The effect of cyclodextrin complexation on the solubility and photostability of nerolidol as pure compound and as main constituent of cabreuva essential oil

• Joyce Azzi,
• Pierre-Edouard Danjou,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2017, 13, 835–844, doi:10.3762/bjoc.13.84

• phase-solubility diagrams were obtained, suggesting the formation of 1:1 CD/Ner inclusion complexes. The solubility of Ner was enhanced by approximately 70-fold in the presence of 10 mM HP-β-CD. Moreover, high EE % values were obtained for 5:1 and 10:1 HP-β-CD:Ner molar ratios. NMR and molecular

• characteristic is their ability to form inclusion complexes with poorly soluble guest molecules which are entrapped in the hydrophobic cavity of CDs. Chemical modifications of the hydroxy groups of CDs can be performed to obtain water-soluble CD derivatives like hydroxypropyl-β-CD (HP-β-CD), methylated CDs

• thus enhancing their biological properties [15][16]. To the best of our knowledge, no literature data reported the encapsulation of Ner in CDs. In this study, for the first time, CD/Ner inclusion complexes were characterized in solution and in solid state. Formation constants (Kf) were determined for

Cyclodextrins tethered with oligolactides – green synthesis and structural assessment

• Cristian Peptu,
• Mihaela Balan-Porcarasu,
• Alena Šišková,
• Ľudovít Škultéty and
• Jaroslav Mosnáček

Beilstein J. Org. Chem. 2017, 13, 779–792, doi:10.3762/bjoc.13.77

• homogenous product, with low polymerization degree, useful for preparation of inclusion complexes. However, for characterization purposes this sample fractionation is useful as long as both fractions are analyzed. MALDI spectra of F2 fractions (Figure 3) are clearly showing that the average number of monomer

Inclusion complexes of β-cyclodextrin with tricyclic drugs: an X-ray diffraction, NMR and molecular dynamics study

• Franca Castiglione,
• Fabio Ganazzoli,
• Luciana Malpezzi,
• Andrea Mele,
• Walter Panzeri and
• Giuseppina Raffaini

Beilstein J. Org. Chem. 2017, 13, 714–719, doi:10.3762/bjoc.13.70

• 7, 20131 Milano, Italy 10.3762/bjoc.13.70 Abstract Tricyclic fused-ring cyclobenzaprine (1) and amitriptyline (2) form 1:1 inclusion complexes with β-cyclodextrin (β-CD) in the solid state and in water solution. Rotating frame NOE experiments (ROESY) showed the same geometry of inclusion for both 1

• explicit water to study the inclusion complexes of two tricyclic aromatic molecules – cyclobenzaprine (1) and amitriptyline (2, Figure 1) – with β-cyclodextrin (β-CD). Previous work already considered certain aspects of the interaction of 2 with β-CD [3][4][5][6][7][8], but no full characterization of the

• those found experimentally. Results and Discussion The guest molecules 1 and 2 form 1:1 inclusion complexes with β-CD in aqueous solution and in the solid state. The Job’s plots are reported in Figure 2. The plots of Figure 2 show that the maximum of the curves is obtained, in both cases, for r = 0.5

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• aqueous medium, which precludes any response to light excitation. Keywords: β-cyclodextrins; fluorescence; photodynamic therapy; photosensitizers; singlet oxygen; xanthene; Introduction Cyclodextrins (CDs) are cyclic oligosaccharides able to form host–guest inclusion complexes with drugs and this

• nitric oxide under illumination with visible light, resulting in amplified cancer-cell mortality [9]. By attaching porphyrin to γ-CD and dimeric β-CD, which are both able to form inclusion complexes with cytotoxic drug molecules such as doxorubicin and paclitaxel, nanocarriers with multimodal therapeutic

Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds

• Sophie Letort,
• Michaël Bosco,
• Benedetta Cornelio,
• Frédérique Brégier,
• Sébastien Daulon,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45

• derivatives. Therefore, the design of new scavengers will require further structural studies on the inclusion complexes and affinity measurements with carefully selected analogs of organophosphates. Conclusion New β-cyclodextrin derivatives were synthesized and their efficiency to degrade the organophosphorus

