Chiral Modifier Research Articles

Direct Synthesis of in-Situ Chirally Modified Palladium Nanocrystals without Capping Agents and Their Application in Heterogeneous Enantioselective Hydrogenations

Shape-controlled metal nanocrystals possess the advantages of specific atomic arrangement on the surface and uniform size, which can act as ideal model catalysts for heterogeneous enantioselective catalytic studies. Nevertheless, capping agents are commonly retained on the surface of the as-synthesized metal nanocrystals, which may hinder the necessary interaction between the substrate and the chiral modifiers coadsorbed on the metal surface for chiral recognition. In this paper, we directly synthesized dendritic or cubic palladium nanocrystals in-situ modified by chiral modifiers such as cinchonidine (CD) or S-proline through a one-pot strategy by replacing the conventional capping agents with the chiral modifiers. The as-prepared CD-modified Pd nanodendrite catalyst already exhibits enantioselectivity in the asymmetric hydrogenation of (E)-α-phenylcinnamic acid without subsequent chiral modification processes. The in-situ S-proline-modified Pd nanocube catalyst shows higher enantioselectivity than nanoc...

Understanding Enantioselective Interactions by Pulling Apart Molecular Rotor Complexes.

Enantioselective interactions underpin many important phenomena from biological mechanisms to chemical catalysis. In this regard, there is great interest in understanding these effects at the molecular level. Surfaces provide a platform for these studies and aid in the long-term goal of designing heterogeneous enantiospecific interfaces. Herein we report a model system consisting of molecular rotors, one intrinsically chiral (propylene oxide) and one that becomes chiral when adsorbed on a surface (propene). Scanning tunneling microscopy (STM) measurements enable the chirality of each individual molecule to be directly visualized, and density functional theory based calculations are performed to rationalize the chiral time-averaged appearance of the molecular rotors. While there are no attractive intermolecular interactions between the molecular species themselves, when mixed together there is a strong preference for the formation of 1:1 heteromolecular pairs. We demonstrate that STM tip-induced molecular manipulations can be used to assemble these complexes, examine the chirality of each species, and thereby interrogate if their interactions are enantioselective. A statistical analysis of this data reveals that intrinsically chiral propylene oxide preferentially binds one of the enantiomers of propene with a 3:2 ratio, thereby demonstrating that the surface chirality of small nonchiral molecules can be directed with a chiral modifier. As such, this investigation sheds light onto previously reported ensemble studies in which chirally seeded layers of molecules that are achiral in the gas phase can lead to an amplification of enantioselective adsorption.

Platinum nanoparticles supported on mesocellular silica foams as highly efficient catalysts for enantioselective hydrogenation

Mesocellular silica foams (MCFs) with different pore size were synthesized and used as supports for Pt catalysts for enantioselective hydrogenation of ethyl pyruvate. The influences of the pore size of MCFs, the amount of Pt loading and H2 pressure on catalytic performance of cinchonidine-modified Pt/MCFs were investigated. Both activity and enantioselectivity of the Pt/MCF catalyst increased with the increase in the pore size. These results were attributed to the fact that the larger mesopores facilitate intraparticle diffusion of bulky chiral modifier molecules and generate more chirally modified Pt sites. The performances of Pt/MCFs were compared to those of Pt supported on non-porous silica (Pt/SiO2) and commercial Pt/Al2O3 catalysts. The 1 wt% Pt/MCFs showed superior performance than the 1 wt% Pt/SiO2 and the commercial 1 wt% Pt/Al2O3 catalysts. Furthermore, the 0.6 wt% Pt/MCF exhibited higher activity and enantioselectivity than the commercial 5 wt% Pt/Al2O3, one of the most efficient heterogeneous catalysts for this reaction, in spite of a considerably less Pt loading. At optimized reaction conditions, the Pt/MCF catalyst gave enantiomeric excess of 96% at 100% conversion. They also maintained high enantioselectivity during 10 successive reaction cycles, exhibiting high reusability.

