Synergistic enhancement of the fluorescence intensity of 4,5-benzopiaselenol by surfactants and β-cyclodextrin in aqueous solution

The synergistic enhancement of the fluorescence intensity of 4,5-benzopiaselenol (I _F ^Se-DAN ) by surfactants (Sf) and -cyclodextrin (-CD) has been studied. The (I _F ^Se-DAN ) in sodium dodecyl sulfate (SDS)//gb-CD was approximately 30 times greater than that in water, and 5–6 times greater than that in either SDS or -CD solutions alone, and a blue-shift of the emission wavelength was observed.¹H-NMR experiments and determination of CMC values of Se-DAN/-CD, Se-DAN/SDS, and Se-DAN/SDS/-CD systems reveal that the synergistic fluorescence enhancement was produced by the SDS monomer/-CD inclusion complex. In essence, the synergistic enhancement is due to the altered microenvironment experienced by Se-DAN upon its transfer from water to the hydrophobic cavity upon complexation.     

Molecular Recognition Study on a Supramolecular System. Part 21. Inclusion Complexation Thermodynamics of Aliphatic Alcohols by Organoselenium Modified β-Cyclodextrins

The spectrophotometric titrations have beenperformed at 25–40 °C in aqueous solution to give the complexstability constants and the thermodynamic parametersfor the stoichiometric 1 : 1 inclusion complexation ofvarious aliphatic alcohols withmono[6-(phenylseleno)-6-deoxy]--cyclodextrin (2),mono[6-(o-, m-,p-tolylseleno)-6-deoxy]--cyclodextrin (3–5),mono[6-(p-chloro-phenyl-seleno)-6-deoxy]--cyclodextrin(6), mono[6-(benzylseleno)-6-deoxy]--cyclodextrin (7) and mono[6-(naphthaleneseleno)-6-deoxy]--cyclodextrin(8). On thebasis of the present and previous results, themolecular binding abilities and selectivities forguest aliphatic alcohols of the host -cyclodextrinderivatives (2–8) are discussed comparatively and globallyfrom the thermodynamic point of view. Thethermodynamic parameters obtained are criticalfunctions of the size/shape of aliphatic alcohols, andthe position and type of the substituent introduced tothe aromatic ring of -cyclodextrin's sidearm,which are elucidatedin terms of the conformational, electrostatic,hydrogen-bonding, and hydrophobic effects.     

Volume change on complex formation between anions and cyclodextrins in aqueous solution

Partial molal volume changes during complex formation between SCN^–, I^–, and ClO₄ ^– -and -cyclodextrin have been determined by two independent methods of measurements; one based on density measurement and subsequent calculation of apparent molal volumes, the other on differentiating the association constants with respect to pressure. Results from the two methods are in good agreement.Negative volume changes were observed for complex formation between the anions and -cyclodextrin while zero or slightly positive values were observed for complex formation with -cyclodextrin. The result is consistent with the idea that the anions do not become dehydrated as they form complexes with cyclodextrins.     

Chiral separations by host-guest complexation with cyclodextrin and crown ether in capillary zone electrophoresis

Summary Capillary zone electrophoresis using cyclodextrins and a chiral crown ether as buffer constituents was studied for the enantiomeric separation of drugs and amino acids. Based on results obtained from separation of racemic -amino acids both chiral selectors are compared with respect to resolution, efficiency and retention time. For (±)-Quinagolide effects of buffer composition and temperature are examined using -cyclodextrin as chiral agent. Optimum conditions were pH 2.5 at 30 mmol L^–1 -cyclodextrin. A linear dependence of retention on -cyclodextrin concentration allowed calculation of formation constants of the host-guest complexes. Buffer concentration and temperature also influence resolution. The application of a chiral crown ether to the separation of optical isomers in capillary zone electrophoresis is described for the first time. Chiral recognition of solutes depends on the formation of protonated alkyl amines and separation is attributed to the formation of diastereomeric host-guest complexes with different interactions for each enantiomer. The effects of crown ether concentration on resolution are presented.     

