Formation Of Inclusion Compounds Research Articles

Ethane clathrate hydrate infrared signatures for solar system remote sensing

Hydrocarbons such as methane and ethane are present in many solar system objects, including comets, moons and planets. The interaction of these hydrocarbons with water ice at low temperatures could lead to the formation of inclusion compounds, such as clathrate hydrates (water based host cages trapping guest molecules), modifying their retention, stability and therefore evolution. The occurrence of clathrate hydrates on solar system surfaces could be established by remote sensing of their spectroscopic signatures. In this study, we measure and analyse ethane clathrate hydrate spectra recorded in the temperature range from 5.3 to 160 K, covering most of the temperature range of interest for solar system objects. Specific infrared band signatures are identified for the ethane encaged guest. We provide evidence that ethane clathrate hydrate outcrops can be detected by remote sensing on the surface of planetary bodies.

Antimicrobial activity of fusidic acid inclusion complexes

ObjectivesTo synthesize and characterize the inclusion complexes of fusidic acid with β – cyclodextrin, followed by the evaluation of their antimicrobial activity against pure strain (Staphylococcus aureus ATCC 25,923) and isolated Staphylococcus from clinical cases. MethodsThe desired compounds were synthesized using molar ratio of fusidic acid: β-cyclodextrin of 1:1. Synthesized compounds were analyzed by Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Thermal Analysis, and the results confirmed the formation of inclusion compounds by fusidic acid with β-cyclodextrin. ResultsPhysical–chemical characterization confirmed the preparation of desired inclusion compounds, and the antimicrobial test confirmed that all compounds obtained have antimicrobial activity. Antimicrobial activity of freeze-drying complex againstS. aureus is similar with pure fusidic acid activity, being better than the cefoxitin one. Similar behavior was observed against methicillin-resistant S. aureus and S. epidermidis. ConclusionsIn the present work, three different inclusion complexes of fusidic acid were prepared using three different preparation methods. All inclusion complexes obtained presented good antimicrobial activity against differentS. aureus strains. Antimicrobial activity of these new prepared compounds was observed to be better than that of cefoxitin.

Novel poly-β-cyclodextrin derivatives as advanced carriers for 5-fluorouracil for tumor: the impact of charge on antitumor efficiency.

BackgroundWith the emergence of more and more cyclodextrin derivatives, cyclodextrin becomes an effective adjuvant for improving the prescription of drugs. Its application in pharmacy, especially in the sustained and controlled release, targeting, transdermal and mucosal drug delivery systems, is also being expanded and deepened. In this study, novel cyclodextrin derivatives were developed to investigate the impact of the charge on antitumor efficiency by introducing different groups (carboxymethyl or quaternary ammonium group) to poly-β-cyclodextrin (β-CD).MethodsThese novel β-CD derivatives were prepared by the nucleophilic substitution reaction and characterized by IR and 1H NMR. Fluorouracil (5-FU) was adopted as a model drug to form inclusion compounds. The content of 5-FU in inclusion compounds was evaluated using fluorine element analysis. Also, the cytotoxicity of poly-β-CD derivatives was studied. Finally, the effect of negative and positive charges on the antitumor activity of poly-β-CD derivatives-5-FU inclusion compounds on HepG2 cancer cells was evaluated. Human liver cancer HepG2 cells (CYP3A4G/7R clone 87, RRID: CVCL_1×10) were purchased from Cell Bank, Shanghai Institutes for Biological Sciences (China).ResultsThe results of IR and 1H NMR indicated consistently that both carboxymethyl poly-β-CD (poly-CM-β-CD) and glycidyl trimethyl ammonium chloride (GTMAC) poly-β-CD (poly-GTAC-β-CD) were successfully prepared. Fluorouracil was successfully loaded into poly-β-CD derivatives. The results of fluorine analysis indicated that the content of 5-FU in 1 g poly-β-CD, poly-GTAC-β-CD and poly-CM-β-CD was 1,214, 921 and 1,187 µg, respectively. No cytotoxicity of poly-β-CD derivatives on HepG2 cells was observed. The killing effect of poly-β-CD-5-FU on HepG2 cells was similar to that of poly-GTAC-β-CD-5-FU. Poly-CM-β-CD-5-FU had the worst killing effect on HepG2 cells.ConclusionsCharge had impact on antitumor efficiency. These novel poly-β-CD derivatives have potential applications in tumor sustained-release targeted therapy.