Tunable Induced Circular Dichroism in Thin Organic Films

In this work, we study the induced optical activity (OA) of spin-coated molecular films made of a pristine optically inactive laser dye (Rhodamine 110) in the visible range. The OA is brought about by a “transparent” chiral modifier (1,1′-Bi-2-naphthol). For the first time, it was experimentally shown how two separate mechanisms yield induced circular dichroism (ICD) in such a film and how they are describable through a model. In one, ICD occurs via a direct interaction between dye and modifier molecules. In the other, ICD takes place in optical transitions of present dye aggregates. It is proposed that this is caused by a chiral bias through an enantiomeric excess in inherently chiral and optically active dye aggregates promoted by the chiral modifier in a sergeant-soldier manner. Further, the strength of ICD strongly depends on the ratio between the modifier and the dye as well as on the preparation conditions. The resulting high tunability of the OA paired with a straightforward film preparation opens ...

New Strategies in Enantioselective Hydrogenation on Supported Transition Metal Catalyst: Effects of Metal Sintering and Support Swelling

The effect of noble metal catalysts supported on an ionic exchange resin for the enantioselective hydrogenation of ethyl pyruvate to ethyl lactate was studied. High activity and moderate enantioselectivity levels were obtained. Pt was the best enantioselective metallic phase, followed by Pd and Au; Rh was the less enantioselective metallic phase. The effect of the active site was evaluated for the most enantioselective catalyst: 2Pt-WA30 (prefix indicates the metal loading). A novel method for sintering the Pt metal particles by nitriles reduction was used, and a controlled migration of the metal particles to the surface layers was observed. There existed an optimal particle size with maximization of the enantiomeric excess, corresponding to 24 h sintering. The hydrogenation of ethyl pyruvate to ethyl lactate was found to be structure-sensitive and the importance of the metal particle size for the adsorption of the chiral modifier was proved. Two different chirality induction methods were tried for the 2Pt-WA30 catalyst: (i) the addition of the chiral modifier (CM) to the reaction media, or (ii) the modification of the catalyst in a swelling medium prior to the reaction in order to encapsulate CM. Lower activity but higher enantioselectivity levels were obtained with method (ii). Finally, the reuse of the catalysts was also assessed by means of consecutive reaction tests.

Enantioseparation of Selected Imidazole Drugs Using Dual Cyclodextrin-Modified Micellar Electrokinetic Chromatography.

Particular attention has been paid to capillary electrophoresis as versatile and environmentally friendly approach for enantioseparations of a wide spectrum of compounds. Cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) is a method of choice to provide effective separation toward hydrophobic and uncharged stereoisomers. The chiral discrimination of the solutes relies upon the partitioning between a given CD in the aqueous phase and micelles formed from a surfactant. Synergistic combinations of chiral selectors, surfactant, and modifier contribute to successful enantioseparations of the enantiomers. In this chapter, an application of CD-MEKC for the enantioseparation of selected imidazole drugs employing a dual CDs system is described.

The enantioselective hydrogenation of acetophenone over Pd concave tetrahedron nanocrystals affected by the residual adsorbed capping agent polyvinylpyrrolidone (PVP)

One promising way to develop efficient noble-metal catalysts is to induce the exposure of specific catalytically active facets of nanocrystals through shape-controlled syntheses. However, as for the as-prepared noble-metal nanocrystals, there are commonly residual capping agents adsorbed on the metal surfaces, which have complex effects on the catalytic activity and selectivity in different catalytic reactions. In this paper, by taking polyvinylpyrrolidone (PVP), the most commonly used capping agents in the shape-controlled synthesis of noble-metal nanocrystals, as an example, we systematically studied the surface-modification effects of residual capping agents in the enantioselective hydrogenation of acetophenone. It was found for the first time that the residual PVP adsorbed on the Pd concave tetrahedron nanocrystals is detrimental to the enantioselectivity, negative to the activity, while positive to increase the chemoselectivity to the carbonyl group. The loss of enantioselectivity over PVP-stabilized Pd concave tetrahedron nanocrystals is probably due to that the residual PVP adsorbed on the Pd surface can interact with the chiral modifier S-proline and prevent the requisite interaction between S-proline and acetophenone co-adsorbed on the Pd surfaces. Thus, the prochiral interaction complexes which play a significant role in determining the enantioselectivity cannot be formed. KBH4 treatment or hot water reflux offers feasible methods to further reduce the amount of residual PVP adsorbed on the Pd nanocrystals and to achieve enantioselectivity in the enantioselective hydrogenation of acetophenone. This study provides useful information to reveal the essence of enantiodifferentiation in heterogeneous enantioselective hydrogenations, which is beneficial for the design of efficient synthetic protocols and the shape-controlled synthesis of noble-metal nanocrystals to obtain pure enantiomers.