Inclusion of Ring A of Cholesterol Inside the β-Cyclodextrin Cavity: Evidence from Oxidation Reactions and Structural Studies

The disposition of cholesterol inside the -cyclodextrin cavity(-CD) was deduced from oxidation of cholesterol secondary alcoholgroups by Ca(OCl)₂ and H₂O₂ in thepyridine–acetic acid system. The amount of cholest-4-ene-3-one formedwas found to be proportional to the concentration of -cyclodextrin,resulting in 56.1% of ketone. The oxidation rate was enhanced by-cyclodextrin and its methyl, polymer and 1 : 1copper(II)–-cyclodextrin derivatives. Detailed investigationsinvolving UV-visible, ¹³C- and ¹H-NMR(T₁, 1D NOE and ROESY) spectroscopic studies were carried out.A binding constant value of 15,385 ± 1500 M^-2 wasobtained for the 2 : 1heptakis-2,6-di-O-methyl--cyclodextrin(DM-CD) : cholesterolcomplex in chloroform from UV studies. Proton and solid state¹³C-CP MAS spectra of the -CD–cholesterol mixtureshowed large magnitude shifts for the protons from the wider end of the-CD cavity as well as those of ring A and ring B of cholesterol. Both1D NOE and ROESY measurements indicated the proximity between ring A andring B protons of cholesterol and the wider end protons of -CD andDM-CD. Besides, analysis of _c,_i and tau;_m from T₁measurements showed not only a lowering of rotational motions but a value of 0.016–0.048 for some of the cholesterol protons, typical of aweak complex. Based on these studies, a probable structure for the 2 : 1complex involving two molecules of -CD/DM-CD was proposed withportions of ring A and ring B being present inside the wider end of the-CD/DM-CD cavity and ring D and the side chain attached atposition 17, projecting into the wider end of the secondCD/DM-CD molecule.     

Thermodynamic study of the β-cyclodextrin benzyl-2-pyridyl ketone 2-pyridyl hydrazone inclusion process

Benzyl-2-pyridylketone-2-pyridylhydrazone and -cyclodextrin form a 1 : 1 adduct in water with a standard free energy change, G ^o, in the region of 14.2 kJ mol^–1 at 25°C, and an association constant of 275 M^–1 in the pH range 5–7. These values have been obtained by using the fluorimetric spectral changes associated with the inclusion process.     

Chiral separation of nanomole amounts of alprenolol with cITP/NMR

On-line cITP–NMR with chiral selectors separates and concentrates analytes and identifies host–guest interactions of analytes with selectivity enhancers in the electrolyte. An NMR microcoil designed for a 200 m i.d. capillary creates a high-mass-sensitivity 30 nL NMR cell and is used as an on-line detector for cITP. Using a mixture of 2 nmol racemic alprenolol in acetate buffer with -cyclodextrin and sulfated -cyclodextrin at pD 6.0, cITP–NMR successfully separates and concentrates both R- and S-alprenolol. The concentration enhancement for the R isomer is 224-fold and for the S isomer is 200-fold. The estimated concentration at peak maximum for R-alprenolol is ~28 mmol L^–1 and a slightly lower concentration, 25 mmol L^–1 is achieved for S-alprenolol. These concentrations convert to placing 76% of the injected S-alprenolol and 84% of the R-alprenolol into the 30 nL detection cell at peak maximum. With on-flow cITP–NMR, intermolecular interactions between the cyclodextrins and the alprenolol are observed in the NMR spectra. Aromatic and methyl moieties of R- and S-alprenolol are identified as two important sites that bind with these particular cyclodextrins.     

Continuous-flow separation and pre-concentration coupled on-line to solid-surface fluorescence spectroscopy for the simultaneous determination of<Emphasis Type="Italic"> o</Emphasis>-phenylphenol and thiabendazole

A novel and single flow-injection system combined with solid-surface fluorescence detection is proposed in this work for the resolution of a mixture of two widely used pesticides (o-phenylphenol and thiabendazole). The continuous-flow methodology is based on the implementation of on-line pre-concentration and separation of both analytes on the surface of C₁₈ silica gel beads placed just inside the flow cell, implemented with gel-phase fluorimetric multi-wavelength detection (using 305/358 and 250/345 nm as excitation/emission wavelengths for thiabendazole and o-phenylphenol, respectively). The separation of the pesticides was possible owing to the different retention/desorption kinetics of their interactions with the solid support in the zone where the stream impinges on the solid material. No previous separation of the analytes before they reach the flow cell is needed thereby simplifying substantially both the procedure and the manifold. By using a sample volume of 2,600 L, the system was calibrated in the range 0.5–16 and 5–120 ng mL^–1 with detection limits of 0.09 and 0.60 ng mL^–1 for thiabendazole and o-phenylphenol, respectively. The RSD values (n=10) were about 1% for both analytes. The proposed methodology was applied to environmental water samples and also to various commercial pesticide formulations containing both analytes. Recovery percentages were 97–103% and 98–102% for thiabendazole and o-phenylphenol, respectively.     