Synthesis, characterization of inclusion compounds of amygdalin with β-cyclodextrin and sod-like activity and cytotoxicity on hela tumor cells

In this work is presented the synthesis of the inclusion complexes of amygdalin with β-cyclodextrin by three methods: kneading, co-precipitation and freeze drying and their characterization.The inclusion compounds were synthesized using a molar ratio of amygdalin: β-cyclodextrin of 1:1. Synthesized compounds were analyzed by FTIR spectroscopy, X-rays, thermal analysis and the results confirm the formation of inclusion compounds by amygdalin with β-cyclodextrin.The studies carried out have shown the protective effect of amygdalin-β-cyclodextrin compounds obtained by freeze drying, kneading and coprecipitation against free radicals (SOD-like activity in vivo) and the results of in vitro cell cytotoxicity of the compounds on HeLa cell line compared to pure amygdalin. Compound obtained by freeze drying has the best SOD-like activity and cytotoxicity on HeLa tumor cells, so it may be considered as potential therapeutic agent.

Smart Molecular Recognition: From Key-to-Lock Principle to Memory-Based Selectivity.

The formation and decomposition of inclusion compounds with a solid-solid phase transition may be very selective to the guest molecular structure. This selectivity may function in essentially different ways than defined by the classical concept of molecular recognition, which implies the preferential binding of complementary molecules. Solid inclusion compounds may take part as an initial or/and final state in several processes of different types summarized in this review, which selectivity is boosted by cooperativity of participating molecular crystals. Some of these processes resemble switching electronic devices and can be called smart giving practically absolute molecular recognition.

Complexation and physicochemical analysis of hydrophobic molecules of methyl jasmonate with Hydroxypropyl-β–Cyclodextrin

In the present study, methyl jasmonate (MeJa) was included in 2-hydroxypropyl-β-cyclodextrin (HPβCD) by grinding (M1), freeze drying (M2), co-precipitation + freeze drying (M3) and by applying supercritical carbon dioxide (M4). FT-IR/ATR, FT-Raman, TGA, and DSC analyses of the complexation products confirmed that MeJa/HPβCD complexes were formed by the four different examined methods of inclusion. FT-IR/ATR supported the inclusion, mainly based on the reduction of intensity of absorption at the wavelength of maximum absorbance of free MeJa (1733 cm-1), which was 27.69 au before inclusion. From these results, M3 (2.29 au) and M4 (0.90 au) were the most efficient techniques for complexation. TGA, and DSC analyses pointed out that the complexes formed by the methods M3 and M4 had the least loss of mass below approximately 305°C (the temperature that free HPβCD starts to decompose thermally). Except for M1, the results of antioxidant activity (AA) based on the DPPH assay revealed that the AA of the inclusion compounds were higher than that of free MeJa (α = 0.05). The best methods in terms of AA and thermal stability of the formed inclusion compounds were M3 and M4.

Hydrophobic nanoprecipitates formed by benzoylphenylureas and β-cyclodextrin inclusion compounds: synthesis, characterization and toxicity against aedes aegypti larvae

The aim of this work was to synthesize and characterize the inclusion compounds formed by the complexation of β-cyclodextrin (βCD) with insecticides from the class of benzoylphenylureas (BPUs), named novaluron (NOV) and diflubenzuron (DIF), beyond evaluate their larvicidal activity against Aedes aegypti larvae. Solid state characterization by FTIR showed changes in the main peaks of BPUs and βCD, suggesting the formation of inclusion compounds in solid phase. DTA and TGA thermal analysis showed changes in temperatures of BPUs decomposition as result of molecular interactions. 1H NMR experiments allowed to observe the occurrence of interactions in solution through changes in chemical shifts of BPUs aromatic hydrogens. However, the presence of H–H intermolecular correlations in 2D ROESY was found only for the DIF/βCD complex, suggesting different topology for each complex. Such hypothesis was corroborated by thermodynamic analysis using ITC, which showed different profile of titration curves, beyond endothermic and exothermic interactions for NOV/βCD and DIF/βCD complexes, respectively. DLS titrations of BPUs or BPUs/βCD DMSO solutions in aqueous solution demonstrated that the spontaneously formed hydrophobic nanoprecipitates (HNPs) have different profile of sizes depending on the BPU/βCD system, corroborating also with the hypothesis about the existence of different topologies for each complex. Finally, the HNPs of inclusion compounds showed to be more efficient than free BPUs, allowing proposing a new insecticide formulation.

