Deriving the 3D structure of organic molecules from their infrared spectra

The representation of the 3D structure of a molecule by a radial distribution function (RDF) code is described. The use of the RDF code for the simulation of an infrared spectrum by a counterpropagation (CPG) neural network is shown. Furthermore, a CPG network can also be operated in reverse mode: on input of an infrared spectrum an RDF code is obtained for which a 3D structure can be searched in a database. An empirical modelling process is used to refine this 3D structure to obtain a three-dimensional model of the molecular structure that corresponds to the infrared spectrum.     

Automatic assignment of absolute configuration from 1D NMR data

[reaction: see text] Opposite enantiomers exhibit different NMR properties in the presence of an external common chiral element, and a chiral molecule exhibits different NMR properties in the presence of external enantiomeric chiral elements. Automatic prediction of such differences, and comparison with experimental values, leads to the assignment of the absolute configuration. Here two cases are reported, one using a dataset of 80 chiral secondary alcohols esterified with (R)-MTPA and the corresponding (1)H NMR chemical shifts and the other with 94 (13)C NMR chemical shifts of chiral secondary alcohols in two enantiomeric chiral solvents. For the first application, counterpropagation neural networks were trained to predict the sign of the difference between chemical shifts of opposite stereoisomers. The neural networks were trained to process the chirality code of the alcohol as the input, and to give the NMR property as the output. In the second application, similar neural networks were employed, but the property to predict was the difference of chemical shifts in the two enantiomeric solvents. For independent test sets of 20 objects, 100% correct predictions were obtained in both applications concerning the sign of the chemical shifts differences. Additionally, with the second dataset, the difference of chemical shifts in the two enantiomeric solvents was quantitatively predicted, yielding r(2) 0.936 for the test set between the predicted and experimental values.     

The effect of parity violation on kinetic models of enantioselective autocatalysis

A detailed analysis of enantioselective autocatalytic reaction models is carried out using both deterministic and stochastic approaches. The models include the small differences between the total energies of enantiomers (DeltaE(PV) approximately 10(-13) J mol(-1)) that arise due to parity violation. Different possible orders of autocatalysis are considered, and the reasons why the predictions of the stochastic and deterministic approaches are different under certain conditions are explored. The continuous time discrete state (CDS) stochastic approach is clearly superior to the deterministic approach. It is concluded that the small difference between enantiomers caused by DeltaE(PV) cannot be amplified under conditions reasonable for the generation of biological chirality. It also seems highly unlikely that biological chirality was determined by any intrinsic difference between enantiomers.     

Chiral Imidazolium Prolinate Salts as Efficient Synzymatic Organocatalysts for the Asymmetric Aldol Reaction

Chiral imidazolium l-prolinate salts, providing a complex network of supramolecular interaction in a chiral environment, have been studied as synzymatic catalytic systems. They are demonstrated to be green and efficient chiral organocatalysts for direct asymmetric aldol reactions at room temperature. The corresponding aldol products were obtained with moderate to good enantioselectivities. The influence of the presence of chirality in both the imidazolium cation and the prolinate anion on the transfer of chirality from the organocatalyst to the aldol product has been studied. Moreover, interesting match/mismatch situations have been observed regarding configuration of chirality of the two components through the analysis of results for organocatalysts derived from both enantiomers of prolinate (R/S) and the trans/cis isomers for the chiral fragment of the cation. This is associated with differences in the corresponding reaction rates but also to the different tendencies for the formation of aggregates, as evidenced by nonlinear effects studies (NLE). Excellent activities, selectivities, and enantioselectivities could be achieved by an appropriate selection of the structural elements at the cation and anion.     

A [5]HELOL analogue that senses remote chirality in alcohols, phenols, amines, and carboxylic acids

A route is developed to a structural analogue of [5]HELOL, a previously reported helically grooved sensor of remote chirality. It gives the material enantiomerically pure and in multigram quantities. The enantiomers of alcohols, phenols, amines, and carboxylic acids, even when their centers of chirality are remote from any functional groups, can be differentiated by 31P NMR spectroscopic analyses of their reaction products with the chlorophosphite of this material.     

