Diyl Hydrogen Phosphate Research Articles

Comparison of structures and properties of lyotropic cholesteric phases induced by center and axial chiral compounds

We studied the phase chirality in disklike lyotropic cholesteric (ChD) phases which were obtained by adding center and axial chiral dopants to achiral lyotropic nematic (ND) host phases. In a lyotropic nematic matrix of the ND phase in the hexadecyldimethylethyl-ammonium bromide/water/n-decanol ternary system, a ChD phase was induced by adding center chiral sterols (cholesterol, prednisolon, taurocholic acid) and the axial optically active compound R(−)-1,1′- binaphthalene-2,2′-diyl-hydrogen phosphate (BDP). The helical twisting power (HTP) of BDP is generally lower than the HTP of inducing substances with center chirality, such as cholesterol, prednisolon, etc. At constant composition of the ND phase, the helix lengths were determined from the ordered fingerprint texture, the so-called “spaghetti-like texture” seen in polarizing microscopy. The reciprocal helix lengths change linearly with the BDP concentration. The properties of the ChD phase (textures, helix lengths, micelle parameters) induced by the chiral compounds and changed by the composition of host phases give information on the mechanism of chirality transfer from the molecular level to that of the micellar aggregates and, eventually, to the liquid-crystalline superstructure. The structure in the ChD phase was described in the form of micelle parameters. For helix formation a minimum concentration of the chiral compounds is necessary. During the helix formation the number of micelles per helix length changes as a function of the concentration of the center and axial chiral molecules. The first step during the formation of the ChD phase is the solubilization of dopants into the micelles. Interaction between the optically active molecules then leads to the formation of hydrogen bridges between adjacent optically active molecules in the helical stack.

NMR Study of the Interaction of Monomeric and Polymeric Chiral Surfactants with (R)- and (S)-1,1‘-Binaphthyl-2,2‘-diyl Hydrogen Phosphate

Chiral discrimination of enantiomers of 1,1‘-binaphthyl-2,2‘-diyl hydrogen phosphate (BNDHP) by monomeric chiral surfactants (CS), sodium N-undecylenyl-l-valine-l-leucine and sodium N-undecylenyl-l...

Resolution of (±)-threo-Methylphenidate with (R)-(−)-Binaphthyl-2,2‘-diyl Hydrogen Phosphate: 0.5 M Equiv of Resolving Agent Is Better than 1 M Equiv

Resolution of (±)-threo-methylphenidate (1) with 0.5 M equiv of (R)-(−)-binaphthyl-2,2‘-diyl hydrogen phosphate (4) is described. Use of 0.5 M equiv of 4 was found to be better than 1 M equiv for the resolution of (±)-threo-methylphenidate (1) under different conditions to yield diastereomeric (2R,2‘R)-threo-methylphenidate·(R)-(−)-binaphthyl-2,2‘-diyl hydrogen phosphate salt (3) with excellent enantiopurity. The diastereomeric salt 3 afforded pure (2R,2‘R)-(+)-threo-methylphenidate hydrochloride (2) in high enantiopurity and yield.

Equilibrium binding model of bile salt-mediated chiral micellar electrokinetic capillary chromatography.

Optimum concentration of bile salts in chiral separations depends on both the aggregation properties of the surfactant and the stability of the analyte-micelle complexes. An equilibrium model is proposed in which these two effects are treated separately. First the aggregation constants should be determined under the experimental conditions of the chiral MEKC analysis. With these data, the equilibrium concentrations of bile salt aggregates can be calculated at any total surfactant concentration. Using the Offord equation to approximate the mobilities of the enantiomer-bile salt complexes, a model function has been derived to fit the experimental mobilities. The method yields the binding constants of the enantiomers to each aggregate present. Those species are assumed to be important in the chiral recognition process, which have significantly different stability constants for the enantiomers. The method is demonstrated by the chiral separation of R- and S-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate with sodium taurodeoxycholate. Based on the calculated binding constants, tetrameric aggregates are assumed to be the discriminating species, while no significant difference in enantiomer binding to dimers was found.

