Structure Of Inclusion Complex Research Articles

Cyclodextrin-enhanced photo-induced fluorescence of tau-fluvalinate, molecular modelling of inclusion complexes and determination in natural waters.

The effect of adding organized supramolecular systems such as β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) on the photochemically-induced fluorescence (PIF) spectral properties of tau-fluvalinate (TFV) in aqueous solutions was examined. The influence of pH, UV irradiation time and photoproduct stability on the cyclodextrin-enhanced photochemically-induced fluorescence intensity was also investigated. The spectral changes associated with the inclusion process yielded values for the formation constants of TFV inclusion complexes between 450 and 640 M-1, which were calculated using the nonlinear iterative regression approach least squares. In addition, host-guest interaction was clearly determined by PIF enhancement and a 1 : 1 stoichiometry was found for the β-CD and HP-β-CD complexes formed with TFV. The negative free energy (ΔG°) value indicated that the reaction of TFV with cyclodextrins was thermodynamically favorable. Furthermore, the structures of inclusion complexes of TFV with cyclodextrins were elucidated by 3-21G ab initio calculations. The limits of detection and quantification obtained ranged between 1.3 and 4.0 ng mL-1 and from 4.4 to 13.0 ng mL-1 in β-CD and HP-β-CD media, respectively. The analytical application in tap and river water samples yielded satisfactory mean recoveries ranging from 98.12 to 102.97%. Due to its sensitivity and ease of use, this method can be reliably applied to routine analysis.

Spectroscopic studies on the supramolecular interactions of methyl benzoate derivatives with p-sulfocalix[6]arene macrocycles

This paper is a continuation of our previous research and aims to further investigate and elucidate the nature and mechanisms of noncovalent supramolecular interactions between four methyl benzoate derivatives (I-IV), which are capable of exhibiting Twisted Intramolecular Charge Transfer (TICT) and/or Excited State Intramolecular Proton Transfer (ESIPT)‐type behavior, and chemical and biological nanocavities. Photophysical and photochemical properties of molecules I-IV in aqueous solution in the presence of well-recognized macrocyclic host p-sulfocalix[6]arenes (SCA[6]) have been studied using steady-state, time-resolved and 1H NMR spectroscopic techniques. The changes in the ground- and excited-state spectroscopic characteristics (absorption and fluorescence spectra, time-resolved fluorescence spectra, fluorescence decay times and 1H NMR spectra) undergo significant modifications upon encapsulation of the investigated methyl benzoate derivative in the macromolecular cavity. For the two compounds (I and II), the interactions with the macrocycles with a hydrophobic SCA[6] cavity lead to the formation of stable inclusion complexes with 1:1 stoichiometry, both in the ground and excited state, while the stoichiometry of the III-SCA[6] and IV-SCA[6] complexes in the ground and excited states is 1:2. The values of the equilibrium constants have been determined from the spectroscopic data using Benesi-Hildebrand and nonlinear regression procedures. The location of the organic molecule inside the SCA[6] has been investigated by 1H NMR experiments. The changes in macrocyclic compound-induced NMR chemical shifts clearly indicate that the chemical structure of inclusion complexes is very different for methyl benzoate derivative-SCA[6] and methyl benzoate derivative-CB[7] systems. Finally, we have shown, using time-dependent fluorescence Stokes shift, that very fast solvation dynamics of pure water is markedly different from that of the confined water molecule in SCA[6] system.

Encapsulation through concern of inter and intramolecular hydrogen bonding of 2-hydroxybenzoic acid with C-alkyl calix[4]resorcinarenes

