Chiral phenethylamine synergistic tricarboxylic acid modified β-cyclodextrin immobilized on porous silica for enantioseparation

In this work, a series of chiral phenethylamine synergistic tricarboxylic acid modified β-cyclodextrin bonded stationary phase for high performance liquid chromatography (HPLC) were synthesized via a simple one-pot synthesis approach. Various racemates (aryl alcohols, flavanones, triazoles, benzoin, etc.) were well separated on the tricarboxylic acid modified chiral stationary phases in both normal and reversed modes with good reproducibility and stability, and the influence of mobile phase composition on resolution (R_s) were deeply investigated. The RSD values of R_s for repeatability and column-to-column were below 1.28% and 3.05%, respectively. Hence, the fabrication of tricarboxylic acid modified chiral stationary phase (CSPs) is a new efficient strategy to improve the application of β-cyclodextrin as CSPs in the field of chromatography.     

Estimation of the molecular weights of noncovalent columnar polymers based on β-cyclodextrin by the measurement of the aggregation rate of their polymer inclusion complexes with polypropylene glycol

Noncovalent columnar polymers (NCPs) based on cyclodextrins (CD) are polymeric assemblies of molecules that have continuous hollow channels, the width of which is determined by the diameter of the cavity of the initial CDs. The repeating fragment in an NCP is the CD molecule. For NCPs that were obtained by the exclusion of polymer backbone macromolecule from the corresponding inclusion complexes (ICs) based on β-cyclodextrin (NCP_excl), the polymer length, expressed as the number of macrocycles in a single chain (n) is determined by the size of the included ligand, polypropylene glycol (PPG), and is the PPG polymerization degree divided by two. The determination of the molecular weight of an NCP obtained by the precipitation method (NCP_prec) is rather difficult, since they are present in the aggregated state rather than in the form of individual molecules in solution. To estimate the molecular weight of NCP_prec, an indirect method is used, which is based on the determination of the aggregation rate of the ICs formed as a result of the interaction between an NCP and polypropylene glycol with a fixed molecular weight (MW), in this case PPG 1000. The comparison of the aggregation rates of the inclusion between NCP_excb (which were synthesized using PPGs with different molecular weights) and PPG 1000 with the aggregation rate of the inclusion complex on the basis of NCP_prec provided the estimation for the MWs of single polymer chains. The fact that the samples of NCPprec contain ∼30% of the monomeric β-CD was taken into account when constructing the calibration curve. It was demonstrated that the MW of the polypropylene glycol corresponding to NCP_prec is 1320 Da. Consequently, ∼11–12 molecules of β-CD are included in the single chains of NCP_prec.     

Label-free and sensitive impedimetric nanosensor for the detection of cocaine based on a supramolecular complexation with β-cyclodextrin,immobilized on a nanostructured polymer film

Cocaine, a powerful addictive stimulant drug, has a variety of adverse effects on the body, thus its sensitive detection is very important. Here, we report on a simple, label-free, and sensitive impedimetric sensor for determination of cocaine based on its affinity to form an inclusion complex with β-cyclodextrin (β-CD). First, we prepared nanostructured poly N-acetylaniline film via electropolymerization of its monomer on a glassy carbon electrode (PNAANI/GC), subsequently overoxidized it, and conjugated β-CD to the polymer backbone. The designed and synthesized nanostructured PNAANI film serves a dual function in the sensor: on one hand, it maintains a high effective surface area on a geometrically small electrode that significantly enhances the number of β-CD molecules immobilized on the electrode; on the other hand, it provides an upright-oriented β-CD conjugation to the polymer backbone, thus all the β-CD receptors are actively involved in responding to the target. Sensitivity of the sensor was further enhanced by preconcentration of cocaine on the modified electrode surface. We attributed the changes in the interfacial charge transfer resistance (R _ct) of the electrode to cocaine concentration. Under optimized condition (pH 7.4, 5-min accumulation at an open circuit voltage), the sensor responded to cocaine concentration in the range of 100 nM–1.0 mM with a detection limit of 50 nM. Selectivity of the sensor for cocaine relative to some potential inferring compounds was also investigated, and the results were promising. The proposed approach exhibited an extended dynamic range, low detection limit, good sensitivity, and a desirable selectivity, which provides an efficient application prospect for on-field cocaine sensing.     

