Perspectives of Cyclodextrins

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Natural and Bio-inspired Molecules".

Deadline for manuscript submissions: closed (31 May 2020) | Viewed by 44301

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Guest Editor
Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Interests: solid-solid reactions by mechanochemistry; cyclodextrin inclusion compounds; solubilization of active pharmaceutical ingredients (APIs); local therapeutic systems for osteosarcoma and osteoporosis; antioxidant flavonoids and their Ru(II) complexes; natural and metallo-organic compounds for cytotoxic and biocidal activities; innovative medicines for leishmaniasis based on inorganic complexes and cyclodextrins
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Special Issue Information

Dear Colleagues,

Cyclodextrins, since their first report in 1891 by Villiers, have already witnessed the turning of two centuries. In the 20th century, these molecules conquered many applications in varied areas such as pharmaceuticals, food, nutrition, cosmetics, crop science, catalysis and analytical chemistry. Now, in the 21st century, CDs are growing even further. A new generation of cyclodextrin scientists is pushing the boundaries of their applications to new and exciting fields. Some CDs are finding applications in medicine, not just as excipients but as novel medicines; the natural sustainability of CDs makes them ideal for bioremediation solutions and their unique host–guest chemistry allows them to be used in the retrieval of noble metals from waste slurry or to remediate water effluent from all sorts of contaminants. Progress in the field of materials science places cyclodextrins in a wide range of novel materials with boundless applications. This Special Issue will create a forum for the presentation of the most relevant progress made by the millennial generation of cyclodextrins, looking at the innovations of the last 19 years and projecting research into the future.

The international cyclodextrin scientific community is invited to present review articles addressing the innovative aspects of CDs in the 21st century, or alternatively, to present strongly original research papers reporting breakthrough applications of CDs.

I will be looking forward to reading your contributions.

Dr. Susana Santos Braga
Guest Editor

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Keywords

  • Host-guest chemistry
  • Data processing and curing
  • Healthcare applications
  • Nutraceutical applications
  • Sustainability

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Published Papers (11 papers)

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Editorial

Jump to: Research, Review

2 pages, 184 KiB  
Editorial
Peering into the Kaleidoscope of Cyclodextrins
by Susana Santos Braga
Biomolecules 2021, 11(1), 121; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11010121 - 19 Jan 2021
Viewed by 1733
Abstract
Cyclodextrins (CDs) are known to us for 130 years, yet they remain ever as new and as fascinating as in their early years, when Villiers marveled at the unexpected growth of “beautiful radiated crystals” in the alcoholic media of his experiments on bacterial [...] Read more.
Cyclodextrins (CDs) are known to us for 130 years, yet they remain ever as new and as fascinating as in their early years, when Villiers marveled at the unexpected growth of “beautiful radiated crystals” in the alcoholic media of his experiments on bacterial fermentation of starches, or when Freudenberg struggled to solve the puzzle of their unusual shape and structure [...] Full article
(This article belongs to the Special Issue Perspectives of Cyclodextrins)

