Interactions between 4-thiothymidine and water-soluble cyclodextrins: Evidence for supramolecular structures in aqueous solutions

• Vito Rizzi,
• Sergio Matera,
• Paola Semeraro,
• Paola Fini and
• Pinalysa Cosma

Beilstein J. Org. Chem. 2016, 12, 549–563, doi:10.3762/bjoc.12.54

• Since several years the inclusion of organic compounds (guests) within the hydrophobic cavity (host) of cyclodextrins (CDs) has been the subject of many investigations. Interestingly, the formation of inclusion complexes could affect the properties of the guest molecules and, for example, the influence

• complexation mode of the inclusion complexes involving 4-thiothymidine (S4TdR, a known photosensitizer) and five CDs, namely 2-hydroxypropyl-α-cyclodextrin (2-HP-α-CD), 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD), 2-hydroxypropyl-γ-cyclodextrin (2-HP-γ-CD), heptakis-(2,6-di-O-methyl)-β-cyclodextrin (DIMEB CD

• presence of CDs to prevent its degradation under irradiation. UV–vis, FTIR–ATR and CV measurements suggested the formation of supramolecular structures involving the employed CDs and mainly the pyrimidine ring of S4TdR. 1H NMR analyses confirmed such indication, unveiling the presence of inclusion

New synthetic strategies for xanthene-dye-appended cyclodextrins

• Milo Malanga,
• Andras Darcsi,
• Mihaly Balint,
• Gabor Benkovics,
• Tamas Sohajda and
• Szabolcs Beni

Beilstein J. Org. Chem. 2016, 12, 537–548, doi:10.3762/bjoc.12.53

• spectroscopically inert molecules by guest-induced spectroscopic changes associated with the formation of inclusion complexes. These fluorescent CDs exhibit remarkable molecular recognition abilities, discriminating shape, bulkiness and polarity of the guests [1][2]. Furthermore, CDs can be directly modified with

• to dissociate inclusion complexes (Supporting Information File 1, Figure S7). The presence of two kinds of signals for the methyl units (at 1.06 ppm and 1.14 ppm) in the spectrum recorded in deuterated DMSO confirms the aforementioned observation. The analysis of the DEPT-ed-HSQC spectrum (see

• of the preferred conformation assumed by Rho-β-CD in solution. These data, together with the results presented by Wang et al. [25] about the crystal structure of rhodamine B in lactone form, allowed us to propose the model shown in Figure 6 for the intermolecular inclusion mode of Rho-β-CD. This

Optimized methods for preparation of 6^I-(ω-sulfanyl-alkylene-sulfanyl)-β-cyclodextrin derivatives

• Eva Bednářová,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2016, 12, 349–352, doi:10.3762/bjoc.12.38

• ability to form supramolecular inclusion complexes with a wide range of guest molecules [2]. From the native CDs (α-CD, β-CD, and γ-CD containing 6, 7, and 8 glucose units, respectively) the β-CD is studied the most due to its lowest price and the highest guest binding ability. A large number of CD

• inclusion complex with β-CD [22], i.e., a suitable accessibility of the cavity should be kept, and further inclusion complexes could be formed with the guests. Strict inert conditions are also required for the next synthetic step – preparation of compounds 5. The air had to be removed from the reaction

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• by reacting β-CD with tosyl imidazole (TsIm) [15]. Great advantages, in terms of yields, reaction times and product purity, were obtained by using a cavitating tube (40 min, 19.2 kHz, 20 W, yield: 55%). Thanks to the fast US-assisted inclusion complex formation between β-CD and TsIm reaction times

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• potential immunogenic risks associated to proteins such as hydrolases [37]. This review focuses on the various aspects of the detoxification process mediated by CD derivatives: (1) the ability of CDs and their derivatives to form inclusion complexes with organophosphorus pesticides and G nerve agents; (2

• ) the hydrolysis of the nerve agents by CDs under specific conditions; (3) the selective modifications of these cyclic oligosaccharides to improve their hydrolytic efficiency at physiological pH and temperature. Review Inclusion studies between CDs and pesticides Due to their toroidal structure, CDs are

• able to interact with organophosphorus compounds. It is well known that many synthetic pesticides (compounds 1–9, Figure 3) can form inclusion complexes with CDs, often resulting in modifications of their chemical and physical properties [38][39]. Thus, valuable information on the stoichiometry, the

Thermal and oxidative stability of Atlantic salmon oil (Salmo salar L.) and complexation with β-cyclodextrin

• Daniel I. Hădărugă,
• Mustafa Ünlüsayin,
• Alexandra T. Gruia,
• Cristina Birău (Mitroi),
• Gerlinde Rusu and
• Nicoleta G. Hădărugă

