Clathrate Complex Research Articles

COMBINED IN SILICO AND EXPERIMENTAL INVESTIGATIONS OF VITAMIN D3 ENCAPSULATION BY STARCH β-OLIGOSACCHARIDE

The relevance of the research lies in the need to develop methods for encapsulating fat-soluble vitamins with natural oligosaccharides to increase their water solubility and use in the production of functional foods. The production ofnanostructured encapsulated vitamins is a new innovative direction in the food industry. This article presents the results of theoretical and experimental studies on the production of a clathrate complex of fat-soluble vitamin D3 (ViD3, cholecalciferol) with β-cyclodextrin (β-CD). The interaction of fat-soluble ViD3 with β-oligosaccharide was carried out by microwave activation. Encapsulation of ViD3 in the β-CD: ViD3 clathrate complex led to a change in the aggregate state of the ViD3 oil solution. The resulting supramolecular water-soluble ViD3 inclusion complex was investigated in silico by molecular docking and molecular modeling methods. The synthesized β-CD: ViD3 complex belongs to host-guest inclusion compounds and has better solubility. The spectral properties of the β-CD: ViD3 inclusion complex are characterized by the data of IR Fourier spectroscopy and the results of thermographic measurements on a differential scanning calorimeter. The activation energy of the reaction of the thermo-oxidative destruction of the β-CD: ViD3 inclusion complexes is calculated, the kinetic parameters of the thermal destruction of clathrates are determined. It is shown that the decisive role in the formation of the clathrate complex belongs to non-specific (hydrophobic, dispersion and van der Waals) interactions. The results obtained are promising for further understanding of the mechanism of molecular encapsulation of ViD3 compounds.

Combined Computational and Experimental Studies of Anabasine Encapsulation by Beta-Cyclodextrin.

The encapsulation of the famous alkaloid, anabasine, with β-CD was studied to obtain a more stable and bioavailable inclusion complex. Various in silico and experimental studies of the obtained β-CD-anabasine complex are presented. Firstly, molecular docking studies were conducted against the α, β, and γ cyclodextrins to explore which subclass is the best for encapsulation. The obtained results that pointed at β-cyclodextrin were further confirmed by five MD simulations and MM-PBSA studies. Experimentally, the spectral properties of the anabasine β-cyclodextrin complex were determined by FT-IR, 1H, and 13C-NMR spectroscopic methods. Additionally, the surface morphology of the anabasine β-cyclodextrin was investigated using a scanning electron microscope. Furthermore, the outputs of the thermographic measurements utilizing a differential scanning calorimeter were displayed. The activation energy of the reaction of thermo-oxidative destruction of the clathrate complex was calculated, and the kinetic parameters of the thermal destruction processes were decided using the Freeman–Carroll, Sharpe–Wentworth, Achar, and Coates–Redfern methods. The kinetic parameters of the thermal decomposition of the anabasine β-cyclodextrin were in agreement and verified the reliability of the obtained results. The obtained computational, spectral, morphological, and thermogravimetric results verified the successful formation of the anabasine β-cyclodextrin complex.

Effect of the clathrate complex of selenopyran and β-cyclodextrin on the rate of healing of a conditionally aseptic full-thickness planar wound in rats

Introduction. Selenopyran is an organic selenium compound with sharply hydrophobic properties. An increase in solubility in water (and as a consequence – and bioavailability) is possible due to the formation of inclusion complexes with cyclodextrins.Aim. The aim of this work was to study the effect of a gel containing a clathrate complex of selenopyran with β-cyclodextrin on the rate of wound healing on a model of a conditionally aseptic full-thickness planar wound in rats.Materials and methods. The object of the study was a gel containing a clathrate complex of selenopyran with β-cyclodextrin (the content of selenopyran in the gel was 0.1 %). A model of a full-thickness planar wound in sexually mature male rats was used. 20 individuals were divided into 2 groups – intact (without treatment) and experimental (received gel treatment). Efficacy was assessed by the change in wound area at 3, 5, 7, 9, 11 and 14 days after application of wound.Results and discussion. The results of the study showed that the relative area of the wounds in the treated animals by the 3rd day of the experiment was less than in the intact ones. On the fifth day of the experiment, the differences were statistically significant (57.49 ± 12.51 % in treated animals versus 85.27 ± 26.61 % in intact animals). By the 14th day of the experiment, there were practically no differences in the groups of animals.Conclusion. The results obtained indicate that when using a gel containing selenopyran in combination with β-cyclodextrin, it accelerates the transition from the inflammation phase to the proliferation phase. This is most likely due to the antioxidant properties of selenopyran. Considering the lower concentration of selenopyran in comparison with the therapeutic concentrations of other antioxidants (taurine, allantoin), it can be considered as a promising wound healing agent for further study.

