Showing papers in "Journal of Inclusion Phenomena and Macrocyclic Chemistry in 2019"

A review of the production of slow-release flavor by formation inclusion complex with cyclodextrins and their derivatives

Abstract: Flavors have been widely used in many products. They are volatile compounds and do not often last long in air especially at high temperature. The techniques for slow flavor release and long-lasting scents, for the stability of sensory perception, are much desired. The inclusion complex method encompasses the idea of molecular recognition and interactions through noncovalent bonding. It can provide protection and prevent the loss of volatile aroma materials, and improve shelf-life and enhance the stability of the entrapped ingredients of flavors. In this article, the production of control-release flavor by inclusion complex method was reviewed in considerable detail. The host materials, the method of production flavor inclusion complex, and the methods of characterization of flavor inclusion complex were depicted. The complexation thermodynamics and calculations were also discussed. Cyclodextrins and their derivatives as the host materials were discussed in this paper. Methods of production flavor inclusion complex include solution method (water or water as the main component of the solution, cosolublizer), suspension method, gas/liquid interface method, and solid phase method (co-grinding method, heating in a closed container method, shaking method at room temperature). The methods of characterization of solid inclusion complex mainly include x-ray diffraction technique, Infrared and Raman spectra, solid nuclear magnetic resonance spectroscopy, thermal analysis, mass spectrometry analysis, scanning and transmission electron microscopy. Structures, energies, and some properties of molecules can be studied by computational chemistry. The application of computational chemistry to the study of flavor compound inclusion complexes were discussed. The review indicates that inclusion complex method is an efficient way for encapsulation of flavor compounds. By this method slow flavor release and long-lasting scents can be obtained.

Allosteric signal-amplification sensing with polymer-based supramolecular hosts

Abstract: The lock-and-key principle is a fundamental substance to create chemosensors that sense target analytes. Our results based on the lock-and-key concept, i.e., inherently chiral molecular clips and resorcin[4]arenes, were introduced and their inherent problems were also explained. Hence, a novel sensing methodology, “supramolecular allosteric signal-amplification sensing” (SASS), has been proposed to develop functional polythiophenes and polysaccharides for amino acids, peptides, and oligosaccharides that are difficult to sense. The polythiophene sensors showed amplified responses through a positive allosterism, and the polysaccharide sensors capture oligosaccharides in aqueous media and then were expanded to an extremely sensitive in situ oligosaccharide sensor that is dynamically controllable. The present SASS strategy using polymer chemosensors that behave very differently from common ones is essentially based on an allosterically molecular information propagation, upon interaction of an analyte to a chemosensor’s binding pocket, to an amplifying polymer reporter.

Applications of macrocyclic compounds for electrochemical sensors to improve selectivity and sensitivity

Abstract: Electrochemical sensing is a promising analytic method with its advantages, such as low cost, fast response, simple operation, high accuracy, low detection limit and so on With the rapid development of electroanalysis, various modified electrodes were synthesized for constructing different kinds of electrochemical sensors on purpose Macrocyclic compounds with their superior supramolecular recognition properties have aroused the research interest, as they can be used as modifiers for enhancing the sensitivity and selectivity of electrodes All five classic macrocyclic compounds, which are crown ethers, cyclodextrins, calixarenes, cucurbiturils, and pillararenes, have been employed as receptors for electrochemical sensors, and these macrocycles have led to a wilder detection range, a lower detection limit, and superior ability of anti-interferences against coexisting ions or molecules The macrocycles modified electrodes have shown greater sensitivity and selectivity in detection Therefore, this review focuses on the results of the studies published in recent 8 years on macrocycles improved electrochemical sensing In this review, the recent development of functionalization of macrocyclic compounds including crown ethers, cyclodextrins, calixarenes, cucurbiturils, pillararenes, on electrochemical sensors has been summarized

Solubilization of ultraviolet absorbers by cyclodextrin and their potential application in cosmetics

Abstract: Conventionally, synthetic organic ultraviolet (UV) absorbers, such as octylmethoxy cinnamate (OMC) and avobenzone, have been formulated into cosmetic sunscreens. However, because of their high skin stimulus, alternative products made from natural compounds are required. Although some botanical flavonoids and ferulic acid derived from rice bran are candidates for natural UV absorbers, because of their poor solubility, it has been difficult to formulate these natural compounds into cosmetics. In this work, we confirmed by screening tests that cyclodextrins could make an inclusion complex with the UV absorbers in aqueous solutions. We found by a phase solubility test and Job plot that hydroxypropylated-γ-cyclodextrin (HP-γ-CD) made an inclusion complex with ferulic acid in a stoichiometry of 1:2. In cosmetic applications, the formulation containing the ferulic acid/HP-γ-CD inclusion complex showed a higher sun-cut effect than that containing OMC. Notably, the ferulic acid/HP-γ-CD inclusion complex showed extraordinarily high protection values for UVA, which will be useful for preparing effective and safe sunscreen formulations.

