From N-vinylpyrrolidone anions to modified paraffin-like oligomers via double alkylation with 1,8-dibromooctane: access to covalent networks and oligomeric amines for dye attachment

• Daniela Obels,
• Melanie Lievenbrück and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 1395–1400, doi:10.3762/bjoc.12.133

• poly(ethylene glycol) side chains. Keywords: double alkylation; modified N-vinylpyrrolidone; oligomeric anthraquinone dye; paraffin-like oligomer; radical thiol-ene click reaction; Introduction Poly(N-vinylpyrrolidone) (PVP) is established in daily life due to its high water solubility and

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

• site, whilst maintaining suitable water solubility. Whilst I was busy doing all of this with Jim, Corinne was working in the labs of Neville Kallenbach, then Chair of the Chemistry Department. Corinne and Neville got on like a house on fire, and so I got to know Neville very well. Jim also had a big

• “coated” with water-solubilizing carboxylic acids/carboxylates to bestow good water solubility under basic conditions, and; 2) possessed a rim of hydrophobicity around the entrance to its interior hydrophobic pocket. We envisioned that driven by the hydrophobic effect this host would readily form 1:1

• -solvents for their ability to break capsular complexes revealed that the most powerful solvent for doing so is acetonitrile, whilst solvents such as DMSO and MeOH require three times as much to do likewise [35]. Water solubility can be bestowed in many ways, and although eight negatively charged

Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• silymarin complex for protection of liver damage, and for preventing skin tumor promotion, these compounds have attracted efforts on their total synthesis (e.g., isosilybin) [6] and structural modification [5][7][8][9] to improve their water-solubility, bioavailability and biological activities. Recently

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

• outside of the CDs cavity results in the hydrophilic character of the molecules [6][7][14]. Different chemically modified CDs are known in literature, which are characterized by a higher water solubility compared with the native CDs. These CDs, i.e., 2-HP-CDs, are widely used [15]. An enhanced solubility

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• increases their water solubility. Further it influences the physicochemical and pharmacological properties of these phenols and often reduces their potential toxicity. Moreover, p-hydroxyarylalkyl glycosides are also key starting building blocks for the synthesis of more complex bioactive natural compounds

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

• . Various analytical tests were used to access such information in the cases of pesticides [40][41][42]. Phase solubility diagrams could be obtained if changes of their water solubility upon inclusion occur, whereas differential scanning calorimetry (DSC) could be used to discriminate inclusion complexes

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

• 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

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

• ” chromophores obeying the NEP), were an obvious attempt to provide water solubility to a highly aromatic structure. In Roger Adams’ Laboratory, Craig Vanzyl, Greg Hamilton, and I were able to prepare molecular tweezer 4 and several substituted analogs, but none that were water soluble [9][10]. Fortunately, the

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

• several benefits, the use of these flavonoids is frequently limited by their low water solubility and stability with a consequence of exerting rather low biological activity. The natural β-cyclodextrin (β-CD) is a cyclic oligosaccharide consisting of seven D-glucopyranose units linked by α-(1,4

• pharmaceutical, medicine, cosmetics, food and agriculture [29]. β-CD and its derivatives have been widely used to increase the water solubility, stability, and consequent bioavailability of poorly water soluble drugs [30][31][32], such as β-CD in complex with piroxicam [33] and etodolac [34] and DM-β-CD in

• . The methyl substitution plays an important role in balancing the CD water solubility and its complexing ability [44]. It was previously reported that increasing the degree of methylation up to an optimum level improves the CD aqueous solubility, and the binding of guests to CDs is increased by

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

• coverage showed 7% water solubility. In addition, better optical quality films could be prepared by spin-coating from 3·TM-βCD and 3·TM-γCD THF, DCM, and CHCl3 solutions. The investigated guest 1 proved binding ability to the hosts TM-βCD and TM-γCD, according to our determination of constant stability (Ks

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• and sodium ascorbate, providing the benzo-thiadiazole-based bistriazole (49 and 51, Scheme 17) [37]. With the aid of the hydrophilic character of the ethylene glycol group, both of the bistriazoles can be endowed with water solubility, and can effectively bind Cu(II) and Ni(II) in water. The thiacalix

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

• -dependence of the supramolecular structures, or the pH dependence of water solubility, so as to improve our understanding of their activity as drug delivery systems [19][20] and of the biological fate of the assemblies [21][22]. The balance between the hydrophobic and the polar groups on the two CD rims

Effective ascorbate-free and photolatent click reactions in water using a photoreducible copper(II)-ethylenediamine precatalyst

• Redouane Beniazza,
• Natalia Bayo,
• Florian Molton,
• Carole Duboc,
• Stéphane Massip,
• Nathan McClenaghan,
• Dominique Lastécouères and
• Jean-Marc Vincent

Beilstein J. Org. Chem. 2015, 11, 1950–1959, doi:10.3762/bjoc.11.211

• in the copper(II) complex [CuII(EDA)2(4-benzoylbenzoate)](4-benzoylbenzoate) (1) was chosen to ensure high water solubility. Complex 1 was synthesized in two steps by first preparing the copper(II)-carboxylate dimer [Cu2(4-benzoylbenzoate)4(THF)2] 4 which was obtained by reacting 2 equivalents of the

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• polyesters are significantly more numerous. Nevertheless, as it has been shown in the initial paragraphs, this methodology allows also the facile synthesis of hybrid derivatives of natural compounds with modified physical–chemical properties (i.e., increased water solubility, different supramolecular

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Synthesis of carbohydrate-scaffolded thymine glycoconjugates to organize multivalency

• Anna K. Ciuk and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 668–674, doi:10.3762/bjoc.11.75