Nematic twist–bend phase in an external field

The response of the nematic twist-bend ([Formula: see text]) phase to an applied field can provide important insight into the structure of this liquid and may bring us closer to understanding mechanisms generating mirror symmetry breaking in a fluid of achiral molecules. Here we investigate theoretically how an external uniform field can affect structural properties and the stability of [Formula: see text] Assuming that the driving force responsible for the formation of this phase is packing entropy, we show, within Landau-de Gennes theory, that [Formula: see text] can undergo a rich sequence of structural changes with the field. For the systems with positive anisotropy of permittivity, we first observe a decrease of the tilt angle of [Formula: see text] until it transforms through a field-induced phase transition to the ordinary prolate uniaxial nematic phase (N). Then, at very high fields, this nematic phase develops polarization perpendicular to the field ([Formula: see text]). For systems with negative anisotropy of permittivity, the results reveal new modulated structures. Even an infinitesimally small field transforms [Formula: see text] to its elliptical counterpart ([Formula: see text]), where the circular base of the cone of the main director becomes elliptic. With stronger fields, the ellipse degenerates to a line, giving rise to a nonchiral periodic structure, the nematic splay-bend ([Formula: see text]), where the two nematic directors are restricted to a plane. The three structures-[Formula: see text], [Formula: see text], and [Formula: see text]-with a modulated polar order are globally nonpolar. But further increase of the field induces phase transitions into globally polar structures with nonvanishing polarization along the field's direction. We found two such structures, one of which is a polar and chiral modification of [Formula: see text], where splay and bend deformations are accompanied by weak twist deformations ([Formula: see text]). Further increase of the field unwinds this structure into a polar nematic ([Formula: see text]) of polarization parallel to the field.

A Derivation of Fluidic Maxwell-Proca Equations for Electrodynamics of Superconductors & Its Implication to Chiral Cosmology Model

Mario Liu described a hydrodynamic Maxwell equations [3] and, also discussed potential implications of these new approaches to superconductors which were made after Tajmar’s paper [4]. In this paper, we present for the first time a derivation of fluidic Maxwell-Proca equations. The name of fluidic Maxwell-Proca is proposed because the equations were based on modifying Maxwell-Proca and Hirsch’s theory of electrodynamics of superconductor. It is hoped that this paper may stimulate further investigations and experiments in superconductor. It may be expected to have some impact to cosmology modeling too, for instance we consider a hypothetical argument that photon mass can be origin of gravitation. Then, after combining with the so-called chiral modification of Maxwell equations (after Sproessig), then we consider chiral Maxwell-Proca equations as possible alternative of gravitation theory. Such a hypothesis has never considered in literature to the best of our knowledge.

Conductive and Chiral Polymer-Modified Metal-Organic Framework for Enantioselective Adsorption and Sensing.

We reported integration of conductivity, chirality, and porosity into MIL-101@chiral-PANI composite for synchronous chiral recognition, adsorption, and sensing toward enantiomers. The core-shell structure of MIL-101@chiral-PANI was characterized in detail by Fourier transform infrared and circular dichroism spectroscopy as well as scanning electron microscopy and transmission electron microscopy. Adsorption behaviors of carvone enantiomers over chiral PANI and MIL-101@chiral-PANI are satisfied with pseudo-first-order fitting. In comparison with chiral PANI, MIL-101@c-PANI exhibits a better enantioselectivity and much higher (>5-fold) adsorption amount over l-carvone than d-carvone. And MIL-101@c-PANI is able to recognize the chirality of carvone via electrochemical sensing, taking advantage of the electric conductivity of chiral PANI. Our result demonstrated the feasibility of applying achiral MOF for enantioselective sensing and adsorption via installing chiral and conductive gates. And this chiral polymer modification strategy represents a universal way to entitle achiral MOFs with chiral functions.

