Extended surface chirality for enantiospecific adsorption

A rapid development of nanotechnology opens up a way for the fabrication of solid surfaces containing unique adsorption properties. In this article, we present the concept of a chiral nanostructured surface as a potential environment for the separation of chiral molecules. In particular, we focus on the effect of size and shape of the adsorbing molecules on the effectiveness of their separation on a surface with a special distribution of active sites. The Monte Carlo simulation method was used to study enantiospecific adsorption of model chiral molecules that differ in molecular footprint and adsorption energy. It was demonstrated that manipulating the footprint offers many possibilities for tuning the preference of the surface for adsorption of a selected enantiomer. One interesting finding was that subtle differences in the interaction pattern of the molecule with the chiral surface can lead to a reversal of enantioselectivity. The results of this work highlight the role of extended surface chirality in enantiospecific adsorption of enantiomers. They also suggest that the proposed mechanism of chiral selection can be a realistic alternative to those inherent in conventional enantioselective adsorbents.     

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.     

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.     

Features of the adsorption of naproxen enantiomers on weak chiral anion-exchangers in nonlinear chromatography

The retention mechanism of the enantiomers of naproxen on a Pirkle-type chiral stationary phase (CSP) was studied. This CSP is made of a porous silica grafted with quinidine carbamate. It can interact with the weak organic electrolyte naproxen either by adsorbing it or by ion-exchange. Using frontal chromatography, we explored the adsorption equilibrium under such experimental conditions that naproxen dissociates or cannot dissociate. Under conditions preventing ionic dissociation, the adsorption isotherms were measured, the adsorption energy distributions determined, and the chromatographic profiles calculated. Three different types of the adsorption sites were found for both enantiomers. The density and the binding energy of these sites depend on the nature of the organic modifier. Different solute species, anions, neutral molecules, solvent-ion associates, and solute dimers can coexist in solution, giving rise to different forms of adsorption. This study showed the unexpected occurrence of secondary steps in the breakthrough profiles of S-naproxen in the adsorption mode at high concentrations. Being enantioselective, this phenomenon was assumed to result from the association of solute molecules involving a chiral selector moiety. A multisite Langmuir adsorption model was used to calculate band profiles. Although this model accounts excellently for the experimental adsorption isotherms, it does not explain all the features of the breakthrough profiles. A comparison between the calculated and experimental profiles allowed useful conclusions concerning the effects of the adsorbate-adsorbate and adsorbate-solvent interactions on the adsorption mechanism.     

Chiral separation on a model adsorbent with periodic surface heterogeneity

Optimization of enantioselectivity in heterogeneous catalysis and chiral chromatography is a challenging task for the production of enantiopure chemicals. Enantioselective adsorbents usually consist of a surface with chiral receptors being either chiral molecules linked to the surface or chiral pockets formed by molecular templating of the surface. In both cases, the enantioselectivity is controlled mainly by the strength of the receptor-enantiomer interaction, such that one-to-one correspondence is usually preserved. The authors use Monte Carlo calculations to show that this steric requirement is not a necessary condition for the effective separation of chiral molecules. In particular, they propose a way in which a chiral surface can be constructed by a suitable spatial distribution of active sites for which the classical concept of a chiral receptor is no longer useful. Their calculations indicate that the effectiveness of the separation is affected mainly by the difference in shape of the adsorption energy distribution functions corresponding to the enantiomers.     

基于L-谷氨酸的手性硅胶球的制备及其应用

无机介孔硅球因其具有足够的机械强度、热稳定性,以及适应多种流动相的优点,成为高效液相色谱(HPLC)柱填料中使用最广泛和最重要的材料.但在此研究领域中,并未见球形的全无机手性硅胶用作HPLC手性固定相.该文以无机球形介孔硅胶作为研究对象,通过堆砌硅珠法,以硅溶胶为原料,L-谷氨酸(L-Glu)为手性源,在手性环境中制造...     

Density functional theory study of enantiospecific adsorption at chiral surfaces

Density functional theory calculations are carried out for the adsorption of a chiral molecule, (S)- and (R)-HSCH(2)CHNH(2)CH(2)P(CH(3))(2), on a chiral surface, Au(17 11 9)(S)(). The S-enantiomer is found to bind more strongly than the R-enantiomer by 8.8 kJ/mol, evidencing that the chiral nature of the kink sites at the Au(17 11 9) surface leads to enantiospecific binding. The adsorption of two related chiral molecules, HSCH(2)CHNH(2)COOH ("cysteine") and HSCH(2)CHNH(2)CH(2)NH(2), does not, however, lead to enantiospecific binding. The results of the density functional calculations are broken down into a local binding model in which each of the chiral molecule's three contact points with the surface provides a contribution to the overall adsorption bond strength. The enantiospecific binding is demonstrated to originate from the simultaneous optimization of these three local bonds. In the model, the deformation energy costs of both the molecule and the surface are further included. The model reveals that the molecule may undergo large deformations in the attempt to optimize the three bonds, while the surface deforms to a lesser extent. The most favorable binding configurations of each enantiomer are, however, characterized by small deformation energies only, justifying a local binding picture.     

