Synthesis and surface grafting of a β-cyclodextrin dimer facilitating cooperative inclusion of 2,6-ANS

• Lars W. Städe,
• Thorbjørn T. Nielsen,
• Laurent Duroux,
• Reinhard Wimmer,
• Kyoko Shimizu and
• Kim L. Larsen

Beilstein J. Org. Chem. 2015, 11, 514–523, doi:10.3762/bjoc.11.58

• voltage of 700 V. MS spectra (2440–2500 Da) of the purified β-CD dimer. Structure of fluorescent guest molecule, 2,6-ANS, used to probe host–guest interaction and two derivatives thereof with methyl substitutions at the anilino moiety. Illustration of potential 1:1 inclusion complexes of the β-CD dimer

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

• . Based on these results the PEMPDA-β-CD was selected for further measurements. Inclusion properties of PEMPDA-β-CD in solution To evaluate the ability of the cationic derivative PEMPDA-β-CD to form inclusion complexes in aqueous solution, we measured the stability constants (Ks) with three model aromatic

• MEQ in acidic and neutral solutions were higher than those obtained for the β-CD. Complexation of NIA with PEMPDA-β-CD was not observed as well as binding of SAL and MEQ at basic pH. In conclusion, we can state that the monosubstituted derivative PEMPDA-β-CD is able to form inclusion complexes with

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

• glucose units with a hydrophilic exterior and a hydrophobic interior. The hydrophobic interior makes them excellent for forming so-called inclusion complexes with a wide range of compounds which has made CDs useful in numerous applications in research and industry [9]. Inclusion complexes are defined as

• ). Binding properties and formation of nanoparticles The ability to form inclusion complexes with β-CD and β-CD-polymers was determined by isothermal titration calorimetry (ITC) and fluorescence spectroscopy. The β-CD polymer (D70HPβ-CD) had been prepared from a 70 kDa dextran backbone modified with 6

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

• -, β- and γ-CDs, respectively). They form a hollow cylindrical structure with a rather hydrophobic inner cavity, which readily adopts hydrophobic molecules forming inclusion complexes [15]. One of the most important effects of complexation is the enhanced solubility of poorly soluble compounds offering

• that it cannot be determined with a precision sufficient for the calculations. The higher complexation efficiency corresponds to a higher affinity for complexation which is manifested in a higher solubilizing effect. Based on these results the inclusion complexes with 1–3% PUFA content were prepared by

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

• three crystalline inclusion complexes were also fully characterized by thermal analysis (hot stage microscopy, thermogravimetric analysis and differential scanning calorimetry). To complement the solid-state data, phase-solubility studies were conducted using a series of CDs (native and variously

• derivatised) to establish their effect on the aqueous solubility of trans-resveratrol and to estimate association constants for complex formation. Keywords: cyclodextrin; inclusion complexes; thermal analysis; trans-resveratrol; X-ray structures; Introduction The naturally occurring phytoalexin trans

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

• copolymer. α-CD must surpass the outer PPO blocks to reach the PEO blocks and form stable structures known as (pseudo)polyrotaxanes. PEO chains and oligoethylenes of different molecular weights form inclusion complexes with α-CD. On the other hand, the wider PPO chains yield inclusion complexes with β and γ

• by the addition of aqueous, protein-loaded α-CD to Tetronic 90R4. The outer PPO blocks of the copolymer interact forming micelles, while inner PEO blocks form inclusion complexes with α-CD. These moieties are also capable of interacting by hydrogen bonding, contributing to the stability of the

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

• (α), seven (β), or eight (γ) glucose units. CDs have hydrophobic cavities that can contain guest molecules and form inclusion complexes (ICs). ICs with α-CD accelerate the nucleation and crystallization of poly(ε-caprolactone), poly(ethylene glycol), poly(butylene succinate), and poly(3

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

• (SBECD)) for the formation of inclusion complexes. HPBCD and SBECD showed low cell cytotoxicity in human keratocytes as assessed by the label-free xCELLigence system for real-time monitoring. The fluconazole–HPBCD complex was incorporated into an ion-sensitive ophthalmic gel composed of the natural

• complexes. Solubility curves can assess drug–cyclodextrin interactions that include the formation of inclusion and non-inclusion complexes. Additionally, they are useful to determine which cyclodextrin host, HPBCD or SBECD, was interacting more successfully with fluconazole [15]. Apparent stability

