Adsorption of Cd(II) ions on magnetic graphene oxide/cellulose modified with ß-cyclodextrin: Analytical interpretation via statistical physics modeling and fractal like kinetic approach.

In the present study, ß-cyclodextrin modified magnetic graphene oxide/cellulose (CN/IGO/Cel) was fabricated for removal of Cd(II) ions. The material was characterized through various analytical techniques like FTIR, XRD, TGA/DTA, SEM, TEM, and XPS. The point of zero charge of the material was obtained as 5.38. The controllable factors were optimized by Taguchi design and optimum values were: adsorbent dose-16 mg, equilibrium time-40 min, and initial concentration of Cd(II) ions-40 mg/L. The material shows high adsorption capacity (303.98 mg/g). The good fitting of Langmuir model to adsorption data (R2 = 0.9918-0.9936) revealed the monolayer coverage on adsorbent surface. Statistical physics model M 2 showed best fitting to adsorption data (R2 > 0.997), suggesting the binding of Cd(II) ions occurred on two different receptor sites (n). Stereographically n > 1 confirming vertical multi-molecular mechanisms of Cd(II) ions adsorption on CN/IGO/Cel surface. The adsorption energies (E1 = 23.71-28.95 kJ/mol; E2 = 22.69-29.38 kJ/mol) concluded the involvement of physical forces for Cd(II) ions adsorption. Kinetic data fitted well to fractal-like pseudo first-order model (R2 > 0.9952), concluding the adsorption of Cd(II) ions occurred on energetically heterogeneous surface. The kinetic analysis shows that both the film-diffusion and pore-diffusion were responsible for Cd(II) ions uptake. XPS analysis was utilized to explain the adsorption mechanism of Cd(II) ions onto CN/IGO/Cel.

Reduction of Beta Cyclodextrin by Curd Washing in Low-Cholesterol Manchego Cheese.

Beta-cyclodextrin (ß-CD) is a cyclic oligosaccharide consisting of seven glucose units. ß-CD is increasingly used in food research to reduce cholesterol due to its affinity for non-polar molecules such as cholesterol and as a natural additive. The purpose of this study was to evaluate the effect of curd washing in ewe's milk cheese on the reduction in cholesterol by ß-CD from pasteurized ewe's milk Manchego cheese and the characteristics of its main components: milk, lipids, and flavor. An approximately 98.45% cholesterol reduction was observed in washed experimental cheeses that were treated by using ß-CD. The remaining residual ß-CD from the effect of curd washing was 0.15% in mature cheese, of the initial 1% ß-CD treatment of the milk. The chemical properties (fat, moisture, and protein) did not change as a result of the curd washing with or without ß-CD. The curd washing with or without ß-CD on the levels of the various lipid fraction (fatty acids, triglycerides, and phospholipids) were comparable in treated and untreated cheeses. The effects of curd washing and the ß-CD treatment did not significantly affect flavor components or short chain free fatty acids. The ß-CD molecules were edible and nontoxic; as a result, they could be used safely in cholesterol removal processing in cheese manufacturing, improving the reduction in residual ß-CD by curd washing by 85%. Therefore, the present study suggests that curd washing combined with ß-CD is an effective process for cholesterol removal in Manchego cheese, preserving its desirable properties.

A New Benzyl Phenethanolamine-ß-Cyclodextrin Bonded Phase: Chiral Chromatography Performance and Application for LC-MS/MS Analysis of Pesticide Enantiomers in Fruits and Vegetables.