The fundamentals of adsorption theory for a mixture of bulky molecules in slit-shaped pores with heterogeneous wall surfaces

The fundamentals of the adsorption theory for a mixture of bulky molecules blocking more than one adsorption site on the surface in slit-shaped pores with heterogeneous wall surfaces are outlined. The adsorbate—adsorbate lateral interactions are taken into account in the quasi-chemical approximation and in the mean-field approximation. The expressions for the partial adsorption isotherms and for the binary coefficients of mixture separation and the way of isolation of the partial contributions of molecules on heterogeneous adsorption sites on pore walls are discussed. A simplified variant of adsorption theory for a binary mixture of molecules of different sizes in two-layer pores with the assumption of complete coverage of the pores is considered. The influence of the energy of binding of molecules to pore walls, lateral interactions, and the ratio of the component sizes on the shape of adsorption isotherms is analyzed. The results of calculations are compared with the experimental data for the benzene—CCl₄—microporous AC carbon adsorbent system.     

Templating mesoporous silica with chiral block copolymers and its application for enantioselective separation

In this paper we describe the synthesis of chiral mesoporous silica based on chiral block copolymers of poly(ethylene oxide) and of d-phenylalanine (PEO-b-D-Phe) as a surfactant template. The resulting porous structures are characterized by nitrogen sorption experiments, transmission electron microscopy, and small-angle XRD. It is shown that chiral block copolymers of PEO-b-D-Phe are effective as a surfactant template for the preparation of silica materials with highly ordered periodic mesoporous structures of hexagonal symmetry with a pore size of ca. 5 nm and high surface areas of ca. 700 m2/g. The enantioselectivity feature of this porous silica, after the extraction of the chiral copolymers, was examined by selective adsorption of enantiomers and racemic solutions of valine. The selective adsorption was measured by circular dichroism (CD) spectroscopy. A chiral selectivity factor of 2.34 was found with the D enantiomer of valine adsorbed preferably.     

Adsorption of the enantiomers of 3-chloro-1-phenyl-propanol on silica-bonded chiral quinidine carbamate

The interactions of 3-chloro-1-phenyl-propanol with a quinidine carbamate-bonded chiral stationary phase under NPLC conditions were studied by measuring the adsorption isotherm data of its enantiomers by frontal analysis, modeling these data with a suitable isotherm model, and comparing the experimental overloaded elution band profiles with those calculated with this isotherm and the equilibrium dispersive model of liquid chromatography. The affinity energy distribution was calculated from the adsorption isotherm data. The results show that the surface of the adsorbent is heterogeneous and exhibits a bimodal adsorption energy distribution. This fact is interpreted in terms of the presence of two different types of adsorption sites on the stationary phase, nonselective and enantioselective sites. Albeit the bi-Langmuir isotherm model successfully accounts for the single-component data corresponding to both enantiomers, the competitive bi-Langmuir isotherm model does not allow an accurate prediction of the overloaded band profiles of the racemic mixture. Thermodynamic data are drawn for explanation. Some aspects of the retention mechanism are discussed in the light of the data obtained.     

Theoretical investigations of the chromatographic separation of interacting enantiomers

Separation of a pair of enantiomers by liquid chromatography is modeled using the equilibrium dispersive (ED) model of chromatography. It is assumed that the chiral stationary phase used for the separation consists of two types of adsorption sites, including chiral selectors linked to the surface and nonselective centers belonging to the achiral matrix. Additionally, intermolecular interactions between adsorbed enantiomers are taken into account. The corresponding equilibrium adsorption isotherms of the enantiomers are derived by means of the mean field approximation (MFA) and used as input data for the ED model. Special attention is paid to the influence of the lateral interactions on the effectiveness of the enantiomer separation. In particular, we examine the effect of the interactions on the shape and relative position of the chromatographic peaks associated with the enantiomers. Furthermore, the influence of the spacer length, which modifies screening of the lateral interactions, on the adsorption process is studied. The obtained results suggest that the lateral interactions combined with the screening effect may cause serious changes in the separation, depending on the nature (attraction or repulsion) and strength of the interactions as well as on the spacer length.     