Turn-on fluorescent detection of captopril in urine samples based on hydrophilic hydroxypropyl β-cyclodextrin polymer

Analytical and Bioanalytical Chemistry - Here, one kind of hydrophilic hydroxypropyl β-cyclodextrin cross-linked polymer (HP-CDP) was prepared and used to establish a “turn-on”...     

The adsorption of mercury(II) on the surface of silica modified with β-cyclodextrin

Multistage chemical modification of the surface of silica with β-cyclodextrin was performed. IR spectroscopy and quantitative analysis of surface compounds were used to prove the structure of modified silica. The adsorption of Hg(II) from dilute solutions was studied. The adsorption affinity of silica for mercury ions increased because of the formation of supramolecular structures with chemically immobilized β-cyclodextrin.     

Influence of β-cyclodextrin on the protolytic and complexing ability of p-aminobenzoic acid

UV spectroscopy was used to study the protolytic properties and determine the ionization constants of p-aminobenzoic acid in the presence of β-cyclodextrin. Formation of supramolecular structures of 1: 1 composition was established. Stability constants of the β-cyclodextrin-p-aminobenzoic acid inclusion complex were calculated, as were the thermodynamic parameters (ΔG°, ΔH°, and ΔS°) of its formation. The complexing process between β-cyclodextrin and p-aminobenzoic acid was found to occur spontaneously in the temperature range under investigation while being accompanied by energy liberation and leading to a reduction in the system’s entropy.     

Monolithic silica columns with chemically bonded β-cyclodextrin as a stationary phase for enantiomer separations of chiral pharmaceuticals

An enantioselective silica rod type chiral stationary phase (CSP) is presented; a novel combination of the well known enantiomer separation properties of -cyclodextrin and the unique properties concerning the flow behavior of silica monoliths. Two different synthesis routes are described, and it was found that the in situ modification of a plain silica rod column turned out to be the best. The chromatographic behaviour of the -cyclodextrin silica rod was studied and compared with a very similar commercially available -cyclodextrin bonded particulate material (ChiraDex^®). Even if the amount of -cyclodextrin bound to the silica rod was only about half of the amount of -cyclodextrin bound to ChiraDex^® particles, good resolutions were achieved for a set of chiral test components like Chromakalin, Prominal, Oxazepam, Methadone and some other drugs. By taking advantage of the unique features of the silica rods relating to their flat H/u (Van Deemter) curves, fast enantiomer separations could be demonstrated.     

A quartz crystal microbalance study of β-cyclodextrin self assembly on gold and complexation of immobilized β-cyclodextrin with adamantane derivatives

Quartz crystal microbalance (QCM) was used to study the self-assembly of per-6-thio-β-cyclodextrin (t₇-βCD) on gold surfaces, and the subsequent inclusion interactions of immobilized βCD with adamantane-poly(ethylene glycol) (5,000 MW, AD-PEG), 1-adamantanecarboxylic acid (AD-C) and 1-adamantylamine (AD-A). From a 50 μM solution of t₇-βCD in 60:40 DMSO:H₂O, a t₇-βCD layer was formed on gold with surface density of 71.7 ± 2.7 pmol/cm², corresponding to 80 ± 3% of close-packed monolayer coverage. Gold sensors with immobilized t₇-βCD were then exposed alternately to six different concentrations of AD-PEG, 500 μM AD-C or 500 μM AD-A aqueous solutions for association, and water for dissociation. Association of AD-PEG conformed to a Langmuir isotherm, with a best fit equilibrium constant K = 125,000 ± 18,000 M⁻¹. For AD-C and AD-A, association (k _a ) and dissociation (k _d ) rate constants were extracted from kinetic profiles by fitting to the Langmuir model, and equilibrium constants were calculated. The parameters for AD-C were found to be: k _a = 100 ± 5 M⁻¹ s⁻¹, k _d = 110 (±18) × 10⁻⁴ s⁻¹, and K = 9,400 ± 1,700 M⁻¹. For AD-A, k _a = 58 ± 6 M⁻¹ s⁻¹, k _d = 154 (±7) × 10⁻⁴ s⁻¹, and K = 3,800 ± 400 M⁻¹. The results demonstrate the utility of QCM as a tool for studying small molecule surface adsorption and guest–host interactions on surfaces. More specifically, the kinetic and thermodynamic data of AD-C, AD-A, and AD-PEG inclusion with immobilized t₇-βCD form a basis for further surface association studies of AD-X conjugates to advance surface sensory and coupling applications.     

