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Voltammetric, spectroscopic and thermal studies on the binding of some heterocyclic azo compounds with α- and β-cyclodextrins: pH effect and association affinity
Abstract
The binding abilities of α- and β-cyclodextrins (α-CD and β-CD) with some heterocyclic azo compounds (1,1'-(azodicarbonyl)dipiperidine (ADP) and azodicarboxylic dimorpholide (ADM)) were studied at different pHs (4, 7.4 and 10) by UV-Vis spectroscopy and square-wave voltammetry techniques. The association constants (Ki) and stoichiometries of the binding of these azo compounds with α-CD and β-CD were determined by using square-wave voltammetry technique. These bindings were formed with a stoichiometry of 1: 1 in solution. The solid samples, obtained from the mixtures (molar ratio of 1: 1) of these azo dyes and CDs in aqueous phase were analyzed by FT-IR spectroscopy and thermal analysis methods. Thermal analysis results showed that ADP and ADM formed the inclusion complexes with α-CD; however, the binding of the azo dyes with β-CD gave non-inclusion complexes.
... Similarly, the protons H3 and H5 which are located inside the conical cavity (Fig. 4b) of the host molecules β − CD, resulted in the most significant changes in chemical shift after complexation at the three different concentration ratios. [34] and also for identifying more easily the vibrational and stretching bands for the imprinted TiO 2 case [35][36][37]. ...
... The result presented in the original absorption spectra (Fig. 6a) confirms the range of absorption for cyclodextrins and propofol in the mid-ultraviolet region between 200 and 300 nm [36]. The second derivative method (Fig. 6b) helps to identify critical points such as the turning point at ca. 286 nm in the original β − CD:Propofol/TiO 2 spectrum (Fig. 6a) which appears as a peak at the same wavelength in Fig. 6b. ...
... For instance, there are zero-crossing points at wavelengths of 258 nm, 304 nm (with negative peaks for the black curve) and 357.5 nm for the red curve. The wavelength of 286 nm is attributable to the absorbance of propofol [41] and 260 nm as the maximum absorbance of β − CD [36,43,44], however, the absorbance of host-guest molecules tend to be shifted to values higher than 300 nm for guest molecules already hosted by β − CD [29,36,43,44] which is clearly visible in the imprinted TiO 2 spectra of Fig. 6a and b. Table 1 shows the bending radii fabricated, the set of concentrations used for the LPD process and the deposition time for functionalization for each of the U-shaped fibres tested. ...
Propofol is used widely for intravenous anaesthesia during surgery and sedation in critical care. There is no method currently to assay the concentration of propofol in plasma in real time. The ability to do so would significantly improve patient safety. A novel approach to propofol assay consisting of Beta-Cyclodextrin (β−CD) assisted propofol-imprinting onto TiO2 films deposited on U-shaped optical fibres was used for the measurement of propofol in aqueous solutions. The sensing mechanism is based on the measurement of the refractive index change induced by the removing and binding of the propofol from and to the β−CD/propofol complex embedded onto TiO2 films, respectively. Complexation between host (β−CD) and guest (propofol) was confirmed by nuclear magnetic resonance (NMR) spectroscopy, UV-Vis spectroscopy, and by Attenuated Total Reflectance- Fourier-transform infrared spectroscopy (FTIR). The developed sensors presented Langmuir adsorption in the mM range and the lowest concentration detected was 0.69 μM=0.12 μg/mL. The approach can be replicated for other compounds in other biomedical applications such as vitamins, hormones, or drugs.
Copper phenanthroline ethylenediaminediacetic acid, [Cu(phen)(edda)]·5H 2O, has been synthesized and characterized using cyclic voltammetry (CV), chronocoulometry (CC), chronoamperometry (CA), and rotating disk electrode (RDE). The copper(II) complex is found to be electroactive as shown by its well defined redox waveforms during cyclic voltammetry at room temperature and at pH 6.8. The interaction between [Cu(phen)(edda)]·5H 2O and DNA was also investigated using cyclic voltammetry at room temperature and at pH 6.8. The above electrochemical interaction was evident as their CV results revealing a slight shift in formal potential (at a range of 5 to 23mV dependant on scan rat, and a significant changes in redox peak currents (at a range of 0.05 to 0.4 times dependant on scan rate) to that of Cu(II) complexes in the presence of DNA. Copper (II) complex dissociates more easily as solution acidity increases as is evident by its larger current and decreases in peaks separation. Based on hydrodynamic voltammetric studies, the diffusion coefficients copper complex is found to be of the order of 10-7cm2/s and kinetic rate constant of 10 -5cm/s.
Abstract To improve the stability and oral bioavailability of Z-ligustilide (LIG), the inclusion complex of LIG with hydroxypropyl- β-cyclodextrin (HP-β-CD) was prepared by the kneading method and characterized by UV-Vis spectroscopy, differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. LIG is capable of forming an inclusion complex with HP-b-CD and the stoichiometry of the complex was 1:1. Stability of the inclusion complex against temperature and light was greatly enhanced compared to that of free LIG. Further, oral bioavailability of LIG and the inclusion complex in rats were studied and the plasma drug concentration-time curves fitted well with the non-compartment model to estimate the absolute bioavailability, which was 7.5 and 35.9 %, respectively. In conclusion, these results show that LIG/HP-β-CD complexation can be of great use for increasing the stability and biological efficacy of LIG.