Beilstein J. Org. Chem. 2016, 12, 179–191, doi:10.3762/bjoc.12.20

• -CD/ASO complexes. The analysis of the complexes by thermogravimetry, differential scanning calorimetry (DSC), and Karl Fischer titration (KFT) as well as the decrease of the “strongly-retained” water content confirm the formation of the inclusion compound. Furthermore, the DSC parameters correlate

• from complexes. According to the TG analysis, the water content is 4.1–6.4% lower than for the β-CD. This observation supports the formation of the inclusion compound by partial replacement of the hydration water from the CD cavity by the guest compounds (FA glycerides). Studies on the evaluation of

• to water release decreases to 91.3 ± 2.9 °C and 74 ± 6.0 °C for the co-crystallization and kneading methods, respectively (Figure 2 and Supporting Information File 1). The decrease of these DSC peak temperatures can be explained by the formation of the host–guest molecular inclusion compound that

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• how two units of Kagan’s ether provide the necessary C-shaped geometry [29]. Then, Harmata himself synthesized tweezer 18, reporting its solution binding studies and a beautiful solid-state inclusion complex with trinitrobenzene [30]. This series of molecular tweezers was reviewed in 2004 [31]. A

Supramolecular structures based on regioisomers of cinnamyl-α-cyclodextrins – new media for capillary separation techniques

• Gabor Benkovics,
• Ondrej Hodek,
• Martina Havlikova,
• Zuzana Bosakova,
• Pavel Coufal,
• Milo Malanga,
• Eva Fenyvesi,
• Andras Darcsi,
• Szabolcs Beni and
• Jindrich Jindrich

Beilstein J. Org. Chem. 2016, 12, 97–109, doi:10.3762/bjoc.12.11

• and even polymers [5]. Modification of the parent CD molecule with an apolar substituent, which can form an inclusion complex with the CD’s cavity results in a conjugate with an ability to self-associate into supramolecular assemblies in polar solvents. The formation of these structures is based

• -inclusion process of the guest part to the parent CD’s cavity [6][7]. These findings showed that a compromise in the flexibility and in the length of the spacer has to be found for efficient formation of intermolecular complexes. Inspired by these works our approach towards SPs was based on the preparation

• of monocinnamyl-α-CDs, where the rigid double bond in the cinnamyl (Cin) moiety should prevent the self-inclusion of the phenyl ring to the CD cavity and prefer the formation of intermolecular complexes in polar solvents. The conjugation of the cinnamoyl (Cio) moiety with α- and β-CD through amide

Aggregation behavior of amphiphilic cyclodextrins in a nonpolar solvent: evidence of large-scale structures by atomistic molecular dynamics simulations and solution studies

• Giuseppina Raffaini,
• Fabio Ganazzoli and
• Antonino Mazzaglia

Beilstein J. Org. Chem. 2016, 12, 73–80, doi:10.3762/bjoc.12.8

• R1 chains (see Scheme 1: these chains were denoted as polar, or P, chains in paper I [11]) could show inclusion within the cavity of the molecule they belong to or of a neighboring molecule thanks to both dispersive and dipolar interactions and possibly with a few hydrogen bonds that may involve the

• glycosidic oxygen atoms. Moreover, one or two R chains (see again Scheme 1: these chains were indicated as hydrophobic, or H, chains in paper I [11]) could also show both self-inclusion and mutual inclusion within the hydrophobic cavity of their own molecule or of an adjacent one thanks to favorable

• interaction close to the secondary rim. Note that the latter interaction strength is somewhat weaker than that due to self- or mutual inclusion of a side chain in an aCD cavity, but still we found that it is strong enough to hold together a molecule to a cluster of other two or three, and that these

Supramolecular polymer assembly in aqueous solution arising from cyclodextrin host–guest complexation

• Jie Wang,
• Zhiqiang Qiu,
• Yiming Wang,
• Li Li,
• Xuhong Guo,
• Duc-Truc Pham,
• Stephen F. Lincoln and
• Robert K. Prud’homme

Beilstein J. Org. Chem. 2016, 12, 50–72, doi:10.3762/bjoc.12.7

• complexes hydrophobic guest species to form host–guest complexes, or inclusion compounds. The host–guest complexes formed by cyclodextrins and their hydrophobic guests, which range from small molecules to polymer substituents and sections of polymer chains, have been widely studied and utilized as building

Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol

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

Beilstein J. Org. Chem. 2016, 12, 29–42, doi:10.3762/bjoc.12.5

• . However, they suffer from poor aqueous solubility and pronounced flavoring ability that limit their application in food systems. These drawbacks could be surpassed by encapsulation in cyclodextrins (CDs). Applications of their inclusion complexes with CDs were reported without investigating the inclusion

• phenomenon in deep. In this study, inclusion complexes were characterized in terms of formation constants (Kf), complexation efficiency (CE), CD:guest molar ratio and increase in bulk formulation by using an UV–visible competitive method, phase solubility studies as well as 1H and DOSY 1H NMR titration

