Cation Complexation Properties of Hexakis(2-O-methyl-3,6-anhydro)-α-cyclodextrin: A 1H NMR Study

Abstract

The affinity of hexakis(2-O-methyl-3,6-anhydro)-α-cyclodextrin (3,6-α-CDM) for Ba²⁺, Pb²⁺, Ca²⁺ and Sr²⁺ has been tested by ¹H NMR. It was shown that 3,6-α-CDM forms strong complexes in water with Pb²⁺ and Ba²⁺. The comparison with the parent hexakis(3,6-anhydro)-α-cyclodextrin bearing hydroxyl groups instead of methoxy groups reveals that the O-CH₃ substitution significantly improves the anhydro-cyclodextrin selectivity.     

Complexation of inorganic anions by β-cyclodextrin studied by polarography and 1H NMR

Abstract

Complexation of o-chloronitrobenzene with β-cyclodextrin has been studied in 0.1 M aqueous solutions containing PF₆ ^?, ClO₄ ^?, C₂O₄ ^2-, SCN^?, SO₄ ^2- and F^? anions by a polarographic method. Using an equation which takes account of the change in the cyclodextrin concentration due to the simultaneous complexation of the anion, both stability constants have been calculated. Interaction of the ClO₄ ^? anion with β-cyclodextrin has been confirmed by ¹H NMR techniques. It has been found that the ClO₄ ^? anion is trapped in the β-cyclodextrin cavity. The stability constant has been calculated. Results of polarographic and ¹H NMR studies have been compared.     

Preparation of a Cyclomaltoheptaose(β-cyclodextrin) Cross-linked Chitosan Derivative via Glyoxal or Glutaraldehyde

Chitosan has been regarded as a multifunctional polymer applicable to various purpos-es1. The potential of the material in medical applications, particularly in drug-delivery formu-lations has been demonstrated2, 3. Recently, a crosslinked chitosan with various crosslink-ing agents was prepared as adsorbents4-7. A -cyclodextrin (?CD) has been subjected to numerous studies, particular in terms of its complexing ability with a variety of components8, 9. The complexing ability of -CD has b…     

An NMR study of inclusion complexes formed by α-cyclodextrin and (R)- or (S)-α-lipoic acid

A ¹H NMR study that explored the ability of α-cyclodextrin (α-CD) to preferentially bind (R)-α-lipoic acid is presented. The interaction between α-CD and (R)-α-lipoic acid was found to be stronger than that between α-CD and (S)-α-lipoic acid. Structures for the (R)-α-lipoic acid/α-CD and (S)-α-lipoic acid/α-CD inclusion complexes were constructed using restraints derived from ROESY spectra and MM2 molecular mechanics calculations. The models built for both complexes have the 1,2-dithiolane ring and the carboxyl moiety of α-lipoic acid oriented toward the secondary and primary hydroxy sides of α-CD, respectively.     

Evaluation of a direct1H NMR method for determining logK and ΔH values for crown ether -alkylammonium cation complexation

A direct¹H NMR method for determining logK and H values for crown ether-ammonium cation complexation using milligrams of sample was tested and evaluated for accuracy and precision by comparing the results with those obtained using a titration calorimetric method. LogK values for the interactions of a non-chiral crown ether, diketopyridino-18-crown-6 (K₂P18C6), with -phenylethylammonium (PhEt⁺) perchlorate in 50%–50% and 90%–10% (v/v) mixtures of deuterated methanol (CD₃OD) and deuterated chloroform (CDCl₃) at four temperatures and, with -(1-naphthyl)ethylammonium (NapEt⁺) perchlorate in 50%CD₃OD-50%CDCl₃ (v/v) at 25°C were determined by a direct¹H NMR method. Values of H for the interactions of K₂P18C6 with PhEt⁺ in the two solvents were calculated from the temperature dependence of logK. LogK values for the interactions of a chiral crown ether, dimethyldiketopyridino-18-crown-6 (M₂K₂P18C6), with (R) and (S) enantiomers of NapEt⁺ in pure CD₃OD at 25.0°C were also determined by the NMR method. The results were compared with those determined by a calorimetric method at 25.0°C in 50%-50% and 90%–10% (v/v) mixtures of plain methanol and chloroform, in 100% plain methanol, and in a 50%-50% mixture of partially deuterated methanol (with deuterium substitution on the methanol OH group, CH₃OD) and deuterated chloroform. The log K values determined by both methods were found to be in good agreement, but the standard deviations associated with the NMR logK values were two to three times greater. The agreement of the H values determined by the two methods was poor, differing by approximately 10 kJ/mol with the NMR method giving more negative values. The standard deviations associated with the NMR H values were approximately ten times greater than those for the calorimetric values. Ion-pairing was observed for the interaction of perchlorate ion with both free and bound PhEt⁺ in 50%methanol-50%chloroform mixture. It is concluded that the NMR procedure is satisfactory for the determination of logK, but not H values.This paper is dedicated to the memory of the late Dr C. J. Pedersen.     