Spatial packing of diols and esters with imidazoquinazoline ring\u2014quantum-mechanical modeling

This work explains the spatial arrangement of two derivatives of 1-phenyl-2H,6H-imidazo[1,5-c]quinazoline-3,5-dione (PIQ), i.e., diester 2,6-bis(ethoxycarbonylmethyl)-1-phenylimidazo[1,5-c]quinazoline-3,5-dione (BEPIQ) and 2,6-bis(2-hydroxyethyl)-1-phenylimidazo[1,5-c]quinazoline-3,5-dione (BHEPIQ). Studies of a single crystal by X-ray crystallography showed a different way of arranging the diol and diester molecules in the crystals. Quantum-mechanical modeling showed the overlapping of the highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO) of BEPIQ enantiomeric molecules in relation to each other in the “head to tail” position. The formation of charge-transfer complexes stabilizes the system and is responsible for the packing density of the BEPIQ molecules in the crystal. The BEPIQ enantiomeric pairs are positioned at an angle of 67° to each other forming the herringbone in the crystal lattice. In addition, the BEPIQ crystal has the ability to form inclusion compounds. Based on the calculations, it was found that the overlapping of molecular orbitals of BHEPIQ molecules is not possible. It results from a different distribution of electron density in imidazoquinazoline ring as compared to the molecule of the BEPIQ. The formation of intermolecular hydrogen bonds is responsible for the spatial arrangement of the BHEPIQ molecules. The BHEPIQ molecules are arranged in a “head to head” position, and in the crystal, they form stackings.

Covalent Immobilization of Amino-β-Cyclodextrins on Glassy Carbon Electrode in Aqueous Media

In the present work, the application of the amine electrooxidation method to achieve the grafting of amino β-cyclodextrins (CD-amines) on glassy carbon electrodes (GCE) in aqueous media has been investigated. The results indicate that the electrooxidation procedure of CD-amines on GCE effects their covalent immobilization without the need of additional linkers or intermediates. Cyclic voltammograms of ferricyanide proved that the immobilized CDs cover at a large extent the GCE surface. This immobilization is due to real grafting and not the result of a weak physisorption interaction. Indeed, the presence of contributions characteristic of amide groups and the absence of peaks typical of amine groups in the XPS N 1s spectra of the modified GCE, support the evidence of the covalent bonding of the CDs to the glassy carbon surface through amide bond formation. Electrochemical experiments demonstrated that ferrocenemethanol and bentazon can be encapsulated within the cavity of the CDs immobilized on GCEs via the formation of inclusion compounds. Overall, the results of the present work show that this simple amine-electrooxidation strategy is suitable to immobilize CDs on glassy carbon surfaces while maintaining their inclusion abilities and, therefore, open the door to design cheap and simple electrochemical sensors for environmental applications.

