Chromatographic enantioseparation of racemic α-(1-naphthyl)ethylammonium perchlorate by a Merrifield resin-bound enantiomerically pure chiral dimethylpyridino-18-crown-6 ligand

Three novel chiral pyridino-18-crown-6 ligands (S,S)-1, (S,S)-2 and (S,S)-3 were prepared and (S,S)-1 was attached to a Merrifield resin. The resulting adsorbent (S,S)-5 was used as a chiral stationary phase in the chromatographic enantioseparation of racemic α-(1-naphthyl)ethylammonium perchlorate. Also, a new chiral pyridono-18-crown-6 ligand (S,S)-6, used for the synthesis of (S,S)-1 and (S,S)-2, was prepared in two different ways.     

Enantiomerically pure chiral pyridino-crown ethers: synthesis and enantioselectivity toward the enantiomers of α-(1-naphthyl)ethylammonium perchlorate

Seven new enantiomerically pure chiral pyridino-crown ethers (S,S)-4–(R,R)-10 were prepared. Three of them [(S,S)-4, (S,S)-7 and (R,R)-10] contain one, and two of them [(S,S)-5 and (S,S)-8] contain two linker chains with a terminal double bond. These linker chains were connected to the carbon atom at position 9 (opposite the pyridine moiety) of the macrocycle. The terminal double bond of the linker makes it possible to attach these ligands to silica gel to obtain chiral stationary phases (CSPs). The enantioselectivity of the new ligands toward the enantiomers of α-(1-naphthyl)ethylammonium perchlorate (NEA) was also determined by a titration ¹H NMR method.     

A structural analysis of the complexes of (S,S)-dimethylpyridino-18-crown-6 with (R) and (S)-[α-(1-naphthyl)ethyl]ammonium perchlorate by NMR techniques and molecular modeling

Significant - interaction is found in the complexes of (S, S)-dimethylpyridino-18-crown-6 with (R)- and (S)-[-(1-naphthyl)ethyl]ammonium perchlorate. This finding is supported by the¹H NOESY NMR spectral technique, greater chemical shift changes of aromatic protons in both host and guest molecules upon complexation, and by molecular mechanics calculations. Because of the flexibility of the ligand, the tripod hydrogen bonding causes¹³C relaxation times of all periphery carbons to decrease without significant selectivity. Rotational energy barrier calculations of the methyl groups of the complexed ligand also show that the (S, S)-host-(R)-guest is the more stable complex.     

Chiral nickel(II) complexes in the preparation of 11C- and 18F-labelled enantiomerically pure α-amino acids

Positron emission tomography (PET) utilises positron emitting radiopharmaceuticals in the study of metabolic and physiological processes. FDG-PET is a useful technique for tumour detection; however FDG has disadvantages. The incorporation of labelled amino acids into brain tumours and into some other organs with high physiological consumption of glucose is a superior diagnostic method due to its much higher selectivity compared to FDG. A Ni(II) complex with a Schiff base of BPB and glycine was one of the first glycine synthons used for asymmetric synthesis of carbon-11 and fluorine-18 labelled α-amino acids. A similar complex was employed for routine preparation of [(18)F]FET. Physico-chemical investigations allowed us to design modified complexes with much stronger stereodiscriminative power including stereospecific ones. Chiral nickel complexes are also used for the preparation of tailored amino acids for the incorporation into peptides followed by labelling the peptides with fluorine-18 labelled "click" reagents. This review covers PET applications of Ni(II) complexes of Schiff base of BPB and α-amino acids from 1989 to date.     