Chiroselective electron transfer at enantiomer-capped ZnO nanocrystalline surfaces

Chiral recognition of amino acid, d- and l-tryptophan, is achieved using (R)-(−)- or (S)-(+)-1,1′-binaphthyl-2,2′-diylhydrogen phosphate (BHP) -capped quantized ZnO nanocrystallites as a fluorescent sensor. The chiroselective electron transfer is caused by the formation of the BHP capping layer on the surface of ZnO nanocrystallites. The ability for chiral recognition depends on the surface coverage and binding strength of the capping molecules on the nanocrystalline surface. Structural analysis of the capping molecules on the surface using circular dichroic spectra proved that screwness of the chiral molecules depends on the surface coverage. The ability of the BHP-capped ZnO system was improved when a well-packed surface capping layer of one enantiomeric form of chiral molecules was formed on the surface of ZnO nanocrystallites.

Amino acid order in polymeric dipeptide surfactants: effect on physical properties and enantioselectivity.

The effect of amino acid order on chiral selectivity in polymeric dipeptide surfactants, as well as the physical properties of the surfactants, is investigated. An understanding of enantioselectivity of such dipeptide surfactants is crucial to the design of more efficient polymeric surfactants and has implications in other areas of research such as enantioselective interactions of amino acid based compounds (i.e., enzymes, hemoglobin, antibodies, etc.). It should be noted that such polymeric surfactants are not easily crystallized. Therefore, in a manner similar to the study of proteins, fluorescence spectroscopy is a powerful tool used to study the structure-function relationship of these polymeric surfactants. The microenvironments inside the core of 18 polymeric surfactants were characterized using the environmentally sensitive probes pyrene and 6-propionyl-2-(dimethylamino)naphthalene (Prodan). The surfactants examined in this study include all possible dipeptide combinations of the L-form of alanine, valine, and leucine and the achiral amino acid glycine (except glycine-glycine) as well as the single amino acid surfactants of alanine, valine, and leucine. The results of the fluorescent probe studies led to a proposed structure of the polymeric dipeptide surfactants in solution. The implications of the proposed structure for chiral selectivity were tested with two model atropisomers, (+/-)1,1'-bi-2-naphthol and (+/-)1,1'-bi-2-naphthyl-2,2'-diyl hydrogen phosphate, using capillary electrokinetic chromatography.

Nonaqueous capillary electrophoresis chiral separations with quaternary ammonium β-cyclodextrin

Chiral separation of nonsteroidal anti-inflammatory drugs (profens), 1,1′-binaphthyl-2,2′-diyl-hydrogen phosphate, N-[1-(1-naphthyl)ethyl]phthalamic acid, and derivatized amino acids by a cationic cyclodextrin, quaternary ammonium β-cyclodextrin (QA-β-CD), was investigated by capillary electrophoresis (CE) in both aqueous and nonaqueous media. Several profens and amino acids could only be separated by QA-β-CD in pure formamide system. No chiral separation of the profens was achieved in the following solvents: N-methylformamide, methanol, dimethyl sulfoxide, and water; however, chiral separations of most of the amino acids were obtained in all of these solvents. The effects of other experimental parameters such as the CD concentration and apparent pH (pH*) were also investigated. The first application of nonaqueous CE chiral separation of ketoprofen in a commercially available sample, Actron, was also examined. In addition, the reversal of electroosmotic flow by QA-β-CD was observed in water, formamide, N-methylformamide, methanol, and dimethyl sulfoxide media.

Chiral Separation of (R,S)-1,1′-Binaphthyl-2,2′-diyl Hydrogenphosphate by Capillary Electrophoresis Using Monosaccharides as Chiral Selectors

Monosaccharides were investigated as chiral selectors in capillary electrophoresis of binaphthyl compounds. Among monosaccharides tested, glucose, mannose and their derivatives, except for methyl-β-D-glucopyranoside, were found to be effective for direct separation of racemic mixture of 1,1′-binaphthyl-2,2′-diyl hydrogenphosphate (BNP). D-Forms of galactose, sorbose, fructose, ribose, arabinose and xylose failed chiral separation of BNP. We tentatively concluded that monosaccharides (in the case of D-forms) must satisfy the following structural requirements for successful chiral separation of BNP enantiomers: (1) oxygen atom at C-1 is in α-configuration, (2) -OH group at C-4 is downward configurated and (3) the presence of a -CH2OH or -CH3 group at C-5. Thus, in the case of D-glucose, the chiral separation of BNP is anticipated to be achieved predominantly through the hydrogen bonding between oxygen atom at C-1 and hydrogen atom of -OH group at C-4 on D-glucose and hydrogenphosphate moiety of BNP.