The host-guest complexation of 2-hydroxybenzoic acid (compound 4) with four C-alkyl calix[4]resorcinarenes (compounds 3a-3d) were investigated in aqueous, solid state and gas phase. The solid inclusion complexes were prepared by solvent evaporation method. The solubility of compound 4, compounds 3a-3d and inclusion complexes were analyzed in different polar, non-polar and dipolar solvents. The binding stoichiometric ratio of inclusion complexes was analyzed by phase solubility and jobs plot method. UV–Visible and fluorescence spectral studies were provided the information about binding constant, stoichiometric ratio and Gibb's free energy values. The solid inclusion complexes were characterized by FTIR, 1HNMR , 13CNMR and powder X-ray diffraction studies to determine the interactions between the compound 4 and compounds 3a-3d. The surface morphology of all were characterized by scanning electron microscopic imagining analysis. The biological activity of all were done by phosphomolybdate antioxidant assay and kirby-bauer antibacterial studies. The proposed structure of inclusion complexes were optimized for the two orientations using DFT B3LYP 3–21 G method in the gas phase. The more stable orientations of inclusion complexes were predicted from energy and band gap energy values

Preparation, physicochemical characterization and computational studies of Plectranthus ornatus codd essential oil/β-cyclodextrin inclusion complex

This study aims to prepare and chemically characterize inclusion complexes (IC) between β-cyclodextrin (β-CD) and Plectranthus ornatus essential oil (OEPO). Samples were evaluated by gas chromatography coupled with mass spectrometry (GC-MS) and Fourier transform infrared spectroscopy (FTIR). Moreover, a theoretical study concerning inclusion complexes of β-CD with the four main compounds of OEPO through Molecular Dynamics (MD) simulations, Density Functional Theory (DFT) and Parametric Method-6 (PM6) calculations was performed. The GC-MS analysis of OEPO resulted in the identification of 36 volatile compounds, with the four main components of this essential oil being: β-caryophyllene (21.52%), terpinen-4-ol (6.89%), phytol (4.00%) and caryophyllene oxide (3.32%). The GC-MS results indicated the presence of OEPO volatile compounds in the ICs prepared by the water/ethanol kneading (KWE) and water kneading (KW) method. More specific, β-CD inclusion complexes with β-butoxyethanol (1.15%), 1,3,8-ρ-menthatriene (0.45%), β-caryophyllene (0.20%), phytol (0.41%) and δ-cadinol (0.20%) prepared by the KWE method were detected, while the KW inclusion method resulted in the encapsulation of β-butoxyethanol (3.98%) only. The higher inclusion content of OEPO molecules in KWE was also confirmed by FTIR, with the KWE complex showing more OEPO absorption bands than KW. The PM6 study showed that hydrogen bonds are important, but hydrophobic interactions are the main driving force for triggering the complex formation of the main OEPO volatile compounds with β-CD. The intermolecular host-guest interactions and the investigation for the most suitable inclusion mode were examined by conducting several Molecular dynamics simulations. Moreover, PM6 and DFT approaches revealed the most stable cyclodextrin inclusion complex structures. These findings are in accordance with the experimental data from GC-MS analysis. The effect of solvent on the interaction energy was also studied through simulations and the results showed that the most stable structures are characterized by the formation of hydrogen bonds between guests and cyclodextrin hosts. The developing of such preparation methods that results in ICs like OEPO/β-CD may be useful in the optimization of existing formulations and therefore, be adopted by the pharmaceutical industry

Vine-Twining Inclusion Behavior of Amylose towards Hydrophobic Polyester, Poly(β-propiolactone), in Glucan Phosphorylase-Catalyzed Enzymatic Polymerization.

This study investigates inclusion behavior of amylose towards, poly(β-propiolactone) (PPL), that is a hydrophobic polyester, via the vine-twining process in glucan phosphorylase (GP, isolated from thermophilic bacteria, Aquifex aeolicus VF5)-catalyzed enzymatic polymerization. As a result of poor dispersibility of PPL in sodium acetate buffer, the enzymatically produced amylose by GP catalysis incompletely included PPL in the buffer media under the general vine-twining polymerization conditions. Alternatively, we employed an ethyl acetate-sodium acetate buffer emulsion system with dispersing PPL as the media for vine-twining polymerization. Accordingly, the GP (from thermophilic bacteria)-catalyzed enzymatic polymerization of an α-d-glucose 1-phosphate monomer from a maltoheptaose primer was performed at 50 °C for 48 h in the prepared emulsion to efficiently form the inclusion complex. The powder X-ray diffraction profile of the precipitated product suggested that the amylose-PPL inclusion complex was mostly produced in the above system. The 1H NMR spectrum of the product also supported the inclusion complex structure, where a calculation based on an integrated ratio of signals indicated an almost perfect inclusion of PPL in the amylosic cavity. The prevention of crystallization of PPL in the product was suggested by IR analysis, because it was surrounded by the amylosic chains due to the inclusion complex structure.