Evaluation of metal ion sensing behaviour of fluorescent probe along with its precursors: PET-CHEF mechanism, molecular logic gate behaviour and DFT studies

Abstract: For the first time, we have reported the metal ion sensing behaviour of a fluorescent probe APAP (derivative of 4-amino/4-formyl antipyrine) along with its precursors (AAP-4-Aminoantipyrine, FAP-4-Formylantipyrine) and explained the tuning of precursors resulted in difference in the sensing behaviour. The two antipyrine precursors (4-amino/4-formyl antipyrine) were condensed together to form a new host molecule APAP, which acts an effective fluorescent chemosensor for detection of Fe3+ ions. The precursors AAP and FAP would able to detect Al3+ and Cr3+ ions respectively. The antipyrine precursors as well as the antipyrine derivative showed fluorescence response towards trivalent cations when treated with various metal ions in CH3OH:H2O (1:9, v/v) medium. Binding stoichiometry between APAP and Fe3+ ion was 1:1 from Jobs’ plot and the binding constant value was calculated as 5.3 × 105 M−1 by Benesi–Hildebrand plot. Addition of Na2EDTA to the [APAP-Fe3+] complex solution quenched the fluorescence emission, indicating the reversible nature of the probe. The binding of APAP with Fe3+ was based on restricted PET with CHEF process. Quantum mechanical studies using time dependent density functional theory (TDDFT) have also been carried out to understand the mechanism of Fe3+ binding mode with APAP probe. With respect to various pH, the probe APAP exhibited an AND molecular logic gate behaviour when H+ and Fe3+ ions were given as inputs. For the first time, the metal recognition property of a fluorescent probe along with its precursors was studied.

Analytical tools for cyclodextrin nanosponges in pharmaceutical field: a review

Abstract: With the growing popularity of the nanomedicine-based pharmaceutical market, active molecules from chemical and natural origin are encapsulated in various nanocarriers enhancing their therapeutic efficacy. Depending upon the fabricated functionality, cyclodextrin based nanosponges has become a potential vehicle to encapsulate the active molecules. To explore nanosponges-based delivery system in pharmacy, knowledge of the analytical tools that could significantly assess their quality parameters, has major role for researchers working in this field. Owing to understand their benefits and potential toxicity, characteristic features like safety, negligible toxicity, superior inclusion capability, marked swelling behaviour and biodegradability are the primarily basis for their use in drug delivery, drug targeting, tissue engineering and regenerative medicine. This review article focuses on the various aspects of analytical techniques applied for characterization of nanosponges, which may affect quality of these nanocarriers. Subsequently, the challenges for characterization of these systems have been especially emphasized. In addition, sincere efforts have been made to compile various analytical techniques for description and understanding of these nanostructures from existing literature. Recommendations and suggestions are also mentioned while selecting suitable analytic techniques to characterize the quality parameters of nanosponges.

Preparation, characterization and cytotoxic evaluation of inclusion complexes between celastrol with polyamine-modified β-cyclodextrins

Abstract: Celastrol (CSL), the major constituent from traditional Chinese medicine Tripterygium wilfordii Hook, has attracted considerable interest in the medicinal society due to its multiple biological activities. However, poor solubility and obvious toxic side effect have limited its application in the pharmaceutical field. To address the problems, the inclusion complexes of mono polyamine-modified β-CD (H1) and the polyamine-brideged bis(β-CD) (H2) with CSL were prepared. The characterization of inclusion complexes was investigated by NMR, XRD FT-IR and SEM, and the binding behaviors of H1-2 with CSL were investigated by UV. The results showed that the H2 gave the binding constant (Ks) towards CSL up to 1.7 times higher than that of H1, through cooperative binding of two hydrophobic CD cavities with one guest. Remarkably, complexation with H1 and H2 improved CSL solubility in water from 0.044 mg/mL up to 2.31 and 2.68 mg/mL, respectively. The in vitro anticancer activity of H1/CSL inclusion complex was better than that of cisplatin (positive control). Meanwhile, the toxicity of CSL was slightly reduced after the formation of the inclusion complex with H1. Therefore, the complexes of CSL with H1-2 favor their use in anticancer drug formulations, broadening the field of application in clinic.

