Molecular inclusion of PCB126 by beta-cyclodextrin: a combined molecular dynamics simulation and quantum chemical study

The effective enrichment and identification of lowly concentrated polychlorinated biphenyls (PCBs) in the environment is attracting much research attention due to human health concerns raised from their emissions. Cyclodextrins (CDs) are known to be capable to form inclusion complexes with a variety of organic molecules. The purpose of this study is to provide theoretical evidences whether CDs can form energetically stable inclusion complexes with PCBs through a host–guest interaction, and if so, whether infrared and Raman techniques are suitable for the detection of CD-modified PCBs. Focusing on a representative PCB molecule, 3,3′,4,4′,5-pentachlorobiphenyl (PCB126), we studied its molecular inclusion by β-CD (BCD) by performing molecular dynamics simulations and density functional theory calculations. Calculated results show that PCB126 and BCD preferentially form the stable 1:1 inclusion complex. The calculated IR spectra of the 1:1 inclusion complexes mainly present the spectra features of BCD and give only a slight indication for bands of the guest molecule. In contrast, the characteristic vibration modes of the guest molecule are remarkably prominent in the Raman spectra of the inclusion complexes. Based on the present results, we propose that BCD can potentially serve as a candidate for including PCB126 to form the stable 1:1 host–guest complex, and that Raman spectroscopy technology is expected to be suitable for the identification of the CD-modified PCBs, whereas IR spectroscopy is not feasible for such an application.     

Preparation and characterization of cyclodextrin complexes of doxycycline hyclate for improved photostability in aqueous solution

Doxycycline hyclate is Biopharmaceutical Classification System, class I drug (high solubility and high permeability), but it is associated with poor photostability. It is in the class of tetracycline antibiotic, which is used to treat various infections, but its bioavailability is compromised due to its sensitivity to light and aqueous instability. In this paper, the influence of inclusion complexation with different cyclodextrins, i.e., αCD, γCD, HPβCD and RMβCD, on the photostability of doxycycline hyclate in aqueous media was investigated. Host–guest inclusion complexes were prepared by freeze- drying method. The prepared complexes were characterized for drug content, SEM, XRPD, in vitro permeation studies and photostability studies. XRPD showed diffused peaks for most of the complexes, while SEM showed irregularly shaped particles. The formulation D20 (Drug: γCD in 1:20 molar ratio) showed the highest % drug content (83.72?±?1.2%), and the formulations D1 (Drug: αCD in 1: 2 molar ratio) showed the lowest % drug content among all the CD complexes. It was found that the photodegradation of the drug was reduced significantly upon complexation. For Drug: CD complexes, the photostability of the aqueous solution of drug/CD complexes was found to be in the order of γCD?>?RMβCD?>?HPβCD?>?αCD with maximum photostability shown by Drug: γCD (1:20 molar ratio) complex. The obtained results suggested that cyclodextrin complexation can be used as an alternative approach for increasing the photostability of doxycycline hyclate.

     

Inclusion complexes of Schiff bases as phytogrowth inhibitors

This article details the preparation, characterization and phytotoxic evaluation of several Schiff base inclusion complexes obtained from β-cyclodextrin and p-sulfonic acid calix[6]arene. The inclusion complexes (1:1 molar ratio) were prepared by mixing a 5 mmol L^?1 aqueous solution (containing 1 % DMSO) of Schiff bases (guests) with aqueous solution (containing 1 % DMSO) of 5 mmol L^?1 of β-cyclodextrin or p-sulfonic acid calix[6]arene (hosts). The host–guest systems were characterized via a series of NMR experiments. The ability of the complexes to interfere with the radicle elongation of Sorghum bicolor (dicotyledonous species) and Cucumis sativus (monocotyledonous species) was evaluated. After 48 h, the inclusion complexes inhibited the radicle elongation of both species from 11 to 56 %. The formation of inclusion complexes was also investigated theoretically by molecular dynamics simulations in aqueous solution through implicit approach. Based on the experimental observation, the phytotoxic activity evaluated can be attributed to the formation of host–guest systems. This was supported by the theoretical findings based on stable interaction energy analyses for all the studied supramolecular systems.     