Determination of endocrine-disrupting chemicals in the liquid and solid phases of activated sludge by solid phase extraction and gas chromatography–mass spectrometry

The highly complex matrix of activated sludge in sewage treatment plants (STPs) makes it difficult to detect endocrine-disrupting chemicals (EDCs) which are usually present at low concentration levels. To date, no literature has reported the concentrations of steroid estrogens in activated sludge in China and very limited data are available worldwide. In this work, a highly selective and sensitive analytical method was developed for simultaneous determination of two classes of EDCs, including estrone (E1), 17β-estradiol (E2), estriol (E3), 17α-ethynylestradiol (EE2), 4-nonylphenol (NP) and bisphenol A (BPA), in the liquid and solid phases of activated sludge. The procedures for sample preparation, extracts derivatization, and gas chromatography–mass spectrometry (GC–MS) quantification were all optimized to effectively determine target EDCs while minimizing matrix interference. The developed method showed good calibration linearity, recovery, precision, and a low limit of quantification (LOQ) for all selected EDCs in both liquid and solid phases of activated sludge. It was successfully applied to determine the concentrations of EDCs in activated sludge samples from two STPs located in Beijing and Shanghai of China, respectively.     

Conductance Study of the Binding of K+ by Dibenzo-pyridino-18-crown-6 and 1,10-N,N′-didecyl-diaza-18-crown-6 in Acetonitrile

The binding of K+ by dibenzo-pyridino-18-crown-6 (B2-py-18-C-6) and1,10-N,N-didecyl-diaza-18-crown-6 (22-DD) has been studiedconductometrically at 10, 15, 20 and 25 °C in acetonitrile. Thecomplexes formed were assumed to have 1 : 1 stoichiometry. The complexes ofK+ with 18-crown-6 (18-C-6) and dibenzo-18-crown-6 (B2-18-C-6) were alsostudied for comparison purposes. The stability constant, K, of a givencomplex and its molar conductance, c, were obtained by subjectingthe conductance data to a non-linear least-squares curve fitting procedure.The values of the enthalpy change, H, the entropy change, Sand the Gibbs free energy, G, associated with the formation of the 1: 1 complexes were derived and compared with relevant literature data. Thevalues of G at 25 °C indicate that the binding capacity of thefour macrocycles follows the order 18-C-6 > 22-DD > B2-18-C-6 >B2-py-18-C-6. The difference between the molar ionic conductance of the freeK+ cation and that of the bound cation, KL+, was estimated and the trend insuch differences correlates with the molecular size of the macrocycle, L.     

Enantiomeric recognition of carboxylic anions by a library of neutral receptors derived from α-amino acids and o-phenylenediamine

A library of eight neutral anion receptors consisting of α-amino acid esters attached to o-phenylenediamine by urea groups was synthesized and analysed in terms of capacity for chiral recognition of carboxylates. The NMR titrations revealed that the association constants of complexes consisting of a chiral guest and a chiral host are two orders of magnitude lower than those of achiral partners. Diverse substituents in the receptor structure modify both the affinities and enantioselectivities.     

Preparation and crystal structure of bis(dibenzo-18-crown-6)-(tetrachlorocuprato(II)-Cl,Cl′, Cl″, Cl‴)dipotassium diaqua(dibenzo-18-crown-6)potassium dichlorocuprate(I)-dibenzo-18-crown-6

New mixed complex compound bis(dibenzo-18-crown-6)(tetrachlorocuprato(II)-Cl, Cl′, Cl″, Cl?) dipotassium diaqua(dibenzo-18-crown-6)potassium dichlorocuprate(I)dibenzo-18-crown-6 [(CuCl₄)[K(Db18C6)]₂]·[K(Db18C6)(H₂O)₂]⁺·[CuCl₂]^?·Db18C6 was prepared and its structure was studied by the X-ray structural analysis. The structure was found to be disordered. The asymmetric part of its unit cell contains 1/4 of each of its four components. For a given [CuCl₄]^2? anion its Cu²⁺ cation is disordered over two equally probable positions and its independent Cl atom is disordered over three positions differing by occupancy. In this structure two [K(Db18C6)]⁺ fragment of the complex molecule and the complex cation [K(Db18C6)(H₂O)₂]⁺ are of guest-host type with K⁺ cation as the guest. In this structure the statistically disordered alternating cations and Db18C6 molecules form infinite chains. The statistically disordered [CuCl₂]^? anions also form infinite chains.     