(+)-/(-)-Angelignanine,a pair of neolignan enantiomers with an unprecedented carbon skeleton from an aqueous extract of the Angelica sinensis root head

A pair of neolignan enantiomers with an unprecedented carbon skeleton,(+)-/(-)-angelignanine[(+)-/(-)-1],was isolated as minor components of an aqueous extract of the Angelica sinensis root heads(guitou).Their structures were determined by spectroscopic data analysis and the absolute configurations were assigned by the circular dichroism(CD) exciton chirality method as well as electronic CD quantum calculations.The enantiomers represent the first 2,7'-cyclo-8,9'-neolignans,of which biosynthetic pathways originating from precursors ferulic acid and coniferyl alcohol is proposed.In an in vivo test,both the enantiomers showed significant hypnotic effects at a dose of 10 mg/kg(i.g.).     

Formation of Chiral Structures in UV-Initiated Formose Reaction

It has been found that the UV-initiated formose reaction in an extremely concentrated aqueous solution of formaldehyde gives sugars and other biologically significant chiral compounds with sp³-hybridized carbon atom. The reaction leads to an optically active condensed phase, which is a result of the spontaneous spatial separation of enantiomers in the racemate into the antipodes, similarly to the separation of enantiomers of different chirality sign in the famous Pasteur experiments. In our opinion, such a scenario is as close as possible to the actually realized de novo scenario of synthesis of chiral prebiotic molecules and matrices.     

Self‐Assembled Ultralong Chiral Nanotubes and Tuning of Their Chirality Through the Mixing of Enantiomeric Components

Enantiomeric L ‐ or D ‐glutamic acid based lipids were designed and their self‐assembly was investigated. It was found that at a certain concentration, either L ‐ or D ‐enantiomeric derivatives could self‐assemble in absolute alcohol to form a white organogel, which was composed of ultralong nanotubes with an aspect ratio higher than 1000. Further investigations revealed that these nanotubes were in chiral forms. The chirality of the nanotubes was determined by that of the enantiomers employed. In addition, when D and L enantiomers were mixed in different ratios, the nanotube could be tuned consecutively from nanotubes with a helical seam to nanotwists, the chirality of which being determined by the excess enantiomer in the mixed systems. In the case of an equimolar mixture of the enantiomers, flat nanoplates instead of helical nanotubes or nanotwists were obtained. The FTIR vibrational data and XRD layer‐distance values showed a consecutive change as a function of the enantiomeric excess. It was further revealed that the slightly stronger interaction between D –L enantiomeric pairs than that between D –D or L –L pairs was responsible for the formation of the diverse self‐assembled nanostructures.     

Structures formed by the chiral assembly of racemic mixtures of enantiomers: iodination products of elaidic and oleic acids

The self-assembled monolayer structure of the products of elaidic acid iodination (the racemic mixture of 9,10-(9S,10R)-diiodooctadecanoic acid and 9,10-(9R,10S)-diiodooctadecanoic acid) and the products of oleic acid iodination (the racemic mixture of 9,10-(9R,10R)-diiodooctadecanoic acid and 9,10-(9S,10S)-diiodooctadecanoic acid) are studied by high-resolution scanning tunneling microscopy. For the iodination products of elaidic acid, the separation of enantiomers into distinct chiral domains during the formation of the 2-D crystal on the highly ordered pyrolytic graphite (HOPG) surface is not observed. Instead, within the diiodooctadecanoic acid SAM, each row of molecules is composed of opposite racemates. The two opposite racemates pack alternately inside a row, using different faces to adsorb on the surface. The unit cell is composed of a pair of opposite racemates, forming a heterochiral structure. For the iodination products of oleic acid, the racemic mixture is observed to exhibit quasi-phase separation during the formation of the 2-D crystal on the HOPG surface. Each row is composed of homochiral acid molecules, either the 9,10-(9R,10R)-diiodooctadecanoic acid (R) or the 9,10-(9S,10S)-diiodooctadecanoic acid (S). The R row and the S row pack alternately, with a unit cell composed of four molecules. Two of the molecules in the unit cell are the 9,10-(9R,10R)-diiodooctadecanoic acid (R) molecules; two are the 9,10-(9S,10S)-diiodooctadecanoic acid (S) molecules. In the unit cell, the two molecules that have the same chirality pack antiparallel inside the homochiral row, using different faces to adsorb on the surface. These results suggest that several different types of chiral assembly are possible. Enantiomers with opposite chirality exhibit many chiral assembly patterns, forming heterochiral structures on the surface in addition to separation to form macroscopic chiral domains. By using different conformations, similar enantiomers with opposite chirality will display many chiral assembly patterns to form heterochiral structures on the surface.     