Structural and thermal investigations of starch polymers as matrices for retention of rhynchophorol aggregation pheromone

The present study aimed to prepare and characterize amylose inclusion complexes with rhynchophorol aggregation pheromone. The potato and cassava V-amylose–rhynchophorol complexes were successfully obtained, but the B-type polymorph was also formed. The potato (64.6%) and cassava (40.9%) amylose complexes have presented high crystalline indexes, confirmed by the XRD technique. No endothermic peaks associated with the melting of crystalline arrays were noticed between 30 and 100°C. The dynamic TG runs demonstrated that both the degree of order of crystalline arrays and molecular weights influence the thermal stabilities of the V-amyloses-rhynchophorol. The isothermal TG showed that the retention of rhynchophorol seems to be directly proportional to the molecular weights of starch polymers. The recovered rhynchophorol contents were in the order of 10^?7 grams per 50 milligrams of dried powders, which would be useful for insect attraction as demonstrated by the GC–MS technique. The starch polymers studied have presented suitable for retention of rhynchophorol guest molecules.

     

Host proficiency of N,N′-bis(9-phenyl-9-thioxanthenyl)ethylenediamine for pyridine and the methylpyridine guests – a competition study

N,N′-Bis(9-phenyl-9-thioxanthenyl)ethylenediamine proved to be an extremely efficient host compound for pyridine and the isomeric methylpyridines. Furthermore, this host displayed selective behaviour during equimolar guest competitions, consistently favouring 3-methylpyridine in binary, ternary and quaternary experiments. Selectivity orders were 3-methylpyridine >> 4-methylpyridine > 2-methylpyridine, and 3-methylpyridine > pyridine > 4-methylpyridine > 2-methylpyridine, for equimolar ternary and quaternary solutions, respectively. When guest concentrations in binary competitions were varied, 3-methylpyridine remained the favoured guest, even at low 3-methylpyridine concentrations. Single crystal X-ray diffraction showed that all four complexes were isostructural (monoclinic, P2₁/n) while guests occupy discrete cavities in the crystal. Only 3-methylpyridine experiences (guest methyl)C–H???π(host) and (guest methyl)C–H???H–Ar(host) interactions, explaining the observed affinity of the host for this guest. DSC analyses provided further affirmation for the host preference: endotherm peak temperatures for the guest release processes correlated directly with the selectivity order for the three methylpyridine isomers.     

Morphological change of poly (ε‐caprolactone) with a wide range of molecular weight via formation of inclusion complex with α‐cyclodextrin

The effect of molecular weight of poly(ε‐caprolactone) (PCL) on the formation and stability of inclusion complexes (ICs) between α‐cyclodextrin (α‐CD) and PCL was investigated by FTIR, WAXD, and DSC measurements. ICs between α‐CD and PCLs with a wide range of number‐average molecular weight, M_n = 1.21 × 10⁴ – 1.79 × 10⁵, were prepared by mixing the aqueous solution of CD and acetone solution of PCL followed by stirring at 60 °C for 1h and at the room temperature for 1 day. FTIR, WAXD, and DSC measurement showed the PCL chains were included into the α‐CD cavity, and the crystallization of PCL was suppressed in the α‐CD cavity. Stoichiometry and yield of each IC varied with the molecular weight of guest PCL, and the effect of IC formation on the crystallization behaviour of guest polymer decreased with the increase of molecular weight of guest polymer. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 1433–1440, 2005     

Metal Ion,Light, and Redox Responsive Interaction of Vesicles by a Supramolecular Switch

Chemical, photochemical and electrical stimuli are versatile possibilities to exert external control on self‐assembled materials. Here, a trifunctional molecule that switches between an “adhesive” and a “non‐adhesive” state in response to metal ions, or light, or oxidation is presented. To this end, an azobenzene–ferrocene conjugate with a flexible N,N′‐bis(3‐aminopropyl)ethylenediamine spacer was designed as a multistimuli‐responsive guest molecule that can form inclusion complexes with β‐cyclodextrin. In the absence of any stimulus the guest molecule induces reversible aggregation of host vesicles composed of amphiphilic β‐cyclodextrin due to the formation of intervesicular inclusion complexes. In this case, the guest molecule operates as a noncovalent cross‐linker for the host vesicles. In response to any of three external stimuli (metal ions, UV irradiation, or oxidation), the conformation of the guest molecule changes and its affinity for the host vesicles is strongly reduced, which results in the dissociation of intervesicular complexes. Upon elimination or reversal of the stimuli (sequestration of metal ion, visible irradiation, or reduction) the affinity of the guest molecules for the host vesicles is restored. The reversible cross‐linking and aggregation of the cyclodextrin vesicles in dilute aqueous solution was confirmed by isothermal titration calorimetry (ITC), optical density measurements at 600 nm (OD₆₀₀), dynamic light scattering (DLS), ζ‐potential measurements and cyclic voltammetry (CV). To the best of our knowledge, a dynamic supramolecular system based on a molecular switch that responds orthogonally to three different stimuli is unprecedented.     

