Cyclodextrins and Their Complexes: Chemistry, Analytical Methods, Applications
Abstract
Offering comprehensive and up-to-date know-how in one compact book, an experienced editor and top authors cover every aspect of these important molecules from molecular recognition to cyclodextrins as enzyme models. Chapters include reactivity and chemistry, chromatography, X-ray, NMR plus other physicochemical methods, as well as model calculations, rotaxane and catenane structures, and applications in the pharmaceutical industry. The book also discusses other applications such as in the cosmetics, toiletries, textile and wrapping industries, agrochemistry, electrochemical sensors, and devices. A must for everyone working with these substances.
... CDs form a subclass of symmetrical, cyclic oligosaccharides and can be derived from the natural product starch. [49][50][51][52] The monomeric units of these oligomers are glucopyranose molecules, which, linked to each other by symmetric glycosidic bonds, form a cyclic structure that has a toroidal shape with a primary and a secondary face. The edges and outer surface of these molecules are hydrophilic while their inner cavity is of hydrophobic nature. ...
... Depending on the number of monomer units in the ring oligomer, common structures are classified as a-, b-, and g-CDs for 6, 7, and 8 monomer units, respectively (Fig. 2b and c). [49][50][51][52] These molecules have a conical cylinder shape with the glucopyranose unit in 4 C 1 configuration, which is why all primary hydroxyl groups are on one edge of the CD molecules while the secondary hydroxyl groups are on the other edge. This arrangement of hydroxyl groups gives a hydrophilic nature to the edges and outer surface of CDs, while the cavity of these molecules is hydrophobic as it is lined with hydrogen atoms. ...
... 61 CDs are commonly synthesized by an enzymatic reaction on starch. 49 There are two different approaches for the synthesis of CDs, namely the solvent process and the non-solvent process, of which the first will be discussed in the following. 62 The main difference between these processes is that in the former a complexing agent is added while it is not in the latter. ...
While there is a tremendous amount of scientific research on metal organic frameworks (MOFs) for gas storage/separation, catalysis and energy storage, the development and application of biocompatible MOFs still poses major challenges. In general, they can be synthesised from various biocompatible linkers and metal ions but particularly cyclodextrins (CDs) as cyclic oligosaccharides are an astute choice for the former. Although the field of CD-MOF materials is still in the early stages and their design and fabrication comes with many hurdles, the benefits coming from CDs built in a porous framework are exciting. Versatile host-guest complexation abilities, high encapsulation capacity and hydrophilicity are among the valuable properties inherent to CDs and offer extended and novel applications to MOFs. In this review, we provide an overview of the state-of-the-art synthesis, design, properties and applications of these materials. Initially, a rationale for the preparation of CD-based MOFs is provided, based on the chemical and structural properties of CDs and including their advantages and disadvantages. Further on, the review exhaustively surveys CD-MOF based materials by categorising them into three sub-classes, namely (i) CD-MOFs, (ii) CD-MOF hybrids, obtained via combination with external materials, and (iii) CD-MOF-derived materials prepared under pyrolytic conditions. Subsequently, CD-based MOFs in practical applications, such as drug delivery and cancer therapy, sensors, gas storage, (enantiomer) separations, electrical devices, food industry, and agriculture, are discussed. We conclude by summarizing the state of the art in the field and highlighting some promising future developments of CD-MOFs.
... CDs consist of six, seven, or eight glucopyranosyl units (called α-, β-, and γ-CD, respectively), which are connected by α-1,4 bonds. CDs are homogeneous crystalline substances, water-soluble, and possess a ring-shaped structure that narrows on one side and widens on the other [5,6]. Due to the specific arrangement of hydroxyl groups on the edges of the ring, cyclodextrins can be easily modified, expanding their applications in various fields such as chemosensors, artificial enzymes, and drug carriers [7]. ...
... The cyclodextrin cavity creates an optimal hydrophobic environment for the encapsulation of organic compounds, while the amino groups enhance interactions through hydrogen bonding and electrostatic forces. This dual functionality is advantageous for the adsorption of diverse pollutants [6,7,24]. ...
The contamination of the natural environment by xenobiotics and emerging contaminants, including pharmaceuticals, poses significant risks to ecosystems and human health. Among these contaminants, hormones and pharmaceutical compounds are particularly concerning due to their persistence and potential biological effects even at low concentrations. In this study, we investigated the efficacy of poly-amino-β-cyclodextrin (PA-β-CD) microparticles in adsorbing and reducing specific xenobiotics and pharmaceuticals from aqueous solutions. Our research focused on four contaminants: two hormones, testosterone and progesterone, and two pharmaceutical drugs, diclofenac and carbamazepine. High-performance liquid chromatography (HPLC) was employed to quantify the adsorption capacity and efficiency of PA-β-CD microparticles.
... Cyclodextrins (CDs) consist of circularly connected glucose units, joined by α-1,4 glycosidic bonds (Figure 1a), and are well-known to encapsulate small molecules forming host-guest complexes [1][2][3][4]. The general structure of CDs is toroidal, with two openings ("faces"), and the primary and secondary alcohol groups are located at the smaller and larger opening, respectively ( Figure 1). ...
... ∆E(kcal/mol)= −223.08 ρ(r BCP ) + 0.7423 (2) Here, the mean absolute percentage error of prediction (MAPE) is 14.7% and ρ(r BCP ) is the electron density at the critical bond point of the corresponding interaction, determined by the Multiwfn program (Version 3.8) [58]. ...
Understanding the non-covalent interactions in host-guest complexes is crucial to their stability, design and applications. Here, we use density functional theory to compare the ability of β-cyclodextrin (β-CD) and heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) to encapsulate the model guest phenol. For both macrocycles, we quantify the intramolecular interactions before and after the formation of the complex, as well as the intermolecular host-guest and host-host dimer interactions. These are individually classified as van der Waals interactions or hydrogen bonds, respectively. The results show a stronger intramolecular binding energy of β-CD, with the absolute difference being −5.53 kcal/mol relative to DM-β-CD. Consequently, the intermolecular interactions of both cyclodextrins with phenol are affected, such that the free binding energy calculated for the DM-β-CD/phenol complex (−5.23 kcal/mol) is ≈50% more negative than for the complex with β-CD (−2.62 kcal/mol). The latter is in excellent agreement with the experimental data (−2.69 kcal/mol), which validates the level of theory (B97-3c) used. Taken together, the methylation of β-CD increases the stability of the host-guest complex with the here studied guest phenol through stronger van der Waals interactions and hydrogen bonds. We attribute this to the disruption of the hydrogen bond network in the primary face of β-CD upon methylation, which influences the flexibility of the host toward the guest as well as the strength of the intermolecular interactions. Our work provides fundamental insights into the impact of different non-covalent interactions on host-guest stability, and we suggest that this theoretical framework can be adapted to other host-guest complexes to evaluate and quantify their non-covalent interactions.
... Furthermore, more attention has been focused on the β-cyclodextrin (β-CD) inclusion due to its effect on the improvement of oral bioavailability of active molecules [20]. Cyclodextrins (CDs) are cyclic oligosaccharides composed of hydrophilic faces and hydrophobic cavity [21]. Recently it has been shown that the positive impact of β-cyclodextrin inclusion technology in enhancing solubility and biological effect of drugs [22][23][24]. ...
... Cyclodextrins (CDs) are macrocyclic carbohydrate polymers possessing 6-8 glucose units for α-, β-and γ-CDs, respectively [21]. They resemble a hollow, truncated cone and are well recognized as encapsulating agents for improvement of stabilities, activities, and solubilities of various bioactive compounds [20]. ...
The β-cyclodextrins (β-CD) as supramolecular have extremely attractive pharmaceutical applications. This study focused on the effects of macrocyclic systems complexation on stability, antioxidant activities, and bioavailability
of the optimized synthesis coumarin incorporating hydrazone moiety. Optimal synthesis of (E)-N’-(1-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)ethylidene)benzohydrazide (7-diEAHC) was performed by using response surface methodology (RSM) with a temperature of 100 ◦C, a reaction time of 10 min in the presence of acetic acid (0.85 M). Physicochemical properties and in silico ADME profiling of 7-diEAHC were also determined. The encapsulation efficiencies of the 7-diEAHC were above 81 % for the micro-encapsulates. After sunlight exposure, the 7-diEAHC-β-CD inclusion complex showed a photostability 19.4 % higher than free 7-diEAHC. Additionally, the encapsulated 7-diEAHC exhibited better stability than free 7-diEAHC for the pH varied between 1 and 9. From the results, storage stability showed that the encapsulation method using β-CD conferred a greater ability of 7-diEAHC against temperature. The NMR and FT-IR techniques were employed to evaluate the chemical stability of 7-diEAHC after encapsulation. In addition, in vivo study showed that the microencapsulation approach increased the oral bioavailability of 7-diEAHC in treated rats.