Characterization of β-cyclodextrin inclusion complex with procaine hydrochloride by 1H NMR and ITC

The inclusion of local anesthetic drug procaine hydrochloride by β-cyclodextrin was investigated by 1D and 2D proton NMR spectroscopy and isothermal titration calorimetry (ITC) at 298 K. The stoichiometry of the complex was determinate by the method of continuous variation, using the chemical induced shift of both host and guest protons. The association constant K, of the obtained complex was calculated and found to be 293.17 M^?1. Rotating frame NOE spectroscopy, was used to ascertain the solution geometry of the host–guest complex. The result reveals that the procaine molecule penetrates into the β-cyclodextrin cavity with the aromatic ring. The energetics of complexation process is investigated by ITC technique. The analysis indicates that the complexation of procaine by β-CD is an exothermic process and show that both enthalpy and entropy contribute to the binding process. The obtained value for the association constant is in good agreement with that obtained from NMR.     

(R)- and (S)-α-Methoxy-(1-naphthyl) acetic acids: resolution by fractional crystallization and use for the NMR stereochemical analysis of alkylsulfoxides

Both enantiomers of α-methoxy-(1-naphthyl) acetic acid (1-NMA) were conveniently obtained via fractional crystallization using the enantiomers of 1-(1-naphthyl) ethylamine. 1-NMA was shown to be very powerful for differentiating the enantiomeric signals of quasi-symmetrical aliphatic sulfoxides.     

Complexation studies of pioglitazone hydrochloride and β-cyclodextrin: NMR (1H, ROESY) spectroscopic study in solution

Pioglitazone hydrochloride (PIO) is an agonist of the peroxisome proliferator-activated receptor γ (PPARγ), used to treat diabetes. ¹H-NMR spectroscopic analysis of varying ratios of β-cyclodextrin (β-CyD) and PIO in D₂O confirmed the formation of β-CyD–PIO inclusion complex in aqueous solution. The 1:1 stoichiometry of β-CyD–PIO inclusion complex was determined by Scott’s plot method and binding constant (K _a ) was calculated to be 155 M^?1. 2D ROESY experiments confirmed that the phenyl ring of PIO act as a guest and deeply penetrate in β-CyD cavity from wider as well as narrower rim side and form two 1:1 stable inclusion complexes. Some of the PIO protons exhibited splitting, in the presence of β-CyD, indicating chiral differentiation of PIO by β-CyD.     

Preparation and characterization of the 1:1 inclusion compound γ-cyclodextrin/[Ni(dmit)2]1-

Abstract

The preparation of a 1:1 inclusion compound involving γ-cyclodextrin and bis(4,5-dimercapto-1,3-dithiole-2-thionato)nickelate (III) complex ion, [Ni(dmit)₂]^1-, is reported. The inclusion complex is characterized by UV-visible and Raman spectroscopy, thermal analysis and X-ray powder diffractometry.     

NMR spectral assignment of 2α- and 3β-methylhopanes and evidence for boat conformation in D ring of 17α(H),21α(H)-hopanes

The full (1)H and (13)C NMR chemical shift assignment of 2α-methyl-17α(H),21β(H)-hopane is presented. This compound is formed in mature sediments from biogenic sources of 2β-methyl-17β(H),21β(H)-hopanoids, which include several cyanobacteria. In addition, full (1)H and (13)C NMR chemical shift data of all four 17,21 isomers of 3β-methylhopane have been assigned. The thermodynamically most stable 3β-configuration corresponds to that found in bacterial sources. The data presented here suggest minor corrections to the (13)C chemical assignments reported earlier for 17α(H)-hopanes. Moreover, spectral evidence indicates an unexpected ring-D boat conformation of 17α(H),21α(H)-hopanes, which may serve to explain the steric strain reported for this isomer.     