Research

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20 pages, 6121 KiB  
Article
Inclusion of Hydroxycinnamic Acids in Methylated Cyclodextrins: Host-Guest Interactions and Effects on Guest Thermal Stability
by Lee E. Hunt, Susan A. Bourne and Mino R. Caira
Biomolecules 2021, 11(1), 45; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11010045 - 31 Dec 2020
Cited by 7 | Viewed by 2234
Abstract
There is ongoing interest in exploiting the antioxidant activity and other medicinal properties of natural monophenolic/polyphenolic compounds, but their generally low aqueous solubility limits their applications. Numerous studies have been undertaken to solubilize such compounds via supramolecular derivatization with co-crystal formation with biocompatible [...] Read more.
There is ongoing interest in exploiting the antioxidant activity and other medicinal properties of natural monophenolic/polyphenolic compounds, but their generally low aqueous solubility limits their applications. Numerous studies have been undertaken to solubilize such compounds via supramolecular derivatization with co-crystal formation with biocompatible coformer molecules and cyclodextrin (CD) complexation being two successful approaches. In this study, eight new crystalline products obtained by complexation between methylated cyclodextrins and the bioactive phenolic acids (ferulic, hydroferulic, caffeic, and p-coumaric acids) were investigated using thermal analysis (hot stage microscopy, thermogravimetry, differential scanning calorimetry) and X-ray diffraction. All of the complexes crystallized as ternary systems containing the host CD, a phenolic acid guest, and water. On heating each complex, the primary thermal events were dehydration and liberation of the respective phenolic acid component, the mass loss for the latter step enabling determination of the host-guest stoichiometry. Systematic examination of the X-ray crystal structures of the eight complexes enabled their classification according to the extent of inclusion of each guest molecule within the cavity of its respective CD molecule. This revealed three CD inclusion compounds with full guest encapsulation, three with partial guest inclusion, and two that belong to the rare class of ‘non-inclusion’ compounds. Full article
(This article belongs to the Special Issue Perspectives of Cyclodextrins)
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26 pages, 9462 KiB  
Article
Rings, Hexagons, Petals, and Dipolar Moment Sink-Sources: The Fanciful Behavior of Water around Cyclodextrin Complexes
by Pablo F. Garrido, Martín Calvelo, Rebeca Garcia-Fandiño and Ángel Piñeiro
Biomolecules 2020, 10(3), 431; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10030431 - 10 Mar 2020
Cited by 15 | Viewed by 4329
Abstract
The basket-like geometry of cyclodextrins (CDs), with a cavity able to host hydrophobic groups, makes these molecules well suited for a large number of fundamental and industrial applications. Most of the established CD-based applications rely on trial and error studies, often ignoring key [...] Read more.
The basket-like geometry of cyclodextrins (CDs), with a cavity able to host hydrophobic groups, makes these molecules well suited for a large number of fundamental and industrial applications. Most of the established CD-based applications rely on trial and error studies, often ignoring key information at the atomic level that could be employed to design new products and to optimize their use. Computational simulations are well suited to fill this gap, especially in the case of CD systems due to their low number of degrees of freedom compared with typical macromolecular systems. Thus, the design and validation of solid and efficient methods to simulate and analyze CD-based systems is key to contribute to this field. The behavior of supramolecular complexes critically depends on the media where they are embedded, so the detailed characterization of the solvent is required to fully understand these systems. In the present work, we use the inclusion complex formed by two α-CDs and one sodium dodecyl sulfate molecule to test eight different parameterizations of the GROMOS and AMBER force fields, including several methods aimed to increase the conformational sampling in computational molecular dynamics simulation trajectories. The system proved to be extremely sensitive to the employed force field, as well as to the presence of a water/air interface. In agreement with previous experiments and in contrast to the results obtained with AMBER, the analysis of the simulations using GROMOS showed a quick adsorption of the complex to the interface as well as an extremely exotic behavior of the water molecules surrounding the structure both in the bulk aqueous solution and at the water surface. The chirality of the CD molecule seems to play an important role in this behavior. All together, these results are expected to be useful to better understand the behavior of CD-based supramolecular complexes such as adsorption or aggregation driving forces, as well as to introduce new methods able to speed up general MD simulations. Full article