The complexation of three isoquinoline alkaloids berberine, palmatine and coralyne with α-, β-, and γ-CDs were studied by absorption, fluorescence, circular dichroism, NMR spectroscopy and microcalorimetric assay techniques. Their binding constant (K
BH) values were determined by Benesi–Hildebrand equation. All the alkaloids formed 1:1 stoichiometry complexes with the cyclodextrins (CDs). The binding affinity is largest in β-CD followed by γ-, and α-CD for coralyne, followed by berberine and then palmatine. The thermodynamic parameters of the complexation were determined by calorimetry. The stoichiometry of complex formation and the variation of the apparent binding constant from spectroscopic studies were confirmed by calorimetry. The formation of the inclusion complexes was entropy driven in almost all the systems. Coralyne formed the strongest complex with all the CDs, followed by berberine and palmatine in that order. Coralyne-β-CD complex was studied through NMR, indicating more than one interaction mode.
The characterization of cyclodextrin(CD) systems by electrochemical methods, mainly by cyclic voltammetry, is discussed. The addition of CD to the electrolyte solution causes a decrease in the peak current and also a shift in the apparent half-wave potential in cyclic voltammetry. Quantitative analysis in the both phenomena affords the formation constants of CD complexes. The formation or dissociation rate constants can be evaluated from the cyclic voltammetric data at high scan rates. Adsorption of CD on the electrode surface is also mentioned.
The spectral characteristics of 2,4-dihydroxyazobenzene (DHAB, sudan orange G) and 4-hydroxy azobenzene (HAB) have been studied in various solvents, different hydrogen ion and β-cyclodextrin (β-CD) concentrations, and are compared with azobenzene (AB). The inclusion complexes of the above molecules with β-CD were analyzed by UV-vis spectrometry, flourometry, FT-IR, 1H NMR, SEM and DFT methods. The solvent study shows that only the azo form is present in DHAB and HAB molecules. The unusually large red shift observed in acidic solutions indicates both molecules exhibit azo-hydrazo tautomerization. In the β-CD solutions, the increase in fluorescence intensity and large bathochromic shift in the S1 state indicates that DHAB and HAB form 2:2 inclusion complexes, whereas AB forms a 1:1 inclusion complex.
Keywords2,4-Dihydroxyazobenzene–Azo-hydrazo tautomerism–
β-Cyclodextrin–Inclusion complex
The interaction of the analgesic prosidol [1-(2-ethoxyethyl)-4-phenyl-4-propionyl-oxypiperidine] and the anaesthetic kazcaine
[1-(2-ethoxyethyl)-4-ethynyl-4-benzoyloxypiperidine] with β-cyclodextrin (β-CD) in aqueous solutions has been studied by nuclear
magnetic resonance (NMR), ultraviolet (UV) and infrared (IR) spectroscopy. The composition and structure of the formed guest:β-CD
inclusion complexes have been determined and were found to have a molar ratio of 1:2, with the guest molecule located in the
cavity formed by two β-CD molecules in head-to-head orientation, with the O(2), O(3) rims interacting. The phenyl and ethoxyethyl
substituents of the guests are in contact with the β-CD molecules. In contrast to prosidol–base and kazcaine–base the complexes
with β-CD show a higher analgesic and local anaesthetic activity.
KeywordsKazcaine and prosidol base–Cyclodextrin–Anaesthetic and analgesic–2D NMR–
1H NMR–UV and IR-spectroscopy
To investigate the molecular interaction between β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD) and riboflavin (RF), and to test the anticancer potential of these formulations.
The physicochemical characterization of the association between RF and CDs was performed by UV-vis absorption, fluorescence, differential scanning calorimetry and NMR techniques. Molecular dynamics simulation was used to shed light on the mechanism of interaction of RF and CDs. Additionally, in-vitro cell culture tests were performed to evaluate the cytotoxicity of the RF-CD complexes against prostate cancer cells.
Neither βCD nor HPβCD led to substantial changes in the physicochemical properties of RF (with the exception of solubility). Additionally, rotating frame Overhauser effect spectroscopy experiments detected no spatial correlations between hydrogens from the internal cavity of CDs and RF, while molecular dynamics simulations revealed 'out-of-ring' RF-CD interactions. Notwithstanding, both RF-βCD and RF-HPβCD complexes were cytotoxic to PC3 prostate cancer cells.
The interaction between RF and either βCD or HPβCD, at low concentrations, seems to be made through hydrogen bonding between the flavonoid and the external rim of both CDs. Regardless of the mechanism of complexation, our findings indicate that RF-CD complexes significantly increase RF solubility and potentiate its antitumour effect.
Cyclodextrins are a family of cyclic oligosaccharides with a hydrophilic outer surface and a lipophilic central cavity. Cyclodextrin molecules are relatively large with a number of hydrogen donors and acceptors and, thus, in general they do not permeate lipophilic membranes. In the pharmaceutical industry cyclodextrins have mainly been used as complexing agents to increase aqueous solubility of poorly soluble drugs, and to increase their bioavailability and stability. Studies in both humans and animals have shown that cyclodextrins can be used to improve drug delivery from almost any type of drug formulation. However, the addition of cyclodextrins to existing formulations without further optimisation will seldom result in acceptable outcome. Currently there are approximately 30 different pharmaceutical products worldwide containing drug/cyclodextrin complexes on the market.
The binding mechanism of aripiprazole (APZ) with human serum albumin (HSA) in the absence and presence of three cyclodextrins (CyDs) (β-cyclodextrin, hydroxypropyl-β-cyclodextrin, and (2,6-di-O-methyl)-β-cyclodextrin) was studied by fluorescence, ultraviolet-visible absorption, nuclear magnetic resonance, and circular dichroism (CD) spectroscopy. The CD results revealed some degree of recovery of refolding caused by APZ after the addition of CyD. The Stern-Volmer quenching constant and binding constant of the APZ-HSA interaction were smaller in the presence of the three CyDs. The ultraviolet-visible absorption results indicated that APZ formed 1:1 complex with the three CyDs. The (1)H NMR spectra of CyD showed chemical shift and resolution loss of proton after the addition of HSA. Molecular modeling studies showed that both APZ and CyD bind to HSA. The process was initiated through inclusion of free APZ molecules by CyD and the increase in steric hindrance of CyD-HSA binding.