... To increase solubility, stability, bioavailability and dissolution rates and to decrease toxicity of drugs and nutraceuticals, preparation of supramolecular self-assembling inclusion complexes with cyclodextrins (CDs), water-soluble nanocontainers (receptors), seems to be very promising [5][6][7][8][9][10]. 2-Hydroxypropyl-β-cyclodextrin (HPβCD) is a synthetic hydroxyalkyl derivative with better water solubility and the least toxicity [7,8]. ...
... To increase solubility, stability, bioavailability and dissolution rates and to decrease toxicity of drugs and nutraceuticals, preparation of supramolecular self-assembling inclusion complexes with cyclodextrins (CDs), water-soluble nanocontainers (receptors), seems to be very promising [5][6][7][8][9][10]. 2-Hydroxypropyl-β-cyclodextrin (HPβCD) is a synthetic hydroxyalkyl derivative with better water solubility and the least toxicity [7,8]. Earlier, the inclusion complexations of βCD or HPβCD with flavanoids (quercetin, rutin, naringenin and naringin) were widely studied by thermodynamic, spectroscopic and quantum chemical methods [5,[11][12][13]. ...
Flavonoids are exogenous phytochemicals with high antioxidative potential. The present work provides the mechanism of the complexations of low water-soluble flavanone naringenin, its glycosylated form naringin, and water-soluble flavan-3-ol catechin with β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD). The flavonoids studied showed high affinity in the interactions with HPβCD (the association constants K and the stoichiometry N were equal to 8500 ± 950 М⁻¹ and 0.85 ± 0.05, 9400 ± 1200 М⁻¹ and 1.7 ± 0.10, 7550 ± 600 M⁻¹ and 1.25 ± 0.05 in the case of naringenin, naringin and catechin, respectively). The formations of the complexes with β-cyclodextrins markedly increased the water solubility of naringenin and naringin. The flavonoid–HPβСD complexations were exothermic (ΔH ˂ 0) and spontaneous (ΔG ˂ 0). The naringenin and naringin complexations with HPβCD were entropy-driven, and the catechin complexation was enthalpy-driven. Flavonoid molecules dispersed in the HPβCD structure during complexations. The flavonoid–HPβCD associations demonstrated enthalpy–entropy compensation. Naringenin (5–50 μM) and, to a lesser extent, catechin inhibited the respiration of isolated rat liver mitochondria. Naringenin, naringin and catechin (5–25 μM) increased the rate of Ca²⁺-induced mitochondrial permeability transition. The complexations with HPβCD did not significantly influence the effects of the flavonoids on respiration and enhanced the effects on mitochondrial permeability transition.
... 1 The hydrophobic cavity, hydrophilic rims, the electron density, and the presence of the highenergy water in the cavity drive the assembly with a large range of different molecules, such as drugs, 2 polymers, [3][4][5] and surfactants, 6,7 affecting their properties. 8 In turn, surfactant molecules and amphiphilic polymers self-assemble in aqueous solutions above a defined concentration. Admixing cyclodextrins to self-assembled copolymer aggregates generally leads to the disruption of the micelles when the hydrophobic moieties are complexed or to the formation of decorated micelles, when the hydrophilic part of the polymer is threaded. ...
... The use of a pH-responsive surfactant allows us, on the one hand, to systematically investigate the effect of the charge density on the supramolecular assembly of the complexes, and on the other hand, is expected to provide pH sensitivity to mixtures for applications in the field of cosmetics, drug delivery, and food science. 8 In detail, we investigated the thermodynamics of the inclusion complexes formation between two alkyl ether carboxylic acids: the pentaoxyethylene dodecyl carboxylic acid (C 12 E 5 Ac) and the decacyloxyethylene dodecyl carboxylic acid (C 12 E 10 Ac), with aCD and bCD by isothermal titration calorimetry (ITC) and densitometry. The structural characterization of the supramolecular aggregates arising from their assembly was conducted by small-angle neutron scattering (SANS) and optical and electron microscopy. ...
In this work, the inclusion complexes of alkyl ethoxy carboxylates with α-cyclodextrin (αCD) and β-cyclodextrin (βCD) were investigated. The thermodynamics of the complexation process was probed by isothermal titration calorimetry (ITC) and volumetry as a function of the degree of ionization of the surfactant. The complexation process was shown to be an enthalpically driven pH-independent process. For both types of cyclodextrins, the complexes were found to spontaneously self-assemble into highly-ordered supramolecular aggregates probed by small-angle neutron scattering and electron and optical microscopy. Herein, we report the formation of thin platelets for nonionized surfactant systems and equally spaced multilayered hollow cylinders for ionized systems in a hierarchical self-assembly process. In addition, the analysis allowed unveiling the effect of the number of ethylene oxides in the surfactants and the CD cavity size on the morphology of the aggregates. Finally, this study also highlights the importance of examining the tuning parameters' influence on the short and long-range interactions involved in the control of the assembly process.
... Cyclodextrins (CDs) have a unique structure with a hydrophobic cavity and a hydrophilic surface. Their cavity is suitable for the inclusion of a wide variety of guests (Szejtli 2004;Dodziuk 2006). The commonly used native CDs are alpha CD (α-CD), beta CD (β-CD), and gamma CD (γ-CD), which contain six, seven, and eight glucose subunits, respectively (Kfoury et al. 2019). ...
Recently essential oils (EOs) encapsulation is experiencing growing applications in agricultural and agri-food sector. Encapsulation is reported as safe environmental technology leading to a reduction of conventional insecticides use. This study concerns the assessment of fumigant toxicity and persistence of Rosmarinus officinalis EO encapsulated in two cyclodextrins β-CD and HP-β-CD against larvae of the date moth, Ectomyelois ceratoniae. The retention capacity, encapsulation efficacy, loading capacity and release behavior of the two inclusion complexes were investigated. Results showed that two studied CDs had in important retention capacity. Additionally, the encapsulation within CDs delayed the release of rosemary EO bioactive components; which explains the effectiveness of the encapsulated rosemary EO in CDs against E. ceratoniae fifth instars larvae. Furthermore, the encapsulation in the two CDs improved the persistence of the insecticidal toxicity. This study supports the use of cyclodextrins, mainly HP-β-CD, in the date industry for the control of insect pests.
... Cyclodextrins (CDs) and their derivatives are molecules composed of glucose units that form compounds with cyclic structures, whose cavities have different dimensions depending on the number of units, as well as the number, composition and location of substituted groups on glucoses [1][2][3]. CDs and their derivatives are extensively used in catalysis and enantiomeric separations due to their ability to form inclusion complexes, in which a molecule (guest) is partially or completely included in their cavity (host). The inclusion complexes formed by CDs and their derivatives have different applications in drug delivery and antimicrobial treatments. ...
Hydroxypropyl-β-cyclodextrin (HPβCD) is a derivatized cyclodextrin in which several H atoms on the hydroxyls of the glucose rings are substituted by 2-hydroxypropyl groups. The cyclic structure of HPβCD creates a cavity capable of totally or partially enclosing different molecules (inclusion complexes), and this capacity makes it useful in the pharmaceutical industry. Rifampicin is an antibiotic commonly used to treat tuberculosis; however, some of its properties such as its low solubility and variable bioavailability need to be improved by encapsulating it in systems such as HPβCD. The inclusion complexes formed by twelve structures of HPβCD and rifampicin with various polar and non-polar solvents are studied using molecular simulation. Diverse solvents are simulated using the zwitterionic or neutral configuration of rifampicin, and different values of relative permittivity in the electrostatic contribution to the total energy. The latter constant has little effect on the formation of inclusion complexes, whereas the type of rifampicin essentially determines the energies and configurations of the complexes. The zwitterion is located near the primary rim of HPβCD and the neutral form of rifampicin is near the secondary one. In both cases, the piperazine tail is incorporated into higher-energy complexes inside the host.