QCM sensors coated with calix[4]arenes bearing sensitive chiral moieties for chiral discrimination of 1-phenylethylamine enantiomers

Abstract: This article describes the enantiomeric discrimination properties of new chiral calix[4]arene derivatives bearing (S)-/(R)-1-phenylethylamine moieties (5a and 5b, respectively) towards the 1-phenylethylamine enantiomers on QCM surface. Initial experiments demonstrated that the 5b coated QCM sensor was the most effective sensing material for enantiomeric discrimination of (R)-/(S)-1-phenylethylamine by exhibiting much more sensing ability towards (R)-enantiomer than (S)-enantiomer. Sensitivity, detection limit and time constant of the 5b coated QCM sensor has been were calculated as 0.082 Hz/µM, 2.7 µM, and 319.2 s, respectively. Additionally, effects of calixarene content and different coating technique on enantiomeric discrimination, and Langmuir and Freundlich isotherms of the sensing results also were studied. As a result, it has been demonstrated that the coating of QCM sensor with a chiral calix[4]arene (5b) having (S)-1-phenylethylamine moieties provides substantially enantiomeric discrimination of 1-phenylethylamine enantiomers.

DFT investigation of host–guest interactions between α-Terpineol and β-cyclodextrin

Abstract: Two models A and B of inclusion complex of α-Terpineol (α-Terp) into β-cyclodextrin (β-CD) were investigated by M06-2X/6-311G(d,p) and ωB97X-D/6-311G(d,p) levels of theory in vacuum and in water. EDA, TD-DFT, NBO, AIM and NCI analyses were also done to give more information about the nature of interaction between α-Terp and β-CD. The calculated complexation energy gives that A model with partial encapsulation of α-Terp in β-CD is more favored than B one where guest molecule is totally embedded into β-CD cavity. EDA calculation shows that dispersion and electrostatic energies contribute greatly on total bonding energy of α-Terp @ β-CD inclusion complexes. Also, electronic transitions obtained by TD-DFT method suggest the charge transfer between α-Terp and β-CD. Finally, NBO and AIM analyses demonstrate the establishment of conventional H-bond interaction and NCI analysis illustrate H-bonds, van der Waals and steric repulsion during inclusion complex formation.

Bioavailability enhancement of hydrophobic nutraceuticals using γ-cyclodextrin

Abstract: Natural hydrophobic bioactives that possess human health benefits often have undesirable characteristics that limit their use as nutraceuticals. These bioactives are usually unstable in the presence of oxygen, ultraviolet radiation, and heat. Furthermore, their solubility in water is low owing to their hydrophobicity or instability, which leads to low bioavailability. Much attention has recently been directed to the use of cyclodextrins (CDs) as complementary and alternative medicinal foods with human health benefits for the current aging population. Systematic studies have been performed to investigate improvements in the stability, water solubility, and bioavailability of hydrophobic nutraceuticals through complexation with CDs. Although hydrophobic nutraceuticals, such as coenzyme Q10, curcumin, and tocotrienol, form insoluble complexes with γ-CD, the bioavailability of the complex dramatically improves compared with conventional technologies. Recently, it was found that hydrophobic bioactives generally aggregate in water, but the dissociated bioactives from γ-CD are captured by bile acid to form micelles without aggregation; thus, both solubility and bioavailability are enhanced. Complexation with γ-CD is a promising method to achieve enhanced bioavailability of hydrophobic nutraceuticals. In this article, an outline of the innovative nanotechnologies that implement γ-CD to enhance stability and control of the solubility and bioavailability of key ingredients for health and beauty in the field of medicinal foods is presented.

Reduced graphene oxide-transition metal hybrids for hydrogen generation by photocatalytic water splitting

Abstract: We report the photocatalytic activities of graphene oxide-metal ion hybrid namely rGO–M (rGO is reduced graphene oxide and M = Mn2+, Fe3+, Ni2+, Co2+ and Al3+). The hybrids exhibit photocatalytic behavior to split water and generate hydrogen gas under UV light irradiation at room temperature.