Syntheses and crystal structures of (18-crown-6)bis(perchlorato-O,O′)strontium and (18-crown-6)bis(perchlorato-O,O′)barium

Two complexes, namely, (18-crown-6)bis(perchlorato-O,O′)strontium (I) and (18-crown-6)bis(perchlorato-O,O′)barium (II), are synthesized. Their crystal structures are determined by X-ray diffraction analysis. The structures of I (space group P2₁/c, a = 15.266 Å, b = 11.080 Å, c = 13.235 Å, β = 109.20°, Z = 4) and II (space group P2₁/n, a = 8.330 Å, b = 11.202 Å, c = 11.752 Å, β = 98.38°, Z = 2) are solved by a direct method and refined by the full-matrix least-squares method in the anisotropic approximation to R = 0.077 (I) and 0.041 (II) against 3714 (I) and 2478 (II) independent reflections (CAD-4 diffractometer, λMoK _α radiation). Complex molecules [Sr(18C6)(ClO₄)₂] in the structure of I and [Ba(18C6)(ClO₄)₂] in II (in the inversion center)—are of the host-guest type. The Sr²⁺ or Ba²⁺ cation is localized in the center of a cavity of the 18-crown-6 ligand and coordinated by its all six O atoms. In compounds I and II, the coordination polyhedron of the Sr²⁺ and Ba²⁺ cations (coordination number 10) can be described as a distorted hexagonal bipyramid with two bifurcated vertices at two O atoms of two ClO ₄ ^? ligands, which are disordered in I and II and each of them has two orientations.     

Separation performance and recognition mechanism of mono(6-deoxy-imino)-β-cyclodextrins chiral stationary phases in high-performance liquid chromatography

Different substituent groups were introduced onto the rim of β-cyclodextrin through rigid CN bonds to form a series of imino-modified β-cyclodextrin derivatives: mono(6-deoxy-phenylimino)-β-cyclodextrin (BCD), mono(6-deoxy-isopropylimino)-β-cyclodextrin (YBCD), mono(6-deoxy-N-1-phenylethylimino)-β-cyclodextrin (R-,S-BYCD), mono[6-deoxy-N-1-(2-hydroxyl)-phenylethylimino]-β-cyclodextrin (R-,S-PGCD), heptakis(2,6-o-diamyl-6-deoxy-phenylimino)-β-cyclodextrin (WBCD), heptakis(2,6-o-diamyl-6-deoxyisopropylimino)-β-cyclodextrin (WYBCD) and heptakis[2,6-o-diamyl-6-deoxy-R-(-)-N-1-phenylethylimino)-β-cyclodextrin (WRBYCD). The obtained derivatives were then bonded to silica gel and used in high-performance liquid chromatography (HPLC) as chiral stationary phases (CSPs). The separation performance of these CSPs was examined by separating disubstituted benzenes, amino acids, ferrocene derivatives andchiral aromatic alcohol compounds. Satisfactory separation results were obtained for most of the compounds. The values for selectivity factors can reach up to 8.50 and 8.16 for separating positional isomers and ferrocene derivatives, respectively, and the best resolution was 6.89 for aromatic alcohol derivative separations. Molecular dynamics (MD) simulations were carried out for chiral discrimination of rac-N-benzoyl-phenylglycinol on S-PGCD CSP to study the recognition mechanism. MD simulation results show that the average free-energy of interaction is −1304.83 kcal/mol for the l-enantiomer and S-PGCD and −1324.23 kcal/mol for the d-enantiomer and S-PGCD. In the recognition stage, the l-enantiomer moves along the exterior of the cyclodextrin cavity from the wider edge to the narrower edge of cyclodextrin whereas the d-enantiomer moves slightly towards the cavity. The l-enantiomer thus is separated first due to weaker interaction with S-PGCD.     

Evaluation of α-fetoprotein (AFP) in human serum by chemiluminescence enzyme immunoassay with magnetic particles and coated tubes as solid phases

In this work, the monoclonal antibodies (McAbs) to α-fetoprotein (AFP) were immobilized on two different solid phases, i.e., magnetic particles (MP) and coated tubes (CT). Based on this, a MP based chemiluminescence enzyme immunoassay (MP-CLEIA) and a CT based CLEIA (CT-CLEIA) were proposed for the evaluation of AFP in human serum and their analytical merits were studied and compared. By detailed discussion of several performance variants, including the concentration of immobilized McAb, dilution ratio of horseradish peroxidase (HRP) labeled McAb (HRP-McAb), total assay time, substrate volume, chemiluminescent kinetics, and hook effect concentration, the advantages of MP-CLEIA became conspicuously apparent. Moreover, in the presence of MP, the catalytic activity of labeled enzyme was kept to high extent and the stability of immunoreagents was satisfied. Finally, 59 human serum samples were detected by the MP-CLEIA and a good correlation was obtained when comparing the results with that from a commercial electrochemiluminescence immunoassay kit.     