... The side or toxic effects that may occur are practically non-existent, which is why they are used in the pharmaceutical, cosmetic and food industries. They are capable of encapsulating, isolating and compartmentalizing a wide variety of compounds, since there are different sizes easily adaptable to the requirements of the compounds to be included [12][13][14] . All this makes them attractive in many different fields of science, from pharmaceutical technology, or chemistry, to nanotechnology. ...
p class="MsoNormal" style="text-indent: 20.0pt; line-height: 15.0pt; mso-line-height-rule: exactly; mso-pagination: widow-orphan; layout-grid-mode: char; mso-layout-grid-align: none;"> Supramolecular chemistry involves non-covalent interactions and specific molecular recognition of molecules/analytes by host molecules or supramolecules. These events are present in synthesis, catalysis, chiral separations, design of sensors, cell signaling processes and drug transport by carriers. The typical behavior of supramolecules is derived from their ability to build well-structured self-assembled and self-organized entities. Cavitands are a particular group of supramolecules possessing a cavity capable to include a variety of compounds thanks to host-guest non-covalent interactions developed among cavitands and analytes. Some typical cavitands are crown ethers, calixarenes, cucurbiturils, porphyrins and cyclodextrins. The two latter families are natural product cavitands that are generally considered models for molecular recognition of cations and organic and inorganic guest molecules, being attractive host molecules from the sustainability point of view. The natural cyclodextrins (α, β and γ-cd) are obtained with reasonable cost by enzymatic treatment of starch under adequate temperature conditions. They are profusely used in pharmaceutical, food and cosmetic industries due to their very low toxicity and side effects. This review is focused on the relevance andapplications of cyclodextrins in pharmaceuticaltechnology for their ability to increase solubility and stabilize drug molecules, thereby enhancing their bioavailability. The association of cyclodextrins with diverse nanostructured materials, i.e., carbon nanotubes, magnetic nanoparticles, silica and molecularly imprinted polymers, allows to synergize the properties of cyclodextrins and these nanostructured materials to reach highly specific molecular recognition of analytes. The exploitation of these benefits for analytical sample pre-treatment and chiral chromatographic separations are described. The use of cyclodextrins as mobile phases additives in hplc provides interesting results for green and sustainable chromatographic separations. Polymers incorporating cyclodextrins show exceptional adsorption properties for retaining toxic compounds and persistent organic pollutants from soils and water samples, allowing satisfactory recoveries of these environmental samples according to the stockholm convection principles.
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... Cyclic oligosaccharides produced from enzymatic starch fermentation and known as cyclodextrins are compounds of six (a-cyclodextrin), seven (b-CD) or eight (g-cyclodextrin) D-glucopyranose units that are bound together by glycosidic a-(1,4) bonds. These units form a chair conformation, giving the CDs a hollow conical cylinder structure (Crini et al., 2019;Dodziuk, 2006;Jansook et al., 2018). This configuration generates a hydrophobic core cavity because it mostly comprises poorly polarized bonds (carbon-carbon and carbon-hydrogen bonds) that do not interact significantly with water. ...
Purpose
This study aims to develop an electrochemical sensor for the detection of benzophenone (BP) as an alternative to conventional techniques that are known, expensive, complex and less sensitive.
Design/methodology/approach
The developed sensor is a platinum electrode modified with a plasticized polymer film based on ß-cyclodextrin, using PVC as the polymer, PEG as the plasticizer and ß-CD as the ionophore. This sensor is characterized by various techniques, such as optical microscopy, scanning electron microscopy and cyclic voltammetry. This latter is also used for analyzing kinetic processes at the electrode/electrolyte interface and to evaluate the selectivity and sensitivity of the sensor.
Findings
The results highlight the performance of our sensor. In fact, it exhibits a linear response extending from 10 ⁻¹⁹ to 10 ⁻¹³ M, with a correlation coefficient of 0.9836. What is more, it has an excellent detection limit of 10 ⁻¹⁹ M and a good sensitivity of 21.24 µA/M.
Originality/value
The results of this investigation demonstrated that the developed sensor is an analytical tool of choice for the monitoring of BP in the aqueous phase. The suggested sensor is fast, simple, reproducible and inexpensive.
... A number of physicochemical methods are used for investigating the formation of inclusion complexes: microcalorimetry (ITC, DSC), UV-VIS absorption spectroscopy, fluorescence, circular dichroism (CD), Fourier transform infrared spectroscopy (FTIR), high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), ionization mass spectrometry (ESI-MS), and occasionally phase solubility diagrams, solid-phase microextraction, or volatilization [20,21]. Obviously some methods are better suited to study such complexes than others, and among the non-separation methods NMR spectroscopy is one of the most efficient and widely used because it delivers a wealth of highly reliable quantitative information at the atomic resolution level providing several independent data sets for the evaluation of association constants K as well as an insight into the conformation of the inclusion complexes [22,23]. ...
Hosts, a key component of inclusion complexes, are cyclic oligomeric compounds containing a cavity in which another component of the complex is bound by non-covalent forces. Chiral hosts are particularly important and interesting because they allow the study of specific intermolecular interactions and molecular recognition. The most important classes of chiral hosts and their physicochemical properties are briefly reviewed. An important part of this Review is the description of selected concepts necessary to understand the properties and behavior of inclusion complexes studied by the most suitable analytical method for studying inclusion complexes—nuclear magnetic resonance.
... One type of electrode modifier is cyclodextrins (CDs), cyclic oligosaccharides composed of a varied number of a-D-glucopyranoside units linked by a-1,4 glycosidic bonds. One of the unique properties of cyclodextrins is the ability to form inclusion complexes, in which the non-polar part of the "guest" molecule enters the cavity of the cyclodextrin ("host") (Radi and Eissa 2010a;Radi and Eissa 2010b;Ibrahim, Shehatta, and Al-Nayeli 2002;Dodziuk 2006). ...
This work involved the determination of the antifungal agent, terbinafine (TR) using a boron-doped diamond electrode (BDD) that was modified with polypyrrole in the presence of cyclodextrin. The obtained modified layer was overoxidized and was used to develop a novel, sensitive method for terbinafine. Scan rate measurements confirmed the diffusion character of the recorded currents. Terbinafine was irreversibly oxidized, producing a well-defined peak at +1.05 V (versus the saturated calomel electrode) in Britton–Robinson (B–R) buffer at pH 6.09. Square wave voltammetry was employed to study the relationship between current and terbinafine concentration in the optimized conditions. A linear range for terbinafine determination was obtained between 7.04 × 10⁻⁸ and 9.09 × 10−7 mol/L with a limit of detection of 2.11 × 10−8 mol/L and good repeatability (2.56%, n = 6 measurements, at 3.7 × 10−7 mol/L). The procedure was employed to determine terbinafine in pharmaceutical preparations. The recovery values between 97.37 and 102.16% demonstrate the accuracy of the developed protocol.
... Because CDs are represented as shallow cones, it is interesting to highlight their dual hydrophilichydrophobic nature. The inner part of the cavity is represented as a surface (as a plane for each glucose unit) containing protons, H3 and H5, and solitary pairs of glycosidic oxygens conferring a hydrophobic behavior to the cavity 189 . On the other hand, the tapered ends have hydroxyl groups exhibiting hydrophilic behavior. ...