Synthesis of silver nanoparticles stabilized by carboxylated methoxypolyethylene glycols: the role of carboxyl terminal groups in the particle size and morphology

Abstract: In this work the effect of the synthesis conditions on the size and morphology of the nanoparticles obtained via the reduction of silver ions by benzyl alcohol in the presence of carboxylated methoxypolyethylene glycols with different molecular weights (mPEG-COOH 350, containing a terminal carboxyl group, MW ~ 350 and 2-[2-(2-methoxyethoxy)ethoxy]acetic acid (MEEAA), MW ~ 200) and non-carboxylated mPEG 350 has been studied. The synthesized nanoparticles were characterized by means of X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), Ultraviolet–Visible (UV–Vis) and Fourier-transform infrared (FT-IR) spectroscopy. The synthesis conditions resulting in the formation of silver nanoparticles stabilized by MEEAA and mPEG-COOH with the average sizes of 6.5 ± 1.1 and 5.2 ± 0.9 nm, respectively, which can be used for the fabrication of ink compositions for flexible electronics, were found. A thermogravimetric (TG) study showed that MEEAA and mPEG-COOH are removed from the surface of the silver nanoparticles at temperatures of 110–300 and 200–310 °C, respectively. Thus, according to the TG data, the particles stabilized by MEEAA can potentially be used in the fabrication of inks for printing on low-temperature polymer substrates. The as-synthesized nanoparticles form a stable dispersion and therefore are suitable for possible applications in printed electronics.

Exploring the entrapment of antiviral agents in hyaluronic acid-cyclodextrin conjugates

Abstract: In the framework of our studies dealing with the development of new platforms for the delivery of antiviral agents, we exploited the covalent approach based on click chemistry to link β-cyclodextrin (CD) on hyaluronic acid backbone (HA). The physico-chemical properties in terms of size, surface charge, interaction with acyclovir (Acy), selected as a model antiviral drug, have been investigated. The release profile and the biological properties (cytotoxicity and inhibition of viral plaque formation) of HA-CD/Acy complex pointed out a good antiviral activity together with a delayed-release of Acy from HA-CD/Acy.

A procession on photocatalyst for solar fuel production and waste treatment

Abstract: Conversion of solar energy into hydrogen is one the most promising renewable energy technology which is stimulated after detection of increasing global energy consumption and climate changes by the emission of fossil fuel. Photocatalytic water splitting use semiconductor materials having the electronic structure suitable for charge (electron and hole) injection for water decomposition to produce H2 and O2. Many inorganic materials are now using as active photocatalyst for water reduction since artificial photocatalytic water splitting has discovered for the very first time in 1971. Beyond, metal oxides, sulfides, and nitrides are the common photocatalytic semiconductor. To material science, research in this compass has brought huge grip that commits to the development of visible light active substances progressively. In this review along with the introduction of solar fuel, photocatalyst and photocatalytic water splitting, up-and-coming photocatalysts for solar-to-fuel conversion and photocatalytic purification of environment are discussed. We address TiO2 based, carbon based and two dimensional materials based photocatalyst for solar fuel production and waste treatment.

New fluorescent sensor based on a calix[4]arene bearing two triazole–coumarin units for copper ions: application for Cu 2+ detection in human blood serum

Abstract: A novel fluorescent chemosensor calix[4]arene L, containing two fluorogenic coumarin units at the lower rim has been synthesized via click reaction. The structure of this chemosensor, was characterized by IR, NMR spectra and elemental analysis. Ion-binding properties of L were investigated in acetonitrile with different metal ions and the recognition process was monitored by fluorescence, UV-Vis and 1H NMR spectral changes. In comparison with other metal ions, chemosensor L showed a specific selectivity toward copper ions‏. The Job plot analysis revealed that the binding between L with Cu2+ is in 1:1 stoichiometry. The association constant (Ka) for the complex L.Cu2+ was found to be 1.6 × 105 M−1. The limit of detection of the sensor L was determined to be 5.4 × 10−7 M. This sensitive and selective chemosensor was successfully applied for the detection of Cu2+ ions in human blood serum with 90–100% recovery.