BACKGROUND: At present, the research on achiral drug and pesticide residue detection methods is still the mainstay at home and abroad, and there is still a lack of systematic research on the enantiomeric analysis of chiral drugs and pesticides. OBJECTIVE: In order to prepare a novel chiral stationary phase, whose "multi-mode" chiral separation chromatographic performance and its utility was verified. METHOD: An S-(-)-2-benzylamino-1-phenylethanol mono-derivative ß-cyclodextrin bonded stationary phase (BzCSP) was prepared based on the "thiol-ene" addition reaction. The chiral compounds including four types of chiral compounds were used as "probes," and their chiral chromatographic properties were evaluated. Furthermore, a new LC-MS/MS method for the determination of the enantiomeric residues of three chiral pesticides in five kinds of fruits and vegetables was established. RESULTS: The study found that the novel stationary phase was suitable for a variety of chromatographic modes (normal phase mode, reversed-phase mode, polar organic mode). The resolutions of hexaconazole (Hex), tebuconazole (Teb), and triticonazole (Trit) enantiomers could be up to 2.31, 1.68, and 1.48, respectively, within 30 min under reversed-phase chromatography. Based on the optimal chromatographic and mass spectrum conditions, a new LC-MS/MS quantitative method for the Hex, Teb, and Trit enantiomers was established by multi-reaction positive ion monitoring (MRM). The detection limits (LODs) of enantiomers were less than 0.89 µg/kg for Hex, 0.93 µg/kg for Teb, and 0.93 µg/kg for Trit, and the averaged recoveries of enantiomers were in the range of 75.8-106.3% for Hex, 77.4-116.3% for Teb, and 78.7-113.4% for Trit. The method had good reproducibility with the RSDs (<5%) for intraday and (<7%) for interday. CONCLUSIONS: The established method had the characteristics of good selectivity, high sensitivity, strong resistance to matrix interference, and good reproducibility. It is indicated that the stationary phase prepared by the "thiol-ene" addition reaction is a new type of multi-mode stationary phase, which has a good development value. HIGHLIGHTS: The study reported a new method for the rapid preparation of a rare "multi-mode" chiral stationary phase BzCSP based on the "thiol-ene" addition reaction and verified the practicability of BzCSP including good selectivity, high sensitivity, strong resistance to matrix interference, and good reproducibility.

Preparation of a polydopamine/ß-cyclodextrin coated open tubular capillary electrochromatography column and application for enantioseparation of five proton pump inhibitors.

An open tubular capillary electrochromatography column was prepared by immobilizing ß-cyclodextrin on the inner wall of pretreated capillary via noncovalent adsorption of polydopamine. The resulting coating layer on the capillary was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Electroosmotic flow was studied to evaluate the variation of the immobilized columns. The prepared columns showed good chiral separation performance toward five proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, rabeprazole, and omeprazole. The influences of ß-cyclodextrin concentration, coating time, buffer pH, buffer concentration, and applied voltage on separation were investigated. In the optimum conditions, the enantiomers of five analytes were fully resolved within 15 min with high resolutions of 4.57 to 8.13. The method was extensively validated in terms of accuracy, precision, and linearity and proved to be robust. The relative standard deviation values for migration times and peak areas of the analytes representing intraday and interday were less than 1.9 and 3.6%, respectively. Further, the polydopamine/ß-cyclodextrin coated capillary column could be successively used over 100 runs without showing significant decrease in the separation efficiency.

Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre, randomized, double-blind controlled trial.

OBJECTIVES: To determine if commercially available mouthwash with ß-cyclodextrin and citrox (bioflavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load. METHODS: In this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive patients aged 18-85 years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8 days were recruited. A total of 176 eligible patients were randomly assigned (1:1) to CDCM or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6 days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2. RESULTS: The intention-to-treat analysis demonstrated that, over the course of 1 day, CDCM was significantly more effective than placebo 4 hours after the first dose (p 0.036), with a median percentage (log10 copies/mL) decrease T1-T2 of -12.58% (IQR -29.55% to -0.16%). The second dose maintained the low median value for the CDCM (3.08 log10 copies/mL; IQR 0-4.19), compared with placebo (3.31 log10 copies/mL; IQR 1.18-4.75). At day 7, there was still a greater median percentage (log10 copies/mL) decrease in salivary viral load over time in the CDCM group (-58.62%; IQR -100% to -34.36%) compared with the placebo group (-50.62%; IQR -100% to -27.66%). These results were confirmed by the per-protocol analysis. CONCLUSIONS: This trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva.

The Enantiomeric Discrimination of 5-Hexyl-2-methyl-3,4-dihydro-2H-pyrrole by Sulfobutyl ether-ß-cyclodextrin: A Case Study.

1-Pyrrolines are important intermediates of active natural products, such as the 2,5-dialkyl-1-pyrroline derivatives found in fire ant venoms. Here, 5-hexyl-2-methyl-3,4-dihydro-2H-pyrrole was synthesized by the enzymatic transamination/cyclization of 2,5-undecadione, and enantiodifferenciation was successfully achieved by capillary electrophoresis with sulfobutyl ether-ß-cyclodextrin as the chiral selector. The rationale of the enantiomeric discrimination was based on the results of a docking simulation that revealed the higher affinity of (S)-5-hexyl-2-methyl-3,4-dihydro-2H-pyrrole for the sulfobutyl ether-ß-cyclodextrin.

