Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

• Mino R. Caira,
• Susan A. Bourne,
• Halima Samsodien and
• Vincent J. Smith

Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281

• (2ME) and a series of cyclodextrins (CDs) was investigated in the solid state using thermal analysis and X-ray diffraction, while the possibility of enhancing its poor aqueous solubility with CDs was probed by means of equilibrium solubility and dissolution rate measurements. Single crystal X-ray

• diffraction studies of the inclusion complexes between 2ME and the derivatised cyclodextrins heptakis(2,6-di-O-methyl)-β-CD (DIMEB) and heptakis(2,3,6-tri-O-methyl)-β-CD (TRIMEB) revealed for the first time the nature of the encapsulation of a bioactive steroid by representative CD host molecules. Inclusion

• -methoxyestradiol; solubility; X-ray diffraction; Introduction This report focuses on the modes of inclusion of the anticancer agent 2-methoxyestradiol (2ME, Figure 1) in the host cyclodextrins (CDs) heptakis(2,6-di-O-methyl)-β-CD (DIMEB) and heptakis(2,3,6-tri-O-methyl)-β-CD (TRIMEB) in the solid state. The

Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

• Giuseppina Raffaini,
• Antonino Mazzaglia and
• Fabio Ganazzoli

Beilstein J. Org. Chem. 2015, 11, 2459–2473, doi:10.3762/bjoc.11.267

• Materiali Nanostrutturati, c/o Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali dell’Università di Messina, Via F. Stagno d'Alcontres 31, 98166 Messina, Italy 10.3762/bjoc.11.267 Abstract Amphiphilically modified cyclodextrins may form various supramolecular aggregates. Here we

• report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics

• correlating their structures with the pharmaceutical properties. Keywords: aggregation; amphiphilic cyclodextrins; micelles; molecular dynamics simulations; nanoparticles; self-assembly; Introduction Inclusion complexes with supramolecular structures formed by native or modified cyclodextrins (CDs) are

Preparation of Pickering emulsions through interfacial adsorption by soft cyclodextrin nanogels

• Shintaro Kawano,
• Toshiyuki Kida,
• Mitsuru Akashi,
• Hirofumi Sato,
• Motohiro Shizuma and
• Daisuke Ono

Beilstein J. Org. Chem. 2015, 11, 2355–2364, doi:10.3762/bjoc.11.257

• to fabricate functional materials such as hollow permeable microcapsules. With regard to biomedical and pharmaceutical fields, emulsifiers derived from natural polymers such as saccharides are attractive compared to Pickering emulsifiers derived from synthetic polymers. Cyclodextrins (CDs) are cyclic

• . We have previously reported urethane-crosslinked CD polymers, which were prepared by reacting heptakis(2,6-di-O-methyl)-β-cyclodextrins (DM-β-CDs) with aromatic diisocyanates such as 4,4’-methylenebis(phenyl isocyanate) (MDI) and 1,4-phenylene diisocyanate (PDI) [18]. Although MDI- or PDI-crosslinked

Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex

• Chompoonut Rungnim,
• Sarunya Phunpee,
• Manaschai Kunaseth,
• Supawadee Namuangruk,
• Kanin Rungsardthong,
• Thanyada Rungrotmongkol and
• Uracha Ruktanonchai

Beilstein J. Org. Chem. 2015, 11, 2306–2317, doi:10.3762/bjoc.11.251

• 10330, Thailand 10.3762/bjoc.11.251 Abstract Cyclodextrins (CDs) have been extensively utilized as host molecules to enhance the solubility, stability and bioavailability of hydrophobic drug molecules through the formation of inclusion complexes. It was previously reported that the use of co-solvents

• addition [2][3][4][5][6][7][8] and surfactant addition [9]. Complexation is one of the most utilized methods for enhancing the solubility of poorly soluble drugs. Cyclodextrins (CDs) are well-known macrocyclic oligosaccharides that are produced by enzymatic degradation of starch. CDs consist of 6, 7 and 8

• . [23] reviewed the hydrophobic effect of supramolecular complexes from MD simulation studies and emphasized that the non-covalent driving force of high-energy water in the cavity of cyclodextrins, cyclophanes and cucurbiturils was an essential factor for complexation with the guest molecule. MD

Self-assemblies of γ-CDs with pentablock copolymers PMA-PPO-PEO-PPO-PMA and endcapping via atom transfer radical polymerization of 2-methacryloyloxyethyl phosphorylcholine