Enhanced host–guest complexation of short chain perfluoroalkyl substances with positively charged β-cyclodextrin derivatives

Abstract: Short chain perfluoroalkyl substances (PFAS), replacements for long chain legacy PFAS such as perfluorooctanoic acid (PFOA), have similar toxicity, negative health effects, and exceptional persistence as long chain PFAS. β-Cyclodextrin (β-CD) is a powerful host–guest complexing agent for a number of legacy PFAS, suggesting potential β-CD-based remediation processes. We report herein that the addition of charged functional groups at the perimeter of β-CD has a pronounced influence on the strength of the β-CD:PFAS complex. The presence of a positively charged amine functionality on the perimeter of β-CD significantly increases the complexation of legacy and short chain PFAS. We assigned the enhanced complexation to electrostatic attraction between the negatively charged PFAS head group and the positively charged β-CD derivative. In comparison to neutral β-CD, addition of a negative charge to β-CD decreases complexation to PFAS due to electrostatic repulsion between the negatively charged polar head group of PFAS and the negatively charged β-CD. 19F NMR titration experiments illustrate the complexation of short chain PFAS by positive charged β-CDs over neutral β-CD, with increases up to 20 times depending on the PFAS guest. The results give further understanding to the nature of the β-CD:PFAS host–guest complex and the various intermolecular forces that drive complexation. Positively charged β-CDs appear to be potential complexing agents for remediation of short chain PFAS.

Synthesis and assessment of compounds trans-N,N′-bis(9-phenyl-9-xanthenyl)cyclohexane-1,4-diamine and trans-N,N′-bis(9-phenyl-9-thioxanthenyl)cyclohexane-1,4-diamine as hosts for potential xylene and ethylbenzene guests

Abstract: In this work, two novel compounds, trans-N,N′-bis(9-phenyl-9-xanthenyl)cyclohexane-1,4-diamine 1 and trans-N,N′-bis(9-phenyl-9-thioxanthenyl)cyclohexane-1,4-diamine 2, were designed and successfully synthesized in our laboratories, and assessed for their host potential in the presence of potential xylene (Xy) isomer and ethylbenzene (EB) guests. Host 1 successfully formed complexes with all four of o-Xy, m-Xy, p-Xy and EB, while 2 only clathrated p-Xy and EB. Equimolar guest/guest competition experiments showed that hosts 1 and 2 possess very similar selectivities for these guests [p-Xy (73.9%) > EB (13.0%) > m-Xy (8.1%) > o-Xy (5.0%) and p-Xy (71.3%) > EB (20.2%) > m-Xy (6.0%) > o-Xy (2.5%) for 1 and 2, respectively]. Single crystal diffraction analyses revealed striking geometry changes for the sulfur host analogue: while the tricyclic fused ring system of the oxygen host remained planar when guest was absent or present, this fused system of the sulfur analogue experienced a dramatic geometry change from buckled (in the absence of guest) to planar (in guest presence). This observation explained the selectivity similarities of both hosts in the presence of these guests. Additionally, the relative thermal stabilities of the four complexes with host 1 were assessed by employing thermal analyses, and the results of these correlated exactly with the selectivity order, since the onset temperature of the guest release processes (Ton) was in the order p-Xy (88.0 °C) > EB (70.9 °C) > m-Xy (59.7 °C) > o-Xy (46.2 °C). Ton values also explained the significant preference of host 2 for p-Xy (115.5 °C) relative to EB (76.6 °C), respectively.

Study of conformation and hydrogen bonds in the p -1-adamantylcalix[8]arene by IR spectroscopy and DFT

Abstract: The hydrogen bonds and the conformations of calix[8]arene molecules with p-tert-butyl and p-1-adamantyl substituents were studied by infrared spectroscopy in different states. The conformations, the reactivity, the charge distribution and the IR spectra of the calixarenes were calculated by the DFT method with the PBE functional and a TZVP basis set. We compare the IR spectra of calix[8]arene molecules in the conformation of the pleated loop and the chair. The optimized geometry of the molecules reproduces the experimental X-ray data. The conformation chair is 20 kcal/mol less preferable than the conformation pleated loop. The conformation of a pleated loop is the most stable in the solid state and solution. Hydrogen bonds determine the stability of this structure. In the p-1-adamantylcalix[8]arene, stronger hydrogen bonds are realized compared to p-tert-butylcalix[8]arene. The observed IR spectra were interpreted using the calculated potential energy distribution with the quantum-chemical force constants. The theoretical absorption curves calculated for the pleated loop conformation correspond to the experimental IR spectra of the calix[8]arenes.