Enantioseparation of atropisomeric 1,1?-binaphthyl-2,2?-diyl hydrogen phosphate in capillary electrophoresis by using di- and oligosaccharides as chiral selectors: di- and oligosaccharide chiral selectors in capillary electrophoresis

Twelve different disaccharides and a series of noncyclic malto- and cello-oligosaccharides were used as chiral selectors in capillary electrophoresis (CE). Most saccharides resolved the enantiomers of atropisomeric 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BDHP) depending on the type (alpha or beta) and position of the linkage between monosaccharides. The effect of chain length of malto- and cello-oligosaccharides on enantioseparation of BDHP was also investigated. The nature of cations in background electrolytes affected significantly the separation of BDHP enantiomers.

Enantioseparation of atropisomeric 1,1?-binaphthyl-2,2?-diyl hydrogen phosphate in capillary electrophoresis by using di- and oligosaccharides as chiral selectors: di- and oligosaccharide chiral selectors in capillary electrophoresis

Enantioseparation of atropisomeric 1,1?-binaphthyl-2,2?-diyl hydrogen phosphate in capillary electrophoresis by using di- and oligosaccharides as chiral selectors: di- and oligosaccharide chiral selectors in capillary electrophoresis

Enantioseparation of atropisomeric 1,1′‐binaphthyl‐2,2′‐diyl hydrogen phosphate in capillary electrophoresis by using di‐ and oligosaccharides as chiral selectors: di‐ and oligosaccharide chiral selectors in capillary electrophoresis

Enantioseparation of atropisomeric 1,1′‐binaphthyl‐2,2′‐diyl hydrogen phosphate in capillary electrophoresis by using di‐ and oligosaccharides as chiral selectors: di‐ and oligosaccharide chiral selectors in capillary electrophoresis

Electron Transfer Reactions of Radical Cation and Anion of (R)-(−)-1,1‘-Binaphthyl-2,2‘-diyl Hydrogen Phosphate in Aqueous Solution. A Pulse Radiolysis Study

(R)-(−)-1,1‘-Binaphthyl-2,2‘-diyl hydrogen phosphate (BiNPO4H) forms radical anions (λmax = 460 nm and e460 = 8600 L mol-1 cm-1) on reaction with hydrated electrons. The radical anion undergoes acid-catalyzed protonation with a rate constant of (5.7 ± 0.9) × 109 L mol-1 s-1 to form H-adduct, which has absorption at λmax = 410 nm. A similar adduct but having a slightly different absorption λmax = 405 nm (e405 = 2900 L mol-1 cm-1) is formed on the addition of H atoms to BiNPO4H. Addition of OH• radicals to BiNPO4- also formed an adduct which absorbs at λmax = 405 nm (e405 = 3100 L mol-1 cm-1). Oxidation of BiNPO4- with strong oxidizing radicals such as SO4•-, Tl2+ and Cl2•- led to the formation of the radical cation. It is also formed by dehydroxylation of the OH-adduct in acidic solution. The radical cation has a broad absorption spectrum with peaks at 340, 405, 460, and 630 nm (e630 = 2000 L mol-1 cm-1). It decays with a rate constant of 5 × 104 s-1. Reduction potentials of the radical cation and the anio...

Enantioseparation using selected polysaccharides as chiral buffer additives in capillary electrophoresis

Selected water-soluble, native polysaccharides – such as amylose, laminaran, pullulan – and derivatized polysaccharides – methyl cellulose, hydroxypropyl cellulose, and carboxymethyl amylose sodium salt (CM-Am) – were investigated as chiral selectors in capillary electrophoresis. Effects of degree of polymerization and concentration of amylose on the separation of enantiomers of 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (BDHP) and a chiral cardiovascular drug cis-diltiazem were also studied. Pullulan and amyloses used in this study showed the same migration order for enantiomers of BDHP. In contrast, the migration order of BDHP enantiomers for cellulose derivatives and laminaran as well as with β-cyclodextrin was opposite to that for amylose and pullulan. The enantioseparation of several chiral drugs was also performed using high-molecular-mass amylose (Am-4900) and CM-Am.