手性化合物的质谱分析研究

运用不含手性碳的非对称化合物Ｓ－ＢＮＰ酸（Ｓ－ｐｈｏｓｐｈｏｒｓａｅｕｒｅ－（１，１＇－ｂｉｎａｐｈｔｈｙｌ－２，２＇－ｄｉｙｌｅｓｔｅｒ））作反应试剂用快原子轰击反应质谱法（ＦＡＢ－ＲＭＳ）测定手性化合物的绝对构型．发现非对称手性化合物可与不对称手性化合物在质谱中发生立体选择性反应，Ｓ－ＢＮＰ酸可作为一种新的反应试剂来测定手性化合物的绝对构型．     

Properties of the material surfaces obtained by pyrolysis of alkanols on boron-enriched controlled porous glasses

Controlled porous glasses (CPG) are often employed as packing materials for gas and liquid chromatography. The characteristic feature of CPG is the presence of surface boron atoms, the concentration of which can easily be changed by appropriate thermal treatment. The use of thermally treated CPG as a support in the pyrolysis of alcohols causes the formation of graphite in the carbon deposit obtained. The properties of thermally treated CPG and the same CPG with a carbon deposit on their surface was investigated by means of the hydrogenolysis reaction of n-butane. The results obtained suggest that the pyrolysis of a constant molar amount of alkanols differing in their chain lengths leads to blocking of the same centres on the CPG surface.     

Inversion of the Supramolecular Chirality of Nanofibrous Structures through Co‐Assembly with Achiral Molecules

To understand the behavior of chiral nanostructures, it is of critical importance to study how achiral molecules regulate the chirality of such nanostructures and what the main driving forces for the regulation processes are. In this work, the supramolecular chirality of helical nanofibers consisting of phenylalanine‐based enantiomers is inverted by achiral bis(pyridinyl) derivatives through co‐assembly. This inversion is mainly mediated by intermolecular hydrogen bonding interactions between the achiral additives and the chiral molecules, which may induce stereoselective interactions and different reorientations for the assembled molecules, as confirmed by calculations. This work not only exemplifies a feasible method to invert the helicity of chiral nanostructures by the addition of achiral molecules, but also provides a method to explore their functions in environments where chiral and achiral molecules are in close proximity.     

Mechanism of asymmetric hydrogenation of alpha-(acylamino)acrylic esters catalyzed by BINAP-ruthenium(II) diacetate