Treating an old disease with new tricks: strategies based on host–guest chemistry for leishmaniasis therapy

Abstract: This critical mini-review is focused on leishmaniasis, namely on the factors causing the re-emergence of the disease, the available therapies and their limitations. It then looks into the tools available within the field of host–guest chemistry and that are now arising as innovative solutions for the treatment of infections caused by different species of the Leishmania genus. These include the use of cyclodextrins as medicinal agents per se, as well as the formation of cyclodextrin inclusion complexes for the amelioration of biophysical properties and in vivo activities of leishmanicidal drugs. A focus is given on the practical utility of the results reported in the literature, evaluating their potencial of transition from the bench to the market.

Encapsulation of plumbagin using cyclodextrins to enhance plumbagin stability: computational simulation, preparation, characterization, and application

Abstract: Encapsulation of plumbagin using cyclodextrins (CDs), including α-cyclodextrin (αCD), β-cyclodextrin (βCD), and γ-cyclodextrin (γCD) to form inclusion complexes was investigated to prevent the loss of plumbagin in pharmaceutical and nutraceutical products. Computational simulations and phase solubility studies suggest that the complex formations of plumbagin with CDs are possible. βCD is chosen, as it has the lowest price and can form the complex in a wide concentration range with 1:1 host–guest molar ratio. Two techniques of the complex formation, co-precipitation and freeze-drying, were evaluated for both pure plumbagin and extracted plumbagin from Plumbago indica root to represent lab-scale and industrial-scale productions, respectively. The complexes from these two techniques can prevent the loss of plumbagin up to three-folds better than plumbagin in free form. The preservation by encapsulation can increase the remaining plumbagin from 22.68 to 60.26% after exposure at 50 °C for 6 weeks.

Cation triggered spring-like helicates based on ketone-substituted bis-catechol ligands

Abstract: The development of switchable molecular units is a challenging task of modern synthetic and supramolecular chemistry. In the present study, alkyl bridged bis(catecholketone) ligands are introduced in order to obtain helicates which cation triggered show some spring type dynamics. The preparation of the ligands as well as of the complexes and corresponding switching processes are described.

Research of covalent organic frame materials based on porphyrin units

Abstract: Covalent organic frameworks (COFs) are one of the most rapidly developed porous materials and have exhibited high surface area and uniform pore size distributions as promising materials for the fields of gas adsorption, catalysis, chemical sensing, photoelectricity devices and energy storage. In this review, we summarized the recent advances on synthesis, structure, and application of porphyrin-containing COFs.

Unraveling the binding nature of hexane with quinone functionalized pillar[5]quinone: a computational study

Abstract: The nature of host–guest interactions between the hexane and pillar[5]arene and its quinone modified pillararenes has been studied using dispersion-corrected density functional theory and wave functional methods. The introduction of quinone in pillararene prompted flexibility in structure and the electrophilicity of pillararenes increases with the number of quinone moiety. Thermochemical as well as energetic results indicate that hexane binding is favorable on all studied systems. The presence of quinone reduces the exothermicity, and exergonic nature and the decrease in temperature increases the free energy of formation. Molecular electrostatic potential analysis indicates the existence of charge transfer between the host and guest molecules. Quantum theory of atoms in molecule analysis reveals in the quinone functionalized pillararenes, the number of interactions arising from quinone is less than that on the 1,4-alkoxybenzene unit. Noncovalent interaction analysis shows a larger area of interactions correspond to C–H···π interactions in the encapsulated complexes. EDA results reveal that dispersion ΔEdisp interaction followed by electrostatic attraction ΔEelstat contributes mainly for the attractive terms. These insights can be used to tune further and improve the binding ability of pillararene guest towards linear host molecules.