Determination of the stoichiometry and stability constants of theβ-cyclodextrin-dextromethorphan inclusion complexes by liquid chromatography and UV spectroscopy

The inclosion of dextromethorphan (DMN) by -cyclodextrin (-CD) was studied by using chromatography, UV spectroscopy and circular dichroism methods at 25 °C, pH 7.4 and 4.2. It was found that the CD : DMN complex has 1 : 1 stoichiometry. It is more stable at pH 7.4 than at pH 4.2. with constants respectively equal to 8000 ± 800 M^–1 and 5750 ± 500 M^–i, as determined by chromatography. The stability of the complex at pH 7.4 decreases as the temperature increases. From the van 't Hoff dependence the standard entropy and enthalpy changes were determined at this pH.     

Absorptiometric and spectrofluorimetric study of the inclusion complexes of 2-naphthyloxyacetic acid and 1-naphthylacetic acid with β-cyclodextrin in aqueous solution

The inclusion complexes of 2-naphthyloxyacetic acid (NOA) and 1-naphthylacetic acid (NAA) with -cyclodextrin have been investigated in aqueous solution. It has been demonstrated that the naphthalene derivatives form 1:1 complexes when included in the cyclodextrin. A possible structure is proposed, having an axial inclusion of the naphthalene derivatives. In the case of the -CD: NOA complex, the naphthyl moiety is included in the cyclodextrin and the acetic acid group protrudes from the cavity, while NAA is only partially included because of the steric effect of the group in position 1. Association constants of 560±100 M^–1 and 100±50 M^–1 have been calculated for the -CD: NOA and -CD: NAA complexes, making use of the increment in the fluorescene emission produced in the inclusion process.     

Cyclodextrin-based optosensor for determination of tryptophan

A flow-through optosensor for tryptophan is described. The sensor is developed in conjunction with a flow-injection analysis system and uses immobilized -cyclodextrin as the sensing agent. The detection limit for tryptophan was 4ng ml^–1. The RSD for determination of 1 g ml^–1 of tryptophan was 2.8%.     

The influence of cyclodextrin complexation on proton transfer in piperidinomethyl-2-naphthol

Summary Piperidinomethyl-2-naphthol forms inclusion complexes with -cyclodextrin with an equilibrium constant of 265M ^–1 in aqueous solution. The proton transfer equilibrium between the neutral and the zwitterionic form is strongly influenced by the association.

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Der Einfluß der Komplexierung mit -Cyclodextrin auf das Protontransfer-Gleichgewicht in Piperidino-2-naphthol (Kurze Mitt.)

Zusammenfassung Piperidinomethyl-2-naphthol bildet Einschlußkomplexe mit -Cyclodextrin mit einer Gleichgewichtskonstante von 265M ^–1. Das Protontransfer-Gleichgewicht zwischen neutraler Form und zwitterionischer Struktur wird durch diese Assoziation stark beeinflußt.

     

\-Cyclodextrin-catalyzed effects on the hydrolysis of esters of aromatic acids

In order to make the behavior of the hydrophobic cavity of -cyclodextrin clear, we have studied -cyclodextrin-catalyzed hydrolysis of a series of nitrophenyl esters of aromatic acids. We defined a new kinetic parameter to determine the structure of the inclusion compounds. The kinetic parameters obtained provide evidence that the aromatic acid moiety rather than the nitrophenyl moiety of the esters mainly enters the hydrophobic cavity of -cyclodextrin to form the inclusion complex.Presented at the Fourth International Symposium on Inclusion Phenomena and the Third International Symposium on Cyclodextrins, Lancaster, U.K., 20–25 July 1986.     

ET-AAS in the Analysis of high-purity mercury

ET-AAS is investigated for the analysis of high purity mercury. Two possibilities are proposed: ET-AAS determination of trace analytes in the presence of high mercury concentrations or after matrix separation by reduction. The ET-AAS analysis of high-purity mercury under optimal instrumental parameters permits fast and reproducible determination of 0.03 gg^–1 Al, Cd and Mn; 0.05 gg^–1 Cu, Co, Cr, Fe, Ni and Pb and 0.2 gg^–1 V. Preliminary mercury matrix reductive separation with ascorbic acid allows determination of 0.005 gg^–1 Cd, 0.02 gg^–1 Cu, Cr and Mn, 0.03 g g^–1 Co, Ni and Pb, 0.05 g g^–1 Al and Fe and 0.1 gg^–1 V, but the reproducibility is lower. The main advantage of the second procedure is that it avoids laboratory and instrument pollution with toxic mercury.     