Effect of the ring size and asymmetry of cyclodextrins on their inclusion ability: a theoretical study

Effect of the ring size and asymmetry upon methylation of cyclodextrins (CDs) on their inclusion ability has been demonstrated for the inclusion complexes of native α-, β-, γ-CDs, dimethylated β-CD (DIMEB) and trimethylated β-CD (TRIMEB) with piperazine (PIZ) by PM3 and ONIOM calculations. In all complexes, PIZ prefers residing mostly in the central CD cavity. The complex stability in the order TRIMEB–PIZ > DIMEB–PIZ > α-CD–PIZ > γ-CD–PIZ > β-CD–PIZ indicates that the CD-ring asymmetry promotes the macrocycle deformation and inclusion ability. Our calculation results suggest that the inclusion complexes of both native and methylated CDs with PIZ in the gas phase are energetically stable, in addition to the β-CD–PIZ inclusion complex that has been evidenced thus far by X-ray crystallographic and spectroscopic analyses. Further calculations in the presence of water and adjacent CD molecules show that the increased intermolecular hydrogen bond interactions enhance the stability of β-CD–PIZ complex.     

Inclusion complexes between cyclic siloxanes and cyclodextrins: synthesis and characterization

Molecular inclusion complexes between cyclodextrins and cyclic siloxanes were prepared and characterized via a combination of liquid and solid state NMR, FT-IR, TGA, powder X-ray diffraction, SEM–EDS and elemental analyses. The crystalline complexes adopted the channel-type conformation. Depending from the size of both the cyclic sugar cavity and the silicon guest, various yields (between 0 and 41%) and host–guest molar ratios (between 1:1 and 4:1) were obtained. α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) were observed to form crystalline inclusion complexes only with D₃ (cyclic dimethyltrisiloxane) due to steric effects, whereas the larger γ-cyclodextrin (γ-CD) formed inclusion complexes both with D₃, D₄ (cyclic dimethyltetrasiloxane) and D₅ (cyclic dimethylpentasiloxane). This study is believed to be the first step towards the selective removal of cyclic siloxanes impurities from commercial PDMS preparations.     

Theoretical studies of inclusion complexes of β-cyclodextrin with methylated benzoic acids

AM1 semiempirical molecular orbital calculations have been performed on the inclusion complexes of β-cyclodextrin (β-CD) with methylated benzoic acids in two orientations, the “head-first” and “tail-first” positions. In the former, the CO₂H group points toward the primary hydroxyls of the CD. In the latter, it points away from them. Out of 30 possible inclusion complexes, AM1 results predict only three clearly stable inclusion complexes. These are β-CD with 4-methyl benzoic acid in the head-first position, β-CD with 2,4-dimethyl benzoic acid in the head-first position, and β-CD with 3,5-dimethyl benzoic acid in the tail-first position. The orientations of the stable inclusion complexes correlate with the total number of intramolecular hydrogen bonds and intermolecular hydrogen bonds. The stability of a complex also correlates with the closeness of the host and guest geometries in the complex to their isolated molecule geometries. © 1997 John Wiley & Sons, Inc. Int J Quant Chem 64 : 711–719, 1997     

Complexation of N-methyl-4-(p-methyl benzoyl)-pyridinium methyl cation and its neutral analogue by cucurbit[7]uril and β-cyclodextrin: a computational study

In this work, molecular dynamics (MD) simulations have been conducted to study the inclusion complexes between cucurbit[7]uril (CB7) and β-cyclodextrin (β-CD) with N-methyl-4-(p-methyl benzoyl)-pyridinium methyl cation, and N-methyl-4-(p-methyl benzoyl)-pyridine in aqueous solutions to gain detailed information about the dynamics and mechanism of the inclusion complexes. The obtained MD trajectories were used to estimate the binding free energy of the studied complexes using the molecular mechanics/Poisson Bolzmann surface area (MM–PBSA) method. Results indicate preference of CB7 to bind to the cationic guest more than the neutral guest, whereas β-CD exhibits more or less the same affinity to complex with either species. Furthermore it was interesting to note that β-CD forms more stable complexes with both guests than CB7. Average structure of each complex and the distances between the center of masses of the guest and the host were also discussed.     