Delivery of Alpha-Mangostin Using Cyclodextrins through a Biological Membrane: Molecular Dynamics Simulation.

α-Mangostin (MGS) exhibits various pharmacological activities, including antioxidant, anticancer, antibacterial, and anti-inflammatory properties. However, its low water solubility is the major obstacle for its use in pharmaceutical applications. To increase the water solubility of MGS, complex formation with beta-cyclodextrins (ßCDs), particularly with the native ßCD and/or its derivative 2,6-dimethyl-ß-CD (DMßCD) is a promising technique. Although there have been several reports on the adsorption of ßCDs on the lipid bilayer, the release of the MGS/ßCDs inclusion complex through the biological membrane remains unclear. In this present study, the release the MGS from the two different ßCDs (ßCD and DMßCD) across the lipid bilayer was investigated. Firstly, the adsorption of the free MGS, free ßCDs, and inclusion complex formation was studied by conventional molecular dynamics simulation. The MGS in complex with those two ßCDs was able to spontaneously release free MGS into the inner membrane. However, both MGS and DMßCD molecules potentially permeated into the deeper region of the interior membrane, whereas ßCD only adsorbed at the outer membrane surface. The interaction between secondary rim of ßCD and the 1-palmitoeyl-2-oleoyl-glycero-3-phosphocholine (POPC) phosphate groups showed the highest number of hydrogen bonds (up to 14) corresponding to the favorable location of ßCD on the POPC membrane. Additionally, the findings suggested that electrostatic energy was the main driving force for ßCD adsorption on the POPC membrane, while van der Waals interactions played a predominant role in DMßCD adsorption. The release profile of MGS from the ßCDs pocket across the lipid bilayer exhibited two energy minima along the reaction coordinate associated with the permeation of the MGS molecule into the deeper region of the POPC membrane.

Spatially Resolved Chemical Detection with a Nanoneedle-Probe-Supported Biological Nanopore.

In this article, we describe the quantitative characterization of a gold nanoneedle ion channel probe and demonstrate the utility of this probe for spatially resolved detection of a small molecule using ion channel activity. Our report builds on recent reports of Ide and co-workers, who reported the use of an etched gold wire modified with a poly(ethylene) glycol monolayer as a support for a lipid bilayer and subsequent single ion channel recordings. Although this nanoneedle electrode approach was reported previously, in our report, we investigate the effects of several operational parameters on the performance of the ion channel measurement and electrochemical phenomenon that occur in the nanoconfined space between the supported bilayer and the gold electrode. More specifically, we address the effects of length of the supporting monolayer and the composition of the electrolyte baths on channel current measurements and provide a quantitative description of what carries current at the working electrode (double-layer charging). In addition, we demonstrate the ability to control the direction of protein insertion (tip side vs bath side) with freely diffusing protein, which has not been previously reported, with the former method (tip side) enabling single-molecule detection of ß-cyclodextrin (ßCD) using a reconstituted α-hemolysin channel. Finally, anticipating future use of a nanoneedle-based biological nanopore probe in a scanned-probe microscopy, we demonstrate the ability to quantify and spatially resolve the concentration of ßCD molecules in a microfluidic channel. We believe, in the long term, the described nanoneedle-based biological nanopore probe can be employed in, for example, scanning ion conductance microscopy using ion channels.

Effect of sulfobutyl ether-ß-cyclodextrin and propylene glycol alginate on the solubility of clozapine.