Preparation of encapsulated α-tocopherol acetate and study of its physico-chemical and biological properties

The article discusses the results of research for obtaining encapsulated vitamin E using a water-soluble oligosaccharide (cyclodextrin). The inclusion complexes of β-CD with α-tocopherol were obtained in an aqueousalcoholic medium by coprecipitation and microwave activation. The highest yields of target clathrate inclusion complexes of vitamin E with cyclodextrin were obtained under microwave synthesis conditions. Molecular modeling of inclusion complexes of α-tocopherol acetate with β-cyclodextrin in the ratios of 1:1, 1:2, 1:3, and 1:4 was performed using the MM+ method. Based on semi-empirical PM3 calculations, without taking into account the influence of the environment, the total energy of the systems under study was estimated. Data on the study of the structure of the clathrate complex of α-tocopherol acetate with β-cyclodextrin was presented. The surface morphology of the resulting “guest-host” clathrate complex was described using a scanning electron microscope. The spectral properties of the inclusion complex were characterized by FT-IR and 1H and 13C NMR spectroscopy data. The study of the 1H NMR and 13C NMR spectra of β-CD in the free and bound state in the form of the β-CD: VE clathrate made it possible to reveal the displacements of the signals of the nuclei (± ∆δ) 1H and 13C of the host molecule both in the region of weak and strong fields. The experimental results confirmed the possibility of the formation of inclusion complexes of α-tocopherol acetate with β-cyclodextrin at various ratios. The data on the study of the effect of encapsulated α-tocopherol acetate on the safety of food meat products was presented.

Properties and possibilities of practical applications of GaSe crystal intercalated with β-cyclodextrin doped with iodine

The clathrate complex of hierarchical architecture was successfully synthesised by the intercalation of beta-cyclodextrin (β-CD) and molecular iodine (J2) in between the layers of five-fold expanded matrix of gallium selenide (GaSe). The obtained clathrate was investigated by the impedance spectroscopy under normal conditions, at illumination and in the constant magnetic field and the character of clathrate response to the ac electric field was established. As a result of studies of the synthesized GaSe<β-CD<J2>> complex the following phenomena were found: the effect of the effect of negative capacitance, magnetoresistivity effect and magnetodielectric and photodielectric effects. The research result of the obtained clathrate indicates its possible practical application for the creation of nongyrator delay nanolines, the parameters of which can be controlled by a constant magnetic field and the light. The clathrate can also be used as a highly sensitive magnetic field sensor of resistive and capacitive type.

Efficacy of "Essential Iodine Drops" against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2).

BackgroundAerosolization of respiratory droplets is considered the main route of coronavirus disease 2019 (COVID-19). Therefore, reducing the viral load of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) shed via respiratory droplets is potentially an ideal strategy to prevent the spread of the pandemic. The in vitro virucidal activity of intranasal Povidone-Iodine (PVP-I) has been demonstrated recently to reduce SARS-CoV-2 viral titres. This study evaluated the virucidal activity of the aqueous solution of Iodine-V (a clathrate complex formed by elemental iodine and fulvic acid) as in Essential Iodine Drops (EID) with 200 μg elemental iodine/ml content against SARS-CoV-2 to ascertain whether it is a better alternative to PVP-I.MethodsSARS-CoV-2 (USAWA1/2020 strain) virus stock was prepared by infecting Vero 76 cells (ATCC CRL-1587) until cytopathic effect (CPE). The virucidal activity of EID against SARS-CoV-2 was tested in three dilutions (1:1; 2:1 and 3:1) in triplicates by incubating at room temperature (22 ± 2°C) for either 60 or 90 seconds. The surviving viruses from each sample were quantified by a standard end-point dilution assay.ResultsEID (200 μg iodine/ml) after exposure for 60 and 90 seconds was compared to controls. In both cases, the viral titre was reduced by 99% (LRV 2.0). The 1:1 dilution of EID with virus reduced SARS-CoV-2 virus from 31,623 cell culture infectious dose 50% (CCID50) to 316 CCID50 within 90 seconds.ConclusionSubstantial reductions in LRV by Iodine-V in EID confirmed the activity of EID against SARS-CoV-2 in vitro, demonstrating that Iodine-V in EID is effective at inactivating the virus in vitro and therefore suggesting its potential application intranasally to reduce SARS-CoV-2 transmission from known or suspected COVID-19 patients.