NMR Spectral Assignment of Per-substituted Key-Intermediates of β-Cyclodextrin and Implications in the Structures of the Derivatives

The compounds, 6-per-O-(t-butyldimethylsilyl)--cyclodextrin(1), 2,3-per-O-benzyl-6-per-O-(t-butyldimethylsilyl)--cyclodextrin(2), 2,3-per-O-benzyl--cyclodextrin (3),2,3,6-per-O-benzyl--cyclodextrin (4),2,3,6-per-O-benzoyl--cyclodextrin (5), are used as keyintermediates in the synthesis of selectively substituted -CD derivatives. Simple and assignable ¹H and ¹³C NMR spectra (chemical shifts and coupling constants) were obtained for compounds1–4 indicating C₇ symmetry, ⁴C₁ glucose conformation and major arrangement of H6, H6' atoms at the primary side. The derivative 5, however, gave very broad peaksat room temperature. The peaks could partially be assigned at 270 K, but the broadening was still present at 220 K. This implies that there exist several conformers of similar energyand C₁ symmetry that continuously interchange, since there is not a single type of stabilizing interaction thatpredominates. We attributed this phenomenon to the presence of the carbonyl group, which probablydisfavors - stacking and induces random arrangements of the aromatic rings.     

Behavior of rifampicin in association with<Emphasis Type="Italic"> β</Emphasis>-cyclodextrin in aqueous media: a spectroscopic and conductometric study

The behavior of rifampicin (D) with -cyclodextrin (-CyD) in aqueous media (W) has been examined by means of UV-vis spectroscopy and conductivity measurements over the temperature range 15–30 °C. The UV-vis study has been used to characterize the systems. The estimated molar absorption coefficient for D/CyD/W system was 10757±280 M^–1 cm^–1 in comparison to the value of 6133±99 M^–1 cm^–1 for D/W system. The conductivity was measured (i) as a function of [D] for binary D/W systems, (ii) as a function of [CyD], keeping the concentration of drug constant, for D/CyD/W system, and (iii) as a function of [D] in the presence of a constant cyclodextrin concentration. Two transition points were observed for D/CyD/W system at constant [CyD], which were assigned as cac-1 and cac-2. The stoichiometry of the association was estimated from the conductivity data. This was obtained from [drug] value at which the change in slope of occurs. The standard free energy change, of aggregation was also calculated from the critical concentration data. An attempt has also been made to estimate the stoichiometry of -cyclodextrin:rifampicin association.     

Inclusion Complexation Thermodynamics of Acridine Red and Rhodamine B by Natural and Novel Oligo(ethylenediamine) Tethered Schiff Base β-Cyclodextrin

A series of Schiff base -cyclodextrin derivatives 2–5 with an oligo(ethylenediamine)tether have been newly synthesized and their inclusion complexation behavior has beenassessed and discussed thermodynamically, employing acridine red (AR) and rhodamine B (RhB) as representative guests. Fluorescence spectrophotometric titrations have been performed in methanol-water (1 : 2) phosphate buffer solution (pH = 7.20) at 25.0–45.0 °C in order to obtain the complex stability constants (K_S) and the thermodynamic parameters ( H° and T S°) for the stoichiometric 1 : 1 inclusion complexation of two guests with the native and modified -cyclodextrins ( 1 and 2–5). As compared with theparent -cyclodextrin 1, all of the chemical modifications to the primary side of -cyclodextrins examined led to substantial decreases for rhodamine B and marked increases for acridine red in complex stability, which are elucidated in terms of the induced-fit interaction and the complementary geometrical relationship between the host -cyclodextrins and guest molecules, as well as the length of the linking chain of -CD derivatives. The induced circular dichroism spectral analyses of these -cyclodextrin derivatives indicated that the aromatic moiety in modified -cyclodextrins is not embeded into the hydrophobic cavity ofcyclodextrin. The inclusion complexation of 2–5 with acridine red possess higher binding constants than that with rhodamine B, which are solely attributed to the increased enthalpic gain. Thermodynamically, the inclusion complexation with the modified -cyclodextrins 2–5 is absolutely enthalpy-driven for acridine red, while for complexation with rhodamine B is mainly entropy-driven.     

