Complexation of Cyclodextrins with Benzoic Acid in Water-Organic Solvents: A Solvation-Thermodynamic Approach

The aim of this research is to obtain new data about the complexation between β-cyclodextrin (β-CD) and benzoic acid (BA) as a model reaction of the complex formation of hydrophobic molecules with cyclodextrins (CDs) in various media. This research may help developing cyclodextrin-based pharmaceutical formulations through the choice of the appropriate solvent mixture that may be employed in the industrial application aiming to control the reactions/processes in liquid phase. In this paper, NMR results for the molecular complex formation between BA and β-CD ([BA⊂β-CD]) in D₂O-DMSO-d₆ and in D₂O-EtOH have shown that the stability of the complex in the H₂O-DMSO-d₆ varies within the experimental error, while decreases in H₂O-EtOH. Changes in the Gibbs energy of BA resolvation in water and water–dimethylsulfoxide mixtures have been obtained and have been used in the analysis of the reagent solvation contributions into the Gibbs energy changes of the [BA⊂β-CD] molecular complex formation. Quantum chemical calculations of the interaction energy between β-CD and BA as well as the structure of the [BA⊂β-CD] complex and the energy of β-CD and BA interaction in vacuum and in the medium of water, methanol and dimethylsulfoxide solvents are carried out. The stability of [BA⊂β-CD] complex in H₂O-EtOH and H₂O-DMSO solvents, obtained by different methods, are compared. The thermodynamic parameters of the [BA⊂β-CD] molecular complexation as well as the reagent solvation contributions in H₂O-EtOH and H₂O-DMSO mixtures were analyzed by the solvation-thermodynamic approach.     

On Complex Formation between 5-Fluorouracil and β-Cyclodextrin in Solution and in the Solid State: IR Markers and Detection of Short-Lived Complexes by Diffusion NMR

In this work, the nuclear magnetic resonance (NMR) and IR spectroscopic markers of the complexation between 5-fluorouracil (5-FU) and β-cyclodextrin (β-CD) in solid state and in aqueous solution are investigated. In the attenuated total reflectance(ATR) spectra of 5-FU/β-CD products obtained by physical mixing, kneading and co-precipitation, we have identified the two most promising marker bands that could be used to detect complex formations: the C=O and C-F stretching bands of 5-FU that experience a blue shift by ca. 8 and 2 cm⁻¹ upon complexation. The aqueous solutions were studied by NMR spectroscopy. As routine NMR spectra did not show any signs of complexation, we have analyzed the diffusion attenuation of spin–echo signals and the dependence of the population factor of slowly diffusing components on the diffusion time (diffusion NMR of pulsed-field gradient (PFG) NMR). The analysis has revealed that, at each moment, ~60% of 5-FU molecules form a complex with β-CD and its lifetime is ca. 13.5 ms. It is likely to be an inclusion complex, judging from the independence of the diffusion coefficient of β-CD on complexation. The obtained results could be important for future attempts of finding better methods of targeted anticancer drug delivery.     

β-Cyclodextrin Derivative Grafted on Silica Gel Represents a New Polymeric Sorbent for Extracting Nitisinone from Model Physiological Fluids

Nitisinone (NTBC) is used in the treatment of disorders affecting the tyrosine pathway, including hereditary tyrosinemia type I, alkaptonuria, and neuroblastoma. An inappropriate dosage of this therapeutic drug causes side effects; therefore, it is necessary to develop a rapid and sensitive method to monitor the content of NTBC in patients’ blood. This study aimed to develop anew polymeric sorbent containing β-cyclodextrin (β-CD) derivatives grafted on silica gel to effectively extract NTBC from model physiological fluids. The inclusion complex formed between β-CD and NTBC was examined by proton nuclear magnetic resonance spectroscopy. The novel sorbents with derivatives of β-CD were prepared on modified silica gel using styrene as a comonomer, ethylene glycol dimethacrylate as a crosslinking agent, and 2,2′-azo-bis-isobutyronitrile as a polymerization initiator. The obtained products were characterized via Fourier transform infrared spectroscopy and then used as sorbents as part of a solid phase extraction technique. High NTBC recovery (70%indicated that the developed polymeric sorbent may be suitable for extracting this compound from patients’ blood samples.     