(This article belongs to the Special Issue Perspectives of Cyclodextrins)
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18 pages, 1923 KiB  
Article
Solid γ-Cyclodextrin Inclusion Compound with Gingerols, a Multi-Component Guest: Preparation, Properties and Application in Yogurt
by Joana M. Pais, Bruna Pereira, Filipe A. Almeida Paz, Susana M. Cardoso and Susana S. Braga
Biomolecules 2020, 10(2), 344; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10020344 - 22 Feb 2020
Cited by 13 | Viewed by 4107
Abstract
Gingerols from the rhizome of fresh ginger (Zingiber officinale) were obtained by a simple extraction, followed by purification. The gingerols extract was composed of 6-gingerol (54%), 8-gingerol (20%), and 10-gingerol (26%). It was included into γ-cyclodextrin by classic co-dissolution procedures. Solid-state [...] Read more.
Gingerols from the rhizome of fresh ginger (Zingiber officinale) were obtained by a simple extraction, followed by purification. The gingerols extract was composed of 6-gingerol (54%), 8-gingerol (20%), and 10-gingerol (26%). It was included into γ-cyclodextrin by classic co-dissolution procedures. Solid-state characterisation of γ-cyclodextrin·gingerols shows that this inclusion compound features 1:1 host-to-guest stoichiometry and that it is a microcrystalline powder with a crystalline cell that belongs to the tetragonal space group 4212, having the host molecules stacked in infinite channels where the gingerols are accommodated. In chimico studies with ABTS•+ scavenging, NO scavenging, β-carotene peroxidation, and 5-LOX inhibition show that γ-cyclodextrin is a suitable carrier for gingerols, because it does not alter their reactivity towards these substances. Yogurt was tested as a matrix for the incorporation of gingerols and γ-cyclodextrin·gingerols into foodstuff. The colour of the fortified yogurt suffered little alterations. In the case of yogurt with the inclusion compound, γ-cyclodextrin·gingerols, as fortificant, these alterations were not perceptible to the naked eye. Moreover, yogurt with γ-cyclodextrin·gingerols showed a good antioxidant activity, thus being suitable for use in nutraceutical applications. Full article
(This article belongs to the Special Issue Perspectives of Cyclodextrins)
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18 pages, 4145 KiB  
Article
New Lipidyl-Cyclodextrins Obtained by Ring Opening of Methyl Oleate Epoxide Using Ball Milling
by Estefania Oliva, David Mathiron, Sébastien Rigaud, Eric Monflier, Emmanuel Sevin, Hervé Bricout, Sébastien Tilloy, Fabien Gosselet, Laurence Fenart, Véronique Bonnet, Serge Pilard and Florence Djedaini-Pilard
Biomolecules 2020, 10(2), 339; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10020339 - 20 Feb 2020
Cited by 14 | Viewed by 3842
Abstract
Bearing grafts based on fatty esters derivatives, lipidyl-cyclodextrins (L-CDs) are compounds able to form water-soluble nano-objects. In this context, bicatenary biobased lipidic-cyclodextrins of low DS were easily synthesized from a fatty ester epoxide by means of alternative methods (ball-milling conditions, use of enzymes). [...] Read more.
Bearing grafts based on fatty esters derivatives, lipidyl-cyclodextrins (L-CDs) are compounds able to form water-soluble nano-objects. In this context, bicatenary biobased lipidic-cyclodextrins of low DS were easily synthesized from a fatty ester epoxide by means of alternative methods (ball-milling conditions, use of enzymes). The ring opening reaction of methyl oleate epoxide needs ball-milling and is highly specific of cyclodextrins in solventless conditions. L-CDs are thus composed of complex mixtures that were deciphered by an extensive structural analysis using mainly mass spectrometry and NMR spectroscopy. In addition, as part of their potential use as vectors of active drugs, these products were submitted to an integrity study on in vitro model of the blood-brain-barrier (BBB) and the intestinal epithelium. No toxicity has been observed, suggesting that applications for the vectorization of active ingredients can be expected. Full article
(This article belongs to the Special Issue Perspectives of Cyclodextrins)
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29 pages, 5943 KiB  
Article
Physicochemical Characterization and Antioxidant Activity Evaluation of Idebenone/Hydroxypropyl-β-Cyclodextrin Inclusion Complex