Role of molecular orientational anisotropy in the chiral resolution of enantiomers in adsorbed overlayers

Separation of chiral molecules using achiral inputs is an interesting alternative to traditional techniques based on the chiral recognition mechanism. In this article we propose a lattice gas Monte Carlo model of two-dimensional chiral segregation induced by breaking of molecular orientational symmetry. Simulations were performed on a square lattice for rigid chain molecules composed of four and five identical segments. Mirror-image flat chain conformations resulting in different enantiomeric pairs were considered for each probe molecule. The enantiomers were assumed to interact via short-ranged segment-segment interaction potential limited to nearest neighbors on the lattice. We considered two qualitatively different situations in which (1) the molecules were allowed to rotate on the surface and adopt any of the four planar orientations and (2) the rotation was blocked, so that only one planar orientation was possible. The results obtained for the racemic overlayers showed clearly that the orientational symmetry breaking can induce spontaneous segregation of the enantiomers into large enantiopure domains. However, this effect was observed only for molecules with sufficiently long linear fragment. In the case of kinked bulky molecules a mixed assembly was formed, demonstrating the role of molecular shape in the orientationally biased segregation of enantiomers in adsorbed films. The insights from this study can be useful in developing strategies for 2D chiral separations in which external directional fields are used.     

Investigation of the adsorption behaviour of a chiral model compound on a tartardiamide-based network-polymeric chiral stationary phase

The adsorption behaviour of the enantiomers of 2-phenylbutyric acid on the chiral stationary phase (CSP) Kromasil CHI-TBB was studied using hexane/MTBE (90/10) as eluent. Adsorption isotherms were acquired at 40 different enantiomer concentrations in the interval between 7.6 microM and 305 mM, an approximately 40,000-fold dynamic range. The adsorption data fitted well to the bi-Langmuir model, indicating a heterogeneous surface with two different types of adsorption sites having different equilibrium constants and capacities; namely one chiral site and one non-chiral site. A comparison with earlier adsorption studies on modern CSPs revealed that the capacity value of the "true" chiral site of Kromasil CHI-TBB is the largest reported so far. The elution profiles simulated with these parameters show excellent agreement with the corresponding experimental profiles. Guidelines for comparisons of loading capacities of CSPs are presented.     

Acetylation of beta-cyclodextrin surface-functionalized cellulose dialysis membranes with enhanced chiral separation

The enhanced enantiomeric separation of racemic phenylalanine solution has been demonstrated by the membrane-based chiral resolution method using an acetylated beta-cyclodextrin-immobilized cellulose dialysis membrane. Beta-cyclodextrin (CD) was first immobilized onto the surface of commercial cellulose dialysis membranes, followed by the acetylation reaction through the treatment of the membranes with acetic anhydride to form the chiral selective acetylated beta-cyclodextrin-immobilized cellulose dialysis membrane. The acetylated CD-immobilized membrane exhibits enantioselectivity in the range of 1.26-1.33 depending on the acetylation time. The improvement in enantioselectivity after acetylation was mainly attributed to the better discrimination ability of acetylated CD and the decrease in membrane pore size. Molecular modeling simulations indicate that the acetylation of hydroxyl groups would result in a CD conformation with torus distortions and would create higher steric hindrance for penetrants. As a result, compared to the original CD, the acetylated CD may have less effective binding but better discrimination of enantiomers. The energy drop is only 3 kcal/mol between different enantiomers before and after the binding of phenylalanine with an unmodified CD. The energy drop increases to 10 kcal/mol if acetylated CD is employed as the chiral selector, showing stronger characteristics for chiral selection.     

Computational study of enantioseparation by amylose tris(3,5‐dimethylphenylcarbamate)‐based chiral stationary phase

The mechanism of chiral separation on amylose tris(3,5‐dimethylphenylcarbamate) is studied with docking simulations of enantiomers by molecular dynamics. All‐atom models of amylose tris(3,5‐dimethylphenylcarbamate) on the modified silica gel surface were constructed for the docking simulations of metalaxyl and benalaxyl. The elution orders and energetic differences were also predicted based on the intermolecular interactions, which were in agreement with the experimental results. The radial distribution function was employed to analyze the structural features of the enantiomer‐chiral stationary phase complex and used to elucidate the mechanism of chiral separation. The separation of metalaxyl and benalaxyl is mainly controlled by the hydrogen bond. And the binding sites had slight differences for the pair of enantiomers, but obvious differences between different chemicals.     