The mechanism of asymmetric hydrogenation of alpha-(acylamino)acrylic esters with Ru(CH(3)COO)(2)[(S)-binap] (BINAP = 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl), giving the S saturated products in >90% ee, has been investigated by means of a kinetic study, deuterium labeling experiments, isotope effect measurements, and NMR and X-ray analysis of certain Ru complexes. The hydrogenation in methanol under a low H2 pressure proceeds via a monohydride-unsaturate mechanism that involves the initial RuH formation followed by a reaction with an olefinic substrate. The migratory insertion in the enamide-RuH chelate complex occurs reversibly and endergonically in an exo manner, giving a five-membered metallacycle intermediate. The cleavage of the Ru-C bond is achieved with either H2 (major) or CH3OH (minor). Both of the pathways result in overall cis hydrogenation products. The hydrogen at C3 is mainly from an H2 molecule, and the C2 hydrogen is from another H2 or protic CH3OH. The major S and minor R enantiomers are produced via the same mechanism involving diastereomeric intermediates. The turnover rate is limited by the step of hydrogenolysis of a half-hydrogenated metallacyclic intermediate. The participation of two different hydrogen donor molecules is in contrast to the pairwise dihydrogenation using a single H2 molecule in the RhI-catalyzed reaction which occurs via a dihydride mechanism. In addition, the sense of asymmetric induction is opposite to that observed with S-BINAP-RhI catalysts. The origin of this phenomenon is interpreted in terms of stereocomplementary models of the enamide/metal chelate complexes. A series of model stoichiometric reactions mimicking the catalytic steps has indicated that most NMR-observable Ru complexes are not directly involved in the catalytic hydrogenation but are reservoirs of real catalytic complexes or even side products that retard the reaction.     

Self-disproportionation of enantiomers via achiral chromatography: a warning and an extra dimension in optical purifications

This tutorial review describes the self-disproportionation of enantiomers (SDE) of chiral, non-racemic compounds, subjected to chromatography on an achiral stationary phase using an achiral eluent, which leads to the substantial enantiomeric enrichment and the corresponding depletion in different fractions, as compared to the enantiomeric composition of the starting material. The physicochemical background of SDE is a dynamic formation of homo- or heterochiral dimeric or oligomeric aggregates of different chromatographic behavior. This phenomenon is of a very general nature as the SDE has been reported for different classes of organic compounds bearing various functional groups and possessing diverse elements of chirality (central, axial and helical chirality). The literature data discussed in this review clearly suggest that SDE via achiral chromatography might be expected for any given chiral enantiomerically enriched compound. This presents two very important issues for organic chemists. First, chromatographic purification of reaction products can lead to erroneous determination of the stereochemical outcome of catalytic asymmetric reactions and second, achiral chromatography can be used as a new, nonconventional method for optical purifications. The latter has tremendous practical potential as the currently available techniques are limited to crystallization or chiral chromatography. However, a further systematic study of SDE is needed to develop understanding of this phenomenon and to design practical chromatographic separation techniques for optical purification of non-racemic mixtures by achiral-phase chromatography.     

Influence of the thermal modification of controlled porosity glass on the affinity chromatography of fungal proteins

Summary The properties and the coverage density of chemically bonded phases depend among others on the properties of their supports. Controlled-porosity glasses (CPG) are materials used as a support of bio-active ligands. Their network mainly consist of SiO₂ as well as of a small amount of B₂O₃ and Na₂O. The characteristic feature of porous glasses is the possibility of a change in the surface boron concentration leading to the change of the properties of their surface.This paper deals with the results of the separation of fungal proteins on packings consisting of vanillin bonded to CPG with different boron concentration on its surface. It appears from the data obtained that the changes in the affinity of the fungal proteins to the packing are related to the extend of the thermal treatment of the CPG. The protein fractions separated by chromatography were confirmed to be homogeneous by poly-acryloamide gel disc electrophoresis.     

Enantioseparation of Chiral Antimycotic Drugs by HPLC with Polysaccharide-Based Chiral Columns and Polar Organic Mobile Phases with Emphasis on Enantiomer Elution Order

The separation of enantiomers of 10 chiral antimycotic drugs was studied on polysaccharide-based chiral columns with polar organic mobile phases. The emphasis was placed on some interesting examples of enantiomer elution order reversal observed depending on the chemistry of the chiral selector, separation temperature, major component, as well as the minor additive in the mobile phase. In particular, it was found that the elution order of enantiomers of chiral drug terconazole was opposite on cellulose- and amylose-based columns with the same pendant group. The affinity pattern of enantiomers of another chiral drug bifonazole was opposite towards to two amylose-based chiral selectors with different pendant groups. The affinity pattern of terconazole enantiomers also changed on some columns when the alcohol-based mobile phase was replaced with acetonitrile. An interesting effect of the minor acidic (formic acid) additives to the mobile phase on the affinity pattern of terconazole enantiomers was observed on Cellulose-2 and Cellulose-4 columns. In addition, a reversal of elution order of bifonazole enantiomers was observed on Amylose-2 column by variation of a separation temperature.     