by Valentina Venuti, Vincenza Crupi, Barbara Fazio, Domenico Majolino, Giuseppe Acri, Barbara Testagrossa, Rosanna Stancanelli, Federica De Gaetano, Agnese Gagliardi, Donatella Paolino, Giuseppe Floresta, Venerando Pistarà, Antonio Rescifina and Cinzia A. Ventura
Biomolecules 2019, 9(10), 531; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9100531 - 25 Sep 2019
Cited by 52 | Viewed by 4228
Abstract
Idebenone (IDE) is an antioxidant drug active at the level of the central nervous system (CNS), whose poor water solubility limits its clinical application. An IDE/2-hydroxypropyl-β-cyclodextrin (IDE/HP-β-CD) inclusion complex was investigated by combining experimental methods and theoretical approaches. Furthermore, [...] Read more.
Idebenone (IDE) is an antioxidant drug active at the level of the central nervous system (CNS), whose poor water solubility limits its clinical application. An IDE/2-hydroxypropyl-β-cyclodextrin (IDE/HP-β-CD) inclusion complex was investigated by combining experimental methods and theoretical approaches. Furthermore, biological in vitro/ex vivo assays were performed. Phase solubility studies showed an AL type diagram, suggesting the presence of a 1:1 complex with high solubility. Scanning electron microscopy (SEM) allowed us to detect the morphological changes upon complexation. The intermolecular interactions stabilizing the inclusion complex were experimentally characterized by exploring the complementarity of Fourier-transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR) with mid-infrared light, Fourier-transform near-infrared (FT-NIR) spectroscopy, and Raman spectroscopy. From the temperature evolution of the O–H stretching band of the complex, the average enthalpy ΔHHB of the hydrogen bond scheme upon inclusion was obtained. Two-dimensional (2D) rotating frame Overhauser effect spectroscopy (ROESY) analysis and computational studies involving molecular modeling and molecular dynamics (MD) simulation demonstrated the inclusion of the quinone ring of IDE inside the CD ring. In vitro/ex vivo studies evidenced that complexation produces a protective effect of IDE against the H2O2-induced damage on human glioblastoma astrocytoma (U373) cells and increases IDE permeation through the excised bovine nasal mucosa. Full article
(This article belongs to the Special Issue Perspectives of Cyclodextrins)
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13 pages, 3168 KiB  
Article
Pharmacokinetic Properties of Fluorescently Labelled Hydroxypropyl-Beta-Cyclodextrin
by Judit Váradi, Anca Hermenean, Rudolf Gesztelyi, Viktória Jeney, Enikő Balogh, László Majoros, Milo Malanga, Éva Fenyvesi, Lajos Szente, Ildikó Bácskay, Miklós Vecsernyés, Pálma Fehér, Zoltán Ujhelyi, Gábor Vasvári, István Árvai, Ágnes Rusznyák, Cornel Balta, Hildegard Herman and Ferenc Fenyvesi
Biomolecules 2019, 9(10), 509; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9100509 - 20 Sep 2019
Cited by 16 | Viewed by 4301
Abstract
2-Hydroxypropyl-beta-cyclodextrin (HPBCD) is utilized in the formulation of pharmaceutical products and recently orphan designation was granted for the treatment of Niemann–Pick disease, type C. The exact mechanism of HPBCD action and side effects are not completely explained. We used fluorescently labelled hydroxypropyl-beta-cyclodextrin (FITC-HPBCD) [...] Read more.
2-Hydroxypropyl-beta-cyclodextrin (HPBCD) is utilized in the formulation of pharmaceutical products and recently orphan designation was granted for the treatment of Niemann–Pick disease, type C. The exact mechanism of HPBCD action and side effects are not completely explained. We used fluorescently labelled hydroxypropyl-beta-cyclodextrin (FITC-HPBCD) to study its pharmacokinetic parameters in mice and compare with native HPBCD data. We found that FITC-HPBCD has fast distribution and elimination, similar to HPBCD. Interestingly animals could be divided into two groups, where the pharmacokinetic parameters followed or did not follow the two-compartment, first-order kinetic model. Tissue distribution studies revealed, that a significant amount of FITC-HPBCD could be detected in kidneys after 60 min treatment, due to its renal excretion. Ex vivo fluorescent imaging showed that fluorescence could be measured in lung, liver, brain and spleen after 30 min of treatment. To model the interaction and cellular distribution of FITC-HPBCD in the wall of blood vessels, we treated human umbilical vein endothelial cells (HUVECs) with FITC-HPBCD and demonstrated for the first time that this compound could be detected in the cytoplasm in small vesicles after 30 min of treatment. FITC-HPBCD has similar pharmacokinetic to HPBCD and can provide new information to the detailed mechanism of action of HPBCD. Full article