Solubility,Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide

Nimesulide (NIM, N-(4-nitro-2-phenoxyphenyl)methanesulfonamide) is a relatively new nonsteroidal anti-inflammatory analgesic drug. It is practically insoluble in water (<0.02 mg/mL). This very poor aqueous solubility of the drug may lead to low bioavailability. The objective of the present study was to investigate the possibility of improving the solubility and the bioavailability of NIM via complexation with polysaccharide arabinogalactan (AG), disodium salt of glycyrrhizic acid (Na₂GA), hydroxypropyl-β-cyclodextrin (HP-β-CD) and MgCO₃. Solid dispersions (SD) have been prepared using a mechanochemical technique. The physical properties of nimesulide SD in solid state were characterized by differential scanning calorimetry and X-ray diffraction studies. The characteristics of the water solutions which form from the obtained solid dispersions were analyzed by reverse phase and gel permeation HPLC. It was shown that solubility increases for all complexes under investigation. These phenomena are obliged by complexation with auxiliary substances, which was shown by ¹H-NMR relaxation methods. The parallel artificial membrane permeability assay (PAMPA) was used for predicting passive intestinal absorption. Results showed that mechanochemically obtained complexes with polysaccharide AG, Na₂GA, and HP-β-CD enhanced permeation of NIM across an artificial membrane compared to that of the pure NIM. The complexes were examined for anti-inflammatory activity on a model of histamine edema. The substances were administered per os to CD-1 mice. As a result, it was found that all investigated complexes dose-dependently reduce the degree of inflammation. The best results were obtained for the complexes of NIM with Na₂GA and HP-β-CD. In noted case the inflammation can be diminished up to 2-fold at equal doses of NIM.     

β-Cyclodextrin Inclusion Complexes with Catechol-Containing Antioxidants Protocatechuic Aldehyde and Protocatechuic Acid—An Atomistic Perspective on Structural and Thermodynamic Stabilities

Protocatechuic aldehyde (PCAL) and protocatechuic acid (PCAC) are catechol derivatives and have broad therapeutic effects associated with their antiradical activity. Their pharmacological and physicochemical properties have been improved via the cyclodextrin (CD) encapsulation. Because the characteristics of β-CD inclusion complexes with PCAL (1) and PCAC (2) are still equivocal, we get to the bottom of the inclusion complexation by an integrated study of single-crystal X-ray diffraction and DFT full-geometry optimization. X-ray analysis unveiled that PCAL and PCAC are nearly totally shielded in the β-CD wall. Their aromatic rings are vertically aligned in the β-CD cavity such that the functional groups on the opposite side of the ring (3,4-di(OH) and 1-CHO/1-COOH groups) are placed nearby the O6–H and O2–H/O3–H rims, respectively. The preferred inclusion modes in 1 and 2 help to establish crystal contacts of OH⋅⋅⋅O H-bonds with the adjacent β-CD OH groups and water molecules. By contrast, the DFT-optimized structures of both complexes in the gas phase are thermodynamically stable via the four newly formed host–guest OH⋯O H-bonds. The intermolecular OH⋅⋅⋅O H-bonds between PCAL/PCAC 3,4-di(OH) and β-CD O6–H groups, and the shielding of OH groups in the β-CD wall help to stabilize these antioxidants in the β-CD cavity, as observed in our earlier studies. Moreover, PCAL and PCAC in distinct lattice environments are compared for insights into their structural flexibility.     