Clozapine (CLZ) is an atypical antipsychotic medication used in the treatment of schizophrenia and is poorly soluble in water (0.05 mM). In this study, we have investigated the effect of ß-cyclodextrin (CD) and its derivatives on the solubility of CLZ. The solubility of the CLZ was measured to generate a phase solubility diagram, and the interaction between CLZ and sulfobutyl ether-ß-cyclodextrin (SBE-ß-CD) in aqueous solution was observed by 1H- and 2D rotating-frame Overhauser enhancement spectroscopy (ROESY)-NMR methods. Moreover, the synergistic effect of SBE-ß-CD and water-soluble polymers, including polyvinylpyrrolidone, hydroxypropyl methylcellulose, carboxymethylcellulose sodium salt, polyvinyl alcohol, sodium alginate, and propylene glycol alginate (PGA), on the solubility of CLZ was investigated. The results show that the solubility of CLZ with 1 w/v% PGA was 7.6 mM, which was almost four times greater than that of CLZ without PGA in a 15 mM SBE-ß-CD solution. In contrast, the solubility of CLZ with 1 w/v % PGA in an aqueous solution decreased by one-third relative to that of CLZ in a 15 mM SBE-ß-CD solution. 2D ROESY-NMR indicated that a CLZ/SBE-ß-CD/PGA ternary complex formed. It was found that the combination of PGA and SBE-ß-CD enhanced the solubility of CLZ.

The effect of intake of sausages fortified with ß-CD-I2 complex on iodine status and thyroid function: A preliminary study.

The present study evaluated influence of boiled sausages consumption fortified with ß-CD-I2 on the urinary iodine excretion (UIE) level of volunteers. Median urinary UIE level was increased from 58.02 (24.0-175.4) µg/L to 110.6 (20.5-231.6) µg/L during 10 days. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were determined by radio immunoassay analysis. As it was expected, intake of sausages fortified with ß-CD-I2 resulted in rise of FT4 level from 1.1 (0.95-1.25) to 1.23 (1.07-1.63) ng/dL, whereas TSH level decreased from 1.53 (0.47-3.37) mIU/L to 1.1 (0.51-3.17) mIU/L. A dynamic gastrointestinal model in vitro was used in order to determine possibility of 3,5-diiodotyrosine (DIT) formation during consumption of the fortified sausages. The DIT concentration was determined by HPLC-MS method and was found to be 0.38 ng/mL in sausage dialyzate. These findings indicate that ß-CD-I2 introduction as an iodine carrier in boiled sausages may help to improve iodine status and to control organic iodine species concentration.

Preparation and characterization of dialdehyde ß-cyclodextrin with broad-spectrum antibacterial activity.

Consumers demand more alternatives of riskless antibacterial agents to prevent microbial contamination in food industry. Oxidized carbohydrate may be a potential option as new antibacterial agent. However, the relatively weak antibacterial property of oxidized carbohydrate is not satisfactory. In this paper, dialdehyde ß-cyclodextrins with different oxidation degree were prepared by periodate oxidation and their antibacterial properties were systematically studied. The results showed that multi-aldehyde groups were successfully introduced into ß-cyclodextrin molecules by periodate oxidation. The aqueous solubility and stability of dialdehyde ß-cyclodextrins were improved as expected. It is interesting that dialdehyde ß-cyclodextrins possessed outstanding antibacterial activity against both Gram-positive and Gram-negative bacteria. The minimal inhibitory concentrations against E. coli, S. aureus and B. subtilis reached 0.63, 1.25 and 0.63 mg/mL, respectively. Moreover, dialdehyde ß-cyclodextrins effectively inhibited bacterial growth on the surface of apples. The results demonstrated that oxidized oligosaccharide with multi-aldehyde groups and good dispersibility in aqueous solution possessed satisfactory antibacterial activity, which can be used as new antibacterial agent in food industry.

Cholesterol of lipid rafts is a key determinant for entry and post-entry control of porcine rotavirus infection.

BACKGROUND: Lipid rafts are major structural components in plasma membranes that play critical roles in many biological processes including virus infection. However, few reports have described the relationship between lipid rafts and porcine rotavirus (PRV) infection. In this study, we investigated whether or not the locally high concentrations (3-5 fold) of cholesterol present in lipid rafts are required for PRV infection, and further examined which stages of the infection process are most affected. RESULTS: When cellular cholesterol was depleted by methyl-ß-cyclodextrin (MßCD), PRV infectivity significantly declined in a dose-dependent manner. This inhibition was partially reversed upon reintroduction of cholesterol into the system. This was corroborated by the co-localization of PRV with a recombinant, GPI-anchored green fluorescent protein, which functioned as a marker for membranous regions high in cholesterol and indicative of lipid rafts. Changes in virus titer and western blot analyses indicated that depletion of cellular cholesterol with MßCD had no apparent effect on PRV adsorption; however, depletion of cholesterol significantly restricted entry and post-entry of PRV into the cell. Both points of inhibition were restored to near normal levels by the addition of exogenous cholesterol. CONCLUSIONS: We conclude from these studies that membrane-based cholesterol and in particular that localized to lipid rafts, is an indispensable biomolecule for PRV infection, and that cholesterol-based control of the infection process takes place during entry and immediately post-entry into the cell.

