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

Anomalous diffusion of Ibuprofen in cyclodextrin nanosponge hydrogels: an HRMAS NMR study

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

Beilstein J. Org. Chem. 2014, 10, 2715–2723, doi:10.3762/bjoc.10.286

• potential of CDNS as drug carriers has been adequately underlined and recently reviewed in this journal [19]. Indeed, CDNS can encapsulate either lipophilic or hydrophilic active pharmaceutical ingredients, protect them against undesired degradation, enhance water solubility when necessary, facilitate their

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

• contrast properties, raising increasing attention [3][6][7][9][10][11][12][13][14]. Compared with other multifunctional nanocarriers reported in the literature, polymeric micelles formed by amphiphilic block copolymers (ABC) may possess many advantages including water-solubility, nontoxicity, selectivity

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

• order to have good water solubility, selectively modified (methylated) CDs are mostly desired [3]. Among the selectively modified CDs, mono-substituded CD derivatives do not only have self-assembly properties, but also have a good water solubility, allowing passive diffusion across a membrane through

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

• considered for comparison with systems where the water-soluble phosphane and the polymer were added separately. Depending on the amount of 1, CD-substituted phosphane-functionalized polymers 2b and 2c (Scheme 1) were obtained. To ensure the water solubility of the resulting polymers and remove the remaining

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

• 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

• purely fictive. Indeed, the combination of advantages is often reported. i) Improvement of water-solubility of organic biocides Commonly, biocides are used in aqueous solution. However, the most highly effective organic biocides have an extremely low water-solubility. Therefore, additives (e.g

• complexation, all organic biocides developed in the following sections also present an enhancement of their water-solubility in addition to the other benefits highlighted. The methyl N-(1H-benzimidazol-2-yl)carbamate (named carbendazim, see Figure 1) was used to illustrate the effect of CDs on its aqueous

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

• high water solubility was obtained and fully characterized both as for its chemical structure and for its capability to encapsulate substances. Fluorescein was used as probe molecule to test the complexation properties of the new material. Keywords: β-cyclodextrin; complexation; gelation

• . Complexation properties and water solubility make CDs very interesting materials especially for pharmaceutical applications, due to their capability to solubilize lipophilic drugs, but also for environmental remediation and as supramolecular carriers in a number of synthetic procedures ranging from

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• reagents like dansyl chloride [27] or p-chlorophenylalanine containing tags [23]. Nevertheless, BPT (1) shows sufficient water solubility when working in aqueous solutions with low amounts of organic co-solvent. For instance during implementation of CuAAC we use 3.5% DMSO and 4.5% t-BuOH in our protocol

A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

• Chrysie Aggelidou,
• Theodossis A. Theodossiou,
• Antonio Ricardo Gonçalves,
• Mariza Lampropoulou and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 2414–2420, doi:10.3762/bjoc.10.251

• in terms of water solubility and lack of aggregation. Keywords: cyclodextrins; PDT; protoporphyrin IX; prodrug; δ-aminolevulinic acid; Introduction Porphyrins have long been used as agents for tumor photodiagnosis (PDD) and photodynamic therapy (PDT) because of their preferential accumulation in

• transporting the chemotherapeutic agent tamoxifen intracellularly to engage its targets while simultaneously acting as a PS. In this sense we created a bimodal system with adequate water solubility (several μM) able to inflict significant chemo- and phototoxicity on cancer cells. One additional benefit of

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

• limited water solubility, stability and poor bioavailability [8][9]. Thus, their encapsulation may enhance their apparent solubility without losing their structural integrity and bioactivity. During the past years, cyclodextrins (CDs) have been widely used as encapsulating agents to enhance the solubility

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• , GIbu) and spacers [Fmoc-(1S,2S)-2-aminocycolpentanecarboxylic acid or (3R,4S)-3-(Fmoc-amino)-1-trifluoroacetylpyrrolidine-4-carboxylic acid] [43] according to the previously published protocol [26][27][31]. Lysine was included at both C- and N-termini to improve the water solubility. After the

Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

• Meriem Smadhi,
• Sophie de Bentzmann,
• Anne Imberty,
• Marc Gingras,
• Raoudha Abderrahim and
• Peter G. Goekjian

Beilstein J. Org. Chem. 2014, 10, 1981–1990, doi:10.3762/bjoc.10.206

• known to significantly modify the HOMO–LUMO orbital energies, and thus change the redox potentials [31][32][33][34]. It also shifts the spectroscopic absorption and emission wavelengths and can lead to a phosphosrescence emission [33]. Additionally, an aza-aromatic core would improve water solubility by

• modifying π–π-interactions and by favoring hydrogen-bonding to water. These compounds also lack the hydrophobic peripheral benzene units of the previous glycoasterisk ligands. They were replaced with a methylene-triazole linker in order to increase water solubility and to modulate the degree of flexibility