The definition of “life” has not yet reached scientific consensus, but it can be understood as organisms with a life cycle built on cells that can undergo various chemical reactions of metabolism. These organisms are maintained in a state of homeostasis but can grow by cell division, reproduce, evolve, and adapt to their environment. Despite its current abundance on Earth, it must be kept in mind that life appeared at some point, spread and resulted in considerable diversity and complexity. At the molecular level, life emerged on Earth through key chemical building blocks capable of polymerizing and/or self-assembling, generating macromolecules such as DNA, RNA and proteins. These structures have the unique and crucial feature of being made of chiral monomers, and only one enantiomer has been selected to build life. This predominance of an enantiomer over the other is common to all organisms and called homochirality. Abiotically, this particularity is difficult to describe because it implies the selection of one enantiomer over its mirror image that is not generally the case without a biological support: racemic proportions are supposed to be obtained under these conditions. This symmetry breaking event, or the creation of an enantiomeric excess followed by its amplification, is still an ongoing question but is of fundamental importance for the appearance of life. Among the existing hypotheses presented herein, a plausible scenario could be the interaction between circularly polarized light (CPL) with organic matter inducing enantiomeric excesses. Indeed, enantioselective photolysis and/or photosynthesis using chiral light could have occurred on dust particles in the interstellar medium (ISM) and enantiomerically enriched compounds could have been incorporated in meteorites and asteroids that later seeded the early Earth. Therefore, the study of extraterrestrial materials such as meteorites, asteroids and comets become essential to obtain clues about the origin of life. The literature supports the existence of an extraterrestrial source of enantio-enriched building blocks, such as L-amino acids and D-sugars, along with the detection of CPL in the ISM. The means to investigate these excesses are discussed by combining a powerful analytical tool such as comprehensive multidimensional gas chromatography coupled to a time-of-flight mass spectrometer (GC×GC-TOFMS) to analyze complex mixtures and suitable derivatization procedures to improve volatility, detection and enantioseparation of chiral biomolecules. Amino acid derivatization has been studied extensively, whereas sugar derivatization is more challenging due to their cyclization behavior and must be adapted to the purpose of the analysis. To simultaneously investigate amino acids and sugars in extraterrestrial or analogous samples, a methodology for sampling, extraction, purification, and fractionation of these sample has been developed using ion exchange chromatography. Applications of this methodology, or parts of it, on samples such as the synthesis of amino acids starting from hexamethylenetetramine and the synthesis of sugars starting from formaldehyde under conditions simulating meteorite parent body alteration processes are highlighted.
... Cyclodextrins (CDs) are cyclic oligosaccharides formed by 6 (α-CD), 7 (β-CD), or 8 (γ-CD) glucopyranose units. They are well known to possess a hydrophobic cavity forming inclusion complexes with organic molecules through host-guest interactions, with dimensional selectivity due to the different sizes of their inner cavity (Dodziuk 2006;Szejtli 1998). CD-containing polymers, either linear or immobilized on solid supports (Allabashi et al. 2007;Fan et al. 2003;Faraji et al. 2011) or crosslinked CD resins García-Zubiri et al. 2007;Romo et al. 2008;Wilson et al. 2011;Yamasaki et al. 2006;Yu et al. 2003) were extensively studied as sorbents of organic pollutants with removal efficacy ranging within ample limits (Crini 2005, Yadav et al. 2022. ...
Hydrophilic cyclodextrin nanosponges were prepared by the oxo-Michael polyaddition in an aqueous solution at pH > 10 of α-, β-, and γ-cyclodextrin with 1,4-bisacryloylpiperazine or 2,2-bisacrylamidoacetic acid. These nanosponges and, for comparison purposes, their precursor cyclodextrins were tested as sorbents of o-toluidine, a carcinogenic wastewater contaminant, by monitoring the depletion of o-toluidine from a 10⁻⁴ M (10 ppm) aqueous solutions. To this aim, an innovative analytical procedure was used: The voltammetric peak currents of o-toluidine in linear sweep voltammetry experiments were registered using multi-walled carbon nanotubes-modified glassy carbon electrodes. The experimental sorption curves fitted a mono-exponential kinetic model, and the residual o-toluidine was 0.16 ppm, one order of magnitude lower than those of all other sorbents reported so far. The sorption capacities ranged from 88 to 199 µmol g⁻¹ (10–21.3 mg g⁻¹), equal to or higher than those of the parent cyclodextrins. All nanosponges were completely regenerated by extracting with methanol. After regeneration, the sorption capacity slightly improved, suggesting a rearrangement of the nanosponge network. Overall, it may be reasonably concluded that the cyclodextrin nanosponges reported in this paper warrant potential as o-toluidine exhaustive sorbents.
... Cyclodextrins, due to their ability to form inclusion complexes (Dodziuk, 2006), are known carriers for pharmaceutical (Mura, 2020), cosmetic (Hwang et al., 2020) and food additives (Astray et al., 2009). Utilising this property, several attempts have been made to trap micropollutants with encouraging results; 87-99% of estrogenic compounds were removed with CD bead-polymer (Nagy et al., 2014), and CD-grafted cellulose filter retained 25 mg DCF per 1 g filter as opposed to < 0.2 mg·g −1 when cellulose filter without functionalisation was used (Ares et al., 2019). ...
Micropollutants are persistent and hazardous materials in low concentrations (ng L⁻¹–μg L⁻¹), including substances such as pharmaceuticals, personal care products and industrial chemicals. The advancement of analytical chemistry has allowed for the detection of micropollutants; however, an efficient and economical treatment solution is yet to be installed. Fungal laccase has been a successful biocatalyst of these compounds. However, large-scale application of free enzyme is currently not feasible for removing water-borne micropollutants, partly due to relatively rapid loss in enzyme stability. In this paper, three types of cyclodextrin, α, β and γCD, were chosen to immobilise the laccase under various conditions with the aim to improve the stability of the enzyme. Laccase activity was chosen as a response parameter, and laccase-cyclodextrin binding was evaluated by Fourier-transform infrared spectroscopy (FTIR). Results showed an optimum using α-cyclodextrin immobilisation. At that level, α-cyclodextrin increased the half-life of laccase and slightly improved its activity in all tested pH by physically bonding to laccase. By protecting the enzyme structure, activity was maintained under a range of circumstances (acidic conditions, from 10 to 50 °C). Under room temperature and at pH 5, α-cyclodextrin-laccase nanocomposite had a better removal efficiency of diclofenac compared to free laccase of the same concentration.
Graphical abstract
This study explores the liquid crystalline properties of novel amphiphilic β-cyclodextrin derivatives functionalized with seven oligoethylene glycol chains at the primary face, terminated with either an O-methyl or an O-cyanoethyl group, and fourteen hydrophobic aliphatic chains (elaidic or oleic acids) at the secondary face. These derivatives were designed to study the impact of chain conformation and terminal group polarity on their mesomorphic behavior. Thermal, microscopic, and X-ray diffraction studies revealed that the elaidic derivatives form columnar hexagonal mesophases, with the O-cyanoethyl derivative undergoing a slow, temperature-dependent transition to a bicontinuous cubic phase. The oleic derivatives, although less stable, also exhibit columnar hexagonal phases, but clear differences were observed in the clearing temperatures between these two groups of molecules, and they are also different from analogous derivatives containing no alkene functionalities. This work provides direct insights into the structure–mesomorphic property relationships of amphiphilic cyclodextrins in terms of the geometry and conformation flexibility of the hydrophobic regions, as well as the functional group attached to the end of the polar region.
In cyclodextrin science, water has been almost exclusively employed as solvent, and this imposes non-negligible limitations to the scope of applications. Accordingly, deep eutectic solvents, constructed from hydrogen-bonding donors and acceptors, have been attracting much interest as important substitutes of water. This review comprehensively covers chemical and physicochemical features of cyclodextrins in these eco-friendly solvents. In one category, cyclodextrins or their derivatives are dissolved as solutes in conventional deep eutectic solvents. All of α-, β-, and γ-cyclodextrins efficiently form inclusion complexes with various guest molecules, exactly as observed in water. Notably, chemically modified cyclodextrins (e.g., 2-hydroxypropyl-cyclodextrins) form still more stable inclusion complexes than native cyclodextrins. Alternatively, deep eutectic solvents are prepared by combining cyclodextrins with other hydrogen-bonding components. The cyclodextrin units in these mixtures also form inclusion complexes with guest molecules. It has been proposed that enhanced flexibility of cylindrical structures of cyclodextrins allows effective induced-fit to stabilize inclusion complexes. The applications of these systems widely range from catalysis for organic synthesis to extraction, analysis, pharmaceutics, and many other fields. High solubilities of CDs and various chemicals in these solvents guarantee high productivity of target transformation, and unprecedentedly novel functions are promising for these unique systems.
This review comprehensively covers recent developments of cyclodextrin-mediated chemical transformations for green chemistry. These cyclic oligomers of glucose are nontoxic, eco-friendly, and recyclable to accomplish eminent functions in water. Their most important feature is to form inclusion complexes with reactants, intermediates, and/or catalysts. As a result, their cavities serve as sterically restricted and apolar reaction fields to promote the efficiency and selectivity of reactions. Furthermore, unstable reagents and intermediates are protected from undesired side reactions. The scope of their applications has been further widened through covalent or noncovalent modifications. Combinations of them with metal catalysis are especially successful. In terms of these effects, various chemical reactions are achieved with high selectivity and yield so that valuable chemicals are synthesized from multiple components in one-pot reactions. Furthermore, cyclodextrin units are orderly assembled in oligomers and polymers to show their cooperation for advanced properties. Recently, cyclodextrin-based metal–organic frameworks and polyoxometalate–cyclodextrin frameworks have been fabricated and employed for unique applications. Cyclodextrins fulfill many requirements for green chemistry and should make enormous contributions to this growing field.