Efficient mechanical toughening of polylactic acid without substantial decreases in stiffness and transparency by the reactive grafting of polyrotaxanes

Abstract: A mechanical tough polylactic acid (PLA) that substantially retains its stiffness and transparency was created through reaction with a polyrotaxane derivative. A graft polyrotaxane (GPR), composed of a linear Polyethylene glycol backbone threaded with cyclodextrins bearing grafted poly(e-caprolactone), was bonded to the hydroxyl end-groups of PLA with hexamethylene diisocyanate (HDI), which then solidified to form a PLA-bonded GPR that was distributed throughout the PLA matrix. The addition of 5 wt% GPR resulted in a seven-fold increase in Izod impact strength and a three-fold increase in fracture elongation, with only an 11% loss of stiffness; the transparency was comparable to neat PLA. Electron microscopy revealed that HDI facilitated the dispersal of GPR in the PLA matrix and avoided the sea-island phase-separated structure observed in the PLA/GPR blend devoid of HDI, and that the homogenized structure led to ductile deformation. A GPR content of only 5 wt% efficiently increased PLA-matrix-chain flexibility.

CycloMolder software: building theoretical cyclodextrin derivatives models and evaluating their host:guest interactions

Abstract: This paper presents a software to build theoretical models of cyclodextrin derivatives and evaluate their host:guest interactions, using a graphical user interface in an intuitive way. This goal was outlined to facilitate the studies of molecular modeling, particularly from experimental groups with demands in this research field. The software (CycloMolder) consists of two modules: CycloGen and CycloDock. The first module builds theoretical models with more than one chemical structure to represent a cyclodextrin derivative. These structures are divided into configurations and conformations. The configurations can be homologous structures, with different molar substitution ratio, or just positional isomers. Conformers are generated from the built configurations. The second module performs the docking calculations between the host (cyclodextrins and/or their derivatives) and guest molecules, using the AutoDock Vina program, and displays the final results of the modeled inclusion complexes, including graphs showing the distribution energy and intermolecular interactions present in the host:guest complex.

Interaction of native cyclodextrins and their hydroxypropylated derivatives with parabens in aqueous solutions. Part 1: evaluation of inclusion complexes

Abstract: Due to their antimicrobial activity, parabens (i.e. alkyl esters of p-hydroxybenzoic acid) are widely used as preservatives in several industries (pharmaceutical, food, cosmetic). Although being extremely effective, their usage is hampered by their low aqueous solubility. Several formulation strategies can be applied to enhance their solubility, one of which is formation of water-soluble cyclodextrin (CD) complexes. Formation of inclusion complexes has been proved to be a good approach to increase solubility of lipophilic drugs and other active ingredients. Some research has been done in this field. However, a complete and comprehensive study on how the alkyl chain length of parabens influences the complex formation, aggregation and formation of insoluble complexes is still lacking. Phase-solubility studies showed that all the very water-soluble hydroxypropylated CDs form linear (AL) type phase-solubility profiles with all tested parabens. The poorly soluble βCD did also form AL-type profiles with methyl and ethyl paraben while the βCD complexes of propyl and butyl paraben have limited solubility in water and, thus displayed B-type profiles. The paraben complexes of αCD and γCD all had limited solubility in water and, thus, displayed B-type phase-solubility profiles. Fourier-transformed infrared spectroscopy, Differential scanning calorimetry and X-ray powder diffraction were applied to elucidate the nature of the solid phases from the phase-solubility studies. They consistently showed the presence of solid pure paraben over the CD concentration range studied when AL-type profiles were observed, and precipitation of poorly soluble paraben/CD complexes when B-type were observed (i.e. during and after the B-type plateau region). These studies demonstrate that the composition of solid phases is related to the type of phase-solubility profile. It was also shown that in aqueous CD solutions, paraben solubilization increase with increasing side chain length (i.e. methyl < ethyl < propyl < butyl), as well as, with increasing size of the CD cavity (i.e. αCD < βCD < γCD). This statement is valid for linear region of phase-solubility diagrams (i.e. A- and B-type).

Interaction of indomethacin–cyclodextrins in water by UV–Vis and ITC

Abstract: In this contribution, we analyze indomethacin–cyclodextrin (IMC–CD) inclusion by means of UV–Vis spectrophotometry and isothermal titration calorimetry (ITC) at 25 °C. Experiments were carried out in water at pH 5 and 7, using β-CD and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD). The study with UV–Vis was made using a molar relation method analyzing the spectra with Stability Quotients from Absorbance Data (SQUAD) to obtain the inclusion constants. In the case of ITC, the study was performed in aqueous-phosphate buffer at pH 7. The values of ΔG, ΔH, − TΔS were determined for the first time for the inclusion of IMC within β-CD and 2-HP-β-CD. Results for logK1:1 obtained by ITC agree reasonably with those determined by UV–Vis, confirming the formation of a complex of stoichiometric ratio IMC:CD of 1:1. Besides the confirmation of formation of the inclusion complex, inclusion is exothermic, and given the sign of entropy it is suggested that IMC inclusion is driven by release of water molecules from the cavity of CD. With the values of logK1:1 we construct the diagrams of species distribution to compare which CD performs better in including IMC.