Inclusion compound formation between hazelnut oil and gamma cyclodextrin

Inclusion compound formation between hazelnut oil and gamma cyclodextrin

Interaction of β-cyclodextrin with tosyl chloride in an aqueous alkaline medium

The regioselective functionalisation of the cyclodextrin matrix provides the possibility of purposefully altering the ability of cyclodextrins to form inclusion compounds, as well as to ensure their solubility, thus expanding the scope of their practical application [1, 2]. The most significant and promising trend in the selective modification of β-cyclodextrins consists in the preparation of tosyl derivatives, given that the substitution of such nucleophilic reagents as iodide, azide, thioacetate, hydroxylamine, alkylamide or polyalkylamide for the tosyl group results in the corresponding monosubstituted derivatives. In this study, we impl emented a method for the synthesis of mono-6-O-(p-toluenesulphonyl)-β-cyclodextrin, which was improved by β-cyclodextrin reacting with tosyl chloride in an aqueous medium in the presence of a base. The reaction of β-cyclodextrin with tosyl chloride in an aqueous alkaline medium produced a 58% yield of mono -6- O-(p-toluenesulphonyl)-β-cyclodextrin not requiring additional purification. The optimal concentrations of β-cyclodextrin and tosyl chloride were found to be 0.0032 mol/l and 0.0015 mol/l, respectively. It was shown that a decrease in the rate of filtering the unreacted tosyl chloride out of the reaction mixture is acc ompanied by an increase in the proportion of ditosyl derivatives and mono(3,6-anhydro)-β-cyclodextrin resulting from the intramolecular cyclisation of mono-6-O-(p-toluenesulphonyl)-β-cyclodextrin at room temperature under alkaline conditions. The structure of the obtained mono-6-O-(p-toluenesulphonyl)-β-cyclodextrin was confirmed using Proton NMR Spectroscopy. The proton NMR spectrum of the product resulting from the reaction of β-cyclodextrin with tosyl chloride contains signals corresponding to a tosyl radical: a singlet (2.42 ppm) and two doublets (7.41–7.43 ppm) produced by hydrogens of the benzene ring having radicals in the para position. Monosubstitution was confirmed by comparing the integrated intensities of signals produced by the protons of the cyclodextrin skeleton and the protons from the aromatic part of the reaction product. Their ratio indicated that only one of the seven primary hydroxyl groups of β-cyclodextrin was substituted.

In Russian

The results of experimental data obtained using UV spectroscopy, due to a comparative study on the interaction of α- and β-cyclodextrins with alpha aromatic amino acids differing in molecular size and substituent structure at the α-carbon atom in aqueous solutions with various pH (L-phenylalanine, L-tyrosine and L‑tryptophan) have been analyzed. The features of the interaction of selected amino acids with cyclodextrins have been clarified. Molecular cationic and zwitterionic forms of amino acids at the same content of components in the solution and an excess of cyclodextrin form 1: 1 host-guest inclusion complexes, regardless of the pH value of the medium. This is manifested by a long-wavelength shift and an increase in the intensity of the characteristic absorption band in the UV spectra of solutions. It has been proved that inclusion complexes are formed due to the van der Waals interactions by partial displacing water molecules and incomplete (in the case of α-cyclodextrin) immersion of the amino acid aromatic radical into the internal hydrophobic cavity of α-cyclodextrin and of β-cyclodextrin. Stabilization of the complexes is due to hydrogen bonds, and the geometric parameter makes the main contribution to the formation of inclusion complexes. It has been found that the hydrogen bond is formed between the nitrogen atom of a-amino group or the oxygen atom of a-carboxyl group of the amino acid molecule with hydrogen of the primary hydroxyl group located on the surface of the wide edge of the torus, as well as between the nitrogen atom of the imino group of the L‑tryptophan molecule and glycoside hydrogen atom within the cyclodextrin cavity. The values of the stability constants (Ks) of the complexes and the thermodynamic parameters of the formation of inclusion compounds (ΔG, ΔH, and ΔS) have been calculated. The use of a smaller macrocycle (a-CD) leads to a decrease in the stability of the inclusion complexes. Negative values of the change in the free Gibbs energy indicate a spontaneous complexation reaction between a- or b-cyclodextrins and alpha aromatic aminoacids. Negative values of the enthalpy DH and entropy DS indicate that the complexes are mostly stabilized due to the entropy contribution.