• experiments. For the first time, a new algorithmic treatment that combines the chemical shifts and diffusion coefficients variations for all guest protons was applied to calculate Kf. The position of the hydroxy group in carvacrol and thymol did not affect the stoichiometry of the inclusion complexes but led

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• improve physical properties and biological activities of the two flavanones hesperetin and naringenin by complexation with β-cyclodextrin (β-CD) and its methylated derivatives (2,6-di-O-methyl-β-cyclodextrin, DM-β-CD and randomly methylated-β-CD, RAMEB). The free energies of inclusion complexes between

• hesperetin with cyclodextrins (β-CD and DM-β-CD) were theoretically investigated by molecular dynamics simulation. The free energy values obtained suggested a more stable inclusion complex with DM-β-CD. The vdW force is the main guest–host interaction when hesperetin binds with CDs. The phase solubility

• inclusion complexes. The data obtained by the dissolution method showed that complexation with RAMEB resulted in a better release of both flavanones to aqueous solution. The flavanones-β-CD/DM-β-CD complexes demonstrated a similar or a slight increase in anti-inflammatory activity and cytotoxicity towards

Synthesis and photophysical characteristics of polyfluorene polyrotaxanes

• Aurica Farcas,
• Giulia Tregnago,
• Ana-Maria Resmerita,
• Pierre-Henri Aubert and
• Franco Cacialli

Beilstein J. Org. Chem. 2015, 11, 2677–2688, doi:10.3762/bjoc.11.288

• conjugated polymers [16][17][18][19][20][26][27][28][29][30][31][32][33][34][35][36][37][38]. The first step in the preparation of conjugated polyrotaxanes is the threading of macrocyclic compounds (hosts) onto linear chains (guests), when a thermodynamically unstable inclusion complex (IC) is obtained. A

• molecules were synthesized according to previously reported procedure [47][48]. Synthesis of 1·TM-βCD: To prepare 1·TM-βCD inclusion complex, 0.572 g (0.4 mmol) of TM-βCD were dissolved in water (5.0 mL) and 0.067 g (0.2 mmol) of 2 were added. The mixture was stirred at room temperature under nitrogen

• atmosphere for 48 h to give a turbid dispersion. The water was removed by lyophilization and the complex, as a white powder was used for the preparation of 1·TM-βCD. The synthesis of the inclusion complex 1·TM-γCD was performed under similar experimental conditions as those used for the preparation of the 1

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

• 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

• host–guest β-CD inclusion complex, prepared by two methods, yielded very rapid dissolution in water at 37 °C relative to untreated 2ME, attaining complete dissolution within 15 minutes (co-precipitated complex) and 45 minutes (complex from kneading). Keywords: complexation; cyclodextrin; 2

• -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

• methods with a “bottom up” approach that can provide important information about the initial aggregates of few molecules. The focus is on the interaction pattern of amphiphilic cyclodextrin (aCD), which may interact by mutual inclusion of the substituent groups in the hydrophobic cavity of neighbouring

• 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

• stabilization only amounts to about 3 kJ/mol. It should be noted that while a P–P interaction may allow for intermolecular hydrogen bonds among the terminal OH groups, in the P–H arrangement a slightly larger number of intramolecular hydrogen bonds is actually present together with some shallow self-inclusion

Size-controlled and redox-responsive supramolecular nanoparticles

• Raquel Mejia-Ariza,
• Gavin A. Kronig and
• Jurriaan Huskens

Beilstein J. Org. Chem. 2015, 11, 2388–2399, doi:10.3762/bjoc.11.260

• -electron oxidation to the ferrocenium cation. At the same time, in its reduced state, Fc is a good guest for CD, but the affinity for CD is practically completely lost upon oxidation [17]. Thus, the formed CD-Fc inclusion complex disassembles when the Fc moiety is converted to the ferrocenium cation by

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

• oligosaccharides, which have subnanometer-sized cavities where guest molecules with an appropriate size and shape are incorporated [10]. CDs have been reported to work as emulsion stabilizers [11][12][13][14]. Previous studies have shown that CDs can form surface-active inclusion complexes with oil molecules at

• the oil–water interfaces that can stabilize emulsions, although they do not alter the surface tension of water alone [15]. Only a few papers have reported Pickering emulsions stabilized by CD inclusion complexes. For example, Inoue et al. prepared oil-in-water (O/W) emulsions with α-, β- and γ-CDs

• , conventional methods depend on the formation of inclusion complexes between the CDs and oil molecules at an interface. The findings herein demonstrate that CD nanogels have efficient adsorption properties at oil–water interfaces to stabilize emulsions. The adsorption properties of CD nanogels, which consist of