Molecular encapsulation of cinnamaldehyde in V-type starch: The role of solvent and temperature

In this study, starch-cinnamaldehyde complexes were prepared by wet method (aqueous ethanol solvent) and dry method (solvent-free) under different temperatures to regulate the formation ability, release behavior, and antibacterial activities of starch-cinnamaldehyde complexes. Successful inclusion complexes (ICs) between V-type starch and cinnamaldehyde were detected only at the wet method preparation over 65 °C. Increasing the complexing temperature facilitated the formation and ordered structures of wet method-prepared starch-cinnamaldehyde ICs, but not for those prepared by dry method. The encapsulation efficiency of cinnamaldehyde in wet method ranged from 15.25 to 62.38 mg/g, significantly higher than that in dry method (12.39–17.20 mg/g). In wet method, ethanol concentration at 50% (w/w) could elevate the complexation efficiency compared with ethanol concentration at 40 and 60% (w/w). Notably, IC prepared using 50% (w/w) aqueous ethanol at 75 °C (75 °C 50% IC) contained the highest cinnamaldehyde content (62.38 mg/g) and largest degree of long- and short-range molecular order. Despite the high volatility of cinnamaldehyde, the 75 °C 50% IC sustainably released the cinnamaldehyde for over two weeks at 50 °C and 57% relative humidity, and it also exhibited significant inhibition against Staphylococcus aureus and Escherichia coli.

NMR study of the inclusion complexes of \u03b2-cyclodextrin with diphenhydramine, clonidine and tolperisone

Forming complexes with β-cyclodextrin can enhance stability, dissolution rate, solubility, and bioavailability of an active pharmaceutical ingredient. In this study, the inclusion behavior between β-cyclodextrin (β-CD) and diphenhydramine, clonidine, and tolperisone in DMSO-d6 was investigated using NMR spectroscopy. 1H, 13C, COSY, HMQC, and ROESY data were applied to determine the structure of inclusion complexes, and molecular docking analysis was engaged to identify the most favorable host–guest interactions in the inclusion complexes. Complexation of β-CD with diphenhydramine, clonidine, and tolperisone is accompanied by the insertion of a molecular fragment of the guest molecule, one molecule of diphenhydramine and tolperisone, and two molecules of clonidine, into the inner sphere of one host molecule. The reported study provides useful information for the potential application of the complexation of β-CD with diphenhydramine, clonidine, and tolperisone. This may be a good strategy for the development of solid pharmaceutical dosage forms based on β-CDs as a drug delivery system.Article highlightsThe inclusion complexes of β-CD and diphenhydramine, clonidine, and tolperisone were synthesized and analyzed using 1Н, 13С, COSY, HMQC, and ROESY spectroscopy.Diphenhydramine, clonidine, and tolperisone interact with β-CD with the formation of stable 1:1 stoichiometric complexes for β-CD:diphenhydramine and β-CD:tolperisone, and 1:2 stoichiometric complex for β-CD:clonidine.Possible structures of the inclusion complexes between β-CD and diphenhydramine, clonidine, and tolperisone were determined using molecular docking in the software AutoDock 4.0.

Formation of the various types of daisy chains constructed by modified cyclodextrin depending on the bond angle of the modified part linked to α-cyclodextrin

ABSTRACT Inclusion complexes (daisy chains) have been widely used in supramolecular chemistry and molecular machines. To develop new molecular machines, it is important to control the inclusion complex structures constructed using modified cyclodextrins (mCDs). To investigate the influence of the bond angle of the modified part linked to the CD on the inclusion complex structures, coarse-grained Brownian dynamics (BD) simulations were conducted. During the simulations, we observed the various types of inclusion complex structures (acyclic, cyclic, branched acyclic, and branched cyclic daisy chains). For the modified part linked to the outer direction of the CD, daisy chains of various sizes were constructed. However, for the modified part linked to the inner direction of the CD, cyclic dimers ([c2] daisy chain) were mainly constructed. To elucidate the formation difference in the daisy chain structures, depending on the bond angle of the modified part linked to the CD, the free energies of the [c2] daisy chain structures were estimated using the histogram reweighting method. It was observed that the formation of the various types of daisy chain structures was determined by the stability of the [c2] daisy chain.