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The inclusion complexation of flavanone with beta-cyclodextrin was studied by ultraviolet absorption, steady state fluorescence, time-resolved fluorescence, and 2D ROESY nuclear magnetic resonance spectroscopic techniques. A 1:1 stoichiometric ratio was determined for the inclusion of flavanone with beta-cyclodextrin. The Stern-Volmer constant for the accessible fraction of the binding of flavanone with beta-cyclodextrin, and the binding constant for the flavanone-beta-cyclodextrin complex are reported. The flavanone- beta-cyclodextrin inclusion complex was characterized by 2D ROESY NMR spectroscopy. The binding of beta-flavanone with ctDNA and the effect of beta-cyclodextrin on the binding of flavanone to ctDNA were studied by absorption and fluorescence techniques. Binding constants are reported for the binding of flavanone with ctDNA and flavanone- beta-cyclodextrin with ctDNA. The mode of binding of flavanone to DNA and formation of inclusion complex with beta-cyclodextrin are proposed, supported by molecular modeling. The studies imply that beta-cyclodextrin acts as carrier of flavanone for binding with DNA.
The solvatochromic behavior of novel synthesized azo-containing viologen-based rotaxanes, combining push-pull linear and α or β-cyclodextrin macrocyclic components is examined. These rotaxanes are stoppered by pentacyanoferrate(II) units. The latter stabilize these systems and furthermore act as strong electron donors. These units are linked to strong electron withdrawing viologen units thus giving rise to an exceptionally intense solvatochromic behavior. Suitable solvent polarity scales and Linear Solvation Energy Relationships (LSERs) were employed in order to rationalize the solvent polarity effects observed, both specific and non-specific ones. The results for the title compounds as well as their Cyclodextrin-Free-Dumbbell (CFD) like analogue, are compared to recent published solvatochromic data regarding similar smaller pentacyanoferrate(II) complexes as
well as other highly solvatochromic compounds. Structural effects on the solvatochromic intensity as well as the contribution of different solvent-solute interactions are rationalized and quantified.
Studies of molecular inclusions of a congener series of guest amino acid molecules into the host cavity of α and β-cyclodextrins in aqueous solution have been focused on modern research gaining far reaching effect. With both the α and β-cyclodextrins, it is found that 1 : 1 hosts–guest inclusion complexes are formed with all the guest molecules at both low and high pH. The variation of the thermodynamic parameters with guest size and state are used to draw inferences about contributions to the overall binding from the driving forces, viz., hydrophobic effect, van der Waals forces, H-bonds, electrostatic forces, structural effect and configurational theory. The formation and comparative study of inclusion complexes have been analyzed by available data supplemented with surface tension, pH, density, viscosity, and refractive index.
The effect of beta-cyclodextrin (β-CD) on the peak height and voltage of the polarographic reduction of several esters of hydroxybenzoic acid has been investigated. Complexation with β-CD decreased both the amount of current conducted upon reduction and the half-wave potential of that reduction for each of the esters of hydroxybenzoic acid. This fall in conducted current resulted from the decreased diffusion rate of the ester when complexed with β-CD as compared to the ester alone. The half-wave potentials of the reductions became more negative in the presence of β-CD. The change in potential was in the rank order ethyl > propyl > butyl. This was a result of the electron redistribution occurring in the presence of β-CD due to the formation of inclusion complexes, and reflected the tendency of these esters to complex with β-CD. These results suggest that polarography is suitable for studying the inclusion complexation phenomenon of β-CD with electroactive molecules in aqueous solution and may prove to be a powerful technique in further elucidating the nature of the inclusion complex.
The UV/Visible spectra of m-methyl red (m-MR) ({3-[4-(dimethyl-amino) phenylazo] benzoic acid}) were examined in basic, acidic and strongly acidic aqueous solutions. The observed spectra of m-MR were analyzed and compared with the tautomeric and resonance structures that suggested theoretically. Three isosbestic points in the spectra were observed around 508, 464 and 443 nm representing three different equilibriums between four different species of m-MR. The inclusion constant (Kf) for the inclusion of basic form of m-MR with alpha-, Beta-, and gamma-Cyclodextrin (α-, β- and γ-CD) was evaluated at different temperatures using Benesi-Hildebrand method. The values of Kf at 25 °C were found to be 8.70 × 103, 4.93 × 103 mol−1 dm3 and 2.95 × 107 mol−2 dm6 basis on the inclusion complex ratios (m-MR:CD) of 1:1, 1:1, and 2:1 respectively. The values of the thermodynamic quantities ΔH°, ΔS°, ΔG° for the different inclusion processes were calculated by using Van’t Hoff plot. For all cases of the studied inclusion processes, these inclusions were favored through entropy and enthalpy changes.
β-Cyclodextrin forms the 1:1 inclusion complex with Crystal Violet, Methylene Blue, Methyl Orange, or Congo Red in water. On the other hand, γ-cyclodextrin forms the 1:2 complex with Crystal Violet, Methylene Blue, or Methyl Orange, while the 1:1 complex is given with Congo Red. The one host-two guest complexations are shown on the bases of the changes of the electronic spectra, dependence of induced circular dichroisms on the concentrations of dyes, and the continuous variation methods with induced circular dichroism. The dissociation constants for the 1:2 complexes are determined with the improved Benesi-Hildebrand equation. Alternation between the 1:1 and 1:2 complexation is discussed in terms of the cavity size of cyclodextrin and the aggregation character of dye.