A Dispersion Corrected DFT Investigation of the Inclusion Complexation of Dexamethasone with β-Cyclodextrin and Molecular Docking Study of Its Potential Activity against COVID-19

The encapsulation mode of dexamethasone (Dex) into the cavity of β-cyclodextrin (β-CD), as well as its potential as an inhibitor of the COVID-19 main protease, were investigated using density functional theory with the recent dispersion corrections D4 and molecular docking calculations. Independent gradient model and natural bond orbital approaches allowed for the characterization of the host–guest interactions in the studied systems. Structural and energetic computation results revealed that hydrogen bonds and van der Waals interactions played significant roles in the stabilization of the formed Dex@β-CD complex. The complexation energy significantly decreased from −179.50 kJ/mol in the gas phase to −74.14 kJ/mol in the aqueous phase. A molecular docking study was performed to investigate the inhibitory activity of dexamethasone against the COVID-19 target protein (PDB ID: 6LU7). The dexamethasone showed potential therapeutic activity as a SARS CoV-2 main protease inhibitor due to its strong binding to the active sites of the protein target, with predicted free energy of binding values of −29.97 and −32.19 kJ/mol as calculated from AutoDock4 and AutoDock Vina, respectively. This study was intended to explore the potential use of the Dex@β-CD complex in drug delivery to enhance dexamethasone dissolution, thus improving its bioavailability and reducing its side effects.     

One-Step Extraction of Olive Phenols from Aqueous Solution Using β-Cyclodextrin in the Solid State,a Simple Eco-Friendly Method Providing Photochemical Stability to the Extracts

The extraction of phenolic compounds from olive mill wastes is important, not only to avoid environmental damages, but also because of the intrinsic value of those biophenols, well-known for their high antioxidant potential and health benefits. This study focuses on tyrosol (Tyr) and hydroxytyrosol (HT), two of the main phenolic compounds found in olive mill wastes. A new, simple, and eco-friendly extraction process for the removal of phenolic compounds from aqueous solutions using native β-cyclodextrin (β-CD) in the solid state has been developed. Several β-CD/biophenol molar ratios and biophenol concentrations were investigated, in order to maintain β-CD mostly in the solid state while optimizing the extraction yield and the loading capacity of the sorbent. The extraction efficiencies of Tyr and HT were up to 61%, with a total solid recovery higher than 90% using an initial concentration of 100 mM biophenol and 10 molar equivalents of β-CD. The photochemical stability of the complexes thus obtained was estimated from ∆E*ab curve vs. illumination time. The results obtained showed that the phenols encapsulated into solid β-CD are protected against photodegradation. The powder obtained could be directly developed as a safe-grade food supplement. This simple eco-friendly process could be used for extracting valuable biophenols from olive mill wastewater.     

Synthesis and characterization of magnetic poly(acrylic acid) hydrogel fabricated with cobalt nanoparticles for adsorption and catalytic applications

The present study aimed to synthesize poly(acrylic acid) hydrogel embedded with magnetic cobalt (Co) nanoparticles and to investigate their potential in adsorption and catalysis. The hydrogel was prepared by facile free radical polymerization reaction and Co nanoparticles were fabricated within hydrogel by reducing Co (II) ions using NaBH₄ as reducing agent. Co nanoparticles within hydrogel system imparted magnetic properties to the resulting composite gel and also increased the adsorption capacity. The swelling study of hydrogel was carried out by gravimetric analysis. Different functional groups were identified by Fourier Transform Infrared Spectroscopy and Transmission Electron Microscopy analysis was done to investigate dispersion of Co nanoparticles in hydrogel. The bare hydrogel along with Co nanoparticles loaded gel were tested as adsorbent systems for the removal of a cationic dye (methylene blue) from aqueous solution. 95% removal of methylene blue was achieved with a highest adsorption capacity of 836.5 mg/g of adsorbent. The famous adsorption isotherms were used to evaluate adsorption data. Results showed that Freundlich isotherm model was followed with R² value of 0.95. The hydrogel was also used for catalytic reduction in a toxic pollutant, i.e., 4-nitrophenol. Experimental data for 4-nitrophenol reduction followed pseudo first order kinetics model. Activation energy and apparent rate constant were calculated as 9.24 kJ/mol and 0.24 min⁻¹, respectively. Recycling of the magnetic poly(acrylic acid) hydrogel fabricated with Cobalt nanoparticles was carried out for four consecutive cycles and no significant loss in catalytic activity was observed.