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

• in such studies may result in ternary (host:guest:co-solvent) complex formation. The objective of this work was to investigate the effect of ethanol as a co-solvent on the inclusion complex formation between α-mangostin (α-MGS) and β-CD, using both experimental and theoretical studies. Experimental

• solubility at all β-CD concentrations studied (0–10 mM). From the equilibrium constant calculation, the inclusion complex is still a binary complex (1:1), even in the presence of ethanol. The results from our theoretical study confirm that the binding mode is binary complex and the presence of ethanol as co

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

• character and deformable cavity size allow for the self-assembly or inclusion of various polymer chains to generate poly(pseudorotaxanes) (PPRs) or polyrotaxanes (PRs) after endcapping with bulky stoppers. Since Harada et al. first reported the α-CD-based single-chain-stranded PPRs constructed from the

• inclusion complexation of α-CDs with poly(ethylene glycol) (PEG) [1], a great variety of polymers with different cross-sectional areas have been shown to thread CDs to create PPRs. For example, β-CDs are single-chain-stranded with poly(propylene glycol) (PPG) but not with PEG [2][3], and γ-CDs are not only

• single-chain-stranded with poly(methyl vinyl ether) (PMVE) [4] or poly(dimethylsiloxane) (PDMS) [5], but also double-chain-stranded with PEG and poly(ε-caprolactone) (PCL) [6]. Recently, Akashi et al. reported the single-chain-stranded inclusion complexation of γ-CDs with poly(methyl methacrylate) (PMMA

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

• Yury A. Sayapin,
• Inna O. Tupaeva,
• Alexandra A. Kolodina,
• Eugeny A. Gusakov,
• Vitaly N. Komissarov,
• Igor V. Dorogan,
• Nadezhda I. Makarova,
• Anatoly V. Metelitsa,
• Valery V. Tkachev,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2015, 11, 2179–2188, doi:10.3762/bjoc.11.236

• elimination of one of the chlorine atoms from the seven-membered ring, the acid-catalyzed reaction between methylene-active nitrogen heterocycles and о-chloranil occurs, depends on the conditions of its performance, with or without inclusion of a stage of dehydrochlorination and leads to 5,6,7-trichloro- or

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

• -β-CyD with cholesterol is thought to play a critical role. However, chemical modification of CyDs may often change the inclusion ability to guest molecules. Therefore, to examine whether Lac-β-CyD has inclusion ability or not, we preliminary determined the dissociation constant of Lac-β-CyD with

• preliminary result suggests that the inclusion ability of Lac-β-CyD is still maintained. Cytotoxicity of Lac-β-CyD To reveal the cytotoxicity of Lac-β-CyD, we examined the WST-1 method (Figure 3). Here, we used U18666A-treated HepG2 cells as NPC-like cells, because U18666A inhibits an intracellular

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• interactions and reduced oral absorption that prevent their use in therapy [4]. On the other hand, peptidomimetics offer the advantage of nearly countless manipulations in order to control the biological functions, stability, potency, and ADME parameters [5]. In particular, the inclusion of the amino acidic

A comprehensive study of olefin metathesis catalyzed by Ru-based catalysts

• Albert Poater and
• Luigi Cavallo

Beilstein J. Org. Chem. 2015, 11, 1767–1780, doi:10.3762/bjoc.11.192

• and the conclusion was that any generalization could be done about the side/bottom stability of the coordination intermediate, as well as it is not possible for the first Grubbs catalysts [9]. Overall, the inclusion of a polar solvent and the absence of strong steric effects, i.e., with less bulky

Synthesis of racemic and chiral BEDT-TTF derivatives possessing hydroxy groups and their achiral and chiral charge transfer complexes

• Sara J. Krivickas,
• Chiho Hashimoto,
• Junya Yoshida,
• Akira Ueda,
• Kazuyuki Takahashi,
• John D. Wallis and
• Hatsumi Mori

Beilstein J. Org. Chem. 2015, 11, 1561–1569, doi:10.3762/bjoc.11.172

• ][17], ethylenedioxy [18], and pyrazino [19]), due to the difficulty of chiral-crystal growth. In order to improve the crystallinity, the inclusion of hydroxy groups in the BEDT-TTF molecule has been postulated to produce hydrogen bonding interactions between electron-donor molecules, electron-acceptor

Why base-catalyzed isomerization of N-propargyl amides yields mostly allenamides rather than ynamides

• Armando Navarro-Vázquez

Beilstein J. Org. Chem. 2015, 11, 1441–1446, doi:10.3762/bjoc.11.156

• that computed for amide 6. Note, however, that whereas inclusion of solvation increases the allenamide → ynamide gap, the allencarbamate → yncarbamate gap is decreased from 3.4 to 2.6 kcal/mol (Table 2). According to Hsung and coworkers, N-propargylphthalimide does not lead to either allenamides or