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

• solution, the complexation is enthalpically and entropically driven. In addition, complementary interactions (e.g., van der Waals forces, H-bonds, etc.) appear between the CD and the guest. The non-polar suitably-sized guest may be bound in numerous molar ratios (e.g., 1:1, 2:1, 1:2, etc.). In all cases

• , the knowledge of the binding constants (Kass) is crucial because these values provide an index of host–guest binding forces. CDs can also form exclusion complexes where the CDs are bound to the guest through a H-bond network. For instance, the complexation of [PMo12O40] anion by β- and γ-CD results in

• complexation of endogenous substances are of potential interest for many applications. Biomolecule/cyclodextrin inclusions complexes Native and modified CDs can be used to complex certain chemicals produced naturally present in cells and tissues (i.e., endogenous substances). Indeed, CDs are able to form

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

• complexation. In that way, it was possible to decorate CDVs with carbohydrates [32][33], with peptides [34], and also with DNA [35]. Moreover CDVs were also shown to form very dense membranes in combination with phospholipids and cholesterol [36]. Previous studies also showed promising results for PDT

• the presence of the aggregated form of AdSq (see Figure S2 in Supporting Information File 1). The fluorescence spectra show a saturation of the intensity maximum for a concentration of 60 µM CDV. Assuming that the accessible concentration of cyclodextrin available for the complexation of guest is only

Radical polymerization by a supramolecular catalyst: cyclodextrin with a RAFT reagent

• Kohei Koyanagi,
• Yoshinori Takashima,
• Takashi Nakamura,
• Hiroyasu Yamaguchi and
• Akira Harada

Beilstein J. Org. Chem. 2016, 12, 2495–2502, doi:10.3762/bjoc.12.244

• decreased with the addition of competitive molecules, indicating that complexation between CD-CTA and the monomer plays an important role in determining polymerization rate. Results and Discussion Preparation of α-CD-CTA We designed a CTA reagent with α-CD or β-CD. Figure 1 illustrates the preparation of α

• inhibiting the molecular recognition of α-CD, the inclusion complexation ratio between the monomer and α-CD-CTA was decreased, which lead to lower yields and higher molecular weight of the resulting polymers due to preceding free radical polymerization. In the reaction of AAm monomer, which has a low

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• explored in terms of their NMR and complexation behavior. However, unsymmetrically substituted piperazines are rarely investigated [12][13]. N,N’-Unsymmetrically functionalized piperazines are the basis of the development of our new building blocks. In this case, one of the nitrogen atoms is used for the

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

• very strong complexes with not only the native but with the substituted CDs, too. Although a solvent-free synthetic method does not solve the problem of complexation but the reduced amount of reagents can simplify the purification. Heptakis(6-azido-6-deoxy)-β-CD is the precursor to per-6-amino-β-CD

• /halogen molar ratios did not change such extent (Table 1). This can be explained satisfactorily by the complexation of the leaving group which might have high affinity to the CD cavity [3][25][26] preventing its departure from the reaction centres resulting in steric blocking. While the halogen → azide

• . The resulting crude mixture was only partially soluble in methylene chloride and MeOH precipitation gave a difficult-to-filter product, which still contained at least one mole of complexed DDS. This complexation resulted in not only technical difficulties, but also confounded the removal of impurities

Diels–Alder reactions in confined spaces: the influence of catalyst structure and the nature of active sites for the retro-Diels–Alder reaction

• Ángel Cantín,
• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2016, 12, 2181–2188, doi:10.3762/bjoc.12.208

• acid sites in the solids We have prepared Ti-Beta [31], Sn-Beta [32] and Al-Beta (Si/Al = 50) [33] considering that Lewis acid catalyzes the DAR [1]. This effect is known to occur by complexation of the carbonyl group of the dienophile with the Lewis acid that increases the electron deficiency of the

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

• material was initially activated by NaHCO3. Discussion To explain the adsorption performance of polyBTCA-CD, a chemisorption mechanism involving several interactions can occur including ion exchange, electrostatic interactions, inclusion complexation and/or precipitation [3][12][13][14][15][16]. The

Amidofluorene-appended lower rim 1,3-diconjugate of calix[4]arene: synthesis, characterization and highly selective sensor for Cu²⁺

• Rahman Hosseinzadeh,
• Mohammad Nemati,
• Reza Zadmard and
• Maryam Mohadjerani

Beilstein J. Org. Chem. 2016, 12, 1749–1757, doi:10.3762/bjoc.12.163

• mode of complexation of L with Cu2+, 1H NMR titrations were carried out (Figure 7). Upon the initial addition of Cu2+ into the CD3CN solution of L, signals related to OH phenolic groups (Hb) and amidic protons (Ha) were first broadened and then finally disappeared. Furthermore, the signals of Ar–CH2

• (Hd, He) and –O–CH2 (Hf) porotons, which are close to the binding site of receptor L were affected and downfield shifted by the complexation of L with Cu2+. A detailed analysis of the 1H NMR spectra reveals the significant changes of almost all the other proton signals in the ligand. For instance, the