• -sensitive bioadhesive hydrogels. Results and Discussion Phase solubility diagrams Phase solubility diagrams for fluconazole with HPBCD and SBECD at 25 °C are shown in Figure 1. With both cyclodextrins, AL-type curve diagrams were obtained [14], which suggests the formation of highly soluble inclusion

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

• . The photoinduced, switchable binding behavior of AZO-CDim 1 was evaluated by ITC, NMR and molecular modeling in the presence of a ditopic adamantyl guest. The results indicate that AZO-CDim 1 can form two different inclusion complexes with an adamantyl dimer depending on its photoinduced isomers. Both

• -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

• cis (Z) and trans (E) isomers, which can be interconverted by both photochemical and thermal means [21]. This transformation by external stimuli induces a molecular movement and a significant geometric change [22][23]. CDs and azobenzene derivatives can form inclusion complexes controlled by

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

• 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

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

• permethylation of all the hydroxy groups of CD. However, the low solubility of PMCD in water as compared with native CDs or other randomly methylated CDs such as 2,6-dimethyl-β-cyclodextrin impedes the formation of self-inclusion complexes via hydrophobic interactions in water. To rise above this problem, we

• in the synthesis of insulated π-conjugated monomers with [1]rotaxane structures using oligo(phenylene–ethylene) units, which have the appropriate length, as the π-conjugated guests for the fixation of self-inclusion complexes by elongation of the guest unit via cross-coupling (Figure 1b). However

• been characterized by 1H NMR in different solvents (Figure 3). The 1H NMR spectrum in CD2Cl2 reveals that the 5,15-di([1,1'-biphenyl]-4-yl)porphyrin moiety is excluded from the cavity of the PM β-CD, while the 1H NMR spectrum in CD3OD reveals a mixture of exclusion and inclusion complexes. On

Binding mode and free energy prediction of fisetin/β-cyclodextrin inclusion complexes

• Bodee Nutho,
• Wasinee Khuntawee,
• Chompoonut Rungnim,
• Piamsook Pongsawasdi,
• Peter Wolschann,
• Alfred Karpfen,
• Nawee Kungwan and
• Thanyada Rungrotmongkol

Beilstein J. Org. Chem. 2014, 10, 2789–2799, doi:10.3762/bjoc.10.296

• (1000 steps) continued by minimization of the whole system with the same minimized process for getting the initial structures to perform the MD simulations. Molecular dynamics simulations Each MD simulation of fisetin/β-CD inclusion complexes was performed by the AMBER 10 software package coupled with

• the representative inclusion complex was performed by using the M06-2X/6-31G(d,p) method. The BSSE correction was also taken into account. Results and Discussion Possible inclusion complexes Taking into account 1000 docked structures, two different groups of orientations of the fisetin guest molecule

• the inclusion complex in solution. To gain detailed insight in the energetic behavior and the geometry of the fisetin/β-CD complex of all four possible inclusion complexes (I–IV) in aqueous solution, MD simulations were then performed with three time repeats for each complex at different initial

Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier

• Kayoko Hayashida,
• Taishi Higashi,
• Daichi Kono,
• Keiichi Motoyama,
• Koki Wada and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2014, 10, 2756–2764, doi:10.3762/bjoc.10.292

• hydrophilic outer surface [1][2]. CDs are acknowledged to form inclusion complexes with various hydrophobic drugs, and improve their pharmaceutical properties [3]. For instance, γ-CD forms inclusion complexes with doxorubicin (DOX) with a stability constant of 345 M−1 [4]. CDs interact with cholesterol

• , phospholipids and proteins of biological membranes in the higher concentration range. Thus, CDs are utilized for studying the functions of caveolae, lipid rafts, and cholesterol transporters in various fields of cell biology [5]. Interestingly, CDs can also form inclusion complexes with linear polymers. Harada

• useful for the confirmation of the PPRXs with CDs, as they provide enough information to distinguish between the herringbone packing of free CDs and the channel packing of inclusion complexes [13]. Therefore, the crystal structure of DOX/PEG-LP/γ-CD was determined by powder X-ray diffraction (Figure 3B

Removal of volatile organic compounds using amphiphilic cyclodextrin-coated polypropylene

• Ludmilla Lumholdt,
• Sophie Fourmentin,
• Thorbjørn T. Nielsen and
• Kim L. Larsen