Detailed solution kinetic and equilibria data in aqueous solution are presented for the molecular recognition by α-cyclodextrin (α-CDx) of structually different types of 2-naphthylazophenol guest. 1H NMR equilibrium titrations and stopped-flow data have allowed the determination of the proposed structure of the intermediate, equilibrium constants, and the rate and mechanism for the molecular recognition by α-cyclodextrin. Some kinetic data are consistent with a two-step inclusion process wherein the intramolecular structural reorganization from the intermediate to the final inclusion complex is the rate-controlling step.1H NMR data also support the existence of stable intermediate species. The steric and charge factors affecting the directional inclusion process are discussed.
Three fluoroionophores Cn (n = 1, 3, 5), in which the crown ether unit and pyrenyl moiety are connected by a −(CH2)n− spacer, have been used to construct supramolecular Cn/γ-cyclodextrin (γ-CyD) complexes for alkali metal ion sensing in water. The Cn (n = 3, 5) are found to selectively form 2:1 complexes with K+ in the presence of γ-CyD and exhibit the pyrene dimer emission in water. Equilibrium analysis of the C3/γ-CyD complex reveals that the observed dimer emission arises from a 2:1:1 complex of C3 with K+ and γ-CyD. In the absence of K+, the fluorescence lifetimes for the dimer species ((C3)2CyD and (C3)2(CyD)2) and the monomer species (C3CyD and C3(CyD)2) are 13−18 and 130−180 ns, respectively. Upon addition of 0.10 M KCl, a rising component corresponding to pyrene excimer formation is observed at the dimer emission region. For the C3/γ-CyD complex, the apparent association constant for K+ of (3.8 ± 1.3) × 109 M-2 is only slightly affected by the presence of Na+. Although the C5/γ-CyD complex shows high sensitivity for K+, the selectivity for K+ over Na+ is lower than that of the C3/γ-CyD complex. In contrast, fluoroionophore C1 with the shortest methylene spacer exhibits no response for alkali metal cations in the presence of γ-CyD. These results demonstrate that the response function of supramolecular Cn/γ-CyD complexes is strongly affected by the methylene spacer length of Cn. The highest K+ selectivity is obtained for the C3/γ-CyD complexes in water.
A novel boronic acid fluorophore 1/beta -cyclodextrin (beta -CyD) complex sensor for sugar recognition in water has been designed. The probe 1 bearing pyrene moiety as a fluorescent signal transducer exhibits no fluorescence emission, due to its aggregation in water containing 2% DMSO; however, the addition of beta -CyD to this solution largely changes UV-vis and fluorescence spectra of 1 by forming an inclusion complex with beta -CyD, and an efficient fluorescence emission response of 1/beta -CyD complex upon sugar binding is found to be obtained at pH 7.5. The pH-fluorescence profile of the 1/beta -CyD complex reveals that the boronate ester formation with fructose induces the apparent pK(a) shift from 7.95 +/- 0.03 in the absence of fructose to 6.06 +/- 0.03 in the presence of 30 mM fructose, resulting in the fluorescence emission response under the neutral condition. The spectral properties of 1 in 95% methanol:5% water (v/v), as well as the fluorescence quenching study of l-methylpyrene with 4-methoxycarbonylphenyl-boronic acid 2, demonstrate that the response mechanism is based on the photoinduced electron transfer (PET) from the pyrene donor to the acid form of phenylboronic acid acceptor in 1, and thus, the proton dissociation of phenylboronic acid induced by sugar binding inhibits the PET system while increasing the fluorescence intensity of the pyrene moiety. To evaluate the binding ability and selectivity of the 1/beta -CyD complex for monosaccharides in water, the response equilibria have been derived. The 1:1 binding constants of the 1/beta -CyD complex obtained from the equilibrium analysis are in the order: D-fructose (2515 +/- 134 M-1) much greater than L-arabinose (269 +/- 28 M-1) > D-galactose (197 +/- 28 M-1) > D-glucose (79 +/- 33 M-1), which is consistent with the binding selectivity of phenylboronic acid.
In this paper, a simple, rapid, sensitive and accurate electroanalytical method of Basic Brown G (BBG) has been established by polarography and voltammetry. In ammonia–ammonium chloride (pH 9.1), a sensitive second derivative reduction peak (ip″) of BBG was found by Linear Sweep Voltammetry (LSV). The peak potential (Ep) is about −0.67V (versus SCE). The peak current (ip″) is proportional to the concentration of BBG over the range 3.0×10−8–1.0×10−4molL−1 (r=0.9935–0.9987) and the limit of detection (LOD) is 9.0×10−9molL−1. The recovery of BBG varied from 95.3 to 102% and the relative standard deviation (RSD) was 2.4% (n=10). The method has been expected to achieve the determination of the concentration of remnants of dyes of wastewater in dye industry. In addition, the supramolecular system of BBG with cyclodextrins (CDs) has been studied. BBG can form 1:2 (BBG:CD) inclusion complex with α-CD and HP-α-CD, respectively, and 1:1 inclusion complex with other six CDs. The inclusion constants were calculated and the inclusion ability of different kinds of CDs was compared, furthermore, the inclusion mechanism is also preliminarily discussed, which provided some valuable information for further application of BBG and CDs.