HPLC Enantioseparation of Menthol with Non-ultraviolet Detectors and Effect of Chromatographic Conditions

Menthol has been widely used in pharmaceuticals, food industry, oral health care products, cosmetic industry, and tobacco products, and its HPLC chiral separation has been less reported till now. Herein, a simple and direct method has been developed for separation of menthol by normal-phase HPLC coupled with refractive index detector and/or optical rotation detector, in which special sample pretreatment and derivatization were not required. The effects of chiral stationary phases, alcoholic modifiers, column temperature, and injection amount were studied in detail. The amylose tris(3,5-dimethylphenylcarbamate)-coated chiral stationary phase showed the best separation performance for menthol with the resolution of 2.84. Through the optical rotation detector, (+)-menthol was first eluted on the amylose-based chiral stationary phase in the hexane-2-propanol mixture, but later eluted on the cellulose-derived chiral stationary phases in the same mobile phase. In addition, retention and resolution of menthol displayed an upward trend along with the content of 2-propanol and column temperature reduction. Chiral separation of menthol could be attributed to an enthalpically driven process, since ΔΔH (− 3.04 kJ mol− 1) and ΔΔS* (− 8.57 J mol− 1 K− 1) for two enantiomers were negative in the experimental temperature range. Moreover, the limits of detection and quantitation for the menthol enantiomers with the refractive index detector were similar to the optical rotation detector. These results would provide useful information for direct resolution for chiral compounds without typical chromophoric groups.

Gold Nanorods as Visual Sensing Platform for Chiral Recognition with Naked Eyes

Chirality plays a key role in modern science and technology. Here, we report a simple and effective sensing platform for visual chiral recognition of enantiomers. In this sensing platform, gold nanorods (AuNRs) prepared through a common synthesis route are used as colorimetric probes for visual recognition of glutamine (Gln) enantiomers. D-Gln could rapidly induce the aggregation of AuNRs, thereby resulting in appreciable blue-to-gray color change of AuNRs solution; however, L-Gln could not induce color change of AuNRs. This distinct color change can be easily distinguished by the naked eyes; as a result, a visual method of chiral recognition was suggested. The method was applied to determine the enantiometric excess of D-Gln through the whole range of −100% ~ 100%. The chiral assay can be performed with a simple UV-vis spectrometer or the naked eyes. Notably, the AuNRs do not need any chiral labeling or modification, and the chiral recognition is based on the inherent chirality of AuNRs. This chiral assay method is simple, sensitive, cheap and easy to operate. This study is the first example using AuNRs for direct visual recognition of enantiomers, and will open new opportunity to construct more chiral recognition methods for some important compounds.

“Pop-On and Pop-Off” Surface Chemistry of Alanine on Ni{111} under Elevated Hydrogen Pressures

The coadsorption of hydrogen with a simple chiral modifier, alanine, on Ni{111} was studied using density functional theory in combination with ambient-pressure X-ray photoelectron spectroscopy and X-ray absorption spectroscopy at temperatures of 300 K and above, which are representative of chiral hydrogenation reactions. Depending on the hydrogen pressure, the surface enables protons to “pop-on and -off” the modifier molecules, thus significantly altering the adsorption geometry and chemical nature of alanine from anionic tridentate in ultrahigh vacuum to predominantly zwitterionic bidentate at hydrogen pressures above 0.1 Torr. This hydrogen-stabilized modifier geometry allows alternative mechanisms for proton transfer and the creation of enatioselective reaction environments.