• Jing Lin,
• Tao Kong,
• Lin Ye,
• Ai-ying Zhang and
• Zeng-guo Feng

Beilstein J. Org. Chem. 2015, 11, 2267–2277, doi:10.3762/bjoc.11.247

• -chain-stranded; pentablock copolymer; poly(pseudorotaxane); polyrotaxane; single-chain-stranded; Introduction Cyclodextrins (CDs) are a series of macrocyclic molecules composed of 6, 7, or 8 (α-, β-, and γ-CD, respectively) glucopyranose units. Their hydrophilic surface and hydrophobic inner cavity

Synthesis, structure, and mechanical properties of silica nanocomposite polyrotaxane gels

• Kazuaki Kato,
• Daisuke Matsui,
• Koichi Mayumi and
• Kohzo Ito

Beilstein J. Org. Chem. 2015, 11, 2194–2201, doi:10.3762/bjoc.11.238

• . These toughness and softness properties are attributable to both the characteristic sliding of polymer chains through the immobilized cyclodextrins on the silica nanoparticle and the entropic contribution of the cyclic components to the elasticity of the gels. Keywords: cyclodextrin; gel; mechanical

• . Polyrotaxane comprising an end-capped backbone polymer and threaded cyclic molecules such as cyclodextrins (CDs) can form a network structure by intermolecular binding of the cyclic components [10]. Since the polymer chains are topologically connected to each other without chemical bonds, the chains can slide

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• cholesterol sequestration is found to be a crucial factor in developing NPC disease. Cyclodextrins (CyDs) are non-reducing cyclic glucose oligosaccharides obtained by enzymatic means from starch-containing raw materials and have been used for the enhancement of drugs solubility, stability and bioavailability

Star-shaped tetrathiafulvalene oligomers towards the construction of conducting supramolecular assembly

• Masahiko Iyoda and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2015, 11, 1596–1613, doi:10.3762/bjoc.11.175

• examples [30][31][32][33]. Other functional units such as fullerenes [34][35], cyclodextrins [36], porphyrin [37], and phthalocyanine [38][39][40] can also be introduced into the core of radial oligo-TTFs. As shown in Figure 1, TTF-annelated porphyrin 1 was synthesized by Becher and co-workers in 2001 [37

Qualitative evaluation of regioselectivity in the formation of di- and tri-6-O-tritylates of α-cyclodextrin

• Keisuke Yoshikiyo,
• Yoshihisa Matsui and
• Tatsuyuki Yamamoto

Beilstein J. Org. Chem. 2015, 11, 1530–1540, doi:10.3762/bjoc.11.168

• ,6C-di-O-trityl-α-CD’s. Keywords: 1H and 13C NMR spectroscopy; quantitative analysis; regioselectivity; tritylation; ultra-fast liquid chromatography (UFLC); Introduction Regioselective modification and deprotection on the primary hydroxy side of cyclodextrins (CDs) are of great importance in

Synthesis of tripodal catecholates and their immobilization on zinc oxide nanoparticles

• Franziska Klitsche,
• Julian Ramcke,
• Julia Migenda,
• Andreas Hensel,
• Tobias Vossmeyer,
• Horst Weller,
• Silvia Gross and
• Wolfgang Maison

Beilstein J. Org. Chem. 2015, 11, 678–686, doi:10.3762/bjoc.11.77

• an effector was prepared. This triscatecholate might be useful for the construction of diamandoid hydrophobic coatings [44] or for the reversible attachment of cyclodextrins to NPs by the formation of cyclodextrin/adamantane inclusion complexes [45]. Alternatively, acrylamide 4 and bromide 12 [42

Superstructures with cyclodextrins: Chemistry and applications II

• Gerhard Wenz

Beilstein J. Org. Chem. 2015, 11, 271–272, doi:10.3762/bjoc.11.30

• Gerhard Wenz Saarland University, Organic Macromolecular Chemistry, Campus C4 2, 66123 Saarbrücken, Germany 10.3762/bjoc.11.30 Keywords: cyclodextrins; Cyclodextrins (CDs) are cyclic α(1→4)-linked oligomeres of anhydroglucose. Since the 6-, 7- and 8-membered rings, called α-, β- and γ-CD