Acute toxicity of nanoscale form of 20-hydroxyecdysone in intragastric administration

The nanoscale 20-hydroxyecdysone was first proposed and obtained in the form of a clathrate complex with arabinogalactan with an average particle size of 35,3 nm. The study of its acute toxicity has revealed that the product belongs to class VI of relatively harmless drugs according to Hodge and to class 5th in accordance with GOST 32644-2014.

Antioxidant Properties of a Nanostructured Clathrate Complex Selenopyran with β-Cyclodextrin in Model Systems of Oxidative Stress.

We studied the effect of nanostructured clathrate complex 9-phenyl-symm-octahydoselenoxanthene (selenopyran) with β-cyclodextrin on the generation of ОН· radicals in the Fenton system and parameters of oxidative stress in rat liver cells incubated at 37°С for 1 h. The complex inhibits the development of free-radical oxidative processes induced by ROS and the most toxic ОН· radicals, reduces the increased level of ROS induced by prooxidants, and exhibits antioxidant activity.

ИНКАПСУЛЯЦИЯ МАСЛЯНОГО РАСТВОРА ВИТАМИНА АЕВИТ β-ЦИКЛОДЕКСТРИНОМ

The present work aimed at encapsulation of fat-soluble vitamin Aevit (vitamins A and E, oil) with β-cyclodextrin. Inclusion complex of vitamins A and E with β-cyclodextrin was prepared in an aqueous alcohol medium by ultrasonic treatment. The surface morphology of the resulting clathrate inclusion complexes was described using a scanning electron microscope. The results of thermographic measurements on a differential scanning calorimeter are presented. The spectral properties of the inclusion complex are characterized by 1H and 13C NMR spectroscopy data. The experimental results confirmed the existence of a complex of inclusion of β-cyclodextrin with vitamin Aevit (2:1). The activation energy of the thermooxidation destruction reaction of the clathrate complex β-cyclodextrin:vitamin Aevit was calculated, kinetic parameters of thermal destruction of clathrate were determined. These parameters were determined based on the Freeman-Carroll, Sharpe-Wentworth, Ahar and Coates-Redfern methods. The use of the above models made it possible to graphically establish the thermodynamic parameters of the thermal decomposition of β-cyclodextrin and its clathrate with vitamin. The data of thermographic measurements on a differential scanning calorimeter showed that the thermal destruction of the Aevite clathrate with β-cyclodextrin begins with the removal of water molecules from the β-cyclodextrin cavity, then the “guest” substance and the cyclic oligosaccharide are destroyed.

The effect of the 3- (2-phenylethyl) -2-thioxo-1,3-thiazolidin-4-one clathrate complex with betadex on protein metabolism, growth and development of Wistar

The clathrate complex of 3- (2-phenylethyl) -2-thioxo-1,3 thiazolidin-4-one with betadex was developed for the first time. 1: 5 ratio obtained by the solid-phase synthesis method, which has a crystalline form in the form of nanoparticles with an average size of 40.5 nm. In the present work, the effect of the created nanoscale form of 3- (2-phenylethyl) -2-thioxo-1,3 thiazolidin-4-one on protein metabolism, growth and development of Wistar rats was first studied. It was shown that the administration of 3- (2-phenylethyl) -2-thioxo-1,3 thiazolidin-4-one nanosized form in rats at doses of 10.0 and 20.0 mg / kg body weight activates the biosynthetic system and promotes an increase in protein deposition in their body. Nitrogen retention in rats of the experimental groups compared with the control increased by 20.0% (P≤0.05) due to a decrease in its endogenous losses, and the urea content in the blood serum was lower by 24.1 and 26.4%, respectively, compared to control. In rats of the experimental groups, the concentration of total protein (P≤0.05), albumin (P≤0.05) and globulins in the blood was higher compared to the control. It was found that in female rats of the experimental groups, in comparison with the control and intact animals, their growth and development were statistically significantly higher. In this case, the optimal dose of the nanoscale form of 3- (2 – phenylethyl) -2-thioxo-1,3 thiazolidin-4-one is a dose of 10.0 mg / kg of rat body weight.