Synthesis of cyclodextrins-metronidazole inclusion complexes and incorporation of metronidazole - 2-hydroxypropyl-β-cyclodextrin inclusion complex in chitosan nanoparticles

Inclusion complexes (ICs) of metronidazole (MTZ) with β-cyclodextrin (BCD) and its derivative 2-hydroxypropyl-β-cyclodextrin (HPBCD) were prepared to improve its apparent solubility. A 1:1 stoichiometry has been proposed for both ICs according to the Job's plots. The estimation of association constants and thermodynamic parameters demonstrated that the incorporation of MTZ in both cavities of cyclodextrins (CDs) is a spontaneous exothermic process. Nuclear magnetic resonance spectroscopy (NMR), two-dimensional (2D) NMR, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) investigations were used to ascertain the structure of ICs and that prove their formation. Thermal analysis showed that the thermal stability of MTZ was improved in the presence of both CDs. The in vitro drug release of ICs showed a considerable increase in the dissolution rate in comparison with the pure MTZ. An improvement of antibacterial activity was observed after encapsulation, especially for MTZ-HPBCD IC. Then chitosan (CS) nanoparticles (NPs) were prepared from the preformed MTZ-HPBCD IC by ionic gelation method. FTIR confirmed that MTZ-HPBCD IC has successfully entrapped in CS NPs. Transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM) images and dynamic light scattering (DLS) show that the NPs have a spherical shape with a uniform diameter. The in vitro release profile of NPs showed a controlled-release of MTZ suggesting that such MTZ-HPBCD IC-loaded CS NPs can be an efficient alternative to modify the MTZ release and increase its solubility.

A comprehensive study on retention of selected model substances in β-cyclodextrin-modified high performance liquid chromatography

The quantitative structure-retention relationship (QSRR) models are not only employed in retention behaviour prediction, but also in an in-depth understanding of complex chromatographic systems. The goal of the present research is to enable the comprehensive understanding of retention underlying the separation in β-cyclodextrin (CD) modified reversed-phase high performance liquid chromatography (RP-HPLC) systems, through the development of mixed QSRR models. Moreover, the amount of β-CD adsorbed on the stationary phase surface (β-CDA) is added as the model's input in order to evaluate its contribution to both model performances and retention. Nuclear magnetic resonance (NMR) experiments were conducted to confirm the predicted inclusion complex structures and support the application of in silico tools. The most significant descriptors revealed that retention is governed by the steric factors 7.5 Å distant from the geometrical centre of a molecule, 3D arrangement of atoms determining the molecular size and shape, lipophilicity indicated by topological distances, as well as the unbound system's energy, related to the inclusion complex formation. In addition, a notable effect of the pH of the aqueous phase on the retention of ionizable analytes was shown. In the case of pH of the aqueous phase and β-CDA the change in retention behaviour of the studied analytes was observed only at the highest β-CDA value (5.17 μM/m2), but it was not related to the ionization state of analytes. When the analytes did not change the ionization form across the investigated studied pH range, and the acetonitrile content in the mobile phase was 25% (v/v), the retention factor had low values regardless of the β-CDA; under these circumstances the retention is probably acetonitrile driven.

Interpreting the nature of interactions in the inclusion complex of danofloxacin, a third-generation fluoroquinolone with Cucurbit[7]uril: A computational study

The Stabilities and electronic structures of inclusion complexes formed between Cucurbit(7)uril and the third generation fluoroquinolone drug, danofloxacin and its zwitterionic form were investigated using the Density Functional Theory. The main aim of this study is to understand the nature of interactions existing between the host–guest molecules in these complexes. The binding and deformation energies, thermodynamic parameters and chemical reactivities of the complexes were calculated. The results indicate that complexation of the zwitterionic form of the drug molecule with CB7 is energetically most favourable. The process of creating these supramolecular complexes is thermodynamically spontaneous and exothermic. The MESP, NCI-RDG, and NBO analysis reveals that the electrostatic interactions and charge transfer between the host and guest molecules contributes to the stability of the complexes. These results are also supported by the Local Energy Decomposition Analysis performed for the complexes.