β-Cyclodextrin complexation of extracts of olive leaves obtained by pressurized liquid extraction

The aim of this work was to investigate different methods of complexation of extracts of olive leaves (EOL) with β-cyclodextrin (β-CD) and to verify how EOL, in its free form and as inclusion complex, behaves as an antioxidant in olive oil. The extracts were obtained by pressurized liquid extraction at 343 K and ∼1 × 104 kPa with ethanol as solvent. Oleuropein represented approximately 75% of the total phenols whose content determined by Folin-Ciocalteu was ∼0.12 kg GAE kg−1, while the IC50 of the dry EOL was 0.043 kg m−3. The antioxidant capacity of the extract determined by the ABTS method was 0.12 kg TEAC kg-1 dry weight. The dry powder extracts were used as guest to form inclusion compounds with β-CD by involving the methods of physical mixture (PM), kneading (KN), PM and KN assisted by supercritical CO2 as complexation medium. Free EOL, free β-CD and EOL/β-CD complexes were characterized in terms of spectral properties by 1H NMR, FT-IR and XRD, and morphology by SEM. Unambiguous interactions between hydrogen atoms in the free EOL and in the host, reduction of relaxation times in the formed complexes, and area under absorption bands in the EOL/β-CD complexes that were significantly smaller than the ones of pure EOL were the results that more markedly supported effective complexation from these analyses. Recorded data of induction time revealed that free EOL, but mainly the formed EOL/β-CD complexes, when used as additives to an olive oil may increase its oxidative stability.

Formation of aqua and tetraammine Cu(II) complexes inside the cavities of cucurbit[6,8]urils: A DFT forecast

AbstractResults of DFT calculations of the structure and thermodynamics of formation of aqua and tetraammine Cu(II) complexes inside CB[n] (n = 6,8) are presented in this study. Formation thermodynamics of the complexes in the cavitands was evaluated by taking into account the most probable number of water molecules inside CB[n]. In this methodology, the complexation was first considered as a substitution reaction in which the guest complex displaces partially or completely the water molecules that are located inside the cavity. The water molecules present in the cavitand were shown to play an important role in the fixation of the guest complex inside the cavity due to the hydrogen bonds with the oxygen portals. The hydration of Cu(II) ion inside CB[6] leads to the formation of an inclusion compound with the formula {[Cu(H2O)4]2+·2H2O}@CB[6] while in CB[8] {[Cu(H2O)6]2+·4H2O}@CB[8] is formed. For the binding of tetraammine Cu(II) complex, CB[8] was determined to be a significantly more suitable “container” than CB[6]. Both a direct embedding of this complex into the CB[8] and another mechanism in which ammonia molecules replace the water molecules in the Cu(II) aqua complex, preexisting in CB[8] were determined to be thermodynamically possible. Both these lead to the formation of the resultant inclusion compound described by the formula {[Cu(NH3)4(H2O)2]2+·4H2O}@CB[8].

A review on thermal analyses of cyclodextrins and cyclodextrin complexes

Cyclodextrins are valuable natural or synthetically modified cyclic oligosaccharides that are widely used for ameliorating properties of biologically active compounds such as food additives and ingredients or medicinal compounds. They protect these compounds against light and oxidative degradation and provide host–guest supramolecular complexes having controlled release properties by molecular encapsulation, enhancing the water solubility and bioavailability. Among many characterization methods that are applicable in both solution and solid state, thermal techniques were widely used for analysis and stability evaluation of cyclodextrins and cyclodextrin complexes. This updated review deals with the use of thermal methods for analysis of cyclodextrins and cyclodextrin complexes. Classical and modern thermal techniques used for evaluation of inclusion compound formation were reviewed. Special attention was gave for thermogravimetry–differential thermogravimetry, differential thermal analysis, differential scanning calorimetry, hot stage microscopy, as well as for the more recent techniques thermogravimetry–mass spectrometry, gas chromatography-time-of-flight-mass spectrometry and isothermal titration calorimetry. In order to evaluate the cyclodextrin complexation capability by thermal methods, we grouped for the first time the guest compound as drugs by anatomical therapeutic chemical classification (ATC), as well as odorants, essential oils and vegetable extracts, antioxidants, fatty acids, oils, fatty acid-based derivatives, other organic, organometallic and inorganic compounds. The formation of cyclodextrin inclusion complexes was emphasized by disappearance of the signal corresponding to the melting or boiling points of the guest compound and the behavior of the hydration water molecules in the complex in comparison with the raw host and guest compounds. The thermal stability of the guest compound after cyclodextrin complexation was also discussed. It was emphasized that thermal methods are some of the most valuable techniques for analyzing cyclodextrin complexes and together with other methods can complete the information related to the host–guest molecular inclusion process and the specific properties of these cyclodextrin complexes.