TOXICITY UNDER A SINGLE INTRAGASTRIC ADMINISTRATION OF THE ACTIVE CLATHRATE COMPLEX OF β-CYCLODEXTRIN WITH 3-(2-PHENYLETHYL)-2-THIOXO-1,3- THIAZOLIDIN-4-ONE

The clathrate complex of 3-(2-phenylethyl)-2-thioxo-1,3-thiazolidin-4-one with β-cyclodextrin in the form of a nanopowder with an average particle size of 40.5 nm, with a wide range of pharmacological properties, was developed for the first time. It belongs to class VI of relatively harmless drugs according to Hodge and to class 5 in accordance with GOST 32644-2014.

Исследование антиоксидантных свойств наноструктурного клатратного комплекса селенопирана с β-циклодекстрином в модельных системах оксидативного стресса

Исследование антиоксидантных свойств наноструктурного клатратного комплекса селенопирана с β-циклодекстрином в модельных системах оксидативного стресса

Pressure-driven structural and spin-state transition in a Hofmann clathrate coordination polymer

Hofmann-type organometallic frameworks are well known for their porous crystal structure, exhibiting interesting electronic, optical, and magnetic properties, and are therefore considered as promising materials for various technological applications. Here, using density functional theory+U (DFT+U) calculations, we investigate the spin-state transition in a newly synthesized Hofmann clathrate, namely the Fe{OS(CH3)2}2{Ag(CN)2}2 complex, by applying hydrostatic pressure as an external perturbation. Our study reveals that under a relatively low isotropic hydrostatic pressure, the complex exhibits a reversible spin switching, whereas it undergoes a structural phase transition when the pressure is larger and anisotropic. The spin state of the Fe atom in the Hofmann clathrate complex transforms from high spin to intermediate spin state under anisotropic compression of the lattice parameters. The coordination polymer complex remains a magnetic semiconductor after the pressure-driven structural transformation.

The effect of the nanoscale form of 20-hydroxyecdysone on the antioxidant status and natural resistance of the rabbit organism

Current trends in the development of new drugs are based on the creation of nanostructured compositions with improved characteristics. One of the approaches to creating a nanoscale form of drugs, in particular 20-hydroxyecdysone, is the synthesis of its clathrate complex with the clathrate-forming arabinogalactan. Thus obtained nanoscale form of 20-hydroxyecdysone provides an improvement in its physico-chemical properties, which leads to increased absorption, increased bioavailability and, ultimately, to reduce therapeutic doses. In the present work, the effect of the created nanoscale form of 20-hydroxyecdysone on the function of the antioxidant defense system, natural resistance, growth and development of Sovetskaya Chinchilla rabbits was studied for the first time. It has been established that the nanoscale form of 20-hydroxyecdysone, when administered to rabbits at doses of 1.0 and 5.0 mg / kg body weight, contributes to a statistically significant increase in serum BASK and LASK levels, increased activity of the enzymatic unit of the antioxidant system, in particular SOD and catalase in erythrocyte lysate. On the contrary, the content of MDA in the blood plasma was statistically significant [P≤0.05 — P≤0.02] was lower in rabbits of the experimental groups compared with the control, which may indicate a decrease in lipid peroxidation processes in animals under the influence of nanoscale form 20-hydroxyecdysone. In the rabbits of the experimental groups, compared with the control, they were statistically significantly higher by 32-38% [P≤0.05–P≤0.01] absolute and average daily weight gain of rabbits. The optimal dose of the nanoscale form of 20-hydroxyecdysone is dose 1, 0 mg / kg rabbit body weight.