• indicated that the synthesized chemosensor L has a lower LOD and a higher Ka in comparison with other chemosensors, which shows a stable and selective complexation with Cu2+. Conclusion In this study, the amidoflourene-appended calix[4]arene 1,3-diconjugated L was synthesized as an efficient colorimetric

Cp₂TiCl/D₂O/Mn, a formidable reagent for the deuteration of organic compounds

• Antonio Rosales and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2016, 12, 1585–1589, doi:10.3762/bjoc.12.154

• cyclic voltammetry, theoretical calculations and electro-paramagnetic resonance techniques studies [28][34]. These results are in agreement with the previously reported results by Wood et al. [35] and Renaud et al. [36] describing the effect of complexation with a Lewis acid on the strength of the O–H

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• contribute significantly to their structural and physical properties as well as to their biological activity [1][2][3]. Heterocycles can for example be involved in cation complexation as known for ionophoric polyethers or introduce conformational rigidity into a molecule, which is crucial for target binding

Flow carbonylation of sterically hindered ortho-substituted iodoarenes

• Carl J. Mallia,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1503–1511, doi:10.3762/bjoc.12.147

• aryl halide, an associative mechanism for the complexation of carbon monoxide on the d8 square planar intermediate would occur prior to the key migratory insertion step. In the complex, the aryl group would be oriented perpendicularly to the plane to minimise steric interactions thus placing the ortho

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• from the secondary phosphines by deprotonation with KH in refluxing THF. The NeoPHOX ligands, which were obtained by this route in high overall yield, proved to be air and moisture stable and could be obtained in analytically pure form by simple filtration through silica gel [19]. Complexation with [Ir

• –76% yields (Scheme 7). From these ligands a library of iridium catalysts was prepared by complexation with bis(1,5-cyclooctadiene)diiridium(I) dichloride, followed by anion exchange with NaBArF. Comparative hydrogenation studies with iridium catalysts derived from 1st and 2nd generation NeoPHOX

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• reagents, also used as solvent, were cyclopentane, cyclohexane and cycloheptane. Two factors are noteworthy in this work. Unlike the carboxamide complexes (R)-18 and (S)-18 previously reported by Doyle and coworkers (Table 2), where the complexation of the chiral ligand to rhodium atoms occurs through the

A modular approach to neutral P,N-ligands: synthesis and coordination chemistry

• Vladislav Vasilenko,
• Torsten Roth,
• Clemens K. Blasius,
• Sebastian N. Intorp,
• Hubert Wadepohl and
• Lutz H. Gade

Beilstein J. Org. Chem. 2016, 12, 846–853, doi:10.3762/bjoc.12.83

• 7 were prepared. It should be noted that ligands 2, 5, and 7 feature a distinct shift of the 31P NMR resonance to lower fields upon complexation of a rhodium(I) or iridium(I) center, whereas a shift to higher fields is observed for ligand 3 [11]. We were able to obtain single crystals of compounds

• ,N-ligand scaffold, ligands 2a and 5 were reacted with the Lewis-acidic precursors [Cp*RhCl2]2 and [Cp*IrI2]2 (Figure 3). As has been pointed out for the analogous Rh(I) and Ir(I) compounds, complexation is accompanied by a 31P NMR shift to lower fields (from 49.7 ppm to 108.9 ppm and 80.6 ppm for

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

• M. Emin Cinar,
• Bernward Engelen,
• Martin Panthöfer,
• Hans-Jörg Deiseroth,
• Jens Schlirf and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 813–824, doi:10.3762/bjoc.12.80

• analyzing the harmonic vibrational frequencies, using analytical second derivatives. To predict the energies plausibly, as recommended for organometallic compounds, single point calculations with M06 functional [52] were performed using the same basis sets (Scheme 6). Complexation of the metal enolate E

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• complexation is as expected. The smallest of guests form 1:1 complexes, whereas with guests larger than ethane a 2:2 or 2:1 capsular complex is formed. In contrast the binding profile of TEMOA is non-monotonic: very small and medium sized guests form 1:1 complexes, whereas small and large guests form dimeric

• facet of these collaborations is the SAMPL exercise in which we and other supramolecular chemists a priori determine the thermodynamics of complexation for a series of processes, and keep the results under wraps whilst computational groups around the world attempt to predict the data [52]. This

Creating molecular macrocycles for anion recognition

• Amar H. Flood

Beilstein J. Org. Chem. 2016, 12, 611–627, doi:10.3762/bjoc.12.60

• counter cations, their binding constants were not constant! In our case, when we changed concentrations, the binding constants for the 1:1 triazolophane–chloride complexes were not constant. We ended up taming our menagerie of ion pairing and complexation equilibria in a tour de force thermodynamics study

• points after 0.5 equiv of chloride are added, which is the equivalence point for the 2:1 complex. We observe the ion pairing of the TBA+ with the 1:1 complex in the cation’s α proton (≈3 ppm), which has an inflection point at 1 equiv. Consistent with its complexation as a 1:1:1 species, the diffusion NMR