Stability and structure in solution of potassium and barium complexes with N,N’-diaryldiaza-18-crown-6: Crystal structure of N,N’-Bis(4-dimethylaminophenyl)diaza-18-crown-6 and its complex with barium perchlorate

It has been shown that N,N’-diaryldiaza-18-crown-6 ethers with p-dimethylamino-and p-methoxy groups in the benzene ring (aryl is 4-Mc₂NC₆H₄) (I) and 4-MeOC₆H₄ (II) form complexes with potassium and barium salts. The influence of these salts on the UV and ¹H NMR spectra of crown ethers I and II has been studied. The stability constants (logβ) of the complexes increase in the series II · Ba(ClO₄)₂ (2.0), I · Ba(ClO₄)₂ (2.3), II · KBr (2.8), I · KBr (3.0). N,N’-bis(4-dimethylphenylamine)diaza-18-crown-6 (L, I) and its complex with barium perchlorate Ba(ClO₄)₂ · L (III) are characterized by X-ray crystallography. The crystals of I are monoclinic: a = 13.778(2) Å, b = 5.9731(9) Å, c = 17.542(3) Å, β = 106.65(1)°, V = 1383.1(4) ų, Z = 2, space group P2₁/n, R = 0.0374 for 990 reflections with I > 2σ(I). The crystals of III are monoclinic: a = 17.275(4) Å, b = 8.017(2) Å, c = 26.935(4) Å, β = 100.47(2)°, V = 3669(1) ų, Z = 4, space group C2/c, R = 0.0320 for 1897 reflections with I > 2σ(I). The molecules of I and III are centrosymmetric. In III, the Ba atom is in the center of substituted diaza-18-crown-6 (DA18C6). The Ba atom is coordinated by all six donor atoms of diaza-18-crown-6 (av. Ba-O, 2.779(3) Å; Ba-N, 3.004(4) Å) and four oxygen atoms of two asymmetrically bound perchlorate groups (Ba-O, 2.832(4) and 3.031(4) Å) arranged below and above the plane of substituted diaza-18-crown-6. The conformations of the macrocycle in free and coordinated L are different.     

Enthalpy parameters for interaction of small peptides with 18-crown-6 and aza-18-crown-6 in water at 25°C

Enthalpies of dilution have been determined for binary aqueous solutions of 1-aza-18-crown-6 as well as for ternary aqueous solutions containing glycine, glycylglycine, glycyl-L--alanine, L--alanyl-glycine, L--alanyl-L--alanine, DL--alanyl-DL--alanine, trialanine and 18-crown-6 and/or 1-aza-18-crown-6 and or 1,10-diaza-18-crown-6 at 25°C. The results have been treated by the McMillan-Mayer approach in order to obtain enthalpic virial coefficients for homotactic and heterotactic interactions. A significant exo-effect is demonstrated by the enthalpically favorable interaction between peptides and the 18-crown-6. The additivity of the positive alanyl group contribution toh _xy has been confirmed on the basis of oligomeric data. The influence on the enthalpy of the 18-crown-6-peptide interaction of the methyl group position, in relation to the ammonium group in peptides, has been found to result in the exo-effect decreasing with a decrease of this distance. Some decrease in enthalpy of L--alanyl-L--alanine and DL--alanyl-DL--alanine by 18-crown-6 has been observed as well.Deceased.     