The most stable adsorption geometries of two chiral modifiers on Pt(111)

The molecular description of chirality transfer on chirally modified metal surfaces is unclear due to the complexity of the systems and the weak energetic biases favoring specific enantioselective pathways. In order to move to an enhanced level of molecular understanding it is critical to define the chemisorption geometries of the modifiers responsible for enantiodifferentiation. Model surface science studies of chiral molecules on single crystals provide an indirect method to probe catalytic chirality transfer molecular mechanisms. Apart from the great difference between ultrahigh vacuum (UHV) and reaction conditions, the extent to which such studies can inform the interpretation of data obtained under reaction conditions depends on the degree to which the model systems are correctly defined. The same holds true for any comparison of UHV surface spectroscopy data to spectroscopic measurements made at the catalyst-solution interface under either in-situ or operando conditions.We present detailed reflection absorption infrared spectroscopy (RAIRS) data on (R)-1-(1-naphthyl)ethylamine, (R)-NEA, and its simple derivative, (R)-1-(8-methyl-1-naphthyl)ethylamine, on Pt(111). Various conflicting proposals for the structure of NEA and analogous modifiers on Pt catalyst particles and extended Pt surfaces are found in the literature. Here, we find that below high sub-monolayer coverages on Pt(111), (R)-NEA adopts a chemisorption geometry where the entire naphthyl group is π-bonded to the surface and the amine group forms a dative bond to the surface. The same general adsorption geometry is found for the methyl-substituted derivative. The study provides reference spectra for these chiral modifiers and confirms the molecular structures described in our previous studies of diastereomeric complexes formed by the (R)-NEA/Pt(111) system.

Enantioselective Dihydroxylation of Alkenes Catalyzed by 1,4‐Bis(9‐O‐dihydroquinidinyl)phthalazine‐Modified Binaphthyl–Osmium Nanoparticles

AbstractA series of unprecedented binaphthyl–osmium nanoparticles (OsNPs) with chiral modifiers were applied in the heterogeneous asymmetric dihydroxylation of alkenes. A remarkable size effect of the OsNPs, depending on the density of the covalent organic shells, on the reactivity and enantioselectivity of the dihydroxylation reaction was revealed. Successful recycling of the OsNPs was also demonstrated and high reaction efficiency and enantioselectivity were maintained.

Infrared absorption spectroscopy characterization of liquid–solid interfaces: The case of chiral modification of catalysts

An overview is provided here of our work on the characterization of chiral modifiers for the bestowing of enantioselectivity to metal-based hydrogenation catalysts, with specific reference to the so-called Orito reaction. We start with a brief discussion of the use of infrared absorption spectroscopy (IR) for the characterization of chemical species at liquid–solid interfaces, describing the options available as well as the information that can be extracted from such experiments and the advantages and disadvantages associated with the technique. We then summarize the main results that we have reported to date from our IR study of the adsorption of cinchona alkaloids and related compounds from solutions onto platinum surfaces. Several observations are highlighted and placed in context in terms of the existing knowledge and their relevance to catalysis. Key conclusions include the uniqueness of the nature of the adsorbed species when in the presence of the solvent (versus when the uptake is done under vacuum, or versus the pure or dissolved molecules), the fact that each modifier adopts unique and distinct adsorption geometries on the surface and that those change with the concentration of the solution in ways that correlate well with the performance of the catalyst, the potential tendency of at least some of these chiral modifiers to bind to the surface primarily via the nitrogen atom of the amine group, not the aromatic ring as it is often assumed, and the observation that the ability of one modifier to dominate the catalytic chemistry in solutions containing mixtures of two or more of those is linked to their capacity for displacing each other from the surface, which in turn is determined by a balance between the strength of their binding to the surface and their solubility in the liquid solvent.

Chiral PEDOT-Based Enantioselective Electrode Modification Material for Chiral Electrochemical Sensing: Mechanism and Model of Chiral Recognition.