Avaliação do impacto causado pela disponibilidade de 17β-estradiol livre ou complexado à β -ciclodextrina no ambiente aquático sobre Oreochromis niloticus (tilápia) / Impact evaluation caused by disponibility of free and complexed 17β -estradiol into cyclodextrin in the aquatic environment in tilapia (Oreochromis niloticus)

Foram avaliados os efeitos tóxicos do hormônio 17β-estradiol (E2) livre e complexado à β-ciclodextrina (CD) sobre o comportamento e a fisiologia de tilápia (Oreochromis niloticus). Os peixes foram observados por 30 dias, em dois estágios do desenvolvimento (alevino e juvenil), pelo método ad libitum, para a confecção de um etograma. Posteriormente, juvenis foram divididos em três grupos: controle e expostos ao E2 (10ng/L) livre e complexado à β-ciclodextrina (β-CD:E2) por 90 dias. Foram avaliados o comportamento pelo método de varredura instantânea, o consumo de ração, o ganho de peso e a mortalidade em diferentes intervalos. Os alevinos e os juvenis apresentaram frequências de exibição comportamentais diferentes (P<0,05) nos eventos: Afastar (4,7±1,3 e 3,6±0,6%) e Ondulação de repulsão (2,3±0,9 e 1,3±1,0%). Os juvenis expostos ao complexo β-CD:E2 apresentaram aumento (P<0,05) na exibição dos comportamentos agressivos, como Afastar, Ataque caudal, Confronto prolongado, Perseguição, Fuga, e menor mortalidade, quando comparados ao grupo exposto ao E2 livre e controle. Pode-se concluir que a complexação do E2 com a β-CD alterou a toxicidade do E2, pois promoveu um aumento na frequência de exibição dos comportamentos agressivos e interferiu na mortalidade dos animais.(AU)

Toxic effects of free and complexed 17β-estradiol (E2) hormone into β-cyclodextrin (CD) on the behavior and physiology of tilapia (Oreochromis niloticus) were evaluated. The fish were observed for 30 days in two stages of development (fingerling and juvenile) by the ad libitum method to make an ethogram. After this, juveniles were divided into three groups: control and exposed to free E2 (10ng/L) and complexed into β-cyclodextrin (β-CD:E2) for 90 days. The behavior was evaluated through scan sampling method, feed intake, body mass and mortality at different intervals. The fingerlings and juveniles showed behavioral patterns with different display frequencies (P<0.05) for events: Move Away (4.7±1.3 and 3.6±0.6%) and Waving Repulsion (2.3±0.9 and 1.3±1.0%). The juveniles exposed to β-CD:E2 complex showed a significant increase (P<0.05) in the frequency of display of aggressive behaviors as Move Away, Caudal Attack, Clash Extended, Chase, Escape and decrease of mortality when compared to group exposed to free E2 and control. In conclusion, complexation of E2 into β-CD modified E2 toxicity, because it promoted an increase in the frequency of display of aggressive behaviors and it affected the mortality of animals.(AU)

Solution stability of Captisol-stabilized melphalan (Evomela) versus Propylene glycol-based melphalan hydrochloride injection.

PURPOSE: The objective of this study was to compare the stability of recently approved Captisol-stabilized propylene glycol-free melphalan injection (Evomela™) against currently marketed propylene glycol-based melphalan injection. The products were compared as reconstituted solutions in vials as well as admixture solutions prepared from normal saline in infusion bags. METHODS: Evomela and propylene glycol-based melphalan injection were reconstituted in normal saline and organic custom diluent, respectively, according to their package insert instructions. The reconstituted solutions were diluted in normal saline to obtain drug admixture solutions at specific drug concentrations. Stability of the solutions was studied at room temperature by assay of melphalan and determination of melphalan-related impurities. RESULTS: Results show that based on the increase in total impurities in propylene glycol-based melphalan injection at 0.45 mg/mL, Evomela admixture solutions are about 5, 9, 15 and 29 times more stable at concentrations of 0.45, 1.0, 2.0 and 5.0 mg/mL, respectively. Results confirmed that reconstituted Evomela solution can be stored in the vial for up to 1 h at RT or for up to 24 h at refrigerated temperature (2-8 °C) with no significant degradation. After storage in the vial, it remains stable for an additional 3-29 h after preparation of admixture solution in infusion bags at concentrations of 0.25-5.0 mg/mL, respectively. In addition, Evomela solution in saline, at concentration of 5.0 mg/mL melphalan was bacteriostatic through 72 h storage at 2-8 °C. CONCLUSION: Formulation of melphalan with Captisol technology significantly improved stability compared to melphalan hydrochloride reconstituted with propylene-glycol based diluents.