• water solubility. Then [2 + 2] photocycloaddition was tested. For irradiation the divalent thymine glycoconjugate 7 was diluted (maximum concentration was 500 μg/1 mL) in a 1:1-mixture of water and acetone in order to favor intramolecular photocycloaddition and avoid the intermolecular reaction. Acetone

• protecting group was observed whereas the Boc-protection remained untouched. Thus, the title glycocluster 13 was obtained in a single deprotection step. The new divalent glycoconjugate 13 shows good water solubility and is thus suited for biological testing. For photodimerization of 13, it was irradiated for

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• cycloaddition (CuAAC) was performed for achieving our synthetic goals (Figure 2) [56][57]. With the objective of increasing water solubility and chemical stability in biological medium, triyne 6b, an analogue of F-BODIPY-based scaffold 6a was prepared by replacing the fluoro groups on the boron center with

• steps from pyrene [53] was reacted with the azide precursors 4, and afterwards deprotected to give the desired tetravalent iminosugars 15 in 37 to 72% yields for the two steps. Despite the good water solubility of alkylated DNJ ligands, pyrene-based multivalent iminosugars were only soluble in water

Functionalized branched EDOT-terthiophene copolymer films by electropolymerization and post-polymerization “click”-reactions

• Miriam Goll,
• Adrian Ruff,
• Erna Muks,
• Felix Goerigk,
• Beatrice Omiecienski,
• Ines Ruff,
• Rafael C. González-Cano,
• Juan T. Lopez Navarrete,
• M. Carmen Ruiz Delgado and
• Sabine Ludwigs

Beilstein J. Org. Chem. 2015, 11, 335–347, doi:10.3762/bjoc.11.39

• polymers from organic solvents to water solubility [44]. “Electro-click” modifications were used for chemically synthesized PEDOT-N3 and copolymers of EDOT-N3 and EDOT with halogens and fluorescent markers [45][46] and of electrochemically synthesized PEDOT-N3 to introduce fluorinated alkyl chains [47]. In

Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

• Hale Ünal,
• Naile Öztürk and
• Erem Bilensoy

Beilstein J. Org. Chem. 2015, 11, 204–212, doi:10.3762/bjoc.11.22

• -shell structures consisting of an inner liquid core (which can be either aqueous or oily depending on the core material) surrounded by a polymeric wall [13][14]. Nanocapsules present many advantages, such as improving poor water solubility, maintaining drug stability by protecting the molecule from the

• inactive carboxylate form in physiological or alkaline pH causing the effectiveness of chemotherapy to be reduced or even inhibited [20]. In addition to its stability problem, CPT has a very poor water solubility which is less than 1 µg/mL and is only soluble in dimethyl sulfoxide (DMSO) and mixtures of

• /or secondary face [25]. It is very common to use CDs as complexing agents with the intention of increasing poor water solubility, maintaining stability, improving permeability and ultimately bioavailability [26]. Furthermore inclusion complexation with CDs can reduce or prevent GI irritation. It is

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• manipulate the charge pattern in the backbone and to enhance nuclease stability. The electroneutral nucleic acid mimic 'peptide nucleic acid' (PNA) [10][11][12] is capable of sequence-specific binding to nucleic acids, but it was found to display limited water solubility and a peptide-like folding behaviour

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

• valuable and sensitive materials [1][2][3]. However, CDs, in particular the most common β-CD, have some limitations both in molecular dimensions and physicochemical properties like water solubility. The low water solubility can present a problem when there is a dedicated use of CDs in a delivery system

• fluorescent labeling, could be an undesired modification of the starting material that can affect some properties such as the water solubility and/or ionizability. Furthermore, the quantification of these (eventual) residual amino groups would be troublesome. The strategy that was applied to overcome the

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• , characterised by the specific fluorescence band sensitive to the pH as well as on the interactions with ds-DNA. Interestingly, all peptide-based phenanthridines revealed excellent water solubility combined with low in vitro toxicity, thus being good candidates for development of new safe fluorimetric DNA and

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

• most eye fungal infections; however, there are resistant species that require higher concentrations than usual [5]. Unfortunately, antifungal eye drops have low ocular bioavailability due to their poor water solubility and known effective eye clearance mechanisms [6]. Thus, after administration of

• per gram of CD, allowing for gels with lower proportions. Ion-sensitive hydrogels synthesized without HPBCDs incorporated a concentration of fluconazole of 0.2% which is limited by its low water solubility. Hence, the incorporation of HPBCDs allows for hydrogels with higher doses. In the present study

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

• isoaromadendrene oxide (22) (up to 0.2%), or the corresponding diols (up to 0.1%). Obtaining of O. basilicum L. essential oil/β-CD complex The O. basilicum L. essential oil/β-CD complex was obtained by using the controlled crystallization method from an ethanol/water suspension (due to the lower water solubility

• complexation process, was 74.2%. This relatively high recovery yield for the β-CD complex can be explained by the lower water (as well as ethanol/water) solubility. The quality of the essential oil/β-CD complex formation was sustained by the morphology of the complex crystals, evaluated by scanning electron

• (Fluka Chemie AG). Methods Synthesis of an O. basilicum L. essential oil/β-CD complex The method used to obtain the essential oil/β-CD complex was the crystallization from a ethanol/water solution. Here, a mass of β-CD hydrate was suspended (due to the lower water solubility of β-CD) in distilled water

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

• cell defense and cell protection from oxidative conditions [15]. Though several pharmaceutical uses of fisetin are possible, the application is frequently confined by its low water solubility (<1 mg/g) [16]. β-Cyclodextrin (β-CD, Figure 2) is a cyclic oligosaccharide composed of seven α-D-glucopyranose