Controlling chiral organization of molecular rods on Au(111) by molecular design

Chiral self-assembled structures formed from organic molecules adsorbed on surfaces have been the subject of intense investigation in the recent decade, owing both to relevance in applications such as enantiospecific heterogeneous catalysis or chiral separation as well as to fundamental interest, for example, in relation to the origin of biomolecular homochirality. A central target is rational design of molecular building blocks allowing transfer of chirality from the molecular to the supramolecular level. We previously studied the surface self-assembly of a class of linear compounds based on an oligo(phenylene ethynylene) backbone, which were shown to form a characteristic windmill adsorption pattern on the Au(111) surface. However, since these prochiral compounds were intrinsically achiral, domains with oppositely oriented windmill motifs and related conformational surface enantiomers were always realized in equal proportion. Here we report on the enantioselective, high yield chemical synthesis of a structurally related but intrinsically chiral compound in which two peripheral tert-butyl substituents are replaced by sec-butyl groups, each containing an (S) chiral center. Using scanning tunneling microscopy under ultrahigh vacuum conditions, we characterize the adsorption structures formed from this compound on the Au(111) surface. The perturbation introduced by the modified molecular design is found to be sufficiently small so structures form that are closely analogous to those observed for the original tert-butyl substituted compound. However, as demonstrated from careful statistical analysis of high-resolution STM images, the introduction of the two chiral (S)-sec-butyl substituents leads to a strong preference for windmill motifs with one orientation, demonstrating control of the chiral organization of the molecular backbones through rational molecular design.     

Functionalization of cellulose dialysis membranes for chiral separation using beta-cyclodextrin immobilization

A membrane-based chiral separation system for the separation of racemic tryptophan solutions is developed by the covalently binding beta-cyclodextrin onto the surface of commercial cellulose membranes. The immobilization process is monitored by XPS. AFM demonstrates the evolutionary transition of membrane surface morphology before and after the CD immobilization. Due to their different complexation with immobilized CD, dialysis transport experiments show d-tryptophan preferential permeability through the immobilized CD membranes, and the enantioselectivity is 1.10. A model based on the existence of a thin chiral solution layer of amino acid at the interface between the feed solution and the membrane has been proposed. This chiral separation model has been verified using the chiral separation results of racemic amino acids and binding constants of amino acids with CD. The effect of membrane's pore size on enantioselectivity has also been investigated. The immobilized CD membrane, having MWCO 1000, exhibits the highest enantioselectivity to the racemic tryptophan solution.     

基于非手性离子液体的毛细管电泳法拆分3种手性药物

建立了以非手性离子液体1-正丁基-3-甲基咪唑氯(［BMIM］Cl)为手性分离的添加剂、β-环糊精作为手性选择剂的毛细管区带电泳(CZE)分离扑尔敏、氯霉素前体和氧氟沙星3种对映体的方法,并与未添加［BMIM］Cl的CZE分离情况进行了对比研究。发现［BMIM］Cl对手性药物的拆分有协同作用,不仅能够增加对映体的分离度,还能有效地抑制毛细管内壁对样品分子的吸附作用,改善峰形。采用离子液体辅助手性选择剂(尤其是环糊精)的CZE改进方法,为其他毛细管电泳难以分离的手性药物的分离分析提供了新的方法。     

Gas-chromatographic separation of enantiomers of 2-chlorobutane and 2-bromobutane on a cyanuric acid-modified Carboblack C adsorbent

The enantiomers of 2-chlorobutane and 2-bromobutane were separated by gas chromatography on a Carboblack C adsorbent modified by 10% cyanuric acid. Upon thorough mechanical stirring of a solution, cyanuric acid was shown to form chiral supramolecular structures on the surface of adsorbent particles analogously to the Kondepudi formation of chiral crystals of achiral molecules. The enantiomers of 2-bromobutane and 2-chlorobutane were found to undergo, respectively, complete and partial separation on the cyanuric acid-modified Carboblack C adsorbent. The separation of enantiomers is due to a high enantioselectivity of the modified adsorbent. The analysis of thermodynamic functions of adsorption showed that the differences in specific retention volumes of enantiomers are caused by the fact that one of enantiomers is adsorbed predominantly within the cavity of the supramolecular structure of cyanuric acid and another one is adsorbed on its surface. Separation on the proposed chiral stationary phase is characterized by the relative standard deviation of retention volumes no more than 7%.     

Application of thin-layer chromatography in enantiomeric chiral analysis-an overview

Several chiral drugs are produced and administered as pure enantiomers, whereas many others, especially of synthetic origin, are used mainly in the form of racemates. The biological and pharmacological activity of chiral compounds depends on their configuration. The racemic drugs may exhibit quite different activity from the optically pure drugs. Often only one of the enantiomers is pharmacologically active and/or even can be toxic. Since numerous enantiomers have been shown to behave differently from at least one point of view, whether pharmacokinetic, pharmacodynamic, toxicological or interaction, there seems to be hardly any exception to the general rule that a racemate cannot be considered as a single drug entity. A variety of chromatographic methods have been developed for optical resolution recently. Usually direct separation of the enantiomers is carried out on HPTLC chiral precoated plates or on plates impregnated with chiral substances. TLC techniques are a developing branch of separation and quantitation of drugs, both in pharmaceutical dosage forms and in biological material. This review presents an overview of the current successful enantioseparations of drugs by TLC and their potential in the analysis of the drug racemates.