Structural mass spectrometry (MS) techniques are fast and sensitive analytical methods to identify noncovalent guest/host complexation phenomena for desirable solution-phase properties. Current MS-based studies on guest/host complexes of drug and drug-like molecules are sparse, and there is limited guidance on how to interpret MS information in the context of host nanoencapsulation and inclusion. Here, we use structural MS strategies, combining energy-resolved MS (ERMS), ion mobility-MS (IM-MS), and computational modeling, to characterize 14 chemically distinct drug and drug-like compounds for their propensity to form guest/host complexes with the widely used excipient, beta-cyclodextrin (βCD). The majority (11/14) yielded a 1:1 guest/host complex, and ion mobility collision cross section (CCS) analysis provided subtle evidence of gas-phase compaction of complexes in both polarities. The three distinct dissociation channels observed in ERMS (i.e., charged βCD, charged guest, and partial guest loss) were used to direct charge-site assignments for computational modeling, and structural candidates were prioritized using helium-derived CCS measurements combined with root-mean-square distance analysis. The combined analytical information from ERMS, IM-MS, and computational modeling suggested that the majority of anhydrous complexes are inclusion complexes with βCD. Taken together, this work demonstrates a roadmap for how multiple MS-based analytical measurements can be combined to interpret the structures that guest/host complexes adopt in the absence of water.
Herein are presented the results of experiments designed to evaluate the effectiveness of host–guest interactions in improving the sensitivity of colorimetric detection based on surface-enhanced photochromic phenomena of tungsten(VI) oxide (WO3) nanocolloid particles. The UV-induced photochromic coloration of WO3 nanocolloid particles in the presence of aromatic α-amino acid (AA), l-phenylalanine (Phe) or l-2-phenylglycine (Phg), and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMβCDx) in an aqueous system was investigated using UV–vis absorption spectrometry. The characteristics of the adsorption modes and configurations of AAs on the WO3 surface have also been identified by using a combination of adsorption isotherm analysis and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). A distinct linear relationship was observed between the concentration of AAs adsorbed on the WO3 nanocolloid particles and the initial photochromic coloration rate in the corresponding UV-irradiated colloidal WO3 in aqueous media, indicating that a simple and sensitive quantification of AAs can be achieved from UV-induced WO3 photochromic coloration without any complicated preprocessing. The proposed colorimetric assay in the Phe/TMβCDx/WO3 ternary aqueous system had a linear range of 1 × 10–8 to 1 × 10–4 mol dm–3 for Phe detection, with a limit of detection of 8.3 × 10–9 mol dm–3. The combined results from UV–vis absorption, ATR-FTIR, and adsorption isotherm experiments conclusively indicated that the TMβCDx-complexed Phe molecules in the Phe/TMβCDx/WO3 ternary aqueous system are preferentially and strongly inner-sphere adsorbed on the WO3 surface, resulting in a more significant surface-enhanced photochromic phenomenon. The findings in this study provided intriguing insights into the design and development of the “label-free” colorimetric assay system based on the surface-enhanced photochromic phenomenon of the WO3 nanocolloid probe.
The ability of β-CD to form inclusion complexes with ibuprofen (IBU) and at the same time to make a two-phase system with citric acid was explored in the present study for achieving improved solubility and dissolution rate of IBU. Mechanical milling as well as mechanical milling combined with thermal annealing of the powder mixtures were applied as synthetic methods. Solubility and dissolution kinetics of the complexes were studied in compliance with European Pharmacopoeia (ICH Q4B). β-CD and citric acid (CA) molecules were shown to interact by both ball milling (BM), thermal annealing, as well as BM with subsequent annealing. Complexes were also formed by milling the three compounds (β-CD, CA and IBU) simultaneously, as well as by a consecutive first including IBU into β-CD and then binding the formed β-CD/IBU inclusion complex with CA. As a result, ternary β-CD/IBU/CA complex formed by initial incorporation of ibuprofen into β-CD, followed by successive formation of a two-phase mixture with CA, exhibited notably improved dissolution kinetics compared to the pure ibuprofen and slightly better compared to the binary β-CD/IBU system. Although the addition of CA to β-CD/IBU does not significantly increase the solubility rate of IBU, it must be considered that the amount of β-CD is significantly less in the ternary complex compared to the binary β-CD/IBU.
Hydroxypropyl-β-cyclodextrin (HPβCD) is one of the derivatized cyclodextrins most widely used as an excipient in the pharmaceutical industry, for its capacity to improve certain drugs properties. Different configurations of HPβCD are possible depending on the number and location of the 2-hydroxypropyl groups substituted on the glucose rings. Rifampicin has become the most commonly clinically used antibiotic against tuberculosis in recent years, despite its low solubility and variable bioavailability. Different techniques and materials have been proposed to enhance the properties of rifampicin: cyclodextrin complexation is one of them. The van der Waals term was the main contribution to the interaction energy, which then decisively conditioned the complex configurations. The size of rifampicin did not allow the whole molecule to fit into the host. Moreover, interaction energy was much greater when the guest was located near each rim of HPβCD, where rifampicin was partially included in the cavity and formed inclusion complexes. The piperazine tail of rifampicin was included inside the host in minimum energy structures and the guest was situated near the primary rim of HPβCD in most cases, although the complex configurations depended on the degree of substitution.
A molecular mechanics simulation based on the GROMOS 53A6 force field was applied in this work to study the inclusion complexes formed by twelve configurations of HPβCD, with different degrees of substitution and rifampicin in water solution. We determined the penetration potential, the complex structures with minimum energies, the possibility of forming inclusion complexes other than those of minimum energies and potential energy surfaces.
Melatonin (MT) is a vital hormone controlling biorhythms, and optimizing its release in the human body is crucial. To address MT's unfavorable pharmacokinetics, we have explored inclusion complexes of MT...
This study uses isothermal titration calorimetry and NMR spectroscopy to characterize 15 phenothiazine-cyclodextrin interactions. It is found that phenothiazine drugs are privileged guests of β–cyclodextrin and its methylated derivatives.
A new polymorph of anhydrous β-cyclodextrin (polymorph III) was obtained and characterized for the first time using powder X-ray diffraction, infrared spectroscopy, and thermal analysis. The solution enthalpy and time of dissolution in water were determined using solution calorimetry for this polymorph and compared with those of the dried commercial form of β-cyclodextrin (polymorph I), its amorphous form, and 2-hydroxypropyl-β-cyclodextrin. The specific heat capacities of polymorphs I and III were determined using differential scanning calorimetry across a wide range of temperatures, providing enthalpy and Gibbs energy values for the polymorphic transition at 298 K. The affinities of polymorph III and 2-hydroxypropyl-β-cyclodextrin for water were characterized by determining their hydration isotherms, which provided values of hydration Gibbs energy. Being energy-rich, the new-found polymorph of β-cyclodextrin has a significantly higher dissolution rate and an increased affinity for water compared with the dried commercial form of β-cyclodextrin. These properties render the new polymorph promising in industrial applications for guest inclusion in aqueous solutions and pastes, and may be a desirable alternative for water-soluble β-cyclodextrin derivatives.
In the search for improved and safer gadolinium-based magnetic resonance imaging (MRI) contrast agents, macrocyclic cyclodextrins (CDs) attract great interest. Our group previously synthesized a cyclodextrin-based ligand with 1,2,3-triazolmethyl residues conjugated to β-CD, called β-CD(A), which efficiently chelates Gd(III) ions. To probe the local structure around the Gd(III) ion in the 1:1 Gd(III): β-CD(A) complex in aqueous solution (pH 5.5), we used extended X-ray absorption fine structure (EXAFS) spectroscopy. Least-squares curve fitting of the Gd L3-edge EXAFS spectrum revealed 5 Gd–O (4 COO− and 1 H2O) and 4 Gd–N (from two imino and two 1,2,3-triazole groups) bonds around the Gd(III) ion with average distances 2.36 and 2.56 ± 0.02 Å, respectively. A similar EXAFS spectrum was obtained from an aqueous solution of the clinically used MRI contrast agent Na[Gd(DOTA)(H2O)], also 9-coordinated in its first shell. Careful analysis revealed that the mean Gd–N distance is shorter in the Gd(III): β-CD(A) (1:1) complex, indicating stronger Gd–N bonding and stronger Gd(III) complex formation than with the DOTA4− ligand. This is consistent with the lower free Gd3+ concentration found previously for the Gd(III): β-CD(A) (1:1) complex than for the [Gd(DOTA)(H2O)]− complex, and shows its potential as an MRI probe.
