majority of the observed adsorption structures, chirality is expressed also in the molecular tiling pattern, and the two levels of chirality display a high degree of correlation. The formation and chiral ordering of the self-assembled structures are shown to result from dynamic interchanges between a diffusing lattice gas and the nucleated islands, as well as from a chiral switching process in which molecules alter their conformation by an intramolecular rotation around a molecular spoke, enabling them to accommodate to the tiling pattern of the surrounding molecular structures. The kinetics of the conformational switching is investigated from time-resolved, variable temperature STM, showing the process to involve an activation energy of approximately 0.3 eV depending on the local molecular environment. The molecule-molecule interactions appear primarily to be of van der Waals character, despite the investigated compounds having functional moieties capable of forming intermolecular hydrogen bonds.     

Expression of molecular chirality and two-dimensional supramolecular self-assembly of chiral, racemic, and achiral monodendrons at the liquid-solid interface

We have investigated the two-dimensional ordering of chiral and achiral monodendrons at the liquid-solid interface. The chiral molecules self-assemble into extended arrays of dimers. As expected, the R enantiomer forms the mirror image type pattern of the chiral two-dimensional structure formed by the S enantiomer. A racemic mixture applied from solution onto the substrate undergoes spontaneous segregation: the enantiomers separate on the surface and appear in different domains. In contrast to the chiral molecules, the achiral analogue self-assembles into cyclic tetramers. Moreover, the pattern formed by the achiral molecule strongly depends on the solvent used. In the case of 1-phenyloctane, solvent molecules are coadsorbed in a 2:1 (dendron:solvent) ratio whereas in 1-octanol, no solvent molecules are coadsorbed. By the appropriate solvent choice, the distance between the potential "supramolecular containers" can be influenced.     

Use of NMR binding interaction mapping techniques to examine interactions of chiral molecules with molecular micelles

NMR spectroscopy was used to investigate the association of four chiral molecules with the molecular micelle poly(sodium N-undecanoyl-l-leucylvalinate) (poly(SULV)). Adding poly(SULV) to the background electrolyte in electrokinetic chromatography (EKC) allows enantiomeric resolution to be achieved because enantiomers interact differentially with the chiral centers on the micelle headgroups as they both move in the electric field. Pulsed field gradient diffusion experiments were used to measure molecular micelle association constants for enantiomers of each analyte. These association constants were consistent with EKC elution order for the compounds 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BNP), 1,1'-bi-2-naphthol (BOH), and Troger's base. In addition, nuclear Overhauser enhancement spectroscopy, nuclear Overhauser effect difference, and intermolecular cross relaxation diffusion experiments were used to generate binding interaction maps for each chiral analyte. These maps showed that BNP and BOH inserted into the surfactant headgroup's major chiral groove and interacted predominately with the leucine chiral center. (+)-Troger's base was also found to insert into the major chiral groove. However, this compound instead interacted with the valine chiral atom. In diffusion experiments with long diffusion times, the linearized diffusion plots for each analyte-molecular micelle mixture showed curvature characteristic of intermolecular cross relaxation. The magnitude of this effect scaled linearly with the analytes' free energies of binding.     

毛细管区带电泳法拆分手性药物萘普生和氟联苯丙酸

 70-72 -------------------------------------------------------------------------------- 以β-环糊精(CD)作为手性选择剂 ,用毛细管区带电泳法成功地拆分了两种弱酸性药物萘普生(naproxen)和氟联苯丙酸(flurb iprofen),并比较了4种环糊精［β-环糊精(β-CD)、二甲基-β-环糊精( DM-β-CD)、羟丙基-β-环糊精(HP-β-CD)和三甲基-β-环糊精( TM-β-CD)］对手性拆分的影响,同时测定了萘普生对映体在不同环糊精中的出峰次 序。通过实验,发现对于此类化合物拆分的最佳pH值为5左右,即接近于该类化合物的pK a值。该方法适用于酸性手性药物的拆分。     

Spontaneous pattern of linear molecules in strongly confined spaces

In this work, we study the tight packing of short linear molecules in confined space by performing molecular dynamic simulations. The short chain-like molecules spontaneously arrange within single-walled carbon nanotubes (SWNTs) and exhibit a variety of chiral and achiral structures, depending on the pore size and molecule length. Simulation results show that the packing structures for these confined short linear molecules are controlled by the competition between positional order and orientational order. For linear molecules with short molecular length, such as the two-site Lennard-Jones molecules, the orientational order gradually decreases as temperature increases, and then the positional order begins to disappear. While for longer molecules, such as four-site Lennard-Jones molecules, the positional order decreases more rapidly than the orientational order as temperature increases. We also investigated the effect of molecular rigidity. For linear molecules with higher rigidity, part of packing structures may slowly rotate as a whole, and the rotation of packing arrangements is found to be induced by the preexisting defects.     