Preparation and characterization of molecularly-imprinted polymers for extraction of sanshool acid amide compounds followed by their separation from pepper oil resin derived from Chinese prickly ash (Zanthoxylum bungeanum).

Molecularly imprinted polymers were prepared using the molecular structure analogs of sanshool as template molecule, 2-vinylpyridine and ß-cyclodextrin as double functional monomers, ethylene dimethacrylate as cross linker, and azobisisobutyronitrile as initiator. The structural characteristics of the polymers were determined by Fourier-transform infrared spectroscopy and scanning electron microscopy. Dynamic adsorption and isothermal adsorption were also investigated. The molecularly imprinted polymers were used to prepare a molecularly imprinted solid-phase extraction column in order to separate acid amide components from pepper oil resin derived from Chinese prickly ash (Zanthoxylum bungeanum). After eluting, the percentage of acid amide components was enhanced to 92.40 ± 1.41% compared with 23.34 ± 1.21% in the initial pepper oil resin, indicating good properties of purification of molecularly imprinted polymers and potential industrial application.

Micro-solid phase extraction of benzene, toluene, ethylbenzene and xylenes from aqueous solutions using water-insoluble ß-cyclodextrin polymer as sorbent.

Water-insoluble ß-cyclodextrin polymer was synthesized by chemical cross-linking using epichlorohydrin (EPI) as a cross-linker agent. The produced water-insoluble polymer was used as a sorbent for the micro-solid phase extraction (µ-SPE) of benzene, toluene, ethylbenzene and xylenes (BTEX) from water samples. The µ-SPE device consisted of a sealed tea bag envelope containing 15mg of sorbent. For the evaluation of the extraction efficiency, parameters such as extraction and desorption time, desorption solvent and salt concentration were investigated. At an extraction time of 30min in the course of the extraction process, analytes were extracted from a 10mL aqueous sample solution. The analytes were desorbed by ultrasonication in 200µL of acetonitrile for 20min. Analysis of the analytes was done by a gas chromatography-flame ionization detector (GC-FID) system. The enrichment factor (EF) was found to be in the range 23.0-45.4 (EFmax=50.0). The method provided linearity ranges of between 0.5 and 500.0ng/mL (depending on the analytes), with good coefficients of determination (r2) ranging between 0.997 and 0.999 under optimized conditions. Detection limits for BTEX were in the range of between 0.15 and 0.60ng/mL, while corresponding recoveries were in the range of 46.0-90.0%. The relative standard deviation of the method for the analytes at 100.0ng/mL concentration level ranged from 5.5 to 11.2% (n=5). The proposed method was concluded to be a cost effective and environmentally-friendly extraction technique with ease of operation and minimal usage of organic solvent.

Synthesis, analytical characterization and capillary electrophoretic use of the single-isomer heptakis-(6-O-sulfobutyl)-beta-cyclodextrin.

This contribution reports the synthesis, characterization and capillary electrophoretic application of heptakis-(6-O-sulfobutyl-ether)-ß-cyclodextrin sodium salt, (6-(SB)7-ß-CD). The compound was obtained through a five-steps synthesis and it represents the first example of single-isomer sulfobutylated cyclodextrin that carries the negatively charged functions exclusively on its primary side and it is unmodified on the lower rim. The purity of each intermediate was determined by appropriate liquid chromatographic methods, while the isomeric purity of the final product was established by an ad-hoc developed HPLC method based on a CD-Screen-IEC column. The structural identification of 6-(SB)7-ß-CD was carried out by 1D, 2D NMR spectroscopy and ESI-MS. The chiral separation ability of 6-(SB)7-ß-CD was studied by chiral capillary electrophoresis using the single-isomer host as a background electrolyte additive to separate the enantiomers of a representative set of pharmacologically significant model compounds such as verapamil, dapoxetine, ondansetron, propranolol, atenolol, metoprolol, carvedilol, terbutaline, amlodipine and tadalafil. The enantiomer migration order and the effects of the selector concentration on the enantiorecognition properties were investigated. NMR spectroscopy was applied to deepen and further confirm the host-guest interactions and in the case of the model compound dapoxetine a potential representation for the supramolecular assembly was developed based on the dataset collected by the extensive 2D NMR analysis. This single-isomer chiral selector offers a new alternative to the widely applied randomly sulfobutylated- and sulfated-beta-cylodextrins as well as to the single-isomer sulfated and carboxymethylated derivatives in chiral separations.