EXAFS spectroscopy revealed a similar Gd(III) 9-coordination although slightly stronger for a modified β-cyclodextrin: Gd(III) 1:1 complex, [Gd(LH4)]7−, in aqueous solution than for the clinically used MRI contrast agent Na[Gd(DOTA)(H2O)].
Nowadays, applying natural, biodegradable, non-toxic, and bioactive materials is the first choice of food, biomedical, cosmetic, and textile industries. Due to this reason, this research focused on the preparation of a biomaterial sheet using natural material and with a low-cost method. Firstly, a silk floss sheet (SFS) was prepared using the waste cocoons by degumming, opening up, and finishing process. Afterward, the biodegradable ß-cyclodextrin (ß-CD) was successfully grafted onto SFS using citric acid (CA) through the pad-dry-cure method. Then, Iranian herbal essential oils (Shirazi thyme and Dermaneh) were loaded into the cavities of ß-CD molecules. Then, the samples were investigated using SEM and elemental analysis. The inclusion complex formed between the herbal essential oils and the ß-CD cavity (HEOs- ß-CD) was also evaluated using high-sensitivity analyses of FTIR, XRD, and UV–Visible. Furthermore, free HEOs and HEOs- ß-CD inclusion complex were assessed for their ability to scavenge the 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) radical, and the results showed that the HEOs- ß-CD inclusion complex can improve antioxidant activity compared to the free HEOs. The antimicrobial activity of the prepared SFS was also determined against Staphylococcus aureus, Escherichia coli, and Candida albicans by quality and quantity methods. The results have shown that the modified SFS has a high resistance against the mentioned microorganisms. In addition, the SFS had no negative effect on the viability of the Vero cell line. It seems that the ß-CD-SFS loaded with essential oils can be a good candidate for biomaterial applications and controlled release systems.
Large water-soluble anions with chaotropic character display surprisingly strong supramolecular interactions in water, for example, with macrocyclic receptors, polymers, biomembranes, and other hydrophobic cavities and interfaces. The high affinity is traced back to a hitherto underestimated driving force, the chaotropic effect, which is orthogonal to the common hydrophobic effect. This review focuses on the binding of large anions with water-soluble macrocyclic hosts, including cyclodextrins, cucurbiturils, bambusurils, biotinurils, and other organic receptors. The high affinity of large anions to molecular receptors has been implemented in several lines of new applications, which are highlighted herein.
Considering the potential of nanostructured titanium dioxide layers as drug delivery systems, it is advisable to indicate the possibility of creating a functional drug delivery system based on anodic TiO2 for celecoxib as an alternative anti-inflammatory drug and its inclusion complex with β-cyclodextrin. First, the optimal composition of celecoxib-β-cyclodextrin complexes was synthesized and determined. The effectiveness of the complexation was quantified using isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR) nuclear magnetic resonance (1 H NMR), and scanning electron microscopy (SEM). Then, nanostructured titanium dioxide layers (TiO2) were synthesized using the electrochemical oxidation technique. The TiO2 layers with pore diameters of 60 nm and layer thickness of 1.60 µm were used as drug delivery systems. The samples were modified with pure celecoxib and the β-cyclodextrin-celecoxib complex. The release profiles shown effective drug release from such layers during 24 h. After the initial burst release, the drug was continuously released from the pores. The presented results confirm that the use of nanostructured TiO2 as a drug delivery system can be effectively used in more complicated systems composed of β-cyclodextrin-celecoxib complexes, making such drugs available for pain treatment, e.g., for orthopedic surgeries.
Cyclodextrins (CDs) are a class of cyclic oligosaccharides consisting of several α-(1,4)-linked d-glucose units. They have a cavity of sub-nanometer size, into which a guest molecule of the appropriate size and shape can be selectively incorporated. The ability of CDs to form inclusion complexes with guest molecules has been widely used both academically and industrially. However, most of inclusion complex formation with CDs has been limited to aqueous media. Recently, the authors succeeded in developing CD derivatives that can effectively include guest molecules in oils and nonpolar organic solvents. This review describes molecular recognition in organic solvents by new CD dimers with different linkers and substituent groups, which were designed and synthesized based on the knowledge obtained so far.
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Aromatic organic acids are among the common environmental pollutants that enter the water with washouts from agricultural lands, wastewater from chemical and pharmaceutical industries. Taking into account the high toxicity of aromatic substances, the important task of water purification is the removal of their trace amounts. This problem can be solved by using chemically modified inorganic materials, such as silicas, which have high mechanical, chemical, hydrolytic, and radiation stability. Therefore, they do not lose their sorption capacity during long-term use and do not pollute water with sorbent degradation products. The purpose of this work is the synthesis of a sorption-active material for removal of toxic aromatic acids by chemical immobilization of β-cyclodextrin functional groups on an aerosilogel (highly dispersed type of amorphous silica). A β-cyclodextrin-containing aerosilogel was synthesized by two-stage liquid-phase chemical modification of hydroxylated silica surface. Using the methods of IR spectroscopy, spectrophotometry, thermogravimetry, pH metry, low-temperature adsorption-desorption of nitrogen, chemical and elemental analysis of the surface, the surface structure and its quantitative chemical composition, and also parameters of porous structure of initial and chemically modified aerosilogels were determined. Sorption of benzoic, salicylic and β-resorcylic acids on aerosilogels from aqueous buffer solutions with pH=1 was studied. The insignificant contribution of silanol and aminopropyl groups and complete participation of chemically fixed β-cyclodextrin in the sorption of aromatic acids were proved. The results obtained are analyzed using kinetic models for pseudo-first and pseudo-second order processes, as well as Langmuir and Freundlich models for equilibrium adsorption on homogeneous and heterogeneous surfaces. It has been found that the sorption kinetic processes are well described by a pseudo-first order equation (in the presence of one type of functional groups on the surface) and a pseudo-second order equation for bi- and trifunctional aerosilogels. Experimental results on the equilibrium sorption of aromatic acids on β-cyclodextrin-containing aerosilogel are in good agreement with the Langmuir adsorption equation. This is evidence of decisive contribution of grafted oligosaccharide groups to the sorption of organic acids. The proposed chemical approach to increasing the sorption activity of aerosilogel can be used to obtain specific chromatographic carriers, as well as inorganic sorbents for the effective removal of small amounts of highly toxic organic substances from water and aqueous solutions.
The development of new formulations can be driven by the knowledge of host–guest complexes using cyclodextrins which have the ability to include guest molecules within their hydrophobic cavities, improving the physicochemical properties of the guest. To rationally explore new pesticide formulations, the effects of cyclodextrins on the properties of such guest molecules need to be explored. Imidacloprid is a neonicotinoid systemic insecticide used worldwide. In this study, the inclusion complexes of Imidacloprid (IMI) with β-cyclodextrin (β-CD) were prepared in the solid state by co-precipitation and the physical mixing method, with a stoichiometry of 1:1 and 1:2 molar ratios. The obtained products, Imidacloprid:β-cyclodextrin inclusion complex (IMI:β-CD), were characterized in the solid state by Fourier transform-infrared (FT-IR) spectroscopy and X-ray powder diffractometry (XRD). In solution, the 1:1 stoichiometry for the inclusion complexes was established by the Job plot method, and the binding constant of IMI:β-CD was determined by UV–vis titration. The toxicity was determined in producers and primary consumers of the freshwater trophic chain, the green alga Raphidocelis subcapitata and the rotifer Brachionus calyciflorus, respectively. The results indicated that Imidacloprid forms inclusion complexes with CDs showing improved physicochemical properties compared to free Imidacloprid. The formation of the inclusion complex reduced the chronic toxicity in rotifers when IMI concentrations were close to those of environmental concern (tenths/hundredths of micromoles/L). Therefore, CD inclusion complexes could provide important advantages to be considered for the future industrial production of new formulations.