Beilstein J. Org. Chem. 2014, 10, 2743–2750, doi:10.3762/bjoc.10.290

• organic compounds are known to form stable inclusion complexes with cyclodextrins. Six different amphiphilic cyclodextrin derivatives were synthesised in order to elucidate whether or not the uptake abilities of the coating depend on the structure of the derivative. Headspace gas chromatography was used

• connected through α-1,4-glycosidic bonds giving them a cone-like structure with a hydrophilic exterior and a relatively hydrophobic cavity [7]. The cavity is known to form inclusion complexes with several different molecules, including many of the previously mentioned, unwanted substances [8][9][10], which

• , see Figure 1. It is known that one of the driving forces in inclusion complex formation in water between CDs (the host) and the included compound (the guest) is the hydrophobicity of the guest [7]. Hence, there is an inherent tendency towards the formation of inclusion complexes with 5 in comparison

Linear-g-hyperbranched and cyclodextrin-based amphiphilic block copolymer as a multifunctional nanocarrier

• Yamei Zhao,
• Wei Tian,
• Guang Yang and
• Xiaodong Fan

Beilstein J. Org. Chem. 2014, 10, 2696–2703, doi:10.3762/bjoc.10.284

• shell layer of MP3 may form inclusion complexes with LND and further retard its release [33]. Therefore, DLMP3 possesses the strongest sustained release capability among these LND-loaded micelles. For further comprehension of the sustained release behaviours, the corresponding release mechanism of LND

A green approach to the synthesis of novel phytosphingolipidyl β-cyclodextrin designed to interact with membranes

• Yong Miao,
• Florence Djedaïni-Pilard and
• Véronique Bonnet

Beilstein J. Org. Chem. 2014, 10, 2654–2657, doi:10.3762/bjoc.10.278

• and cosmetic applications and food industry thanks to their ability to encapsulate the hydrophobic molecules by forming inclusion complexes [1]. Moreover, the modified amphiphilic CDs are able to form nanoparticles without cosolvent or surfactant which could be ideal for drug delivery systems [2]. In

Cyclodextrin-grafted polymers functionalized with phosphanes: a new tool for aqueous organometallic catalysis

• Jonathan Potier,
• Stéphane Menuel,
• David Mathiron,
• Véronique Bonnet,
• Frédéric Hapiot and
• Eric Monflier

Beilstein J. Org. Chem. 2014, 10, 2642–2648, doi:10.3762/bjoc.10.276

• chemical shift. However, a simplification of the 31P spectra occurred at 60 °C. Only three peaks could be observed at −20.88, −21.85 and −21.98 ppm (Figure 3). We believed that the increase in temperature disfavoured the CD/phosphane inclusion complexes, thus greatly reducing the number of possible

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• release antimicrobial agents with time. In this paper, the general features of CDs and their applications in the field of biocides have been reviewed. As the key point is the formation of biocide–CD inclusion complexes, this review deals with this in depth and the advantages of biocide encapsulation are

• solubilization of CDs in water. In contrast, the cavity has a hydrophobic character due to carbons and ethereal oxygen atoms and allows the formation of inclusion complexes with hydrophobic molecules [3][4][5]. This property is useful to solubilize and to stabilize highly hydrophobic molecules in aqueous

• environment. However, inclusion complexes in the solid state can also be obtained [6]. Since the water-solubility of native CDs ranges from 18 to 232 g/L, a variety of modified CDs has been developed and most widely employed to improve the formation of inclusion complexes and their solubility [7]. Indeed, the

Synthesis and characterization of a hyper-branched water-soluble β-cyclodextrin polymer

• Francesco Trotta,
• Fabrizio Caldera,
• Roberta Cavalli,
• Andrea Mele,
• Carlo Punta,
• Lucio Melone,
• Franca Castiglione,
• Barbara Rossi,
• Monica Ferro,
• Vincenza Crupi,
• Domenico Majolino,
• Valentina Venuti and
• Dominique Scalarone

Beilstein J. Org. Chem. 2014, 10, 2586–2593, doi:10.3762/bjoc.10.271

• structure with an arrangement of secondary and primary hydroxy groups that makes the inner surface of the toroid lipophilic and the outer surface highly hydrophobic. This peculiar structure allows CDs to efficiently form molecular inclusion complexes with various organic and inorganic guest compounds

• particular. This finding suggests that this fragment of SF is the major site of interaction with the branched β-CD polymer, possibly via formation of a real inclusion complex with the β-CD cavity. More detailed NMR analysis are in progress and will be reported elsewhere. The formation of inclusion complexes