The inclusion complexation of pyrimethamine in 2-hydroxypropyl-β-cyclodextrin has been investigated by 2D 1H NMR, FTIR and UV/visible spectroscopy and also by molecular modelling methods (AM1, PM3, MM3). From the phase-solubility diagram a linear increase was observed in pyrimethamine aqueous solubility in the presence of 2-hydroxypropyl-β-cyclodextrin, evidencing the formation of a soluble inclusion complex. According to the continuous variation method (Job’s plot) applied to fluorescence measurements, a 1:1 stoichiometry has been proposed for the complex. Concerning the structure of the complex, a Cl-in orientation of pyrimethamine in the 2-hydroxypropyl-β-cyclodextrin cavity has been proposed from the theoretical calculations, being confirmed by two-dimensional 1H NMR spectroscopy (ROESY). The thermal behaviour has also been studied, providing complementary evidences of complex formation.
Cyclodextrins are frequently used as building blocks, because they can be linked both covalently and noncovalently with specificity. Thus one, two, three, seven, fourteen, eighteen, or twenty substituents have been linked to one β-cyclodextrin molecule in a regioselective manner. Furthermore, Cyclodextrins may serve as organic host molecules. Their internal cavity is able to accommodate one or two guest molecules. Conversely, suitable guest molecules can be used to thread one, two, or many (one hundred or more) cyclodextrin rings. The resulting supramolecular structures are often formed in solution, which allows characterization by high-resolution spectroscopic methods. Chemical conversion of these structures provides molecular architectures such as catenanes, rotaxanes, polyrotaxanes, and tubes, which are not readily prepared by other methods. The particular properties of Cyclodextrins can also be employed, for example, for the chromatographic separation of complex mixtures of substances, even racemates, by molecular recognition. Cyclodextrins and their derivatives have been found to be remarkably active catalysts as well. Finally, since Cyclodextrins can favorably influence the release of drugs, many new applications will certainly be developed in the near future.
α-, β-, and γ-Cyclodextrins are cyclic oligosaccharides consisting of six, seven, or eight glucose units, which can be obtained on a large scale from starch. They form inclusion compounds with smaller molecules which fit into their 5—8 Å cavity. These (crystalline) complexes are of interest for scientific research as, contrary to the classical clathrates, they exist in aqueous solution and can be used to study the hydrophobic interactions which are so important in biological systems. Cyclodextrins also serve as models both for polymeric starch and, in the form of their polyiodide complexes, for “blue iodine-starch”. As cyclodextrins catalyze several chemical reactions they and their functionalized derivatives provide useful enzyme models. Cyclodextrins can be used to advantage in the production of pharmaceuticals, pesticides, foodstuffs, and toilet articles—the (micro-encapsulated) active and aromatic substances enclosed within them are protected from the effects of light and atmosphere and can be easily handled and stored in powder from. Substances which are not very soluble in water become more soluble in the presence of cyclodextrins—creams and emulsions can be stabilized, and the growth and yield of grain harvests can be increased. Cyclodextrins can be chemically modified for many different purposes; polymerized cyclodextrin or cyclodextrin bound to a polymer carrier have already been employed in gel inclusion and affinity chromatography.
The formation of an inclusion complex of methylene blue with β-cyclodextrin is testified by voltammetry and spectroscopy and its stable constant is determined to be 4.4×103M−1. The interactions of methylene blue and the inclusion complex with DNA have been investigated by means of voltammetry. The binding constants of methylene blue and the inclusion complex to DNA are obtained through the changes of peak currents and their values are 1.1×104M−1 and 7.2×103M−1, respectively. The experimental results reveal that the inclusion complex does not decompose when it interacts with DNA, and β-cyclodextrin itself does not interact with DNA.Their binding numbers (n) are 1 both methylene blue and the inclusion complex. According to the experimental data, it can be inferred that the binding model of methylene blue to DNA may be `electrostatic binding' under our experimental conditions. This can clearly explain the experimental phenomena.
The adsorption of α- and β-cyclodextrins on the surface of the dropping mercury electrode was examined in a phosphate buffer solution by means of voltammetry with a triangular potential sweep. The α- and β-cyclodextrins gave two capacitive peaks corresponding to the adsorption and desorption processes respectively. The α-cyclodextrin additionally gave two cathodic peaks and an anodic peak, probably due to reorientation processes. The effects on the peak heights were investigated in terms of the sweep rate, the cyclodextrin concentration, the temperature, the ionic strength, and the pH. The adsorption of both cyclodextrins followed the Langmuir isotherm, and the equilibrium constants for the adsorption were evaluated to be 1.2×104 M−1 for α-cyclodextrin and 1.0×105 M−1 for β-cyclodextrin at 25°C and pH 6.5.
A calix[4]arene-based oligomer 5 and a β-cyclodextrin polymer 6 were synthesized by the condensation of p-tert-butylcalix[4]arene and β-cyclodextrin, respectively, with hexamethylene diisocyanate. In their batch sorption of selected azo dyes, the β-cyclodextrin polymer 6 was found to be a better azo dye sorbent than the p-tert-butylcalix[4]arene-based oligomer 5. In addition, oligomer 4 containing pendant calix[4]arene units with crown-6 functionalities on the lower rim was synthesized and its complexation of the azo dyes was investigated by liquid–liquid extraction. The calix[4]crown-6 oligomer 4 showed the highest affinity for the azo dyes.
The hydrophobic effect was used to assemble encapsulated azo dyes such as 1 in water. The dumbbell-shaped dyes were synthesized inside α-cyclodextrin, β-cyclodextrin, or a cyclophane to yield stable rotaxanes.
The thermal decomposition of the solid inclusion complexes of ferrocene and its derivatives with β-CD was studied by DTA, TG and DTG. The inclusion complexes contain crystallization water and the first decomposition stage corresponds to the dehydration of the complexes. The second stage is related to the liberation of the ferrocene and its derivatives, and the degradation of the β-CD structure takes place in the third stage. However, the second and third stages of decomposition for some of the inclusion complexes occur in the same temperature ranges and are impossible to distinguish. The final decomposition products formed around 500°C consist mainly of Fe2O3. The thermal behaviour of physical mixtures of these ferrocene derivatives and β-CD was also investigated. The thermal analysis results show that the interaction of ferrocene and its derivatives with β-CD is a chemical phenomenon. The ferrocene derivatives gain an additional thermal stability after inclusion complexation into the β-CD cavity. Thermal analysis methods can be used satisfactorily for the recognition of inclusion complexation.