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• well known [16], rather few examples are known whose excited-state acidity is affected by the formation of inclusion complexes [28][29][30][31][32][33][34]. Remarkably, among the latter, examples of photoacidic hydroxyarenes are rather rare. For example, it was shown that the pKa* of a

Dynamics and interactions of ibuprofen in cyclodextrin nanosponges by solid-state NMR spectroscopy

• Monica Ferro,
• Franca Castiglione,
• Nadia Pastori,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2017, 13, 182–194, doi:10.3762/bjoc.13.21

• formation of a host–guest inclusion complex – does not occur, confirming the situation already described by HR-MAS NMR data for the same system in the gel state [9] and outlining a different scenario on passing from monomeric CD, capable to form well characterized inclusion complexes with IbuH [29][30][31

• -mono-6-amino-6-deoxy-β-CD (GMA-NH2-β-CD) co-polymerized with ethylene dimethacrylate [32]. The corresponding cross-linked polymers are thus decorated with cyclodextrin units, easily accessible to small molecules to give rise to inclusion complexes. This type of polymers showed excellent efficiency as

• formation as the main mechanism of absorption [33]. We may conclude that the type of monomer and the cross-linker agent both play a key role in driving the absorption towards inclusion complexes or segregation in the polymer pores, although a sufficient number of data is still missing to formulate a general

Phosphated cyclodextrins as water-soluble chiral NMR solvating agents for cationic compounds

• Cira Mollings Puentes and
• Thomas J. Wenzel

Beilstein J. Org. Chem. 2017, 13, 43–53, doi:10.3762/bjoc.13.6

• inclusion complexes with CDs and the differing sizes of α-, β- and γ-CD allow the study of substrates of different sizes. Furthermore, the secondary hydroxy groups at the 2 and 3-positions and the primary hydroxy groups at the 6-position of CDs can be derivatized with a variety of functional groups. Such

• that at the primary side. Native, underivatized CDs are effective chiral NMR solvating agents in water [8][9]. Water-soluble substrates with hydrophobic moieties such as aryl rings typically form inclusion complexes by insertion of the aryl ring into the CD cavity. Neutral CDs with permethylated [10

• -containing compounds form inclusion complexes more favorably with the larger β- and γ-cyclodextrins so the general ineffectiveness of P-α-CD-LDS and P-α-CD-HDS for 27–29 is not surprising (Table 5). Both the P-β-CDs and P-γ-CDs are effective at causing enantiomeric differentiation in resonances of 27–29. An

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

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

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• cholesterol [25]. NPC2 interacts with NPC1 and delivers cholesterol to the limiting membranes [25], while β-CDs form inclusion complexes with cholesterol. Hence, β-CDs may have the potential to bypass the functional NPC1 or NPC2 and deliver cholesterol directly to the limiting membranes. Once the cholesterol

Stabilization of nanosized titanium dioxide by cyclodextrin polymers and its photocatalytic effect on the degradation of wastewater pollutants

• Tamás Zoltán Agócs,
• István Puskás,
• Erzsébet Varga,
• Mónika Molnár and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2016, 12, 2873–2882, doi:10.3762/bjoc.12.286

• oligosaccharides consisting of 6–8 glucose units (α-, β- and γ-CD) primarily used in the pharmaceutical, cosmetic and household chemical industry [8]. They form non-covalent inclusion complexes with a great number of the organic contaminants in soil (petroleum hydrocarbons, polycyclic aromatic hydrocarbons, etc

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• great variety of modified CDs has been developed to improve the stability and the solubility of inclusion complexes [8][9][10]. Nowadays, CDs are widely applied in many fields [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] due to their host–guest properties, their origins

• a one-dimensional columnar structure through a combination of intermolecular [C−H···O=Mo] and [O−H···O] interactions [30]. Unfortunately, the natural CDs as well as their inclusion complexes are of limited aqueous solubility leading to their precipitation. Fortunately, native CDs are effective

• useful to form inclusion complexes with a wide range of drugs and become a very valuable tool for the formulator in order to overcome delivery limitations [37][38]. As a result, numerous formulations that use CDs are now on the market worldwide (Table 2). iv) Toxicity and biological effects of native and

A self-assembled cyclodextrin nanocarrier for photoreactive squaraine

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2016, 12, 2535–2542, doi:10.3762/bjoc.12.248