Synthesis of graft polyrotaxane by simultaneous capping of backbone and grafting from rings of pseudo-polyrotaxane

• Kazuaki Kato,
• Katsunari Inoue,
• Masabumi Kudo and
• Kohzo Ito

Beilstein J. Org. Chem. 2014, 10, 2573–2579, doi:10.3762/bjoc.10.269

• (PEG) and the formation of inclusion complexes with α-cyclodextrin (α-CD). PEG with multiple functional groups at each end was prepared by the condensation of PEG-amine and D-gluconic acid; the PEG derivative formed an inclusion complex with α-CD. The polymerization of multiple hydroxy groups at the

Host–guest-driven color change in water: influence of cyclodextrin on the structure of a copper complex of poly((4-hydroxy-3-(pyridin-3-yldiazenyl)phenethyl)methacrylamide-co-dimethylacrylamide)

• Nils Retzmann,
• Gero Maatz and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 2480–2483, doi:10.3762/bjoc.10.259

• studied extensively, causing for example a blue to red color transition of polydiacetylenes (PDAS) due to the formation of inclusion complexes [6][7]. Azo dyes, with their remarkable ability to form stable azo–metal chelate complexes with outstanding thermal and optical properties have been studied widely

Loose-fit polypseudorotaxanes constructed from γ-CDs and PHEMA-PPG-PEG-PPG-PHEMA

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

Beilstein J. Org. Chem. 2014, 10, 2461–2469, doi:10.3762/bjoc.10.257

• to not only small guest molecules, but also to linear polymeric guest molecules. They can self-assemble into novel inclusion complexes (ICs), or polypseudorotaxanes (PPRs) and polyrotaxanes (PRs) end-capped by bulky stoppers. For example, α-CDs typically include PEG, but not PPG, β-CDs contain PPG

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• inclusion complexes with β- (A) and α-CD (C), measured in D2O (600 MHz, 25 °C). A) [17] = 1.0 mM, [β-CD] = 10 mM. B) [17] = 1.0 mM. C) [17] = 1.0 mM, [α-CD] = 10 mM. Schematic drawing of the complexation of the serine derivatives 17 (A) and 18 (B) with α- and β-CD. The shown binding constants were

• determined by ITC, the structures by NMR. n.d. = not detectable by ITC. 1H NMR spectra of 18 (B) and its inclusion complexes with β- (A) and α-CD (C), measured in D2O (600 MHz, 25 °C). A) [18] = 1.0 mM, [β-CD] = 10 mM. B) [18] = 1.0 mM. C) [18] = 1.0 mM, [α-CD] = 10 mM. Selected binding models for the

Effect of cyclodextrin complexation on phenylpropanoids’ solubility and antioxidant activity

• Miriana Kfoury,
• David Landy,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2014, 10, 2322–2331, doi:10.3762/bjoc.10.241

• -1,4)-linked α-D-glucopyranose units, respectively. Owing to their molecular structure, consisting of a hydrophilic outer surface and a hydrophobic cavity, CDs can form inclusion complexes with organic compounds which enter partly or entirely into their cavity. Inclusion complexes can be obtained

• either in solution or in solid state [14]. The relative stabilities of inclusion complexes are governed by different factors such as hydrogen bonding, hydrophobic interactions, solvation effects as well as the guest molecule's space filling ability [15][16]. CD derivatives are also of great importance

• , since they generally have higher aqueous solubility than native CDs and enhanced binding affinities and selectivity [17]. The aim of this study was to investigate the binding ability of five CDs with seven naturally occurring PPs. Formation constants (Kf) of CD/PP inclusion complexes were calculated by

End group functionalization of poly(ethylene glycol) with phenolphthalein: towards star-shaped polymers based on supramolecular interactions

• Carolin Fleischmann,
• Hendrik Wöhlk and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 2263–2269, doi:10.3762/bjoc.10.235

• of stable inclusion complexes was observed, representing an interesting approach towards the formation of star shaped polymers. The decolorization of a basic polymer solution caused by the complexation was of great advantage since this behavior enabled following the complex formation by UV–vis

• cyclodextrin (CD) and phenolphthalein (PP) moieties were introduced as the complex-forming groups. Regarding the formation of inclusion complexes, one of the major driving forces is the displacement of enthalpy-rich water molecules from the cyclodextrin cavity, which requires working in aqueous media, ideally