Molecular and crystal structure of 1∶1 guest-host bis(hexafluoroacetylacetonato)calcium complex with 18-crown-6

We have carried out an X-ray structural study of the title complex (a CAD-4F diffractometer, MoK, graphite monochromator, /2 scan mode, _max, direct methods, 1465 reflections, R=0.036). Crystals are monoclinic with a=17.971(13), b=13.475(3), c=13.379(8) , =106.67(5)°, Z=4CaO₁₀C₂₂H₂₆F₁₂, space group C2/c, d _calc =1.537 g/cm³. The complex (C₂ symmetry) has a molecular structure and belongs to the guest-host type. The Ca atom is located in the center of the 18-crown-6 cavity; bidentate hexafluoroacetylacetonate guest ligands occupy the trans-positions relative to the plane of a maxidentate macrocycle. The Ca–O distances in a ten-vertex Ca polyhedron are 2.474–2.666 . The macrocycle conformation is characterized by six gauche C–C bonds and two gauche and ten trans C–O bonds. The dihedral COCC angle differs significantly (by 38.1°) from the angle of 60°, which is common to a gauche conformation. The six-membered cycle formed by oxygen atoms has a twist form with the annular O–O distances of 5.132–5.329 . Structural features explaining an easy sublimation of the compound are discussed.X-ray structural analysis and the interpretation of results.Synthesis of single crystals.Institute of Inorganic Chemistry, Siberian Branch, Russian Academy of Sciences. Translated fromZhurnal Strukturnoi Khimii, Vol. 34, No. 6, pp. 56–65, November–December 1993.Translated by T. Yudanova     

Molecular recognition as shown by the solvent extraction of (R)- and (S)-[α-(1-naphthyl)ethyl] ammonium picrate or orange 2 by chiral pyridino-crown ethers

A solvent extraction technique was used to determine equilibrium constants for the reactions occurring when an aqueous phase containing [-(1-naphthyl)ethyl]ammonium ions [(R)- and (S-isomers] is equilibrated with a chloroform phase containing chiral substituted pyridino-18-crown-6 ligands. Selectivity coefficients and equilibrium constants for the interactions in chloroform solutions were calculated. The existence of two different types of ion pairs separated by the macrocycle molecule was detected from the UV spectra. One ion pair has a nearly complete separation of the picrate anion from the protonated amine by the ligand. The other has the picrate ion only partly separated from the cation by the macrocycle.     

Enantioseparation of α-amino acids on an 18-crown-6-tetracarboxylic acid-bonded silica by capillary electrochromatography

(−)-(18-Crown-6)-2,3,11,12-tetracarboxylic acid-bonded silica was used as the chiral stationary phase in capillary electrochromatography (CEC) for enantioseparation of some α-amino acids. Separation data in CEC were measured in mobile phases of varying pH, and composition of methanol and buffer, and compared with those in capillary liquid chromatography (CLC). In CEC better enantioseparation was generally obtained in the eluent of lower pH, higher buffer concentration and intermediate MeOH content, usually at the expense of analysis time. CEC showed generally better enantioselectivity and resolutions than CLC for the amino acids investigated.     

Separation of 18α(H)-, 18β(H)-oleanane and lupane by comprehensive two-dimensional gas chromatography

18α(H)-, 18β(H)-oleanane and lupane are angiosperm-derived biomarkers that are used as age indicators for the Late Cretaceous onwards when the first proliferation of angiosperms occurred. In addition, the 18α(H)-/18β(H)-oleanane ratio is employed as a thermal maturity parameter of crude oil. However, evidence has shown that accurate quantification of these compounds has been impeded by inadequate chromatographic separation by traditional one-dimensional gas chromatography. In this study, we present the separation of 18α(H)-, 18β(H)-oleanane and lupane with comprehensive two-dimensional gas chromatography (GC×GC). Furthermore, it was observed that 18β(H)-oleanane elutes earlier than 18α(H)-oleanane in second dimension (polarity) which we attribute to steric hindrance effects. Two GC conditions have been developed in order to achieve baseline separation of the triterpenoids of interest in complex mixtures such as sediment extracts and crude oils.     