Cyclodextrins are highly functional compounds with a hydrophobic cavity capable of forming supramolecular inclusion complexes with various classes of molecules including surfactants. The resultant rich nanostructures and their dynamics are an interesting research problem in the area of soft condensed matter and related applications. Herein, we report novel dynamical supramolecular assemblies based on the complexation of β-cyclodextrin with 3 different sulfonic surfactants, which are sodium hexadecylsulfate, sodium dodecylbenzenesulfonate, and myristyl sulfobetaine. It was observed that a β-cyclodextrin : surfactant/2 : 1 molar ratio was ideal for inducing axial growth and imparting large viscosities in the suspensions. Such complexation processes were accompanied by intriguing nanostructural phase behaviors and rheological properties that were very sensitive to the molecular architecture of sulfonic surfactants. The presence of an amino group in the head group of the surfactant allowed for large viscosities that reached 2.4 × 104 Pa s which exhibited gel-like behavior. In contrast, smaller viscosity values with a lower consistency index were observed when a bulky aromatic ring was present instead. DIC microscopy was used to visually probe the microstructure of the systems with respect to sulfonate molecular architecture. Additionally, surface tension measurements, and FTIR and NMR spectroscopies were used to gain insights into the nature of interactions that lead to the complexation and nanostructural characteristics. Finally, mechanics correlating the supramolecular morphologies to the rheological properties were proposed.
Formononetin, a naturally occurring isoflavone exhibits a wide range of therapeutic applications including antioxidant, anti-tumor, antiviral, anti-diabetic and neuroprotective activities. However, the low hydro-solubility of formononetin has limited its prospective use in cosmetic, neutraceutical and pharmaceutical industries. Cyclodextrins (CDs), especially β-CD and its derivatives have emerged as promising agents to improve the water solubility of poorly hydrosoluble compounds by the formation of inclusion complexes. We employed multiscale (1000 ns) explicit solvent and umbrella sampling molecular dynamics (MD) simulations to study the interactions and thermodynamic parameters of inclusion complex formation between formononetin and five most commonly used β-CD derivatives. Classical MD simulations revealed two possible binding conformations of formononetin inside the central cavity of hydroxypropyl-β-CD (HP-β-CD), randomly methylated-β-CD (ME-β-CD), and sulfobutylether-β-CD (SBE-β-CD). The binding conformation with the benzopyrone ring of formononetin inside the central cavity of β-CD derivatives was more frequent than the phenyl group occupying the hydrophobic cavity. These interactions were supported by a variety of non-bonded contacts including hydrogen bonds, pi-lone pair, pi-sigma, and pi-alkyl interactions. Formononetin showed favorable end-state MD-driven thermodynamic binding free energies with all the selected β-CD derivatives, except succinyl-β-CD (S-β-CD). Furthermore, umbrella sampling simulations were used to investigate the interactions and thermodynamic parameters of the host-guest inclusion complexes. The SBE-β-CD/formononetin inclusion complex showed the lowest binding energy signifying the highest affinity among all the selected host-guest inclusion complexes. Our study could be used as a standard for analyzing and comparing the ability of different β-CD derivatives to enhance the hydro-solubility of poorly soluble molecules.
To systematically study the influence of host–guest interactions on the analytical performance of direct analysis in real time mass spectrometry (DART-MS), the interactions between cyclodextrins (CDs) and different Sudan dyes were investigated. The results showed that the host–guest interaction between CDs and Sudan dyes did not affect qualitative analysis of the target compounds, but led to a lower signal intensity for Sudan dyes, thus affecting quantitative analysis of the target compounds. The stronger the host–guest interaction, the weaker the signal intensity of target compound on DART-MS. The results also show that both in solution and in solid-phase microextraction (SPME), the addition of organic solvents can weaken the host–guest interaction between CDs and Sudan dyes, thus improving the signal intensity in DART-MS. In SPME, adding organic solvents has a certain practical value and can improve the efficiency of Sudan dye analysis. This study suggests that appropriate sample pretreatment is needed to weaken noncovalent interactions prior to DART-MS analysis to obtain more accurate quantitative results. The data provide some insight into the effects of other noncovalent interactions on the efficiency of DART-MS as an analytical tool, as well as the potential to study intermolecular interactions with DART-MS.Graphical Abstract
Hydroxypropyl-β-cyclodextrin (HPβCD) is a derivative of cyclodextrin extensively used in the pharmaceutical industry, since it improves the solubility of drugs, and widens their oral bioavailability and safety profile. Theoretical studies about HPβCD configurations are important so as to simulate by molecular mechanics and dynamics, the complex formation and enantiomeric separations of these cyclodextrins with other molecules. Twelve structures and charge distributions of 2-, 3- and 6-hydroxypropyl-β-cyclodextrin (2-, 3-, 6-HPβCD) with different degrees of substitution were obtained using ab initio methods. The atomic positions of glucose units, dihedral angles of hydroxypropyl groups (HPs), radius of gyration, and H-bonds formed were analysed in the structures. The 3-HPβCD configurations showed the greatest variations in their atomic positions, their HPs groups being slightly rotated towards the interior of the rim of cyclodextrin and hence narrowing its opening. The structures of 2-HPβCD are the least influenced by the degree of substitution and include fewer H-bonds. Different values for the partial atomic charges for each glucose unit in a molecule were obtained, as well as for all HPβCD configurations. This result, consequence of the ab initio methods used, is a new contribution that can be important to simulate processes in which small energy differences decisively influence the results. The electric potential due to the charge distribution of HPβCDs was calculated inside and outside the cavity. It was found that the changes at each position were mainly due to atomic configurations, since the differences in partial atomic charges are one or two orders of magnitude smaller than in atomic positions.
Communicated by Ramaswamy H. Sarma
We present the design, tailoring and physicochemical properties of a multicomponent PEG-based polymer doped with spherical nanoparticles modified with a lipoic acid derivative of cyclodextrin and its application for the electrochemical sens-ing of a ferrocene derivative and ibuprofen at low concentrations. Each of the components of this hybrid material has specific properties that can be useful for the preparation of sensors characterized by high selectivity and a low detection limit. Elec-trochemical studies have previously shown that the cyclodextrin derivative with an aromatic triazole linker in the structure enhances binding of the analyte, ensuring its preconcentration on the electrode, and, therefore, enabling improvement of the sensor detection limit. On the other hand, the introduction of evenly dispersed spherical gold nanoparticles in the polymer matrix increases the conductivity of the film and enhances the analytical signal. The third component - a biocompatible and easily wettable cross-linker, polyethylene glycol – allows for uninterrupted diffusion within the polymer film. This signifi-cantly increases the analytical performance of the sensor, supports further improvement of the detection limit and enables the determination of the analyte after saturation of cyclodextrin cavities (high concentration of analyte) based on its diffusion response. The designed hybrid material was used for the direct and indirect determination of aromatic analytes - ferrocene derivative and ibuprofen – with a very low detection limit
In this paper, we fabricated semi-interpenetrating polymeric network (semi-IPN) of hydroxypropyl-β-cyclodextrin-grafted-poly(acrylic acid)/poly(vinyl pyrrolidone) (HP-β-CD-g-poly(AA)/PVP) by the free radical polymerization technique, intended for colon specific release of dexamethasone sodium phosphate (DSP). Different proportions of polyvinyl pyrrolidone (PVP), acrylic acid (AA), and hydroxypropyl-beta-cyclodextrin (HP-β-CD) were reacted along with ammonium persulphate (APS) as initiator and methylene-bis-acrylamide (MBA) as crosslinker to develop a hydrogel system with optimum swelling at distal intestinal pH. Initially, all formulations were screened for swelling behavior and AP-8 was chosen as optimum formulation. This formulation was capable of releasing a small amount of drug at acidic pH (1.2), while a maximum amount of drug was released at colonic pH (7.4) by the non-Fickian diffusion mechanism. Fourier transformed infrared spectroscopy (FTIR) revealed successful grafting of components and development of semi-IPN structure without any interaction with DSP. Thermogravimetric analysis (TGA) confirmed the thermal stability of developed semi-IPN. X-ray diffraction (XRD) revealed reduction in crystallinity of DSP upon loading in the hydrogel. The scanning electron microscopic (SEM) images revealed a rough and porous hydrogel surface. The toxicological evaluation of semi-IPN hydrogels confirmed their bio-safety and hemocompatibility. Therefore, the prepared hydrogels were pH sensitive, biocompatible, showed good swelling, mechanical properties, and were efficient in releasing the drug in the colonic environment. Therefore, AP-8 can be deemed as a potential carrier for targeted delivery of DSP to treat inflammatory bowel diseases.