Dextran and dextrin as chiral selectors in capillary zone electrophoresis

Polysaccharides such as dextrins, which are mixtures of linear α-(1,4)-linked D-glucose polymers, and dextrans, which are polymers of D-glucose units linked predominantly by α-(1,6) bonds, have been employed as chiral selectors in the capillary electrophoretic (CE) separation of enantiomers. Because these polymers are electrically neutral, the method is applicable to ionic compounds. Among the compounds tested the enantiomers of ibuprofen, naproxen, warfarin and the diltiazem synthetic intermediate 1,1′-binaphthyl-2,2′diyl hydrogen phosphate, which are anionic compounds, were successfully recognized by employing dextran or dextrin under neutral conditions. The enantiomers of basic or cationic drugs such as timepidium, primaquine, sulconazole, trimetoquinol, diltiazem and clentiazem were also successfully separated under acidic conditions. The effects of molecular mass and polysaccharide concentration on enantioselectivity were investigated. High concentrations of these polymers, especially dextrin, led to delayed migration times after repeated injections of the solutes into an uncoated capillary under neutral conditions. Consequently the capillary washing process was found to be very important to obtaining reproducible migration times in the system. A coated capillary was also investigated to overcome this problem. Finally, the method using electrically neutral polysaccharides was applied to the testing of the optical purity of the drug substances.

Application of sulfated cyclodextrins to chiral separations by capillary zone electrophoresis.

Mixtures of randomly substituted sulfated cyclodextrins (degree of substitution, approximately 7-10) were successfully used as chiral additives for the enantioseparation of 56 compounds of pharmaceutical interest, including anesthetics, antiarrhythmics, antidepressants, anticonvulsants, antihistamines, antihypertensives, antimalarials, relaxants, and bronchodilators. The separations were accomplished at pH 3.8, with the anode at the detector end of the column. Under these conditions, in which electroosmotic flow is directed toward the injection end of the column and the electrophoretic mobility of the negatively charged cyclodextrin is toward the detector, none of the analytes reached the detector in the absence of the sulfated cyclodextrin. Most (40) of the successfully resolved enantiomers contained basic functionality and a stereogenic carbon. However, the versatility of this sulfated cyclodextrin additive was also demonstrated by the fact that three atropisomers, 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate, 1.1'-binaphthyl-2,2'-diol, and Troger's base, and several neutral analytes were also successfully enantioresolved under these conditions. The separation mechanism seems to involve inclusion complexation.

Mechanism for chiral recognition of binaphthyl derivatives by cyclodextrins

The mechanism for chiral recognition of 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (BNP) and 1, 1′binaphthyl-2,2′-dicarboxylic acid (BNC) by β-cyclodextrin (β-CDx) and heptakis(2,3,6-tri-O-methyl)β-CDx (TMe-βCDx) has been investigated by ′H NMR spectroscopy, thermodynamic parameters for complexation and molecular mechanics-molecular dynamics (MM-MD) calculations. TMe-β-CDx recognizes axial chiralities of the BNP anion and undissociated BNC, (S)-BNP and (R)-BNC being the preferable guest enantiomers. The ability of β-CDx to recognize the axial chiralities is inferior to that of TMe-β-CDx. ′H NMR spectra suggest that (S)-BNP is shallowly bound to the wider side of the TMe-β-CDx cavity where a hydrophilic phosphate group is located inside the hydrophobic CDx cavity. Meanwhile, (R)-BNP seems to form the complex of TMe-β-CDx where the C2 symmetry axis of (R)-BNP is perpendicular to the C7 symmetry axis of TMe-β-CDx. The complexation of the preferable enantiomer of the guest with TMe-β-CDx is entropically favourable while that of the undesirable enantiomer of the guest is entropically unfavourable. The MM–MD calculations suggest that the orientation of the preferable guest is determined by the dipole-dipole interactions between the host and the guest. Similar orientation in the cases of the undesirable enantiomers may be prevented by steric factors. The positive entropy changes in the complexation of (S)-BNP and (R)-BNC seem to be ascribed to the extended dehydration from both the hydrophilic groups of the guest and the ethereal oxygen atoms of the wider side of the TMe-β-CDx cavity upon inclusion.