The development of electrochemical methods for enantioselective recognition is a focus of research in pharmaceuticals and biotechnology. In this study, a pair of water-soluble chiral 3,4-ethylenedioxythiophene (EDOT) derivatives, (R)-2'-hydroxymethyl-3,4-ethylenedioxythiophene ((R)-EDTM) and (S)-2'-hydroxymethyl-3,4-ethylenedioxythiophene ((S)-EDTM), were synthesized and electrodeposited on the surface of a glassy carbon electrode (GCE) via current-time (I-t) polymerization in an aqueous LiClO4 electrolyte. These chiral PEDOT polymers were used to fabricate chiral sensors and to investigate the enantioselective recognition of d-/l-3,4-dihydroxyphenylalanine, d-/l-tryptophan, and (R)-/(S)-propranolol enantiomers, respectively. The results indicated that the (R)-PEDTM/GCE sensor showed a higher peak current response toward the levo or (S) forms of the tested enantiomers, while the opposite phenomenon occurred for (S)-PEDTM/GCE. The mechanism of the stereospecific interaction between these enantiomers and the chiral polymers was determined. Therefore, a model of the chiral recognition by the chiral conducting polymer electrodes and an electrochemical method was proposed. The chirality of the enantiomers was confirmed by two parameters: the chirality of the electrode and the peak current response. These findings pave the way for the application of chiral PEDOT as electrode modification material in the electrochemical chiral recognition field.

Mirror-Image Thymidine Discriminates against Incorporation of Deoxyribonucleotide Triphosphate into DNA and Repairs Itself by DNA Polymerases.

DNA polymerases are known to recognize preferably d-nucleotides over l-nucleotides during DNA synthesis. Here, we report that several general DNA polymerases catalyze polymerization reactions of nucleotides directed by the DNA template containing an l-thymidine (l-T). The results display that the 5'-3' primer extension of natural nucleotides get to the end at chiral modification site with Taq and Phanta Max DNA polymerases, but the primer extension proceeds to the end of the template catalyzed by Deep Vent (exo-), Vent (exo-), and Therminator DNA polymerases. Furthermore, templating l-nucleoside displays a lag in the deoxyribonucleotide triphosphate (dNTP) incorporation rates relative to natural template by kinetics analysis, and polymerase chain reactions were inhibited with the DNA template containing two or three consecutive l-Ts. Most interestingly, no single base mutation or mismatch mixture corresponding to the location of l-T in the template was found, which is physiologically significant because they provide a theoretical basis on the involvement of DNA polymerase in the effective repair of l-T that may lead to cytotoxicity.

Correlation between Chiral Modifier Adsorption and Enantioselectivity in Hydrogenation Catalysis.

Infrared absorption spectroscopy performed in situ at the solid-liquid interface revealed that the adsorption on platinum supported catalysts of 1-(1-naphthyl)-ethylamine, which is used as a chiral modifier in hydrogenation catalysis, occurs through the amine group, not the aromatic ring as is widely believed. Comparisons were performed against a set of related modifier compounds with targeted substitutions to help identify the key moiety involved in the adsorption. It was determined that neither naphthalene-based modifiers without amine groups nor those with tertiary amine moieties are capable of adsorbing on the metal surface to any significant extent. A direct correlation was also found between the ability of the amines to adsorb on the platinum surface and their performance as chiral modifiers that impart enantioselectivity to the hydrogenation of α-keto esters such as ethyl pyruvate.

Correlation between Chiral Modifier Adsorption and Enantioselectivity in Hydrogenation Catalysis

AbstractInfrared absorption spectroscopy performed in situ at the solid–liquid interface revealed that the adsorption on platinum supported catalysts of 1‐(1‐naphthyl)‐ethylamine, which is used as a chiral modifier in hydrogenation catalysis, occurs through the amine group, not the aromatic ring as is widely believed. Comparisons were performed against a set of related modifier compounds with targeted substitutions to help identify the key moiety involved in the adsorption. It was determined that neither naphthalene‐based modifiers without amine groups nor those with tertiary amine moieties are capable of adsorbing on the metal surface to any significant extent. A direct correlation was also found between the ability of the amines to adsorb on the platinum surface and their performance as chiral modifiers that impart enantioselectivity to the hydrogenation of α‐keto esters such as ethyl pyruvate.