Molecular dynamics simulations and theoretical calculations of cyclodextrin-polydatin inclusion complexes

In our previous work, the PD/γ-cyclodextrin complex was discovered to have higher calculated Kc and Gibbs free energy (ΔG0) values by the phase-solubility diagram method, and molecular dynamics (MD) simulations were carried out to investigate the structure and dynamics of the 1:1 inclusion complexes formed by β- and γ-cyclodextrins (CD) with PD in water. The simulation results indicated that γ-CD provides the most stable inclusion complex of among all PD-CD complexes in this study. Similar to the MD results, the thermodynamics of the selected inclusion complex structure was calculated by semi-empirical (PM3) and DFT (B3LYP/6-31G) methods. The statistical thermodynamics calculations also suggested that orientation b (including in CD's cavity from the wide side) of the PD/γ-CD inclusion complex is a favourable binding mode and in good agreement with the experimental and MD data. Most importantly, the simulation results of present study are in good agreement with the experimental data.

Crystallographic evaluation of the conformation of quetiapine included in β-cyclodextrin.

Single-crystal X-ray diffraction and theoretical calculations were conducted for insights into the β-cyclodextrin (β-CD)-quetiapine inclusion complex structure. β-CD and quetiapine form a host-guest inclusion complex at a ratio of 2:1 in which the β-CD molecules form head-to-head dimers with their secondary hydroxyl groups linked by multiple hydrogen bonds. Quetiapine is totally contained within the β-CD cavity and exhibits two kinds of disorder (parts 1 and 2) in opposite directions in the β-CD complex. To clarify the mobility of the guest molecule in the β-CD cavity, theoretical molecular conformational calculations, crystal optimization and crystal energy calculations were conducted using CONFLEX software. The results of theoretical molecular conformation calculations showed that the mobility of quetiapine is restricted because its tricyclic structure is covered by β-CD. The results of crystal energy calculations indicated that the conformation of disorder part 1, which has high occupancy, was more stable.

Morphological Characteristics of Amylose‐Poly(tetrahydrofuran) Inclusion Complexes Depending on Temperature and Concentration

AbstractIn this study, inclusion complexes of amylose using poly(tetrahydrofuran) (PTHF) as a guest molecule are studied. The effect of PTHF inclusion into the hydrophobic cavity of amylose is studied with different concentrations of PTHF. Attenuated total reflection fourier transform infrared spectroscopy and differential scanning calorimetry are used to confirm the formation of inclusion complexes and the structural properties of inclusion complexes are analyzed with synchrotron small angle X‐ray scattering (SAXS) and wide angle X‐ray scattering. SAXS patterns show that the complex does not display any self‐assembled lamellar structures due to the lower mobility of PTHF chains as compared to fatty acids. Different crystalline structures of inclusion complexes and arrangements of the PTHF molecules inside the amylose cavity are obtained at different temperatures. The results can play an effective role to understand the structural information of host–guest complexes with different physical and chemical properties of the guest compounds.

Ordered structure of starch inclusion complex with C10 aroma molecules

The ordered structure of inclusion complexes (ICs) between high amylose starch and nine C10 aroma molecules were investigated using experimental approaches (diffractive, spectroscopic and thermal techniques) and theoretical molecular dynamics (MD) simulation. The starch-linear alkyl aroma ICs had a V6I crystalline structure and possessed a higher proportion of single-helix, as well as larger enthalpy changes. Starch-cycloalkyl aroma ICs showed a V7 crystalline structure, with greater crystallinity and a higher dissociation temperature. Starch-lactone aroma ICs were a mix of V6I and V7 crystalline structures whose inhomogeneous polymorphism caused a less-crystalline structure and lower thermal stability. The starch-naphthol IC showed a V8 crystalline structure, with lower transition temperatures. The MD simulation also confirmed the conformational changes of ICs. Intramolecular hydrogen bonds appeared to be the main interactions maintaining the helical structure of amylose, and hydrophobic interactions may be the main factor stabilizing the inclusion of aroma molecules in the hydrophobic inner channel.