In this paper, the interactions of meso-Tetrakis (4-sulfonatophenyl) porphyrin (TPPS 4 ) and six cyclodextrins have been studied, respectively, by fluorescence spectroscopy, polarography and thin-layer chromatography. The inclusion constants of different methods are determined and the comparison of inclusion capacity of various cyclodextrins indicates that for the ionic cyclodextrins the charge interaction plays an important role in the inclusion procedure. The thermodynamic parameters of interaction imply that the inclusion process shows the enthalpy-entropy compensation effect. Cyclodextrin, being regarded as an artificial analogue of proteinoid of heme, provides a protective sheath for porphyrin. However, the TPPS 4 , encapsulated within this saccharid-coated barrier, its solubility is enhanced prominently, which exhibits that this interaction may modify the biological properties of TPPS 4 that owned the similar properties as hematoporphyrin.
The inclusion complex of capric (C10) and caprilic (C8) acids with β- and γ-cyclodextrins (CDs) was analyzed, in the solid state, by differential scanning calorimetry (DSC), thermogravimetry (TGA), and infrared spectroscopy (FT-IR). Special attention was paid to the acid behavior in terms of the quantity incorporated and the thermal stability. The results showed that the maximum amount of incorporated acid in β-CD occurred at molar ratio (CD:acid) of 1:1 and 1:1.5 for C10 and C8, respectively. For the same acids in γ-CD, the proportions increased to 1:1.5 (C10) and 1:2 (C8). The heat for the water volatilization was higher in γ-CD (ca. 91 cal g−1) than β-CD (ca. 52 cal g−1) systems, for both acids, probably because of the high cavity size of γ-CD. Although, both systems improved additional thermal stability with the complex formation, the acids acquired a higher thermal stability in the β-CD inclusion complex.
The thermodynamics properties of the 1 guest−1 host ground-state complex were determined from near UV absorbance measurements as a function of temperature. Entropy changes for formation of the binary and ternary complexes suggest that the brominated end of the guest molecule is attached to the first host molecule, and the hydroxyl end is encapsulated by the second host. The enthalpy of stabilization is approximately twice as great for the ternary complex as for the binary complex in the ground state. A molecular kinetics mechanism is presented that is used to determine some of the dynamics properties of the 1 guest−2 host complex from measurements of the pulsed laser-induced phosphorescence that emanates from the triplet state of 6-bromo-2-naphthol. The rate of dissociation of the triplet-state ternary complex is governed by a large Arrhenius activation energy (82 ± 1 kJ/mol), and the dissociation rate constant (k-d = 8400 s-1 at 25 °C) is more than an order of magnitude smaller than that in typical binary complexes of cyclodextrins. It is suggested that the apparent increased stability of the ternary complex over the binary complex is due to general van der Waals interactions and/or hydrogen bonding between host molecules.
The photoisomerization of methyl orange (MO) encapsulated in the cavities of α-, β-, and γ-cyclodextrins (CDs) was measured by the ultrafast transient lens (UTL) method and transient absorption spectroscopy. The signal for free MO was well-fitted to the sum of two exponential functions, except for the component of the optical Kerr effect (OKE), and their time constants were 1 (τ1) and 10 ps (τ2). The UTL signal of the 1:1 complex, in which one MO molecule was included in one CD molecule, was almost the same as that of free MO. On the other hand, MO in two α-CD molecules showed slower relaxation and considerably lower yield of cis isomer. Thus, there were clear confinement effects when MO was capped at both ends by two CD molecules. The observed changes of ultrafast dynamics and yield of the isomer were explained in terms of CD−MO interactions and a steric effect. In the case of γ-CD, which included two MO molecules as a dimer, these confinement effects were also observed even when each MO was capped on only one side (2:1 complex). These results showed that a strong intermolecular interaction was induced between two MO molecules by confinement in a nanospace and this also hindered the isomerization. In particular, the complex with two γ-CD molecules (2:2 complex) showed significantly slower relaxation than the others, and no cis isomer was formed. It seemed that the intermolecular interaction of two MO molecules was further enhanced by photoexcitation in the 2:2 complex and this resulted in the formation of an aggregate-like intermediate in the γ-CD nanocavity.
The cis−trans thermal isomerization of p-methyl red (1), o-methyl red (2), and methyl orange (3) was inhibited by β-cyclodextrin (β-CD) at constant pH. Their isomerization rate decreased 4, 8, and 1.67 times, respectively, in a solution containing 0.01 M β-CD. This effect can be attributed to the formation of an inclusion complex between the substrate and β-CD which hinders the rotation of the NN bond. The isomerization rate of methyl yellow (4), 4-(dimethylamino)-4‘-methoxyazobenzene (5), and naphthalene-1-azo[4‘-(dimethylamino)benzene] (6) was not affected by β-CD due to the presence of an organic cosolvent in the solution which displaces the azobenzene from the cavity, and the complex formed is probably equatorial. In addition, the transition state for the isomerization of compounds 1−3 involves rotation and that of 4−6, which have only electron-donating groups, inversion. This latter process brings about less volume change than rotation so it is less hindered by the complexation with β-CD.