Quinine as a chiral additive in nonaqueous capillary zone electrophoresis

Quinine was used as a chiral additive in nonaqueous capillary zone electrophoresis. The separation buffer consisted of ammonium acetate and quinine in methanol. Quinine was able to enantioresolve a number of N-3,5-dinitrobenzoylated amino acids as well as (±)-1,1′-binaphthyl-2,2′diyl hydrogen phosphate and N-[1-(1-naphthyl)ethyl]phthalamic acid. Enantioresolution deteriorated as the concentration of ammonium acetate was increased but improved with the addition of acetic acid. Chiral recognition seems to arise through an ion-pairing mechanism. © 1996 John Wiley & Sons, Inc.

Enantiomeric resolution of anionic R/ S-1,1′-binaphthyl-2,2′-diyl hydrogen phosphate by capillary electrophoresis using anionic cyclodextrin derivatives as chiral selectors

The enantioseparation of racemic 1,1′-bi-2-naphthol (1), 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (2) and 1,1′-binaphthyl-2,2′-diamine (3) using native β-cyclodextrin (β-CD) and its anionic derivatives such as carboxymethyl-β-CD (CM-β-CD), sulfoethyl ether of β-cyclodextrin (SEE-β-CD) and sulfobutyl ether of β-cyclodextrin (SBE-β-CD) has been studied. The successful resolution of 2 in the anionic form using negatively charged cyclodextrin derivatives shows that the role of the Coulombic interactions is not critical for the chiral guest-host recognition in capillary electrophoresis (CE). The application of SEE-β-CD as a chiral selector in CE has been demonstrated for the first time. Comparison of the enantioseparation efficiencies of SEE-β-CD and SBE-β-CD shows that the spacer length and the substitution pattern are factors with rather low importance and that the resolution efficiency is mainly determined by the counter-current mobility of the chiral selector.

Ability of non-cyclic oligosaccharides to form molecular complexes and its use for chiral separation by capillary zone electrophoresis

The binding constants ( K) for complexation of the phenyl acetates with linear α-1,4-linked dextrins have been determined from the kinetics of the hydrolyses of the esters. The K value tends to increase with increasing the number of the glucopyranose units, suggesting hydrophobic interaction as a binding force. The weak ability of the linear dextrins to form the molecular complexes makes it possible to separate the enantiomers of binaphthyl derivatives such as 1,1′-binaphthyl-2,2′-dicarboxylic acid, 1,1′-binaphthyl-2,2′-diyl hydrogenphosphate and 2,2′-dihydroxy-1,1′-binaphthyl-3,3′-dicarboxylic acid in their anionic forms. Hydrogen bonding as well as hydrophobic interaction is suggested as an essential force for enantioselective complexation between saccharide and anionic binaphthyl.

Mechanisms of enantiomeric resolution in cyclodextrin‐modified capillary electrophoretic separations of binaphthyl compounds

AbstractThe enantiomers of 1,1′‐bi‐2‐naphthol, 1,1′‐binaphthyl diyl hydrogen phosphate, and 1,1′‐binaphthyldicarboxylic acid are separated using capillary electrophoresis with cyclodextrins added to the running buffer. It is demonstrated that the type and concentration of cyclodextrin employed are critical for maximum enantiomeric resolution. A modified version of a previously described model of enantiomeric separations in capillary electrophoresis is shown to support the observed separation behavior. Molecular modeling is employed to calculate interaction energies between the various enantiomers and cyclodextrins. A reasonable correlation between these computationally derived interaction energies and separation behavior resulted from a statistical mechanical treatment of the molecular modeling data. The importance of hydrogen bonding in inclusion complex formation was probed and the effects of minimization and solvation in molecular modeling calculations are also discussed. © 1995 Wiley‐Liss, Inc.