(This article belongs to the Special Issue Perspectives of Cyclodextrins)
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18 pages, 3064 KiB  
Article
Interactions of Mycotoxin Alternariol with Cyclodextrins and Its Removal from Aqueous Solution by Beta-Cyclodextrin Bead Polymer
by Eszter Fliszár-Nyúl, Beáta Lemli, Sándor Kunsági-Máté, Lajos Szente and Miklós Poór
Biomolecules 2019, 9(9), 428; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9090428 - 30 Aug 2019
Cited by 21 | Viewed by 3261
Abstract
Alternariol is an Alternaria mycotoxin that appears in fruits, tomatoes, oilseeds, and corresponding products. Chronic exposure to it can induce carcinogenic and xenoestrogenic effects. Cyclodextrins (CDs) are ring-shaped molecules built up by glucose units, which form host–guest type complexes with some mycotoxins. Furthermore, [...] Read more.
Alternariol is an Alternaria mycotoxin that appears in fruits, tomatoes, oilseeds, and corresponding products. Chronic exposure to it can induce carcinogenic and xenoestrogenic effects. Cyclodextrins (CDs) are ring-shaped molecules built up by glucose units, which form host–guest type complexes with some mycotoxins. Furthermore, insoluble CD polymers seem suitable for the extraction/removal of mycotoxins from aqueous solutions. In this study, the interactions of alternariol with β- and γ-CDs were tested by employing fluorescence spectroscopic and modeling studies. Moreover, the removal of alternariol from aqueous solutions by insoluble β-CD bead polymer (BBP) was examined. Our major observations/conclusions are the following: (1) CDs strongly increased the fluorescence of alternariol, the strongest enhancement was induced by the native γ-CD at pH 7.4. (2) Alternariol formed the most stable complexes with the native γ-CD (logK = 3.2) and the quaternary ammonium derivatives (logK = 3.4–3.6) at acidic/physiological pH and at pH 10.0, respectively. (3) BBP effectively removed alternariol from aqueous solution. (4) The alternariol-binding ability of β-CD polymers was significantly higher than was expected based on their β-CD content. (5) CD technology seems a promising tool to improve the fluorescence detection of alternariol and/or to develop new mycotoxin binders to decrease alternariol exposure. Full article
(This article belongs to the Special Issue Perspectives of Cyclodextrins)
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15 pages, 2773 KiB  
Article
Cyclodextrins Can Entrap Zearalenone-14-Glucoside: Interaction of the Masked Mycotoxin with Cyclodextrins and Cyclodextrin Bead Polymer
by Zelma Faisal, Eszter Fliszár-Nyúl, Luca Dellafiora, Gianni Galaverna, Chiara Dall’Asta, Beáta Lemli, Sándor Kunsági-Máté, Lajos Szente and Miklós Poór
Biomolecules 2019, 9(8), 354; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9080354 - 09 Aug 2019
Cited by 14 | Viewed by 4094
Abstract
Zearalenone (ZEN) is a Fusarium-derived xenoestrogenic mycotoxin. In plants, zearalenone-14-O-β-d-glucoside (Z14G) is the major conjugated metabolite of ZEN, and is a masked mycotoxin. Masked mycotoxins are plant-modified derivatives, which are not routinely screened in food and feed samples. [...] Read more.
Zearalenone (ZEN) is a Fusarium-derived xenoestrogenic mycotoxin. In plants, zearalenone-14-O-β-d-glucoside (Z14G) is the major conjugated metabolite of ZEN, and is a masked mycotoxin. Masked mycotoxins are plant-modified derivatives, which are not routinely screened in food and feed samples. Cyclodextrins (CDs) are cyclic oligosaccharides built up from D-glucopyranose units. CDs can form stable host–guest type complexes with lipophilic molecules (e.g., with some mycotoxins). In this study, the interaction of Z14G with native and chemically modified β- and γ-CDs was examined employing fluorescence spectroscopy and molecular modeling. Furthermore, the removal of Z14G from aqueous solution by insoluble β-CD bead polymer (BBP) was also tested. Our results demonstrate that Z14G forms the most stable complexes with γ-CDs under acidic and neutral conditions (K ≈ 103 L/mol). Among the CDs tested, randomly methylated γ-CD induced the highest increase in the fluorescence of Z14G (7.1-fold) and formed the most stable complexes with the mycotoxin (K = 2 × 103 L/mol). Furthermore, BBP considerably reduced the Z14G content of aqueous solution. Based on these observations, CD technology seems a promising tool to improve the fluorescence analytical detection of Z14G and to discover new mycotoxin binders which can also remove masked mycotoxins (e.g., Z14G). Full article
(This article belongs to the Special Issue Perspectives of Cyclodextrins)
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Review