The Cn molecular symmetry implicated by the schemes with which cyclodextrins (CDs), the well-known cyclic oligosaccharides, are introduced in the literature, is not valid. Numerous studies have shown that CDs are rather flexible with their macrocycle adopting various conformations that enable the inclusion complexation of guest molecules of various shapes. In this work, the loss and gain of the C7 symmetry of the heptakis (2, 3, 6-tri-O-methyl)-β-CD (TM-β-CD) is investigated by means of its conformation geometrical features in its hydrated form and upon complexation with molecules of different shapes. For this, the crystal structure of the inclusion complex of a bulky guest molecule (giberellic acid) in TM-β-CD is presented for the first time and compared with the previously determined crystal structures of monohydrated TM-β-CD and the inclusion complex of a linear monoterpenoid (geraniol) in TM-β-CD. The structural investigation was complemented by molecular dynamics simulations in an explicit solvent, based on the crystallographically determined models. The crucial role of the guest, in the symmetry gain of the host, reveals a pronounced induced-fit complexation mechanism for permethylated CDs.
Pre-loading bovine sperm with cholesterol prior to freezing is known to increase cryosurvival, though the timing of capacitation in these sperm has not been evaluated. The objective of this study was to determine if there is a potential delay in capacitation timing in these sperm due to the increased cholesterol content. Flow cytometric evaluation was utilized to assess viability, and stain technology to assess acrosome intactness (Propidium Iodide/FITC-PNA), intracellular calcium levels (Propidium Iodide/FLUO 3-AM), and membrane fluidity (Merocyanine 540/YO-PRO-1). Cholesterol-loaded cyclodextrin (CLC) (2 mg/mL) improved post thaw viability to 61% from 45% in control sperm (P<0.05). The addition of ionomycin (0.05 mM) induced capacitation in sperm by 1 hour, resulting in increased intracellular calcium and increased acrosome reaction, and consequently viability loss by 3 hours. Treatment with CLC significantly decreased membrane fluidity in sperm (P<0.05). In conclusion, CLC treated sperm required 1 hour more to capacitate when compared with non-treated sperm based on percentage of live cells with high membrane disorder (P<0.05). Increased cryosurvival and viability over time was observed, but longer time to capacitate may hinder fertilization capacity and/or require adjustments to timing of in vitro fertilization (IVF).
Artificial insemination using cooled-transported semen has marked importance in equine breeding programs around the world, and the high value of mules has generated avid interest in donkey semen biotechnology. However, donkey semen cools poorly in commercially available equine extenders. Therefore, this study aimed to develop approaches to improve the ability of donkey semen to tolerate cooling. Ejaculates of seven donkeys (n = 21) were cooled at 5°C for 48 h in three different extenders (milk-based, SM; sodium caseinate-based, SC; or egg yolk-based, EY) in the presence or absence of seminal plasma (centrifugation, C). Sperm motility, plasma membrane integrity (PMI), plasma membrane stability (PMS), mitochondrial membrane potential (HMMP), intracellular hydrogen peroxide (H2O2), and intracellular superoxide (O2−) were assessed before, 24 h, and 48 h post-cooling. In addition, 15 mares (163 estrous cycles) were randomly inseminated with semen from two jacks (Jack 1, n = 90; Jack 2, n = 73) previously cooled for 24 h under one of the treatments (SM, SC, EY, SM-C, SC-C, or EY-C). Groups EY, SC-C, and EY-C (P < 0.05) demonstrated superior sperm analytical parameters to SM at 24 and 48 h. Centrifugation positively affected sperm analytical parameters in cooled donkey semen extended in SM and SC (P < 0.05). Mares bred with semen extended in SC (67%, 18/27), SC-C (89%, 24/27), EY (89%, 25/28), or EY-C (74%, 20/27) had significantly greater conception rates than mares bred with SM (33%, 9/27; P < 0.05). Mares bred with SM-C had intermediate conception rates (59%, 16/27). In conclusion, SC and EY improved the cooling ability and fertility of donkey semen in horse mares, and centrifugation positively affected donkey semen extended in SM.
In this study, the silk floss sheet (SFS) modified with β‐cyclodextrin (β‐CD) is used to adsorb various dyes (anionic: Acid Red 33/ AR33, cationic: Basic Blue 9/ BB9, and non‐ionic: Disperse Yellow 26/ DY26) from colored solutions. The various analyses (fourier transform infrared spectroscopy (FTIR), X‐ray diffraction (XRD), ultraviolet‐visible spectroscopy (UV‐Vis), and elemental analysis) are used to study the inclusion complex between β‐CD and the mentioned dyes. In addition, the influence of experimental parameters on the adsorption process (such as dye molecular size, adsorbent dosage, initial dye concentration, contact time, and pH) is assessed. The results show that the molecular size and pH have more effect on the adsorption capacity of SFS. It is found that optimum adsorption of acid and disperse dyes occurrs at pH 4, while basic dye can adsorb at around pH 10. Also, the experimental data have a good fit with the Langmuir equation and the kinetic data can correlate with the second‐order equations. Finally, the desorption studies show that this natural adsorbent can be reused many times without any change in its adsorption capacity. Natural silk floss sheet (SFS) modified with biodegradable ß‐cyclodextrin (β‐CD) can absorb anionic, cationic, and non‐ionic dyes from colored solutions. The dye adsorption process occurs via either chemical (ionic and hydrogen bonding) or physical (inclusion complex) interactions. This ecofriendly and low‐cost adsorbent can be reused a minimum of five times without significant changes to its adsorption capacity.
Carbazole is a unique template associated with several biological activities. It is due to the diverse and versatile biological properties of carbazole derivatives that they are of immense interest to the research community. 1-keto-1,2,3,4-tetrahydrocarbazoles are important synthetic intermediates to obtain carbazole derivatives. Several members of this family emit fluorescence on photoexcitation. In the context of biochemical and biophysical research, designing and characterising small molecule environment sensitive fluorophores is extremely significant. This article aims to be a state of the art review with synthetic and photophysical details of a variety of fluorophores based on 1-keto-1,2,3,4-tetrahydrocarbazole skeleton.
Graphical Abstract
The electrical conductivities of aqueous solutions of sodium salts of trans-4-hydroxycinnamic acid (trans-p-coumaric acid), trans-3,4-dihydroxycinnamic acid (trans-caffeic acid), trans-4-hydroxy-3-methoxycinnamic acid, (trans-ferulic acid) and trans-3-phenylacrylic acid (trans- cinnamic acid) with α-cyclodextrin were measured in the temperature range of 288.15 K–318.15 K. For the first time in the literature, using the limiting molar conductivity obtained from conductivity measurements, the values of the complexation constants (Kf) of the salts of phenolic acid derivatives with α-cyclodextrin were determined using a modified low concentration chemical model (IcCM). An attempt was also made to analyze the individual thermodynamic functions and describing the complexation process as a function of temperature changes. The obtained results show that the process of formation of inclusion complexes is exothermic and is spontaneous.
The study aims to develop wash-resistant antibacterial cotton fabrics without using
synthetic chemicals. Therefore, natural active agents of thyme, thymol and carvacrol were selected. The inclusion complexes were formed with β-cyclodextrin using
kneading method which is a simple and reproducible method for the encapsulation
with high production yield. Differential scanning calorimeter analysis showed that 1:1
and 1:2 β-CD: Guest Molecule (M:M) for thymol and carvacrol from different ratios
studied has the highest complexation degree as 50% and 100%, respectively. It is
also revealed that the volatile agents are retained and showed better thermal stability as a result of complexation. Carvacrol inclusion complexes were found relatively
more stable (Zeta potential: −28.2 mV) than thymol complexes with smaller particle
sizes (204.9 nm). Chemical structures of the inclusion complexes were revealed with
Fourier transform-infrared spectroscopy and nuclear magnetic resonance analyses.
The optimum formulations for each active agent were applied to cotton fabrics as per
the impregnation method and the capsule treated fabrics were washed 1, 10 and 20
times. The images exhibited the presence of inclusion complexes on the fabrics after
20 washing cycles. Although the antibacterial efficacy of fabrics decreased with increasing washing, the fabrics showed the antibacterial effect after 20 washes against
Klebsiella pneumoniae and Staphylococcus aureus. This study showed that the developed products can be an alternative to the other products in the market as the longlasting fragrant natural antibacterial.
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