• fitting of 1H NMR titration data. Both software have their limitations but their usage as tools to unravel complex equilibria is without parallel. Cooperativity of ion–pair complexation The most recent undertaking of ion pairing is to make it a feature and to examine, in glorious detail, how ion pairs can

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

• 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

• (TdR) as the main product was obtained [26]. The use of a delivery system could be a method to improve the photochemical behavior and to prevent the degradation of the thiobase [27]. In fact, literature suggests that one method to avoid the drug degradation is the complexation with CDs, and, as

• get further insight into the complexation constants, the thermodynamic stability of the 2-HP-CD complexes was studied as described in [40], using Equation 2 and the obtained results are reported in Figure 4D. Interesting results were obtained (Figure 4D) by comparing experimental data with theoretical

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

• known that β-CD has the ability to preferably complex the cyclic form of rhodamine B [21], complexation may play a role in the stabilization of the lactam form of the rhodamine-appended CD derivative. All this information taken together confirms the presence of the product/conjugate and add to the

• scaffold. Because of the chirality of the cyclodextrin part, the two phenyl rings of the xanthene moiety are formally diastereotopic, and consequently, anisochronous even without any complexation. This fact can be proven by recording the 1H NMR spectrum of the Rho-β-CD in deuterated DMSO, a solvent known

• model for the supramolecular assembly is also in agreement with previous data about the inclusion complexation of organic dyes with β-CD dimers [26]. In more detail, the analysis of the 2D ROESY spectrum reveals that the methyl units of the rhodamine side chains that resonate at 0.81 ppm (the side

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

• derivatives [3] which have been prepared up to now can be divided into several groups according to their intended use. The largest group is the one containing CD derivatives with modified complexation properties, used mainly as solubilizers and/or stabilizers in pharmaceutical, cosmetic, agricultural and food

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• . Alternatively, for a similar 1,3-shift, Nolan and coworkers proposed two sequential 1,2-shifts to occur after π-complexation of the triple bond by Au(I) [49]. Methanolysis (NaOMe/MeOH) of cyclopentenylacetate 50 afforded cyclopenta[f]indolinone 48 (96%). Conclusion It was our goal to explore how to efficiently

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

• CD derivatives, CD grafted materials and polymers. Mechanochemical methods have successfully furnished greener, solvent-free syntheses and efficient complexation, while flow microreactors may well improve the repeatability and optimization of critical synthetic protocols. Keywords: ball milling

• facilitate the purification steps [9]. Noteworthy examples are the mechanochemical derivatization of saccharides [10][11], the functionalization of CDs and their complexation with organic molecules [12]. Solid state organic reactions using CD cavities as nanoreactors have also been reported [13]. Among non

• entrance via confocal laser scanning microscopy [30]. Several types of dye moiety/CD derivatives have been suggested as "switch on" or "switch off" fluorescent chemical sensors. In these systems, the complexation with a guest molecule allows to enhance or decrease the fluorescence intensity. Two water

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

• sequential binding of two CD molecules to one chlorpyriphos molecule. Compared to other pesticides, the low K1 values observed for chlorpyrifos with α-CD and β-CD may lie in the steric hindrance resulting from the three chlorine atoms, which may inhibit the complexation. No correlation was found between the

• (Scheme 1). However, the outcome of this complexation strongly depends of the host–guest system. Indeed, α-CD displays a weak inhibitive effect on parathion hydrolysis whereas a mild promotive effect is noticed for methyl parathion and paraoxon hydrolysis. β-CD inhibits parathion and methyl parathion

• binding constants of β-CD/soman and β-CD/pinacolyl alcohol complexes were then investigated. The similar data obtained proved that the pinacolyloxy group was at the origin of the strong complexation of soman into the β-CD cavity. They then focused their work on the interaction between soman and β-CD due

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

• Sciences and Veterinary Medicine “King Mihai I of Romania” - Timişoara, Calea Aradului 119, 300645 Timişoara, Romania 10.3762/bjoc.12.20 Abstract The thermal and oxidative stability of Atlantic salmon oil (Salmo salar L.) as well as its β-cyclodextrin (β-CD) complexation ability has been verified for the

• encapsulated [37][38][39][40][41][42]. Thus, the access of oxygen to the reactive center is drastically reduced and the stability of unsaturated fish oil components is enhanced. On the other hand, the water solubility of fish oil components can be enhanced by CD complexation. The combination of CD complexation

• and microencapsulation of fish oil is also used [43][44]. However, no CD complexation studies on ASO have been published up to now. The goal of this study was to evaluate the thermal and oxidative stability of ASO (Salmo salar L.) and the β-CD complexation by using co-crystallization and kneading

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

• complexation and, indeed, multiple guests could be measured at once [14]. The HPLC method of determining complexation ΔΗ° values was extended by Vincent Kwan to hydrogen bonding host–guest complexes [15]. Molecular tweezers that complex adenine and analysis of binding interactions The idea of incorporating

• host–guest chemistry [33]. Perry Corbin, Steven Dell, and I were pleased to work with Frank Klärner and his group on linking a host analogous to 20 to silica and to study the solvent effects on host–guest complexation chemistry using our HPLC method [34]. Many of the molecular tweezers described above