One Stone for Three Birds‐Rhodium‐Catalyzed Highly Diastereoselective Intramolecular [4+2] Cycloaddition of Optically Active Allene‐1,3‐dienes

RhCl(PPh₃)₃‐catalyzed [4+2] intramolecular cycloaddition of optically active axially chiral allene‐dienes afforded cis‐fused [3.4.0]‐bicyclic products with three chiral centers in good yields with an excellent chemo‐ and diastereoselectivity. A pair of enantiomers of such products was generated highly selectively from both enantiomers of starting allene‐dienes, indicating that the axial chirality dictated the absolute configurations of the three in situ generated chiral centers with a very high efficiency of chirality transfer.     

Hydrogen‐Bond‐Induced Chiral Axis Construction: Theoretical Study of Cinchonine–Thiourea‐Catalyzed Enantioselective Intramolecular Cycloaddition

Theoretical calculations were performed to investigate the mechanism and enantioselectivity of cinchonine–thiourea‐catalyzed intramolecular hetero‐Diels–Alder cycloaddition of ethynylphenol derivatives to afford axial chirality naphthalenylpyran products via a vinylidene ortho‐quinone methide (VQM) intermediate. The results show that this transformation occurs through a reaction pathway involving the deprotonation of the naphthol moiety by the quinuclidine base, intramolecular proton transfer in ammonium naphthalenolate, and [4+2] cycloaddition. It is found that the axial chirality of the VQM intermediate is generated by the protonation step, which affects the enantioselectivity of the reaction. The enantioselectivity for the generation of the VQM intermediate is controlled by steric repulsion with the cinchonine framework, which provides an R‐axial chirality VQM as the major intermediate. Moreover, the enantioselectivity for the axial chirality of the naphthopyran product is controlled by the cycloaddition step, in which an extra hydrogen bond between the naphthalenol and cinchonine moieties leads to a favorable configuration for the generation of the S‐axial chirality naphthopyran product. The calculated enantioselectivity and enantiomeric excesses coincide with experimental observations.     

Enantioselective DNA threading dynamics by phenazine-linked.

The interactions between the stereoisomers of the chiral bis-intercalator [mu-C4(cpdppz)(2)-(phen)(4)Ru(2)](4+) and DNA reveal interesting dynamic discrimination properties. The two enantiomers Delta-Delta and Lambda-Lambda both form very strong complexes with calf thymus DNA with similar thermodynamic affinities. By contrast, they display considerable variations in their binding kinetics. The Delta-Delta enantiomer has higher affinity for calf thymus DNA than for [poly(dA-dT)](2), and the association kinetics of the dimer to DNA, as well as to polynucleotides, requires a multiexponential fitting function. The dissociation reaction, on the other hand, could be described by a single exponential for [poly(dA-dT)](2), whereas two exponentials were required for mixed-sequence DNA. To understand the key mechanistic steps of the reaction, the kinetics was studied at varied salt concentration for different choices of DNA and chirality of the threading complex. The enantiomers were found to have markedly different dissociation rates, the Lambda-Lambda enantiomer dissociating about an order of magnitude faster than the Delta-Delta enantiomer. Also, the salt dependence of the dissociation rate constants differed between the enantiomers, being stronger for the Lambda-Lambda enantiomer than for the Delta-Delta enantiomer. Since the dissociation reaction requires unthreading of bulky parts of the bis-intercalator through the DNA helix, a considerable conformational change of the DNA must be involved, possibly defining the rate-limiting step.