Chiral nanopatterned surfaces as versatile enantiospecific adsorbents: a Monte Carlo model

This paper deals with the application of the Monte Carlo simulation method for modeling of adsorption of chiral molecules on a planar surface patterned with active binding sites. The enantiomers are assumed to be rigid chains composed of four identical segments, each occupying one binding site. The energy of interaction between a segment and a binding site is characterized by epsilon(a) and epsilon(b) depending whether the site is active or it is inert. We demonstrate that epsilon(a)>epsilon(b) imposed in our previous work [J. Chem. Phys. 126, 144709 (2007)] is not a necessary condition for the separation of enantiomers form their racemate. The obtained results suggest that the major source of enantioselectivity of the surface lies in its geometrical properties. The active adsorption sites which form the chiral pattern do not have to interact stronger with the adsorbing molecules to ensure enantioseparation. In this context, the proposed chiral surface offers more flexibility in selection of the energetic properties of the binding sites. This, in practice, means wider possibilities of manipulating chemical composition of the surface.     

Chiral HPLC and physical characterisation of orthoconic antiferroelectric liquid crystals

New orthoconic antiferroelectric liquid crystalline materials were synthesised and characterised in their racemic forms and as (S) enantiomers. The materials possess oligo-methylene spacers of different lengths in semi-fluorinated achiral chains and lateral substitution by fluorine at two different positions of the molecular core. For comparison purposes, analogical materials without fluorine lateral substitutions were also prepared. Polysaccharide chiral stationary phases based on two different chiral selectors were used for the separation of the enantiomers of the individual racemic mixtures by high-performance liquid chromatography. A baseline separation of (S) and (R) enantiomers was obtained for four of the six studied liquid crystalline materials. Two of the materials were partially separated under the optimised separation conditions. The elution order of the individual enantiomers in the racemic mixtures was successfully assigned, as pure (S) enantiomers of all the studied materials were available. Both the position of the fluorine atom within the molecular core and the size of the achiral moiety had significant effects on the separation of the individual enantiomers of the studied compounds. Moreover, it was also found that the structure of the chiral stationary phase selector significantly influenced the enantiomeric resolution.     

Antibodies as Tailor-Made Chiral Selectors: an Interdisciplinary Approach to Enantiomer Separation and Detection

 It has long been known that the configurational isomers of biologically active compounds, e.g., nutrients, pesticides, and drugs, may exhibit different activities in a chiral environment such as the human body. Although the majority of drugs presently in development are chiral, analytical and preparative methods for the quantitative determination and purification of stereoisomers still lag behind. One reason is that commonly used chiral selectors for the direct resolution of enantiomers are not tailor-made for a specific analyte. The identification of suitable selectors for a particular pair of enantiomers still requires considerable experimentation and is generally demanding with regard to material, time and labor. The rational design of chiral host molecules, therefore, represents a challenge in facilitating enantiomer analysis. In this article, we describe how a combination of techniques ranging from organic synthesis to molecular biology yields antibodies of predetermined specificity and stereoselectivity that can be used as tailor-made chiral selectors for the chromatographic separation of enantiomers and their sensitive detection in immunosensors.     

A study of the phase behavior of a simple model of chiral molecules and enantiomeric mixtures

We present a study of the solid-fluid and solid-solid phase equilibrium for molecular models representative of chiral molecules and enantiomeric mixtures. The models consist of four hard sphere interaction sites of different diameters in a tetrahedral arrangement with the fifth hard sphere interaction site at the center of the tetrahedron. The volumetric properties and free energies of the pure enantiomers and binary mixtures were calculated in both fluid and solid phases using isobaric Monte Carlo simulations. The models exhibit essentially ideal solution behavior in the fluid phase with little chiral discrimination. In the solid phase the effects of chirality are much greater. Solid-fluid phase behavior involving the pure enantiomer solids and also racemic compounds was calculated. The calculations indicate that, depending on the relative sizes of the hard sphere interaction sites, packing effects alone can be sufficient to stabilize a racemic compound with respect to the pure enantiomer solids.