Obtaining and Investigation of the β-Cyclodextrin Inclusion Complex with Vitamin D 3 Oil Solution.

Background. The research results of fat-soluble vitamin D3 (cholecalciferol) encapsulation with β-cyclodextrin have been presented in this work. The vitamin D3 inclusion complex with β-cyclodextrin was obtained under microwave radiation. The surface morphology of obtained clathrate inclusion complexes was described with the help of a scanning electron microscope. The thermographic measurement results on a differential scanning calorimeter have been presented. The activation energy of the β-cyclodextrin : vitamin D3 clathrate complex thermal oxidative destruction reaction was calculated. The clathrate thermal destruction kinetic parameters were determined. The inclusion complex spectral properties were characterized by IR-Fourier and 1H and 13C NMR spectroscopy. The existence of β-cyclodextrin inclusion complex with vitamin D3 in a 2 : 1 ratio was confirmed by the experimental results. The activation energy of thermal destruction of the inclusion complex of β-cyclodextrin with vitamin D3 was calculated using four different methods.

In Vitro Efficacy of Essential Iodine Drops against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2)

Background: Aerosolization of respiratory droplets is considered the main route of coronavirus disease 2019 (COVID-19). Therefore, reducing the viral load of Severe Acute Respiratory Syndrome- Coronavirus 2 (SARSCoV- 2) shed via respiratory droplets is potentially an ideal strategy to prevent the spread of the pandemic. The in vitro virucidal activity of intranasal Povidone-Iodine (PVP-I) has been demonstrated recently to reduce SARS-CoV-2 viral titres. This study evaluated the virucidal activity of the aqueous solution of Iodine-V (a clathrate complex formed by elemental iodine and fulvic acid) as in Essential Iodine Drops (EID) with 200 μg elemental iodine/ml content against SARS-CoV-2 to ascertain whether it is a better alternative to PVP-I. Methods: SARS-CoV-2 (USAWA1/2020 strain) virus stock was prepared by infecting Vero 76 cells (ATCC CRL- 1587) until cytopathic effect (CPE). The virucidal activity of EID against SARS-CoV-2 was tested in three dilutions (1:1; 2:1 and 3:1) in triplicates by incubating at room temperature (22 ± 2°C) for either 60 or 90 seconds. The surviving viruses from each sample were quantified by a standard end-point dilution assay. Results: EID (200 μg iodine/ml) after exposure for 60 and 90 seconds was compared to controls. In both cases, the viral titre was reduced by 99% (LRV 2.0). The 1:1 dilution of EID with virus reduced SARS-CoV-2 virus from 31,623 cell culture infectious dose 50% (CCCID50) to 316 CCID50 within 90 seconds. Conclusion: Substantial reductions in LRV by Iodine-V in EID confirmed the activity of EID against SARS- CoV-2 in vitro , demonstrating that Iodine-V in EID is effective at inactivating the virus in vitro and therefore suggesting its potential application intranasal to reduce SARS-CoV-2 transmission from known or suspected COVID-19 patients.

Quadruply-labeled serum albumin as a biodegradable nanosensor for simultaneous fluorescence imaging of intracellular pH values, oxygen and temperature.

The construction of multiple fluorescent nanosensors for intracellular studies is a challenging task because spectral overlap of indicator probes can lead to cross-talk and mutual interference. This work describes biodegradable nanosensors that can simultaneously measure three intracellular parameters (temperature, pH and oxygen concentration). Bovine serum albumin (BSA) is selected as the scaffold to construct the triple nanosensor by covalent immobilization four fluorophores on BSA. The following luminophores were used: (a) fluorescein as a probe for pH values, (b) a platinum(II) porphyrin complex for oxygen; (c) a europium(III) clathrate complex for temperature, and (d) a rhodamine B as a reference dye. The nanoparticles have a size of 20nm and show excellent biocompatibility and good brightness. The nanosensors were used for ratiometric imaging of intracellular pH values, oxygen and temperature in HeLa cells. The triple nanosensor responds reversibly and this can be used for real-time tracing of these key parameters. Owing to their biodegradable feature, the use of this kind of triple nanosensor reduce the stress on cellular activities because less nanosensors can be used to gather the total information. Graphical abstractA triple nanosensor for simultaneously ratiometrically sensing intracellular pH, oxygen and temperature values was constructed by covalently labelling four fluorophores on a single serum albumin protein. The nanosensor shows good sensitivity, biocompatibility, is biodegradable and suitable for continuously measuring these important parameters.