Complexes of TETROL with selected heterocyclics: unconventional host–guest hydrogen bonding and the correlation with host selectivity

Here we investigate and compare the more salient characteristics of host–guest complexes of (+)-(2R,3R)-1,1-4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) with four heterocyclic guests, morpholine, piperidine, pyridine and dioxane. These guests each formed inclusion compounds with TETROL, and host:guest ratios were either 1:2 or 1:1. Single crystal diffraction experiments revealed unprecedented host behaviour in the presence of both piperidine and dioxane with respect to the mode of host–guest hydrogen bonding employed. Furthermore, by utilizing 1H-NMR spectroscopy or gas chromatography (as applicable) as methods for analysing complexes obtained from competition experiments, we were able to identify the host selectivity order, and were gratified to discover that this order correlated precisely with host–guest hydrogen bond distance.

EFFECT OF 2-HYDROXYPROPYL- β -CYCLODEXTRIN ON SOLUBILITY OF NOVEL CYTOTOXIC COMPOUNDS

Complexation processes in the systems of 2-hydroxylpropyl-β-cyclodextrin − cytotoxic substances within the temperature range of 293 – 315 К were studied by the UV-spectroscopy method. It was proved that complexation leads to the formation of supramolecular inclusion compounds with 1:1 component ratio. Stability constants of the complexes and thermodynamic parameters of the formation of the inclusion compound 2-hydroxylpropyl-β-cyclodextrin – tris(1-pentyl-1Н-indol-3-yl)methanol were calculated. The obtained complex of 2-hydroxylpropyl-β-cyclodextrin – tris(1-pentyl-1Н-indol-3-yl) methylium chloride was found to be unstable.

An unexpected relationship between solvent inclusion and gas sorption properties of chiral calixsalen solids

Experimental evidence is provided that tentatively shows a relationship between inclusion and sorption properties within a series of halogenated homochiral calixsalens. Calixsalens with Cl and Br substituents at the C5 position on the aromatic rings display remarkable sorption properties for all of the investigated gases, as well as the ability to form inclusion compounds with chemically different solvents, while unsubstituted (H-) and F-substituted calixsalens do not show any of these properties.

Formation of β-Cyclodextrin inclusion compound with doxycycline: A theoretical approach

Recently, the inclusion compound formed by doxycycline and modified CD was investigated. In the inclusion compound, the unstable site of doxycycline was protected by the hydrophobic CD cavity. However, the guest arrangement inside CD cavity has not identified. In some situations, the correlation between protons of the guest and host in a 2D-ROESY experiment can be compatible with head and tail spatial arrangements. In the present work, the most stable guest spatial arrangement for the inclusion of doxycycline into β-CD was evaluated at B97-D/6-311++(2d,p) level of theory. For sake of comparison, tetracycline inclusion compound was also studied.

Water‐Encapsulated Ni(II) Salphen‐Type Host Complexes: Experimental and Theoretical Analysis of Potentially Bioactive Quasi‐Isostructural Polymorphs

AbstractIn this study, we report the formation of two quasi‐isostructural polymorphs (α and β) of a Ni(II) salphen‐type Schiff base complex using solvent evaporation technique. The polymorphs are inclusion compounds with guest water molecules exhibiting similar spectroscopic and thermal characteristics. Single crystal XRD (X‐ray Diffraction) analyses reveal the subtle differences in packing and supramolecular interactions which are quantified using Hirshfeld and 2D finger print analyses. Electrostatic potential analysis shows significant difference in potential distribution in the two molecules. The compositional analysis of the frontier orbitals and differences among the atomic charge distribution of the polymorphs are established using DFT (Density Functional Theory) calculations. Apart from highlighting the strength of encapsulation, DFT study substantiates the formation of inclusion compounds through single point energy calculations. Effects of inherent differences in the polymorphs on potential biological activity are probed using in silico molecular docking with B‐DNA and Human Serum Albumin (HSA). The α form shows superior bioactivity while β form excels in water encapsulation.