Voltammetric methods were used to probe the interaction (electrostatic or intercalative) of metal complexes, ML33+/2+ (M = Fe, Co; L = 1,10-phenanthroline, 2,2′-bipyridine), with calf thymus DNA. Binding constants (Kn+) and binding site sizes (s) were determined from voltammetric data, i.e., shifts in potential and changes in limiting current with addition of DNA. The exact magnitude for the parameters depends on whether the ML33+/2+/DNA reaction is assumed to be static (S) or mobile (M) within the characteristic time of a voltammetric experiment. Co(phen)33+/2+ binds via intercalation with K3+ = 1.6 (±0.2) × 104 M-1 (S, s = 6 bp) to 2.6 (±0.4) × 104 M-1 (M, s = 5 bp). The 2+ ion interacts more favorably via hydrophobic interaction with the nucleotide bases than does the 3+ ion. Both forms of the Fe(phen)32+/3+ couple bind with approximately the same affinity, K2+ = 7.1 (±0.2) × 103 M-1 (S, s = 5 bp) and 1.47 (±0.04) × 104 M-1 (M, s = 4 bp). Co(bpy)33+/2+ shows appreciable electrostatic binding in 50 mM NaCl solution [K3+ = 9.4 (±1.5) × 103 M-1 (S) to 1.4 (±0.3) × 104 M-1 (M), s = 3 bp in each case], whereas Fe(bpy)32+/3+ does not bind at these ionic strengths. At lower ionic strength (10 mM NaCl, 10 mM Tris, pH 7.1), binding of Fe(bpy)32+/3+ is enhanced [K2+ = 1.1 (±0.6) × 103 M-1 nS, s = 4 bp) to 1.4 (±0.1) × 103 M-1 (M, s = 3 bp)].
Enzymatic synthesis, employing horseradish peroxidase (HRP), has been used to prepare a novel photoactive azopolymer, poly(4-phenylazophenol), from 4-phenylazophenol. FTIR, FT-Raman, and NMR (1H, 13C) spectroscopy show that the coupling reaction occurs primarily at the ortho positions with some coupling at the meta positions of the phenol ring of the monomer as well. This results in the formation of a branched polyphenylene backbone with pendant azo functionalities on every repeat unit of the macromolecules. This enzymatically synthesized azophenol polymer has an extremely high dye content (nearly 100%) and is soluble in most polar organic solvents, and good optical quality thin films are easily formed. Polymer solutions show reversible trans to cis photoisomerization of the azobenzene groups with long relaxation time. The poly(azophenol) film exhibits photoinduced absorption dichroism and large photoinduced birefringence with unusual relaxation behavior. The resulting azobenzene loaded polymer behaves as a new type of glassy “macromolecular dye”.
The state of the art of the electrochemistry of α-, β-, and γ-cyclodextrins (CDs) and cyclodextrin inclusion complexes and their polarographic and voltammetric assay are reviewed. The polarographic and voltammetric determination of physicochemical parameters of CD inclusion complexes are discussed. Practical applications of adsorption and inclusion effects for electroanalytical purposes are presented future prospects are discussed, and 95 references are given.
β-Cyclodextrin was tested as a dye complexing agent – as a dye retardant in the dyeing of PAN fibres with cationic dyes. Significant improvement of colour uniformity and some improvements in colour depth were observed when PAN fibres were dyed in the presence of β-cyclodextrin as compared to dyeing in the presence of a commercial retardant.
Two novel -cyclodextrin (-CD) derivatives possessing azobenzene functional groups as a spectral probe, i.e., mono{6-O-[4-(phenylazo)phenyl]}--cyclodextrin (1) and mono{6-O-[4-((4-nitrophenyl)azo)phenyl]}--cyclodextrin (2), were synthesized in high yields, and their complexation behaviors with aliphatic alcohols were evaluated by using UV-vis, circular dichroism, and 1 H NMR spectroscopy. The induced circular dichroism (ICD) and 2D NMR spectroscopy investigations revealed that azobenzene groups attached to the -CD rim can be deeply embedded to the -CD cavity to form the intramolecular inclusion complexes in 10% DMSO aqueous solution. Increasing the ratio of DMSO in solution results in the gradual exclusion of the azobenzene sidearm from the -CD cavity. Upon complexation with guest adamantanols, modified -CD 1 or 2 displays two different binding models, that is, the competitive inclusion model for 2-adamantanol and the co-inclusion model for 1-adamantanol. These two different models reasonably explain the different binding behaviors and molecular selectivities of host -CDs toward guests. Therefore, besides acting as a spectral probe, azobenzene modified -CDs can also effectively recognize the size/shape of guest molecules, giving good molecular selectivity up to 91 for 2-adamantanol/(+)-borneol pair by 1 and the moderate enantioselectivity (K -/K +) 2.1) for (-)-/(+)-borneol pair by 2.
In this paper, the electrochemical behavior of the interaction of Reactive Brilliant Red K-2G (C.I. Reactive Red 15) with cyclodextrins in 0.1mol · l−1 NaCl (pH 6.9) has been studied by polarography and voltammetry. In a supporting electrolyte of NaCl (pH 6.9), a sensitive second derivative reduction peak (i
p
″) of Reactive Red 15 was found by linear sweep voltammetry (LSV). The peak potential is about −0.78V (versus SCE). On the addition of CDs into the Reactive Red 15 solution, the reduction peak current (i
p
″) of Reactive Red 15 decreases and the peak potential (E
p
) shifts to a more positive potential. The study shows that Reactive Red 15 can form 1:1 inclusion complexes with nine CDs. The inclusion constants were calculated by “electric current method”. Furthermore, the inclusion ability of different kinds of cyclodextrins was compared, which provided some elemental data for application of Reactive Red 15 and cyclodextrins.