Синтез и строение аддукта бензоата тетрафенилфосфора с бензойной кислотой

Синтез и строение аддукта бензоата тетрафенилфосфора с бензойной кислотой

Interactions in inclusion complex of β-cyclodextrin/l-Metheonine: DFT computational studies

In the present work, the host–guest complexation between l-Metheonine/β-Cyclodextrin was investigated using the DFT/B97-D3/6-31G (d) level of the theory. The results obtained clearly indicate that the Orientation B (the carboxylic group of l-Metheonine points toward the primary hydroxyl of β-CD) is energetically favored than that one of the Orientation A (the carboxylic group of l-Metheonine points toward the secondary hydroxyl of β-CD). The energy decomposition analysis, thermodynamic parameters, HOMO, LUMO, the global reactivity descriptors and non covalent interactions-reduced density gradient analysis of the two complexes were calculated and interpreted. The QAIM theory has been used to examine the properties of the bond critical points. Finally, the 1H nuclear magnetic resonance (NMR) chemical shift of the complexes was studied using the Gauge-Including Atomic Orbital (GIAO) method and compared with experimental values. The structures of inclusion complexes of l-Metheonine@β-CD.

Deciphering Structures of Inclusion Complexes of Amylose with Natural Phenolic Amphiphiles.

Amylose inclusion complexes were prepared in aqueous solution with the amphiphilic moiety 3-pentadecylphenol via a direct mixing method. Attenuated total reflection Fourier transform infrared spectroscopy as well as differential scanning calorimetry confirmed the formation of amylose inclusion complexes. The morphology of the synthesized complexes is sensitive to temperature, and X-ray data revealed that the inclusion complexes exhibited distinct structures at different temperatures. Small-angle X-ray scattering data indicated ordered lamellar structures of the synthesized complexes at room temperature, and wide-angle X-ray scattering profiles showed the transformation of the crystalline structure as a function of the temperature. The results of this research will help to understand the relationship between the inclusion complex structures with temperature.

Host-guest interactions accompanying the cationic nitrogen heterocyclic guests encapsulation within pillar[5]arene: A theoretical research

The formation of host-guest inclusion complexes by Pillar [5]arene (P [5]) and cationic nitrogen heterocyclic molecules were studied by DFT calculations at B3LYP-D3/6-311 + G** level, together with their equilibrium geometries, binding energies and electronic structures. MESP, NCI-RDG and AIM topography analysis were performed to explore underlying interactions. Geometric structures of inclusion complexes were changed compared with the individual molecules; MESP analysis revealed the driving force for the binding process; QTAIM and NCI-RDG methods were utilized to reveal the underlying non-covalent interactions. The inclusion complexes in 1:1 ratio were stabilized through weak C–H⋯O hydrogen bonds, C–H···π, π+···π and van der Waals interactions. The calculated electrophilic charge transfer indicated that charge flowed from P [5] to guests. Gibbs free energy accompanying the recognition process certified that formation of complexes were spontaneous and thermodynamically favorable.

Preparation, characterization and molecular modelling of inclusion complex between α-naphthylacetic acid with ethylenediamine-β-cyclodextrin

Using ethylenediamine-β-cyclodextrin and α-naphthylacetic acid as raw material, a novel inclusion complex (en-β-CD@NAA) was synthesized. The inclusion complex structures and properties were analyzed by reliable spectroscopic and physicochemical techniques. The stoichiometry of the inclusion complex was 1:1 and the stability constant (KS) value was found to be 2511 M−1 at 293 K. Molecular thermodynamic parameters indicated that the spontaneous and exothermic nature of the process. The inclusion form was foreseen by Chem 3D program combined with 1H-NMR experimental data. The solubilization curves (K1 = 2.05) and in-vitro dissolution data demonstrated that the en-β-CD@NAA inclusion complex has satisfactory water solubility.