Investigation of indole chalcones encapsulation in β-cyclodextrin: determination of stoichiometry,binding constants and thermodynamic parameters

The study focuses on the formation of inclusion complexes of indole chalcone (IC) derivatives with β-cyclodextrin (β-CD), which involves absorption and steady state fluorescence spectroscopies. The formation of inclusion complexes is validated by increase in their absorbance and fluorescence intensity as well as the blue shift with increase in the concentration of β-CD in the aqueous solution. The stoichiometries and binding constants (K_in) of these complexes have been investigated by monitoring their absorbance and fluorescence spectral profiles. The data are analyzed by Benesi–Hildebrand plots as well as Job’s method, which indicate 1:1 stoichiometry of IC:β-CD complexes. Fluorescence measurements are also used to investigate the effect of temperature on the stability of inclusion complexes. Stability of IC:β-CD complexes is significantly affected with variation in substituents on the phenyl ring and temperature. It is observed that the stability of the inclusion complex decreases with increase in temperature; K_in(293 K)?>?K_in(298 K)?>?K_in(308 K)?>?K_in(318 K). All the experimental results and the geometrical data obtained using PM3 semiempirical method illustrate the partial inclusion of IC derivatives from the phenyl ring side in β-CD cavity. The binding process of IC derivatives with β-CD is found to be exothermic in nature and seems to be controlled by electrostatic and hydrophobic forces. The binding free energies calculated using semiemprical PM3 method for IC:β-CD complexes are found to be in the order: I?<?OH–I?<?Me–I?<?OMe–I?<?NH₂–I, which largely supports the findings based on the experimental binding constants.     

Preparation and characterization of the crystalline inclusion complexes between cyclodextrins and poly(1,3-dioxolane)

The preparation and characterization of the crystalline inclusion complexes between a polymeric guest, poly(1,3-dioxolane) (PDXL), and small-molecular hosts, cyclodextrins (CDs) are reported. It is observed that the polymer guest can form crystalline inclusion complexes with three kinds of cyclodextrins, which may be attributed to the high oxygen atom density in PDXL chain. The crystalline inclusion complexes were characterized with FTIR , TGA, X-ray diffraction, SEM, 1H NMR and 13C CP/MAS NMR spectroscopes. It was found that the crystalline inclusion complexes have higher temperature stability than the pure CDs. The X-ray powder diffraction patterns of the crystalline inclusion complexes proved that they have columnar structures. 13C CP/MAS NMR spectra of the crystalline inclusion complexes indicate that CDs adopt a more symmetrical conformation in the complexes, while pure CDs assume a less symmetrical conformation in the crystal without a guest inside their cavities. The morphology of the crystal was     

Inclusion of chlorophenols by 4,4′‐(cyclohexane‐1,1‐diyl)diphenol: structures and kinetics of decomposition

The structures of the inclusion compounds 4,4′‐(cyclohexane‐1,1‐diyl)diphenol–3‐chlorophenol (1/1) and 4,4′‐(cyclohexane‐1,1‐diyl)diphenol–4‐chlorophenol (1/1), both C₁₈H₂₀O₂·C₆H₅ClO, are isostructural with respect to the host molecule and are stabilized by extensive host–host, host–guest and guest–host hydrogen bonding. The packing is characterized by layers of host and guest molecules. The kinetics of thermal decomposition follow the R2 contracting‐area model, kt = [1 − (1 − α)^½], and yield activation energies of 105 (8) and 96 (8) kJ mol⁻¹, respectively.     

Spectral properties and supramolecular inclusion complex formation between 2-styrylbenzothiazolium dye and cyclodextrins

The effect of native and randomly methylated β-CDs on the absorption and steady-state fluorescence spectra of 2-(4-dimethylaminostyryl)-3-(2-hydroxyethyl)-benzothiazolium chloride (DHB) in aqueous buffer solutions with various pH values was studied. The inclusion with both CDs at pH 7.2 barely changed the UV spectra, whereas significant variations were produced in the emission spectra in all buffer solutions. In all cases the CDs increase guest fluorescence. The 1:1 stoichiometry of the inclusion complexes of the dye with both CDs was established according to the modified Benesi-Hildebrand method. Binding constant values were calculated using the iterative nonlinear least-squares regression approach. The pH of the solution and the type of the CD affected complex stability. The results indicate that native β-CD possesses better complexing ability towards DHB than randomly substituted β-CD and that the most stable inclusion complexes are formed in basic medium because of the structural changes in the guest molecule. In basic medium an attempt is made to interpret the proposed mechanism in terms of molecular rearrangement which take place as the dye penetrates the CD cavity.     