• polyrotaxanes [5][6][7]. The solubility and stability of CD complexes are controllable through the derivatization of CDs. Remarkable progress has been achieved over the past 10 years regarding the regioselective derivatization of cyclodextrins. Synthetic procedures for CD key derivatives such as mono-6-O-tosyl

Properties of cationic monosubstituted tetraalkylammonium cyclodextrin derivatives – their stability, complexation ability in solution or when deposited on solid anionic surface

• Martin Popr,
• Sergey K. Filippov,
• Nikolai Matushkin,
• Juraj Dian and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2015, 11, 192–199, doi:10.3762/bjoc.11.20

• , yet robust and a straightforward process as well. Keywords: cyclodextrins; inclusion properties; solid surface; tetraalkylammonium derivatives; thermal stability; Introduction Cyclodextrins (CDs) are a very interesting group of natural macrocyclic carbohydrates, which were first described by

Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• -cyclodextrin polymers. In aqueous solution nanoparticles were formed from association between the (S)-camptothecin–dextran polymers and the β-cyclodextrin polymers. Keywords: (S)-camptothecin; cyclodextrins; fluorescence; nanoparticles; ITC; Introduction Cancer remains to be the major cause of mortality in

• size. Interaction with suitable correspondent polymers with pendent cyclodextrins may form nanoparticles with the target properties. In recent years cyclodextrin (CD) polymer-based drug-delivery systems have attracted much attention in this field [7][8]. CDs are cyclic sugar molecules constituted of

Effects of RAMEA-complexed polyunsaturated fatty acids on the response of human dendritic cells to inflammatory signals

• Éva Rajnavölgyi,
• Renáta Laczik,
• Viktor Kun,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3152–3160, doi:10.3762/bjoc.10.332

• Solubilization of n−3 PUFAs Cyclodextrins (CDs) are efficient solubilizers of lipids [42]. The water-insoluble n−3 PUFAs were solubilized in aqueous solutions of randomly methylated α- and β-CD (RAMEA and RAMEB, respectively), but the similar γ-CD derivative, RAMEG was ineffective to modulate the solubility

• solubilized by RAMEA provide with a new tool for optimizing the anti-inflammatory effects exerted on human moDC and mediated via the GPR120 receptor without interfering with the cell membrane structure. Experimental Fatty acids, cyclodextrins The fatty acids were purchased from Sigma-Aldrich. The randomly

Inclusion of trans-resveratrol in methylated cyclodextrins: synthesis and solid-state structures

• Lee Trollope,
• Dyanne L. Cruickshank,
• Terence Noonan,
• Susan A. Bourne,
• Milena Sorrenti,
• Laura Catenacci and
• Mino R. Caira

Beilstein J. Org. Chem. 2014, 10, 3136–3151, doi:10.3762/bjoc.10.331

• , poor aqueous solubility) limit such applications and its inclusion in cyclodextrins (CDs) has potential for addressing these shortcomings. Here, various methods of the attempted synthesis of inclusion complexes between trans-resveratrol and three methylated cyclodextrins (permethylated α-CD

• shortcoming [5], among them inclusion complexation with cyclodextrins (CDs), which are well-known solubilisers of lipophilic molecules [6]. In addition to enhancing the solubility of guest molecules, CDs can confer chemical stability on bioactive molecules through inclusion of sensitive guest moieties within

• preparation of binary mixtures was a generous gift from Denk Feinchemie GmbH (München, Germany). For co-precipitation experiments, the RSV used was supplied by Sigma-Aldrich (South Africa). Cyclodextrins were purchased from Wacker Chemie Italia Srl (Milan, Italy) and Cyclolab (Budapest, Hungary). All other

Release of β-galactosidase from poloxamine/α-cyclodextrin hydrogels

• César A. Estévez,
• José Ramón Isasi,
• Eneko Larrañeta and
• Itziar Vélaz

Beilstein J. Org. Chem. 2014, 10, 3127–3135, doi:10.3762/bjoc.10.330

• : controlled release; cyclodextrins; lactase; polypseudorotaxane; supramolecular gel; Introduction In the Western diet, carbohydrates contribute about 50% of calories, distributed in the following ratio: starch (50%), sucrose (30%), lactose (6%), maltose (1–2%), and others (12%: trehalose, glucose, fructose

• nanocarriers, they have the ability to hold/release drugs as a function of pH [9]. Cyclodextrins (CD) are macrocyclic compounds consisting of several glucose units linked by α-D-1,4-glycosidic bonds. Despite their high solubility in water, the internal cavity of cyclodextrins is non-polar and these compounds