Investigation on the inclusion behaviour of baicalein with β-cyclodextrin and derivatives and their antioxidant ability study

The formation of the complexes of baicalein (Ba) with β-cyclodextrin (β-CD) and β-CD derivatives (HP-β-CD and Me-β-CD) was studied by UV–vis absorption spectroscopy, fluorescence method, nuclear magnetic resonance spectroscopy and phase-solubility measurement. The solid–inclusion complexes of Ba with CDs were synthesised by the co-precipitation method. The characterisations of the solid–inclusion complexes have been proved by infrared spectra and differential scanning calorimetry. Experimental conditions including the concentration of various CDs and media acidity were investigated in detail. The results suggested that the inclusion ratio of HP-β-CD with Ba was the highest among the three kinds of CDs. The binding constants (Ks) of the inclusion complexes were determined by fluorescence method and phase-solubility measurement. Kinetic studies of DPPH√ with Ba and CDs complexes were also done. The results indicated that the Ba/HP-β-CD complex was the most reactive form.     

Adsorption of organic molecules on a porous polymer surface modified with the supramolecular structure of melamine–cyanuric acid

The adsorption of organic molecules on the surface of a porous polymeric sorbent modified with a mixed cyanuric acid–melamine supramolecular structure is studied. The parameters of thermodynamic adsorption are considered and the contributions from intermolecular interactions to the Helmholtz energy of adsorption are assessed. Analysis of the molar changes in internal energy and adsorption entropy shows that the supramolecular structure formed on the surface could not exhibit dimension effects, indicating there were no cavities. The contributions from nonspecific interactions to the Helmholtz energy of adsorption generally fall, while those of specific interactions increase, indicating an increase in the polarity of the sorbent surface.

     

Effect of the concentration of organic modifier in an aqueous-ethanol mobile phase on the chromatographic retention and thermodynamic characteristics of the adsorption of enantiomers of α-phenylcarboxylic acids on silica gel with immobilized eremomycin antibiotic

Regularities of the chromatographic retention and thermodynamics of the adsorption of enantiomers of α-phenylcarboxylic acids on a chiral stationary phase with immobilized macrocyclic antibiotic eremomycin under conditions of reversed-phase liquid chromatography with aqueous-ethanol mobile phases are studied. Relationships between the retention characteristics of the acids, the enantioselectivity of their separation, and the concentration of organic modifier in the mobile phase are found. It is shown that the sterical structure of substituents on the chiral atoms of the acids affect the mechanism of retention. The compensation effect in the studied systems is considered.     

Mesoporous silica particles for selective detection of dopamine with β-cyclodextrin as the selective barricade

A mesoporous silica nanoparticle (MSN) based fluorescent sensor for dopamine was constructed with probes inside particle pores and β-cyclodextrin (β-CD) molecules on the particle surface as the selective barricade. The synergistic action of both the hydrophilic rim and hydrophobic cavity of β-CD ensures that the sensor can distinguish dopamine from other biological competitors.     

An aptamer based assay for the β-adrenergic agonist ractopamine based on aggregation of gold nanoparticles in combination with a molecularly imprinted polymer

A sensitive visual aptamer-based assay is presented for the determination of ractopamine (RAC) in animal feed beef. In the absence of RAC, the aptamer binds to gold nanoparticles (AuNPs) and this prevents the AuNPs to undergo salt-induced aggregation which usually is accompanied by a color change from red to blue. If however, RAC is present, it will bind to the aptamer while the AuNPs remain uncoated so that aggregation and a color change will occur due to salt-induced aggregation. This can be monitored by spectrophotometer or even with bare eyes. Under optimal conditions, the aptasensor exhibits a linear range that covers the 10 to 400 ng.mL￣¹ RAC concentration range. The limit of detection is as low as 10 ng.mL￣¹. In order to further improve selectivity, a RAC-selective molecularly imprinted membrane was prepared and used to pre-extract RAC from complex samples. The combined method (molecularly imprinted membrane and aptasensor) was applied to the determination of RAC in spiked animal feed and beef and gave recoveries that ranged from 72.7 % to 87.3 % for complete feed and from 78.2 % to 86.5 % for beef, respectively.