     

Comprehensive Characterisation of the Ketoprofen-β-Cyclodextrin Inclusion Complex Using X-ray Techniques and NMR Spectroscopy

Racemic ketoprofen (KP) and β-cyclodextrin (β-CD) powder samples from co-precipitation (1), evaporation (2), and heating-under-reflux (3) were analysed using X-ray techniques and nuclear magnetic resonance (NMR) spectroscopy. On the basis of NMR studies carried out in an aqueous solution, it was found that in the samples obtained by methods 1 and 2, there were large excesses of β-CD in relation to KP, 10 and 75 times, respectively, while the sample obtained by method 3 contained equimolar amounts of β-CD and KP. NMR results indicated that KP/β-CD inclusion complexes were formed and the estimated binding constants were approximately 2400 M⁻¹, showing that KP is quite strongly associated with β-CD. On the other hand, the X-ray single-crystal technique in the solid state revealed that the (S)-KP/β-CD inclusion complex with a stoichiometry of 2:2 was obtained as a result of heating-under-reflux, for which the crystal and molecular structure were examined. Among the methods used for the preparation of the KP/β-CD complex, only method 3 is suitable.     

Encapsulation of α-Pinene in Delivery Systems Based on Liposomes and Cyclodextrins

The essential oil component α-pinene has multiple biological activities. However, its application is limited owing to its volatility, low aqueous solubility, and chemical instability. For the aim of improving its physicochemical properties, α-pinene was encapsulated in conventional liposomes (CLs) and drug-in-cyclodextrin-in-liposomes (DCLs). Hydroxypropyl-β-cyclodextrin/α-pinene (HP-β-CD/α-pinene) inclusion complexes were prepared in aqueous solution, and the optimal solubilization of α-pinene occurred at HP-β-CD:α-pinene molar ratio of 7.5:1. The ethanol-injection method was applied to produce different formulations using saturated (Phospholipon 90H) or unsaturated (Lipoid S100) phospholipids in combination with cholesterol. The size, the phospholipid and cholesterol incorporation rates, the encapsulation efficiency (EE), and the loading rate (LR) of α-pinene were determined, and the storage stability of liposomes was assessed. The results showed that α-pinene was efficiently entrapped in CLs and DCLs with high EE values. Moreover, Lipoid S100 CLs displayed the highest LR (22.9 ± 2.2%) of α-pinene compared to the other formulations. Both carrier systems HP-β-CD/α-pinene inclusion complex and Lipoid S100 CLs presented a gradual release of α-pinene. Furthermore, the DPPH radical scavenging activity of α-pinene was maintained upon encapsulation in Lipoid S100 CLs. Finally, it was found that all formulations were stable after three months of storage at 4 °C.     

Highly Efficient Methylene Blue Dye Removal by Nickel Molybdate Nanosorbent

Removing methylene blue (MB) dye from aqueous solutions was examined by the use of nickel molybdate (α-NiMoO₄) as an adsorbent produced by an uncomplicated, rapid, and cost-effective method. Different results were produced by varying different parameters such as the pH, the adsorbent dose, the temperature, the contact time, and the initial dye concentration. Adsorbent dose and pH had a major removal effect on MB. Interestingly, a lower amount of adsorbent dose caused greater MB removal. The amount of removal gained was efficient and reached a 99% level with an initial methylene blue solution concentration of ≤160 ppm at pH 11. The kinetic studies indicated that the pseudo-second-order kinetic model relates very well with that of the obtained experimental results. The thermodynamic studies showed that removing the MB dye was favorable, spontaneous, and endothermic. Impressively, the highest quantity of removal amount of MB dye was 16,863 mg/g, as shown by the Langmuir model. The thermal regeneration tests revealed that the efficiency of removing MB (11,608 mg/g) was retained following three continuous rounds of recycled adsorbents. Adsorption of MB onto α-NiMoO₄ nanoparticles and its regeneration were confirmed by Fourier transform infrared spectroscopy (FTIR) analysis and scanning electron microscopy (SEM) analysis. The results indicated that α-NiMoO₄ nanosorbent is an outstanding and strong candidate that can be used for removing the maximum capacity of MB dye in wastewater.     