A High Sensitivity Fluorescent Chemo-sensory System Based on β-Cyclodextrin Dimer Modified with Dansyl Moieties

-Cyclodextrin dimer linked with ethylenediamine at the upper rim of the cyclodextrin has been synthesized and then modified with two dansyl moieties inthe presence of N,N'-dicyclohexylcarbodiimide. The sensing ability and bindingproperty of the title compound were investigated for steroids and terpenoids. Thefluorescence intensity of this dimer was decreased when a host–guest complex was formed. The value I/I⁰, where I⁰ and I are fluorescence intensitiesin the absence and presence of a guest and I is I⁰- I, was used as a parameter of sensitivity. This host exhibited a much higher sensitivity and selective molecular recognition ability for bile acids such as ursodeoxycholic acid andchenodeoxycholic acid and terpenoids such as (-)-borneol than the dansyl-modifiedcyclodextrins reported previously including -cyclodextrin dimer. The behaviors of the appended moieties of the host during the formation of host–guest complexes were studied using induced circular dichroism (ICD) and fluorescence spectra. The ICD intensityof this dimer was decreased on accommodation of a guest and this spectral pattern of the title dimer was opposite to that of bis dansyl-modified -cyclodextrin monomer. Theguest-induced variations in the fluorescence and ICD intensities suggest that this dimer formed a 1 : 1 host–guest complex and the appended moieties act as a hydrophobic cap.     

Simultaneous chiral separation of leucovorin and its major metabolite 5-methyl-tetrahydrofolate by capillary electrophoresis using cyclodextrins as chiral selectors: Estimation of the formation constant and mobility of the solute-cyclodextrin complexes

Summary Capillary electrophoresis with an electrolyte containing cyclodextrin was investigated for the simultaneous separation of the diastereoisomers of 6R,S-leucovorin and its active metabolite 6R,S-5-methyl-tetrahydrofolate. , and -cyclodextrin separated the diastereoisomers of 5-methyl-tetrahydrofolate, while only -cyclodextrin was found to be effective for the chiral separation of leucovorin. The effect of -cyclodextrin concentration was investigated, and subsequently a curve-fitting analysis for the quantitative estimation of the binding constants was attempted. The binding constants were found to be very small, in the range 2–4 M^–1. Although the interaction between -cyclodextrin and the tetrahydrofolates is weak, the high efficiency of capillary electrophoresis and the use of high concentrations of -cyclodextrin allow baseline chiral separation of the diastereoisomers of leucovorin and 5-methyl-tetrahydrofolate. Changes in temperature exert differing effects on the separations of leucovorin and 5-methyl-tetrahydrofolate; higher temperatures improved the separation of leucovorin diastereoisomers but reduced the resolution of 5-methyl-tetrahydrofolate diastereoisomers. The effects of urea and buffer salt concentrations and of buffer pH were also investigated. Capillary electrophoresis with -cyclodextrin was used to analyse plasma samples spiked with clinically-relevant levels of leucovorin and 5-methyl-tetrahydrofolate. Resolution of these compounds in ultrafiltered plasma was demonstrated, but detection sensitivity was not adequate for the routine use of this method for the determination of leucovorin and 5-methyl-tetrahydrofolate in plasma. In addition, a simple technique to reverse the elution order of ionic stereoisomers was demonstrated. By adding a cationic surfactant into the buffer and reversing the separation potential, the elution order of the diastereoisomers of leucovorin and 5-methyl-tetrahydrofolate was reversed.     

The inclusion complex of piromidic acid with dimethyl-β-cyclodextrin in aqueous solution and in the solid state

Inclusion complex formation of piromidic acid (PA) with dimethyl--cyclodextrin (DM--CD) in aqueous solution and in the solid state was confirmed by the solubility method, differential scanning calorimetry (DSC) and proton nuclear magnetic resonance (¹H-NMR) spectroscopy. The apparent stability constant,K _c , of the complex was estimated to be 244 M^–1. The stoichiometry of the complex was given as the ratio 1:2 of PA to DM--CD. The dissolution rate of the PA/DM--CD complex was much greater than that of intact PA.Presented at the Fourth International Symposium on Inclusion Phenomena and the Third International Symposium on Cyclodextrins, Lancaster, U.K., 20–25 July 1986.