Preparation and characterization of hydroxypropyl-β-cyclodextrin inclusion complex of eugenol: differential pulse voltammetry and (1)H-NMR

The objective of present investigation was to improve the solubility of Eugenol by preparing the inclusion complex of Eugenol with hydroxypropyl-β-cyclodextrin (Hp-β-CD) and characterize the prepared complex by using NMR and differential pulse voltammetry (DPV). Phase solubility curve was plotted using Hp-β-CD in ranging from 0-40 mM of Hp-β-CD and found to be linear. Therefore, inclusion complex was prepared in equimolar ratio of Eugenol and Hp-β-CD by lyophilization method. Fourier transform infrared spectroscopy (FT-IR), (1)H-NMR and DPV were performed for Eugenol, Hp-β-CD and prepared inclusion complex of Eugenol. 2D (two dimensional) NMR was also performed for prepared inclusion complex. The proton of phenol moiety of Eugenol experienced a pronounced chemical shift variation in (1)H-NMR. The positive sign of the variation for proton in (1)H-NMR indicated that the proton was located near to an oxygen atom in the Hp-β-CD cavity and its magnitude showed a strong interaction between -OH proton of Eugenol and Hp-β-CD. 2D NMR confirms the interaction between phenolic group and hydrogen atoms of Hp-β-CD. A well defined anodic peak current corresponding to oxidation of Eugenol in non-encapsulated and Hp-β-CD-Eugenol inclusion complex in phosphate buffer (pH 6.8) was obtained at about 0.35 V and 0.40 V, respectively. The positive shift in oxidation potential indicated the formation of complex via hydrophobic interactions. The oxidant power of Eugenol was retained in complex form as indicated by DPV results. Thus, its oxidation dependent pharmacological property such as antimicrobial activity is not affected after complexation with Hp-β-CD. Thus, (1)H-NMR, 2D-NMR and DPV techniques can be used as valuable tools to determine the mechanism of complexation and state of electrochemical active drug in inclusion complex.     

NMR as a tool for simultaneous study of diastereoisomeric inclusion complexes formed by racemic mixture of 4′-hydroxyflavanone and heptakis-(2,6-O-dimethyl)-β-cyclodextrin

The complexes formed by (±)-4′-hydroxyflavanone (OHFL) and heptakis-(2,6-O-dimethyl)-β-cyclodextrin (DM-β-CD) were obtained using the racemic mixture of OHFL. These complexes were able to be studied due to their enantiodifferentiation by ¹H-NMR spectroscopy. Stoichiometry, association constants and thermodynamic parameters were obtained from these NMR data, and inclusion geometries were proposed from ROESY and docking experiments. The results show that diastereoisomeric complexes can be studied even when they are formed by enantiomeric mixtures.     

Binding of vitamin A byβ-cyclodextrin and heptakis(2,6-O-dimethyl)-β-cyclodextrin

Inclusion complexation of all-trans-retinol, retinal and retinoic acid with -cyclodextrin (-CD) and heptakis(2,6-O-dimethyl)--cyclodextrin (DM--CD) were investigated by means of UV-vis spectroscopy. The association constants (K _a) obtained for vitamin A with DM--CD is greater than with -CD. On the other hand, for the same host compoundK _a values of retinol, retinal and retinoic acid are very close to each other.     

Hydrothermal Preparation and Photophysical Properties of a Ni(Ⅱ) Complex Containing Quinoline Derivative and Phen Ligands

A novel nickel complex[Ni_2L_2Phen_3]·3H_2O (HL=3-hydroxy-2-methylquioline-4-carboxylic acid)has been synthesized by a hydrothermal approach and is structurally determined by single-crystal X-ray diffraction.The title complex crystallizes in triclinic space group ■.Crystal data for the title complex:C_(58)H_(44)N_8Ni_2O_9,M_r=1108.35,a=11.8648(4),b=12.7369(4),c=17.0728(5)?,α=97.694(3),β=96.702(2),γ=99.566(3)°,V=2495.66(14)?~3,Z=2,T=293(2) K,D_c=1.475 g/cm~3,μ(Mo Kα)=0.824 mm~(–1),F(000)=1140,R=0.0757,w R=0.2129 and GOF=1.017.The nickel ions are surrounded by five oxygen and six nitrogen atoms to yield two slightly distorted octahedral geometries.Solid-state photoluminescence spectrum reveals that it shows blue purple emission.Solid-state UV/Vis diffuse reflectance spectroscopy exhibits that it has an optical band gap of 1.702 e V.     