A Novel Solid Nanocrystals Self-Stabilized Pickering Emulsion Prepared by Spray-Drying with Hydroxypropyl-β-cyclodextrin as Carriers

A drug nanocrystals self-stabilized Pickering emulsion (NSSPE) with a unique composition and microstructure has been proven to significantly increase the bioavailability of poorly soluble drugs. This study aimed to develop a new solid NSSPE of puerarin preserving the original microstructure of NSSPE by spray-drying. A series of water-soluble solid carriers were compared and then Box-Behnken design was used to optimize the parameters of spray-drying. The drug release and stability of the optimized solid NSSPE in vitro were also investigated. The results showed that hydroxypropyl-β-cyclodextrin (HP-β-CD), rather than solid carriers commonly used in solidification of traditional Pickering emulsions, was suitable for the solid NSSPE to retain the original appearance and size of emulsion droplets after reconstitution. The amount of HP-β-CD had more influences on the solid NSSPE than the feed rate and the inlet air temperature. Fluorescence microscopy, confocal laser scanning microscopy and scanning electron microscopy showed that the reconstituted emulsion of the solid NSSPE prepared with HP-β-CD had the same core-shell structure with a core of oil and a shell of puerarin nanocrystals as the liquid NSSPE. The particle size of puerarin nanocrystal sand interfacial adsorption rate also did not change significantly. The cumulative amount of released puerarin from the solid NSSPE had no significant difference compared with the liquid NSSPE, which were both significantly higher than that of puerarin crude material. The solid NSSPE was stable for 3 months under the accelerated condition of 75% relative humidity and 40 °C. Thus, it is possible todevelop the solid NSSPE preserving the unique microstructure and the superior properties in vitro of the liquid NSSPE for poorly soluble drugs.     

Release of Cinnamaldehyde and Thymol from PLA/Tilapia Fish Gelatin-Sodium Alginate Bilayer Films to Liquid and Solid Food Simulants,and Japanese Sea Bass: A Comparative Study

This study aimed to develop an active biodegradable bilayer film and to investigate the release behaviors of active compounds into different food matrices. Cinnamaldehyde (CI) or thymol (Ty) was encapsulated in β-cyclodextrin (β-CD) to prepare the active β-CD inclusion complex (β-CD-CI/β-CD-Ty). The tilapia fish gelatin-sodium alginate composite (FGSA) containing β-CD-CI or β-CD-Ty was coated on the surface of PLA film to obtain the active bilayer film. Different food simulants including liquid food simulants (water, 3% acetic acid, 10% ethanol, and 95% ethanol), solid dry food simulant (modified polyphenylene oxide (Tenax TA)), and the real food (Japanese sea bass) were selected to investigate the release behaviors of bilayer films into different food matrixes. The results showed that the prepared β-CD inclusion complexes distributed evenly in the cross-linking structure of FGSA and improved the thickness and water contact angle of the bilayer films. Active compounds possessed the lowest release rates in Tenax TA, compared to the release to liquid simulants and sea bass. CI and Ty sustained the release to the sea bass matrix with a similar behavior to the release to 95% ethanol. The bilayer film containing β-CD-Ty exhibited stronger active antibacterial and antioxidant activities, probably due to the higher release efficiency of Ty in test mediums.     

Preparation and characterization of poly(2-acrylamido-2-methylpropane-sulfonic acid)/Chitosan hydrogel using gamma irradiation and its application in wastewater treatment

Radiation grafting of chitosan with 2-acrylamido-2-methyl propane sulfonic acid (AMPS) has been successfully performed. The effect of absorbed dose (kGy) and the chitosan:AMPS ratio on graft hydrogelization was studied. The structure of the prepared hydrogel was confirmed using infrared spectroscopy (IR). Thermal properties were simultaneously studied by thermogravimetric analysis (TGA). The effect of the polymerization variables on the swelling % of the prepared hydrogel was investigated. The highest equilibrium degree of swelling (38.6 g/g) and gel % (94.7%) of the prepared chitosan–AMPS hydrogel was at 40% AMPS and absorbed dose of 10 kGy. The removal of methylene blue, acid red dye, Cd (II) and Cr (III) from composed wastewater was also investigated. The effect of pH, the chitosan:AMPS ratio and the concentration of the pollutant on the adsorption process were studied.     