Analytical Characterization of Methyl-ß-Cyclodextrin for Pharmacological Activity to Reduce Lysosomal Cholesterol Accumulation in Niemann-Pick Disease Type C1 Cells.

Methyl-ß-cyclodextrin (MßCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease type C1 (NPC1) patient fibroblasts. However, the pharmacological activity of MßCD reported by different laboratories varies. To determine the potential causes of this variation, we analyzed the mass spectrum characteristics, pharmacological activity of three preparations of MßCDs, and the protein expression profiles of NPC1 patient fibroblasts after treatment with different sources of MßCDs. Our data revealed varied mass spectrum profiles and pharmacological activities on the reduction of lysosomal cholesterol accumulation in NPC1 fibroblasts for these three preparations of MßCDs obtained from different batches and different sources. Furthermore, a proteomic analysis showed the differences of these three MßCD preparations on amelioration of dysregulated protein expression levels in NPC1 cells. The results demonstrate the importance of prescreening of different cyclodextrin preparations before use as a therapeutic agent. A combination of mass spectrum analysis, measurement of pharmacological activity, and proteomic profiling provides an effective analytical procedure for characterization of cyclodextrins for therapeutic applications.

Benchmarking Micropollutant Removal by Activated Carbon and Porous ß-Cyclodextrin Polymers under Environmentally Relevant Scenarios.

The cost-effective and energy-efficient removal of organic micropollutants (MPs) from water and wastewater is challenging. The objective of this research was to evaluate the performance of porous ß-cyclodextrin polymers (P-CDP) as adsorbents of MPs in aquatic matrixes. Adsorption kinetics and MP removal were measured in batch and flow-through experiments for a mixture of 83 MPs at environmentally relevant concentrations (1 µg L-1) and across gradients of pH, ionic strength, and natural organic matter (NOM) concentrations. Performance was benchmarked against a coconut-shell activated carbon (CCAC). Data reveal pseudo-second-order rate constants for most MPs ranging between 1.5 and 40 g mg-1 min-1 for CCAC and 30 and 40000 g mg-1 min-1 for P-CDP. The extent of MP removal demonstrates slower but more uniform uptake on CCAC and faster but more selective uptake on P-CDP. Increasing ionic strength and the presence of NOM had a negative effect on the adsorption of MPs to CCAC but had almost no effect on adsorption of MPs to P-CDP. P-CDP performed particularly well for positively charged MPs and neutral or negatively charged MPs with McGowan volumes greater than 1.7 (cm3 mol-1)/100. These data highlight advantages of P-CDP adsorbents relevant to MP removal during water and wastewater treatment.

Mobility-based correction for accurate determination of binding constants by capillary electrophoresis-frontal analysis.

Capillary electrophoresis frontal analysis (CE-FA) can be used to determine binding affinity of molecular interactions. However, its current data processing method mandate specific requirement on the mobilities of the binding pair in order to obtain accurate binding constants. This work shows that significant errors are resulted when the mobilities of the interacting species do not meet these requirements. Therefore, the applicability of CE-FA in many real word applications becomes questionable. An electrophoretic mobility-based correction method is developed in this work based on the flux of each species. A simulation program and a pair of model compounds are used to verify the new equations and evaluate the effectiveness of this method. Ibuprofen and hydroxypropyl-ß-cyclodextrinare used to demonstrate the differences in the obtained binding constant by CE-FA when different calculation methods are used, and the results are compared with those obtained by affinity capillary electrophoresis (ACE). The results suggest that CE-FA, with the mobility-based correction method, can be a generally applicable method for a much wider range of applications.