A porous glass-based KI/α-CD chip for ozone sensing: Improvement in the humidity response of the chip through optimizing reagent concentrations in the impregnation process

To improve the performance of our previously-reported KI/α-CD ozone sensing chip, the present work carried out a series of experiments based on exposing these chips to ozone under static conditions. This device was confirmed to operate on a passive principle by monitoring the absorption at 360 nm due to the formation of a clathrate complex of α-CD with triiodide ions generated by the reaction of O3 with KI on a porous glass surface. The sensing capabilities of chips fabricated under different conditions were evaluated by plotting absorbance at 360 nm against total ozone exposure, and KI and α-CD concentrations of 104 and 19.4 mM, respectively, in the immersion solution employed during fabrication were found to be optimal. The data also show that chips prepared by immersion in this solution are as sensitive (based on a 3 ppb limit of detection with a 1 h exposure) at 90% RH as the previously-reported units, and that the performance of the present chips is unchanged over the RH range of 37% to 80%.

Stabilization and prolonged reactivity of aqueous-phase ozone with cyclodextrin

Recalcitrant organic groundwater contaminants, such as 1,4-dioxane, may require strong oxidants for complete mineralization. However, their efficacy for in-situ chemical oxidation (ISCO) is limited by oxidant decay and reactivity. Hydroxypropyl-β-cyclodextrin (HPβCD) was examined for its ability to stabilize aqueous-phase ozone (O3) and prolong oxidation potential through inclusion complex formation. Partial transformation of HPβCD by O3 was observed. However, HPβCD proved to be sufficiently recalcitrant, because it was only partially degraded in the presence of O3. The formation of a HPβCD:O3 clathrate complex was observed, which stabilized decay of O3. The presence of HPβCD increased the O3 half-life linearly with increasing HPβCD:O3 molar ratio. The O3 half-life in solutions increased by as much as 40-fold relative to HPβCD-free O3 solutions. Observed O3 release from HPβCD and indigo oxidation confirmed that the formation of the inclusion complex is reversible. This proof-of-concept study demonstrates that HPβCD can complex O3 while preserving its reactivity. These results suggest that the use of clathrate stabilizers, such as HPβCD, can support the development of a facilitated-transport enabled ISCO for the O3 treatment of groundwater contaminated with recalcitrant compounds.

Thermodynamic stability and crystallization behavior of molecular complexes with TEP host

In the crystallization of molecular complex (co-crystal, clathrate complex), polymorphism in regard to the host structure frequently appears. Previously, we studied the release process of the biocide, CMI (5-chloro-2-methyl-4-isothiazolin-3-one) from the molecular complex with TEP (1,1,2,2-tetrakis(4-hydroxyphenyl)ethane) (TEP·2CMI) in methanol–water mixed solvents. It was clear that the release process of the biocide (CMI) is composed of the transformation from the TEP·2CMI crystal to a more stable molecular complex crystal with solvent. In this work, the crystallization was performed in the methanol solutions including TEP and CMI at constant temperature (298K and 308K). It appeared that two kinds of TEP molecular complexes (TEP·2CMI and TEP·2MeOH) crystallize competitively. The crystallization zone of each molecular complex was shown in the map using the coordinates of initial concentrations of TEP and CMI. In the boundary zone both molecular complexes appeared and the transformation from TEP·2CMI to TEP·2MeOH was observed, indicating that the stable form is TEP·2MeOH. Without the boundary zone the corresponding stable form crystallized in each zone. The value of the initial concentration ratio of CMI/TEP for the selective crystallization of TEP·2CMI was higher at 298K (1.54) than that (1.36) at 308K. The equilibrium concentrations of TEP and CMI in the presence of two molecular complexes were expressed using the dissociation constants of the molecular complexes and it was indicated that the dissociation of TEP·2CMI highly increases with temperature