Open image in new window

Graphical abstract A sensitive visual aptamer-based assay based on aggregation of gold nanoparticles in combination with a molecularly imprinted polymer was developed for the determination of ractopamine (RAC) in animal feed and beef.

     

Polyelectrolyte microcapsules containing molecules of sulfated β-cyclodextrin in the structure of nanosized shell

Alternate adsorption of the molecules of poly(allylamine hydrochloride) (PAA) and sulfated β-cyclodextrin (sulfo-β-CD) is studied by piezoelectric microweighing upon the formation of coatings of nanosized thicknesses by the polyionic assembly procedure. The thickness of planar coatings on the surface of single-crystalline silicon is determined by ellipsometry. The layer-by-layer character of the formation of planar nanosized coating is revealed and assumptions about the structure of the PAA and sulfo-β-CD bilayers are stated. A comparison of the spherical microparticles of polystyrene, as well as manganese and calcium carbonates, demonstrated that it is feasible to use microparticles of calcium carbonate as a template for producing microcapsules. Microcapsules with shells containing five (PAA/sulfo-β-CD) layers are prepared and studied by confocal fluorescent microscopy.     

Influence of the surface structure of β-cyclodexrin-containing silica on the adsorption of mercury nitrate from dilute solutions

The construction of adsorption sites for mercury(II) by chemical immobilization of β-cyclodextrin and its functional derivatives on a surface of macroporous amorphous silica is proposed. It is shown that the adsorption of mercury(II) is adequately described by the Langmuir isotherm equation for monolayer adsorption on localized sites of energetically homogeneous surfaces. It is established that the considerably increased sorption of mercury nitrate on silica modified by different β-cyclodextrins is due to the formation of 1: 1 β-cyclodextrin-nitrate ion inclusion complexes on the surface and the participation of side functional groups of the upper edge of immobilized β-cyclodextrin molecules in the formation of mixed-ligand mercury(II) complexes.     

Synthesis of bifunctional peptide derivatives based on a β-cyclodextrin core with drug delivery potential

A selective, versatile, robust methodology for bifunctionalization of β-cyclodextrin is achieved allowing the attachment of peptides in varying C- and/or N-terminal combinations on resin using Fmoc SPPS. Two linkers are attached to cyclodextrin enabling selective binding to the resin (or a peptide attached to the resin). Continuation of peptide growth and/or cleavage from the resin follows, thus various combinations of peptide-cyclodextrin species are achieved. A model peptide (Gly-Ala) is used in this study to illustrate the potential of this system for attaching one or more bioactive peptides for drug transport and release purposes.     

NMR and molecular modelling studies on the interaction of fluconazole with β-cyclodextrin

Background  

Fluconazole (FLZ) is a synthetic, bistriazole antifungal agent, effective in treating superficial and systemic infections caused by Candida species. Major challenges in formulating this drug for clinical applications include solubility enhancement and improving stability in biological systems. Cyclodextrins (CDs) are chiral, truncated cone shaped macrocyles, and can easily encapsulate fluconazole inside their hydrophobic cavity. NMR spectroscopy has been recognized as an important tool for the interaction study of cyclodextrin and pharmaceutical compounds in solution state.     

Zwitterionic polymers—I. Synthesis of a novel series of poly(vinylsulphobetaines). Effect of structure of polymer on solubility in water

Six novel poly(vinylsulphobetaines) have been prepared by polymerization of the corresponding monomers. The monomers were obtained by addition of tertiary amines to alkenylsulphonylchlorides. The zwitterionic polymer derived from vinylsulphonylchloride exhibited the usual water solubility characteristics, i.e. insoluble in water, soluble in dilute sodium chloride solutions. By contrast, the polymer derived from 1-propenesulphonylchloride was found to be soluble both in water and in 0–2 M sodium chloride solutions. Furthermore, the intrinsic viscosity of the latter polymer undergoes only a very small change upon addition of salt. These results are rationalized by assuming the operation of steric effects on intrasalt interactions in the macromolecules.