Jump to: Editorial, Research

19 pages, 2358 KiB  
Review
Cyclodextrins: Emerging Medicines of the New Millennium
by Susana Santos Braga
Biomolecules 2019, 9(12), 801; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9120801 - 28 Nov 2019
Cited by 114 | Viewed by 7777
Abstract
Cyclodextrins, since their discovery in the late 19th century, were mainly regarded as excipients. Nevertheless, developments in cyclodextrin research have shown that some of these hosts can capture and include biomolecules, highlighting fatty acids and cholesterol, which implies that they are not inert [...] Read more.
Cyclodextrins, since their discovery in the late 19th century, were mainly regarded as excipients. Nevertheless, developments in cyclodextrin research have shown that some of these hosts can capture and include biomolecules, highlighting fatty acids and cholesterol, which implies that they are not inert and that their action may be used in specific medicinal purposes. The present review, centered on literature reports from the year 2000 until the present day, presents a comprehensive description of the known biological activities of cyclodextrins and their implications for medicinal applications. The paper is divided into two main sections, one devoted to the properties and applications of cyclodextrins as active pharmaceutical ingredients in a variety of pathologies, from infectious ailments to cardiovascular dysfunctions and metabolic diseases. The second section is dedicated to the use of cyclodextrins in a range of biomedical technologies. Full article
(This article belongs to the Special Issue Perspectives of Cyclodextrins)
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17 pages, 25645 KiB  
Review
Nanoscale Restructuring of Polymer Materials to Produce Single Polymer Composites and Miscible Blends
by Alan E. Tonelli
Biomolecules 2019, 9(6), 240; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9060240 - 19 Jun 2019
Cited by 3 | Viewed by 3080
Abstract
I summarize work conducted in our laboratories over the past 30 years using small host molecules to restructure polymer materials at the nanometer level. Certain small molecules, such as the cyclic starches cyclodextrins (CDs) and urea (U) can form non-covalent crystalline inclusion compounds [...] Read more.
I summarize work conducted in our laboratories over the past 30 years using small host molecules to restructure polymer materials at the nanometer level. Certain small molecules, such as the cyclic starches cyclodextrins (CDs) and urea (U) can form non-covalent crystalline inclusion compounds (ICs) with a range of guest molecules, including many polymers. In polymer-CD- and -U-ICs, guest polymer chains reside in narrow channels created by the host molecule crystals, where they are separated and highly extended. When the host crystalline lattice is carefully removed, the guest polymer chains coalesce into a bulk sample with an organization that is distinct from that normally produced from its melt or from solution. Amorphous regions of such coalesced polymer samples have a greater density, likely with less chain entanglement and more chain alignment. As a consequence, after cooling from their melts, coalesced amorphous polymers show glass-transition temperatures (Tgs) that are elevated above those of samples prepared from their solutions or melts. Upon cooling from their melts, coalesced samples of crystallizable polymers show dramatically-increased abilities to crystallize more rapidly and much closer to their melting temperatures (Tms). These unique behaviors of polymers coalesced from their CD- and U-ICs are unexpectedly resistant to extended annealing above their Tgs and Tms. Taking advantage of this behavior permits us to create polymer materials with unique and improved properties. Among these are amorphous polymers with elevated Tgs and semi-crystalline polymers with finer more uniform morphologies. Improved mechanical properties can be achieved through self-nucleation with small amounts of the same polymer made rapidly crystallizable through coalescence from its CD- or U-IC. This can lead to single polymer composites with as-received polymer matrices and self-nucleated reinforcements. Through simultaneous formation and subsequent coalescence from their common CD–ICs, stable well-mixed blends can be achieved between any two or more polymers, despite their inherent immiscibilities. Such coalesced and well-mixed blends are also resistant to phase segregation when heated for extensive periods well above their Tgs and Tms. Full article
(This article belongs to the Special Issue Perspectives of Cyclodextrins)
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