• are able to form host–guest complexes by the inclusion of hydrophobic molecules. Cyclodextrins also act as hosts in the formation of inclusion compounds with polymer chains through non-covalent interactions [10]. For instance, incorporation of 5% α-CD transforms dilute Tetronic solutions into gels

Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives

• Lisa Markenstein,
• Antje Appelt-Menzel,
• Marco Metzger and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 3087–3096, doi:10.3762/bjoc.10.325

• ; occupancy; polymer; sevoflurane; solubility; starch; Introduction Cyclodextrins (CDs), α(1→4) linked cyclic oligomers of anhydroglucose, are produced nowadays in industrial scale [1]. CDs are able to complex hydrophobic or amphiphilic guest molecules in aqueous phase [2]. β-CD, the seven membered ring

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers

• Milo Malanga,
• Mihály Bálint,
• István Puskás,
• Kata Tuza,
• Tamás Sohajda,
• László Jicsinszky,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3007–3018, doi:10.3762/bjoc.10.319

• Cyclodextrins (CDs) are cyclic oligosaccharides consisting of 6, 7 or 8 glucopyranose units (α-, β- or γ-CD, respectively). The capability for complexation, as well as their ability to stabilize and solubilize guest compounds, makes these substances prime candidates for incorporation in delivery systems for

• that has contact with water, or when CD is to be used for the removal of specific component(s) of a water-based process. In addition, free CDs are more difficult to recover for commercial recycling. A solution to these challenges is encoded in polymeric cyclodextrin structures. The cyclodextrins fixed

• , the process of purification and the characterization for the epichlorohydrin branched water soluble polymers obtained from native cyclodextrins are well established processes [9][10]. The characteristics of the cyclodextrin polymers can be modulated by appending neutral or ionic functional groups

Modification of physical properties of poly(L-lactic acid) by addition of methyl-β-cyclodextrin

• Toshiyuki Suzuki,
• Ayaka Ei,
• Yoshihisa Takada,
• Hiroki Uehara,
• Takeshi Yamanobe and
• Keiko Takahashi

Beilstein J. Org. Chem. 2014, 10, 2997–3006, doi:10.3762/bjoc.10.318

• orientation [17][18][19][20][21][22][23][24][25][26][27]. However, the brittleness of PLLA prevents drawing. To improve this, it is necessary to control the interchain interactions and lower the glass transition temperature (Tg) of the amorphous phase. Cyclodextrins (CDs) are cyclic molecules composed of six

Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs

• Lisa F. Becker,
• Dennis H. Schwarz and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 2920–2927, doi:10.3762/bjoc.10.310

• displacement reactions starting from the corresponding per-(6-deoxy-6-bromo)cyclodextrins. Further modification of all 2-OH positions by etherification with iodo terminated triethylene glycol monomethyl ether (and tetraethylene glycol monomethyl ether, respectively) furnished water-soluble hosts. Especially

• anaesthesia. Keywords: active pharmaceutical ingredient; binding constant; cyclodextrin; derivatization; gas chromatography; sevoflurane; substitution pattern; Introduction Cyclodextrins (CDs) are cyclic oligomers of α-1,4-linked glucose units. Those CDs consisting of 6, 7, and 8 glucose units are called α

Cyclodextrin–polysaccharide-based, in situ-gelled system for ocular antifungal delivery

• Anxo Fernández-Ferreiro,
• Noelia Fernández Bargiela,
• María Santiago Varela,
• Maria Gil Martínez,
• Maria Pardo,
• Antonio Piñeiro Ces,
• José Blanco Méndez,
• Miguel González Barcia,
• Maria Jesus Lamas and
• Francisco.J. Otero-Espinar

Beilstein J. Org. Chem. 2014, 10, 2903–2911, doi:10.3762/bjoc.10.308

• Pharmacy, University of Santiago de Compostela (USC), Praza Seminario de Estudos Galegos s/n, Santiago de Compostela, 15701, Spain 10.3762/bjoc.10.308 Abstract Fluconazole was studied with two different hydrophilic cyclodextrins (hydroxypropyl-β-cyclodextrin (HPBCD) and sulfobutyl ether-β-cyclodextrin