The driving forces leading to the inclusion complexation of cyclodextrins were reviewed, which included the electrostatic interaction, van der Waalsinteraction, hydrophobic interaction, hydrogen bonding, release of conformational strain,exclusion of cavity-bound high-energy water, and charge–transferinteraction. It was shown that except for the release of conformation strain and exclusion of cavity-bound water, the otherinteractions were indeed contributive to the complex formation. However, it was concludedthat the enthalpy and entropy changes of the complexation were not good criteria to be used injudging whether a particular driving force was present or important, mainly because of theoccurrence of enthalpy-entropy compensation. On the other hand, the multivariate quantitativestructure-activity relationship analyses usually could illustrate which driving forces wereimportant in certain inclusion complexation systems.
The preparation and characterization of the crystalline inclusion complexes between a polymeric guest, poly(1,3-dioxolane)
(PDXL), and small-molecular hosts, cyclodextrins (CDs) are reported. It is observed that the polymer guest can form crystalline
inclusion complexes with three kinds of cyclodextrins, which may be attributed to the high oxygen atom density in PDXL chain.
The crystalline inclusion complexes were characterized with FTIR, TGA, X-ray diffraction, SEM, 1H NMR and 13C CP/MAS NMR spectroscopes. It was found that the crystalline inclusion complexes have higher temperature stability than the
pure CDs. The X-ray powder diffraction patterns of the crystalline inclusion complexes proved that they have columnar structures.
13C CP/MAS NMR spectra of the crystalline inclusion complexes indicate that CDs adopt a more symmetrical conformation in the
complexes, while pure CDs assume a less symmetrical conformation in the crystal without a guest inside their cavities. The
morphology of the crystal was observed by means of SEM.
The interaction of progesterone with beta-cyclodextrin (beta-CD) was studied by differential pulse polarography. The aim of the present work was to study the effect of beta-CD on the electrochemical behavior of progesterone in aqueous solution and also to analyze the molecular interactions involved in formation of the inclusion complex. The complex with stoichiometry of 1:1 was thermodynamically characterized. In addition, steered molecular dynamics (SMD) was used to investigate the energetic properties of formation of the inclusion complex along four different pathways (reaction coordinates), considering two possible orientations. From multiple trajectories along these pathways, the potentials of mean force for formation of the beta-CD progesterone inclusion complex were calculated. The energy analysis was in good agreement with the experimental results. In the beta-CD progesterone inclusion complex, a large portion of the steroid skeleton is included in the beta-CD cavity. The lowest energy was found when the D-ring of the guest molecule is located near the secondary hydroxyls of the beta-CD cavity. In the most probable orientation, one intermolecular hydrogen bond is formed between the O of the C-20 keto group of the progesterone and a secondary hydroxyl of the beta-CD.
Simple chemical catalysts have been designed to achieve some desirable features of enzymes. These novel catalysts are not proteins, but they may incorporate the typical enzyme catalytic groups and they achieve selectivity in their reactions by use of geometric control, as do enzymes. Catalysts that carry out geometrically controlled chlorinations of aromatic rings and steroids have been constructed. Other catalysts achieve the selective synthesis of amino acids, and still others imitate ribonuclease in detailed mechanism and hydrolyze RNA. Optimization of geometries has led to a rate acceleration of over 10(8) in one instance.
The interaction of lumazine, an antibacterial drug, with alpha-, beta-cyclodextrins and DNA in aqueous solution was studied by differential pulse stripping voltammetry and cyclic voltammetry as well as UV-vis spectroscopy. The electrochemical and absorption spectral data indicated a 1:1 complex formation of lumazine with alpha-, beta-cyclodextrins and DNA. The nature of the process, taking place at the hanging mercury drop electrode, was clarified. It was found that the complexation of lumazine molecules enhances the stacking interactions which might facilitate the formation of a perpendicularly stacked layer of lumazine-alpha-cyclodextrin complex on the electrode surface. Based on the variations in the current or absorbance, the formation constants and consequently, the Gibbs energy of these complexes were determined. The small size cavity of alpha-cyclodextrin was found to have a greater affinity for lumazine than the beta-cyclodextrin. Moreover, the interactions of lumazine-alpha-cyclodextrin or lumazine-beta-cyclodextrin inclusion complex with DNA have been investigated by means of voltammetry. The results suggest that lumazine displayed high affinity for DNA and the inclusion complex decomposed when it binds to DNA.
Monolayers of cyclodextrin host molecules on gold substrates are used as "molecular printboards" for the stable attachment of functionalized molecules through multiple supramolecular interactions. Adsorption is achieved through delivery as a supramolecular complex (see picture), whereas the desorption kinetics can be tuned by varying the cyclodextrin concentration in solution.
Three's company: The construction of a three-component organic free radical has been obtained with symmetric nitroxides and β-cyclodextrin. Its formation can be reversibly controlled by changing pH or temperature (see scheme).
Cyclodextrins are useful functional excipients, which are being used in an ever-increasing way to camouflage undesirable pharmaceutical characteristics, especially poor aqueous solubility. It has generally been assumed that the mechanism whereby cyclodextrins exert their effects, especially their augmentation of solubility, is via the formation of noncovalent, dynamic inclusion complexes. This is a model, which regards drug-cyclodextrin interactions as a discrete phenomenon and ignores the possible interaction of these complexes with one another. It is becoming increasingly apparent that such assumptions may not be universally applicable or all encompassing. Specifically, there is a growing body of evidence that supports the important contribution of non-inclusion-based aspects for drug solubilization by cyclodextrins including surfactant-like effects and molecular aggregation. This short review attempts to assess the available literature for areas in which such non-inclusion mechanisms are apparent and tries to interpret these in the context of a broader working theory as to how cyclodextrins exert their beneficial effects.