Precision studies in supramolecular chemistry: a 1H NMR study of hydroxymethoxyacetophenone/β-cyclodextrin complexes

The association constants for the interactions of 2-hydroxy-4-methoxyacetophenone, 2-hydroxy-5-methoxyacetophenone, 2-hydroxy-6-methoxyacetophenone, 3-hydroxy-4-methoxyacetophenone and 4-hydroxy-3-methoxyacetophenone with β-cyclodextrin in water were measured by (1)H NMR and by isothermal titration calorimetry. Very good agreement was obtained between the different methods. The errors associated with the NMR method for measuring mM binding affinities were estimated to be 10-30%, and by isothermal titration calorimetry, 10-20%. Rotating frame nuclear Overhauser effect spectroscopy studies show that the solution phase host-guest complexes formed by β-cyclodextrin with these hydroxymethoxyacetophenone derivatives are not structurally well defined but that the hydroxymethoxyacetophenone derivatives are mostly associated with the narrow primary hydroxyl rim.     

Inclusion of (aminostyryl)-1-methylpyridinium dyes byβ-cyclodextrin and its use for fluorescent-probe studies on association of cationic and neutral molecules withβ-cyclodextrin

An inclusion complex between TRIMEB and (S)-naproxen has been crystallised and characterised by physicochemical methods including X-ray analysis. The complex crystallises in the orthorhombic crystal system, space groupP2₁2₁2₁, witha=15.179(4),b=21.407(5),c=27.67(1) Å andZ=4. The structure was solved using published coordinates for the skeleton atoms of TRIMEB in an isomorphous complex. Refinement by full-matrix least-squares analysis yieldedR=0.0571 for 6573 unique observed reflections. Hydrophobic forces are responsible for the inclusion of the drug, which has its methoxy group buried in the cavity of the host and its propionic acid moiety protruding from the O(2), O(3) side of the TRIMEB molecule. Both host and guest undergo conformational changes on complexation relative to their conformations observed in the TRIMEB monohydrate and naproxen crystal structures respectively. Complex units pack in a screw-channel mode in a head-to-tail fashion with their axes almost parallel to theb-axis.     

X-ray Structure of a 1:2 Complex of Hexakis (3-O-acetyl-2,6-di-O-methyl)-α-cyclodextrin with Butylacetate

Abstract

Crystal structure of a 1:2 complex of hexakis(3-O-acetyl-2,6-di-O-methyl)-α-cyclodextrin (ADMACD) with butylacetate was determined by the X-ray method. The space group of the crystal is P2₁2₁2₁ with Z = 4 and D _x = 1.293 g cm^?3, and the cell dimensions are a = 11.087(2), b = 23.543(3), and c = 31.739(6) Å. The structure was solved by the direct method and refined to the R-value of 0.123 for all the 4993 observed reflections with 1<0. The ADMACD molecule is in a round shape with the pseudo hexagonal symmetry. Methyl and acetyl groups point towards the outside of the molecule. Because of the acetyl groups attached to O3 and methyl groups attached to O6, the intramolecular cavity is ca. 3 Å deeper than the cavity of native α-CD. One butylacetate molecule is coaxially accommodated with its acetyl group at the O6 side in the host cavity while the other guest molecule is located in an intermolecular space between host molecules which are stacked to form a head-to-tail channel-type packing structure along the a axis.     

Preparation of (−)-(R)-2-(2,3,4,5,6-pentafluorophenoxy)-2-(phenyl-d5)acetic acid: an efficient 1H NMR chiral solvating agent for direct enantiomeric purity evaluation of quinoline-containing antimalarial drugs

The title compound was prepared as a racemate from (±)-mandelic acid-d₅ in one step. The corresponding (−)-(R)-enantiomer (98% ee) was obtained by resolution with (−)-(R)-1-phenylethylamine and evaluated as a chiral solvating agent (CSA) for direct ¹H NMR enantiomeric excess determination of mefloquine (Lariam®), chloroquine (Chloroquine Bayer®), and hydroxychloroquine (Plaquenil®) enantiomers. The displayed non-equivalence was high for signals in the aromatic region of all three antimalarials. Thus, the mandelic acid derivative described herein may be considered as the first efficient CSA ‘invisible’ in the aromatic region, useful for direct ¹H NMR ee value determination of chiral quinoline-containing antimalarial drugs.