Sequential Analysis of α-Glucooligosaccharides with α-(1→4) and α-(1→6) Linkages by Negative Ion Q-TOF MS/MS Spectrometry

Negative ion Q-TOF MS/MS spectra are shown to be very useful for sequential analysis of the glycosidic linkage in the α-gluco-oligosaccharides (DP 3-6) derived from an amylopectin molecule. The composition of the fragmentation ions generated from these compounds enabled us to distinguish two kinds of glycosidic linkage, α-(1→4) and α-(1→6), at same time to determine the glucose sequence from the reducing end of the oligosaccharide.     

A thermodynamic study of enantiomeric recognition of organic ammonium cations by pyridino-18-crown-6 type ligands in methanol and a 1: 1 methanol-1,2-dichloroethane mixture at 25.0°C

LogK, H, andTS values for interactions of (R) and (S) enantiomers of -(1-naphthyl)ethylammonium perchlorate (NapEt), -phenylethylammonium perchlorate (PhEt), and the hydrogen perchlorate salt of 2-amino-2-phenylethanol (PhEtOH) with a series of chiral and achiral pyridino-18-crown-6 type ligands and 18-crown-6 (18C6) were determined from calorimetric titration data valid in methanol and in a 1: 1 (v/v) methanol-1,2-dichloroethane (MeOH-1,2-DCE) mixture at 25.0°C. In the MeOH-1,2-DCE solvent mixture, the chiral macrocyclic ligands exhibit excellent recognition for enantiomers of the three organic ammonium cations as shown by large differences in logK values ( logK) which range from 0.4 to 0.6 (2.5- to 4.0-fold difference in binding constants). The logK values in the solvent mixture MeOH-1,2-DCE are increased by 0.1–0.5 logK units over those in absolute methanol, indicating a favorable effect of 1,2-dichloroethane on enantiomeric recognition. In 1,2-dichloroethane, however, the interactions are too strong (logK>6) to observe the degree of recognition by a direct calorimetric method. Complexation of organic ammonium cations by these macrocyclic ligands is driven by favorable enthalpy changes. The entropy changes ure unfavorable in all cases. The thermodynamic origin of enantiomeric recognition for NapEt in 1:1 (v/v) MeOH-1,2-DCE is enthalpic, but those for PhEt and PhEtOH are entropic. Effects of the ligand structure and flexibility and of the organic cation structure on recognition and complex stability are discussed on the basis of the thermodynamic quantities. Different thermodynamic behaviors of achiral 5 and 18C6 from those of chiral macrocyclic ligands indicate a difference between chiral and achiral macrocycle interactions with the chiral organic ammonium cations. The different thermodynamic behavior of NapEt enantiomers compared to those of PhEt and PhEtOH enantiomers supports the idea that the solution complex conformation of NapEt is different from those of PhEt and PhEtOH. - interaction is absent for the PhEt and PhEtOH complexes with diesterpyridino-18-crown-6 ligands in solution. Therefore, the higher degree of enantiomeric recognition for NapEt than for either PhEt or PhEtOH by these chiral macrocyclic ligands is a result of the presence of - interaction in the NapEt system.     

133Cs NMR Study of Cs+ Ion Complexes with?Aza-18-crown-6, Diaza-18-crown-6 and?Dibenzyldiaza-18-crown-6 in Binary Acetonitrile?CNitromethane Mixtures

Cesium-133 nuclear magnetic resonance spectroscopy was used as a sensitive probe to investigate the stoichiometry and stability of Cs⁺ ion complexes with aza-18-crown-6 (A18C6), diaza-18-crown-6 (DA18C6) and dibenzylediaza-18-crown-6 (DBzDA18C6) in different binary acetonitrile?Cnitromethane mixtures. In all cases, the exchange between free and complexed cesium ion was fast on the NMR time scale and only a single population average resonance was observed. The ¹³³Cs chemical shift?Cmole ratio data indicated that the cesium ion forms 1:1 cation?Cligand complexes with the investigated aza-crowns in all acetonitrile?Cnitromethane mixtures. The formation constants of the resulting complexes were evaluated from computer fitting of the chemical shift?Cmole ratio data. The stability of the resulting 1:1 complexes with Cs⁺ were found to vary in the order A18C6 > DBzDA18C6 > DA18C6. In all cases, there is the inverse relationship between the complex stability constants and the amount of acetonitrile in the mixed solvent.