• aqueous solution of the vesicle [30]. The hydrophobic cyclodextrin cavities are well known to form size-selective inclusion complexes with apolar compounds such as adamantane [31]. In several publications, we have shown that CDVs retain this ability by keeping the cavity available for host–guest

Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

• Laszlo Jicsinszky,
• Marina Caporaso,
• Katia Martina,
• Emanuela Calcio Gaudino and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230

• most noted for their ability to form non-covalent associations called “inclusion complexes”. Natural CDs exhibit many favourable properties, which advance their use in a wide range of applications. However, syntheses for many special applications, such as DNA sequencing [4][5], gene delivery [6], and

• because of the high boiling polar aprotic solvents used; their complete removal is a difficult task under laboratory conditions, even at high vacuum. Ball milling is an effective method for the preparation of inclusion complexes which has recently begun to be appreciated by organic chemists for its

Cross-linked cyclodextrin-based material for treatment of metals and organic substances present in industrial discharge waters

• Élise Euvrard,
• Nadia Morin-Crini,
• Coline Druart,
• Justine Bugnet,
• Bernard Martel,
• Cesare Cosentino,
• Virginie Moutarlier and
• Grégorio Crini

Beilstein J. Org. Chem. 2016, 12, 1826–1838, doi:10.3762/bjoc.12.172

• groups and CD cavities, the adsorption mechanism involves four main interactions: ion exchange, electrostatic interactions and precipitation for metal removal, and inclusion complexes for organics removal. In industrial discharge waters, competition effects appeared, especially because of the presence of

• inclusion complexes with PAH guest molecules (organic substances) [3][20]. If the guest compounds present an appropriate molecular size and structure to enter into the CD cavity the more hydrophobic the organic substances, the more stable the inclusion complexes. The material was also able to efficiently

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

• [9]. In fact, in the formation of inclusion complexes [10][11][12] the inner diameter of the cavity of the CDs and the size of the guest molecule play an important role. CDs are often described as a toroid having a large and narrow cavity. The wider side is formed by the secondary 2- and 3-hydroxy

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

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

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

• 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

• stability and the mode of entry of the guest into the host could be obtained by the characterization of the inclusion complexes in solution or in solid state. These three parameters have to be considered because they strongly determine the potential of CDs as scaffolds for the development of enzyme mimics

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

• intermolecular inclusion complexes: pulse field gradient spin-echo NMR experiments (PFGSE NMR) PFGSE NMR experiments were performed in order to estimate and compare the sizes of the supramolecular assemblies formed by the two regioisomers. This technique allows the quantification of the diffusion coefficient (D

• intermolecular inclusion complexes and other assemblies: DLS experiments In order to further investigate the supramolecular structures and the effect of different external stimuli on the size distribution of the supramolecular assemblies a series of DLS experiments were performed. As a first parameter, the

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

• 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

• physical properties and biological activities of hesperetin and naringenin through complexation with cyclodextrins. Computational tools (molecular dynamics simulation) were adopted to first predict the stability of flavanones/CDs inclusion complexes. Consequently, the experimental phase solubility and

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

• structures to be described are the first for crystalline CD inclusion complexes of a representative bioactive steroid and as such, their molecular structures shed some light on the nature of cyclodextrin-steroid interactions, including the phenomenon of ‘mutually induced fit’ accompanying complexation. This

• investigated to gain insight into CD–steroid interaction modes and the stability of the resulting inclusion complexes. These researchers also used Fourier transform infrared spectroscopy (FTIR), thermal analysis and powder X-ray diffraction (PXRD) to infer the existence of solid native CD–steroid inclusion

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

• 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

• 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

• α-D-glucopyranose units and are depicted as α-CD, β-CD and γ-CD, respectively. CDs are able to bind non-polar molecules, including poorly soluble drugs, in their hydrophobic cavities to form binary inclusion complexes [10][11][12]. Inclusion of the drug can result in its enhanced solubility

• steepest descent, and followed by 2000 steps of conjugated gradients to remove bad contacts. Then, the relaxed inclusion complexes were solvated by the TIP3P water molecules with a set distance of 15 Å from the system surface. In aqueous solvation, the system consists of 3,100 water molecules within a 45.0