Development of Taccalonolide AJ-Hydroxypropyl-β-Cyclodextrin Inclusion Complexes for Treatment of Clear Cell Renal-Cell Carcinoma

Background: Microtubule-targeted drugs are the most effective drugs for adult patients with certain solid tumors. Taccalonolide AJ (AJ) can stabilize tubulin polymerization by covalently binding to β-tubulin, which enables it to play a role in the treatment of tumors. However, its clinical applications are largely limited by low water solubility, chemical instability in water, and a narrow therapeutic window. Clear-cell renal-cell carcinoma (cc RCC) accounts for approximately 70% of RCC cases and is prone to resistance to particularly targeted therapy drugs. Methods: we prepared a water-soluble cyclodextrin-based carrier to serve as an effective treatment for cc RCC. Results: Compared with AJ, taccalonolide AJ-hydroxypropyl-β-cyclodextrin (AJ-HP-β-CD) exhibited superior selectivity and activity toward the cc RCC cell line 786-O vs. normal kidney cells by inducing apoptosis and cell cycle arrest and inhibiting migration and invasion of tumor cells in vitro. According to acute toxicity testing, the maximum tolerated dose (MTD) of AJ-HP-β-CD was 10.71 mg/kg, which was 20 times greater than that of AJ. Assessment of weight changes showed that mouse body weight recovered over 7–8 days, and the toxicity could be greatly reduced by adjusting the injections from once every three days to once per week. In addition, we inoculated 786-O cells to generate xenografted mice to evaluate the anti-tumor activity of AJ-HP-β-CD in vivo and found that AJ-HP-β-CD had a better tumor inhibitory effect than that of docetaxel and sunitinib in terms of tumor growth and endpoint tumor weight. These results indicated that cyclodextrin inclusion greatly increased the anti-tumor therapeutic window of AJ. Conclusions: the AJ-HP-β-CD complex developed in this study may prove to be a novel tubulin stabilizer for the treatment of cc RCC. In addition, this drug delivery system may broaden the horizon in the translational study of other chemotherapeutic drugs.     

Husk of Agarwood Fruit-Based Hydrogel Beads for Adsorption of Cationic and Anionic Dyes in Aqueous Solutions

Hydrogel beads based on the husk of agarwood fruit (HAF)/sodium alginate (SA), and based on the HAF/chitosan (CS) were developed for the removal of the dyes, crystal violet (CV) and reactive blue 4 (RB4), in aqueous solutions, respectively. The effects of the initial pH (2–10) of the dye solution, the adsorbent dosage (0.5–3.5 g/L), and contact time (0–540 min) were investigated in a batch system. The dynamic adsorption behavior of CV and RB4 can be represented well by the pseudo-second-order model and pseudo-first-order model, respectively. In addition, the adsorption isotherm data can be explained by the Langmuir isotherm model. Both hydrogel beads have acceptable adsorption selectivity and reusability for the study of selective adsorption and regeneration. Based on the effectiveness, selectivity, and reusability of these hydrogel beads, they can be treated as potential adsorbents for the removal of dyes in aqueous solutions.     

Removal of Cu(II) Contamination from Aqueous Solution by Ethylenediamine@β-Zeolite Composite

The low cost β-zeolite and ethylenediamine modified β-zeolite (EDA@β-zeolite) were prepared by self-assembly method and used for Cu(II) removal from contaminated aqueous solution. Removal ability of β-zeolite toward Cu(II) was greatly improved after ethylenediamine (EDA) modification, the removal performance was greatly affected by environmental conditions. XPS results illustrated that the amide group played important role in the removal process by forming complexes with Cu(II). The EDA@β-zeolite showed desirable recycling ability. The finding herein suggested that the proposed composite is a promising and suitable candidate for the removal of Cu(II) from contaminated natural wastewater and aquifer.     