Simple circular dichroism method for selection of the optimal cyclodextrin for drug complexation

Abstract: Cyclodextrins are very important excipients in the pharmaceutical industry. Given the multitude of native and semisynthetic cyclodextrin derivatives, there is a need for a rapid and reliable method for the selection of the optimal cyclodextrins for further pharmaceutical testing. During our research, circular dichroism (CD) spectroscopy has been successfully used to describe the qualitative and quantitative complexation of model compounds with different cyclodextrins. For the appearance of a circular dichroism signal, either a chiral or a chirally perturbed chromophore is required. Achiral or racemic compounds do not have corresponding circular dichroism spectra and neither do chiral cyclodextrins due to the absence of a chromophore group. During complexation of a chromophoric guest molecule, its absorption transition becomes chirally perturbed in the proximity of a cyclodextrin molecule and an induced circular dichroism (ICD) signal appears. This phenomenon gives an inherent selectivity to the method. The sign and intensity of the induced circular dichroism signal in case of different cyclodextrins provides information about the approximate structure of the complex as well as their stability relative to each other. In this study, we report a straightforward induced circular dichroism -based approach for the rapid preselection of the optimal cyclodextrin. The distinctive features of the method were demonstrated using five azole-type antifungal drug molecules (fluconazole, miconazole, clotrimazole, bifonazole and tioconazole) along with native α-, β-, and γ-cyclodextrins, as well as dimethyl-, trimethyl-, carboxymethyl-, hydroxypropyl- and sulfobuthylether-β-cyclodextrins. In addition, with the aid of this method, 27 stability constants were determined, amongst which 16 have been unavailable in the literature previously.

Inclusion of ethanol in a nano-porous, bio-based metal organic framework

Abstract: More than 15,000 types of metal–organic framework (MOF) structures have been synthesized to date. The vast majority of these structures have been synthesized by linking transition metal ions with organic linkers, which limits their potential applications due to toxicity and environmental concerns. In this study we synthesized, bio-based nano-porous crystalline MOF using γ-Cyclodextrin (γ-CD) and potassium ions by vapor diffusion process. Gamma-cyclodextrin MOF (CDMOF) crystals were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and thermo-gravimetric analysis (TGA). We hereby report inclusion complex (IC) formation between nano-porous γ-CDMOF and ethanol molecules. Ethanol, a generally recognized as safe compound and well-known antibacterial and antimicrobial compound, can be used for various industrial applications such as energy, food packaging, pharmaceuticals, gas sensing devices etc. Around ~ 20% ethanol encapsulation was observed in the CDMOF as substantiated by FTIR, TGA and differential scanning calorimetry. Observations from XRD supported the IC formation. CDMOF analyzed before and after IC formation using SEM and XRD indicated that CDMOF crystals retained the crystal structure after the complex formation. This study helps advance our understanding of ethanol-CDMOF host–guest interactions.

Structure and physical properties of poly(lactic acid) and cyclodextrin composite

Abstract: The addition effects of cyclodextrin (CD) and methylated cyclodextrin (Me-CD) on the structure and mechanical properties of PLLA were investigated. Inclusion complexes (IC) of α, β and γ-CD and PLLA were prepared. The formation of IC was confirmed from 13C NMR chemical shifts and the number of peaks for α, β and γ-CD/PLLA IC. 10% of α, β and γ-CD/PLLA IC were mixed with PLLA and formed into films. The tensile test of the obtained films revealed the breaking strain is improved up to 350%. Me-CD was mixed with PLLA and prepared into films. The breaking strain of the films reached up to 250% and the addition effect was largest for Me-γ-CD10. From DSC measurements, one melting peak was observed and the peak moved to lower temperature as the amount of Me-CD increased. These results indicate Me-CD distributes homogeneously in PLLA. Solid state NMR of Me-α, β and γ-CD50 gave broad peaks and the molecular mobility of the mobile component increased. Therefore, Me-α, β and γ-CD do not form IC, but act as the plasticizer for PLLA.