Fe-MCM-41 with highly ordered mesoporous structure and high Fe content: synthesis and application in heterogeneous catalytic wet oxidation of phenol

Raman spectroscopy has been successfully employed in order to investigate the formation of β-cyclodextrin host–guest inclusion molecular complexes with several different azo-dye structures. The Raman pattern of the carbohydrate framework results negligible when neared to the magnificent intensity of the highly polarisable guest systems and a complete and feasible comparison of the spectral features between the free and the complexed situation of the guest molecule is allowed. In general, with respect to the free guest state, it was found within the complex that a hampering of Raman intensity displays, accompanied by a levelling directed variation of the relative peak intensities, and peculiar Raman peak broadening with shifts occur, relatable to the host–guest settling of inclusive intermolecular interactions. Supportively to the other commonly established characterising methods, or in valid alternative, Raman technique has proved astoundingly useful under the perspective of the diagnostic evaluation of cyclodextrin host–guest molecular inclusion for azo-dyes and, more generally, for a highly polarisable guest structure. It features sample non-destructivity, handiness, fastness and sensitive reproducibility, occasionally providing useful suggestions about the complexation topology.     

Dissolution properties of cypermethrin/cyclodextrin complexes

Cypermethrin—a very effective pyrethroid-type insecticide—has been complexed with β-cyclodextrin and peracetylated-β-cyclodextrin with different guest content. Dissolution measurements by reversed phase HPLC method, together with UV-spectrophotometry, differential scanning calorimetry and thermogravimetry were applied to prove the inclusion complex formation and characterize the complexes. With the help of the thermal analysis the really complexed (strongly bound) and surface-bound guests were distinguished. All of the β-cyclodextrin complexes show better dissolution rate than the pure guest. In case of inclusion complexes an oversaturated solution was formed with extremely high concentration of active substance (6–19 mg L^?1) during the first couple of minutes then the concentration decreased gradually until it reached the equilibrium solubility value of the complex (2 mg L^?1). The cypermethrin/peracetylated-β-cyclodextrin complexes prepared with organic solvent method showed slightly retarded dissolution profile compared to the pure guest. The area under the dissolution curves was introduced for quantitative characterization of the dissolution rate. The release was found to depend on the complexed guest content of the samples. The continuous variation plots used first for this parameter gave information on the stoichiometry of the complexes: 1:2 cypermethrin/β-cyclodextrin and 1:1.25 cypermethrin/peracetylated-β-cyclodextrin.     

1H NMR spectroscopic investigation of β-cyclodextrin inclusion compounds with parecoxib

The inclusion complexes of β-CD and parecoxib [PRB] in aqueous solution were investigated using ¹H NMR spectroscopic study revealed the existence of four different equilibria for 1:1 inclusion complexes in which both the aromatic rings of the guest are tightly held by the host cavity. The NMR spectra of the PRB studied in the presence of β-CD are fully assigned and interpreted by means of COSY spectrum for the unambiguous assignment of guest aromatic ring protons. The parallel interpretation of β-CD chemical shift changes and dipolar contacts, with the aid of 2D ROESY, allows the mode of binding to be established for four possible structures of 1:1 PRB-β-CD inclusion complexes.     

Electrospray‐Ionization Mass Spectrometry for Screening the Specificity and Stability of Single‐Stranded‐DNA Templated Self‐Assemblies

Supramolecular complexes consisting of a single‐stranded oligothymine ( dTn ) as the host template and an array of guest molecules equipped with a complementary diaminotriazine hydrogen‐bonding unit have been studied with electrospray‐ionization mass spectrometry (ESI‐MS). In this hybrid construct, a supramolecular stack of guest molecules is hydrogen bonded to dTn . By changing the hydrogen‐bonding motif of the DNA host template or the guest molecules, selective hydrogen bonding was proven. We were able to detect single‐stranded‐DNA (ssDNA)–guest complexes for strands with lengths of up to 20 bases, in which the highest complex mass detected was 15 kDa; these complexes constitute 20‐component self‐assembled objects. Gas‐phase breakdown experiments on single‐ and multiple‐guest–DNA assemblies gave qualitative information on the fragmentation pathways and the relative complex stabilities. We found that the guest molecules are removed from the template one by one in a highly controlled way. The stabilities of the complexes depend mainly on the molecular weight of the guest molecules, a fact suggesting that the complexes collapse in the gas phase. By mixing two different guests with the ssDNA template, a multicomponent dynamic library can be created. Our results demonstrate that ESI‐MS is a powerful tool to analyze supramolecular ssDNA complexes in great detail.