Complexation of Ketoconazole by Native and Modified Cyclodextrins

Complexation of ketoconazole (KET), a broad-spectrum antifungal drug, with β- and γ-cyclodextrins (CDs), heptakis (2,6-di-O-methyl)-β-CD (2,6-DM-β-CD), heptakis (2,3,6-tri-O-methyl)-β-CD (TM-β-CD), 2-hydroxypropyl-β-CD (2HP-β-CD) and carboxymethyl-β-CD (CM-β-CD) was studied. The stability constants were determined by the solubility method at pH = 6 and for 2,6-DM-β-CD and CM-β-CD at pH = 5. At pH = 6, the stability constants increased in the order: TM-β-D < γ-CD < 2HP-β-CD < β-CD < CM-β-CD < 2,6-DM-β-CD. At pH = 5, due to the increased ionization of KET, the stability constant with CM-β-CD increased and with 2,6-DM-β-CD decreased. For complexes of KET with 2HP-β-CD and 2,6-DM-β-CD, the thermodynamic parameters of complexation were determined from the temperature dependence of the corresponding stability constants. For β–γ and TM-β-CD complexes, calculations using HyperChem 6 software by the Amber force field were carried out to gain some insight into the host–guest geometry.     

Role of Basic Surface Groups of Activated Carbon in Chlordecone and β-Hexachlorocyclohexane Adsorption: A Molecular Modelling Study

The influence of nitrogen-containing surface groups (SGs) onto activated carbon (AC) over the adsorption of chlordecone (CLD) and β-hexachlorocyclohexane (β-HCH) was characterized by a molecular modelling study, considering pH (single protonated SGs) and hydration effect (up to three water molecules). The interactions of both pollutants with amines and pyridine as basic SGs of AC were studied, applying the multiple minima hypersurface (MMH) methodology and using PM7 semiempirical Hamiltonian. Representative structures from MMH were reoptimized using the M06-2X density functional theory. The quantum theory of atoms in molecules (QTAIM) was used to characterize the interaction types in order understanding the adsorption process. A favorable association of both pesticides with the amines and pyridine SGs onto AC was observed at all pH ranges, both in the absence and presence of water molecules. However, a greater association of both pollutants with the primary amine was found under an acidic pH condition. QTAIM results show that the interactions of CLD and β-HCH with the SGs onto AC are governed by Cl···C interactions of chlorine atoms of both pesticides with the graphitic surface. Electrostatic interactions (H-bonds) were observed when water molecules were added to the systems. A physisorption mechanism is suggested for CLD and β-HCH adsorption on nitrogen-containing SGs of AC.     

Preparation,Characterization, and Bioavailability of Host-Guest Inclusion Complex of Ginsenoside Re with Gamma-Cyclodextrin

This work aimed at improving the water solubility of Ginsenoside (G)-Re by forming an inclusion complex. The solubility parameters of G-Re in alpha (α), beta (β), and gamma (γ) cyclodextrin (CD) were investigated. The phase solubility profiles were all classified as AL-type that indicated the 1:1 stoichiometric relationship with the stability constants Ks which were 22 M⁻¹ (α-CD), 612 M⁻¹ (β-CD), and 14,410 M⁻¹ (γ-CD), respectively. Molecular docking studies confirmed the results of phase solubility with the binding energy of −4.7 (α-CD), −5.10 (β-CD), and −6.70 (γ-CD) kcal/mol, respectively. The inclusion complex (IC) of G-Re was prepared with γ-CD via the water-stirring method followed by freeze-drying. The successful preparation of IC was confirmed by powder X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In-vivo absorption studies were carried out by LC-MS/MS. Dissolution rate of G-Re was increased 9.27 times after inclusion, and the peak blood concentration was 2.7-fold higher than that of pure G-Re powder. The relative bioavailability calculated from the ratio of Area under the curve AUC₀–_∞ of the inclusion to pure G-Re powder was 171%. This study offers the first report that describes G-Re’s inclusion into γ-CD, and explored the inclusion complex’s mechanism at the molecular level. The results indicated that the solubility could be significantly improved as well as the bioavailability, implying γ-CD was a very suitable inclusion host for complex preparation of G-Re.