• polysaccharides gellan gum and κ-carrageenan. This system showed good bioadhesive properties and effective control of fluconazole release. Keywords: cyclodextrins; eye drops; fluconazole; hydroxypropyl-β-cyclodextrin; sulfobutylether-β-cyclodextrin; Introduction Fungal keratitis is a serious disease that can

• solutions of both polysaccharides have characteristic properties related to their temperature dependence and cation-induced gelation [12]. A challenge in the design of bioadhesive ion-sensitive hydrogels is the incorporation of drugs with poor aqueous solubility. Cyclodextrins (CDs) are useful

Synthesis and characterization of a new photoinduced switchable β-cyclodextrin dimer

• Florian Hamon,
• Claire Blaszkiewicz,
• Marie Buchotte,
• Estelle Banaszak-Léonard,
• Hervé Bricout,
• Sébastien Tilloy,
• Eric Monflier,
• Christine Cézard,
• Laurent Bouteiller,
• Christophe Len and
• Florence Djedaini-Pilard

Beilstein J. Org. Chem. 2014, 10, 2874–2885, doi:10.3762/bjoc.10.304

• cavities of cis-AZO-CDim 1 are complexed simultaneously by two adamantyl units of the guest forming a 1:1 complex while trans-AZO-CDim 1 seems to lead to the formation of supramolecular polymers with an n:n stoichiometry. Keywords: azobenzene; cyclodextrins; inclusion complex; photoisomerization

• ; switchable binding behavior; Introduction α-, β- or γ-Cyclodextrins (CDs) are cyclic oligosaccharides composed of 6, 7 or 8 α-D-1,4 glucopyranose moieties, respectively. They are natural compounds produced from starch by the reaction of 4-α-glucanotransferases [1]. Their toroidal shape, with C6-primary

• -cyclodextrin (β-CD) is known to form supramolecular inclusion complexes with molecules, and such inclusion usually enhances the solubility of water-insoluble substances [1][2][3][4]. Pharmaceutical companies already use these cyclodextrins or their derivatives in their formulations [5][6]. In fact, they have a

Synthesis of modified cyclic and acyclic dextrins and comparison of their complexation ability

• Kata Tuza,
• László Jicsinszky,
• Tamás Sohajda,
• István Puskás and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 2836–2843, doi:10.3762/bjoc.10.301

• compared the complex forming ability of α-, β- and γ-cyclodextrins (α-CD, β-CD and γ-CD) with their open ring analogs. In addition to the native cyclodextrins also modified cyclodextrins and the corresponding maltooligomers, functionalized with neutral 2-hydroxypropyl moieties, were synthesized. A new

• capillary electrophoresis (CE) using model guest compounds. In some cases cyclodextrins and their open-ring analogs (acyclodextrins) show similar complexation abilities, while with other guests considerably different behavior was observed depending on the molecular dimensions and chemical characteristics of

• from the three native α-, β-, and γ-cyclodextrins, respectively, are also suitable complexing agents. These maltooligomers are often considered as linear dextrins unable to form inclusion complexes [4]. Komiyama et al. found that there is complex formation but the complex forming ability of closed ring

Thermal and oxidative stability of the Ocimum basilicum L. essential oil/β-cyclodextrin supramolecular system

• Daniel I. Hădărugă,
• Nicoleta G. Hădărugă,
• Corina I. Costescu,
• Ioan David and
• Alexandra T. Gruia

Beilstein J. Org. Chem. 2014, 10, 2809–2820, doi:10.3762/bjoc.10.298

• compounds. One of the most frequently used matrices for molecular encapsulation, protection against oxidation or other degradation processes, as well as controlled release of relatively small bioactive compounds, are cyclodextrins (CDs) [30][31][32][33][34][35]. These are cyclic oligosaccharides consisting

Synthesis of an organic-soluble π-conjugated [3]rotaxane via rotation of glucopyranose units in permethylated β-cyclodextrin

• Jun Terao,
• Yohei Konoshima,
• Akitoshi Matono,
• Hiroshi Masai,
• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2014, 10, 2800–2808, doi:10.3762/bjoc.10.297

• . Partial ROESY NMR spectrum of 26 (400 MHz, CDCl3) showing the NOEs between aromatic protons of the axial hexa(para-phenylene) and inner protons of cyclodextrins. The synthetic route to the PMβ-CD based linked [3]rotaxane with a 5,15-di([1,1'-biphenyl]-4-yl)porphyrin backbone. Selective synthesis of fixed