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

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• pharmaceutical areas not only to enhance water solubility and reduce immunogenicity but also to increase in vivo circulation half-life by preventing enzymatic degradation and renal clearance [4]. Numerous examples of bioconjugation with PEG have been reported including, among others, proteins located in

Substitution effect and effect of axle’s flexibility at (pseudo-)rotaxanes

• Friedrich Malberg,
• Jan Gerit Brandenburg,
• Werner Reckien,
• Oldamur Hollóczki,
• Stefan Grimme and
• Barbara Kirchner

Beilstein J. Org. Chem. 2014, 10, 1299–1307, doi:10.3762/bjoc.10.131

• generation of these kinds of rotaxanes – showed water solubility and contained appropriate locations for substitutions in order to improve its properties [16]. Theoretical investigations on rotaxanes accompanied or even preceded experimental work frequently, thus showing that theory offers many viable tools

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• , possible reduced water solubility restricts their drugability. In the last years, remarkable efforts have been made to modulate the bioavailability of peptides. Basically, delivery challenges of peptide drug candidates can be overcome by chemical modification or innovative formulation techniques such as

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• positively charged centers in oligonucleotide analogues results in increased water solubility and higher thermal stability of complementary duplexes of such oligonucleotide mimics with nucleic acids [14][15]. Some conformationally restricted protonated PNA or pyrrolidine oligonucleotide mimics exhibit

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• inexpensive phosphites (P(OR)3) have only been applied as phosphine substitutes in one single example: Beal [46] utilized tri-isopropylphosphite in a Mitsunobu condensation of a guanine-derived nucleoside analog with benzylic alcohols providing simplified byproduct separation through improved water solubility

N,N'-(Hexane-1,6-diyl)bis(4-methyl-N-(oxiran-2-ylmethyl)benzenesulfonamide): Synthesis via cyclodextrin mediated N-alkylation in aqueous solution and further Prilezhaev epoxidation

• Julian Fischer,
• Simon Millan and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2834–2840, doi:10.3762/bjoc.9.318

• with two equivalents of randomly methylated β-cyclodextrin (β-CD) to give 3β, water solubility could be increased distinctively. Characterization of the inclusion complex of β-CD with 3 in D2O solution was conducted using 2D NMR ROESY spectroscopy (Figure 1). Thereby, proton signals at 7.0 and 7.4 ppm

• -agglomeration of the tosyl groups of 3 with β-CD. Further confirmation of these findings is a perceivable downfield shifting of the proton signals of 3β compared to 3 suspended in D2O, since they are magnetically shielded by the β-CD cavity. Additionally, the water solubility of 4 is limited as well (3.83 g L−1

• ]. Therefore, the water solubility of 4 was increased by addition of α-CD (4α). 2D NMR ROESY spectroscopy was also performed for 4α. As expected, the protons of the allyl-group at 5.9 ppm, 5.1 ppm and 4.0 ppm correlate with the α-CD protons in the range of 3.9 to 3.5 ppm (Figure S1, Supporting Information File

Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

• Julian Fischer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2803–2811, doi:10.3762/bjoc.9.315

• found. This effect is a result from insoluble to soluble transition which depends on the shape and size distribution of polymer particles. Furthermore, 10 also showed an increase in water solubility by adding 150 mol % of RAMEB-CD 10β. Hereby, a cloud point of about 49 °C on heating and 29 °C on cooling

Synthesis and testing of the first azobenzene mannobioside as photoswitchable ligand for the bacterial lectin FimH

• Vijayanand Chandrasekaran,
• Katharina Kolbe,
• Femke Beiroth and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2013, 9, 223–233, doi:10.3762/bjoc.9.26

• was found to be highly effective, yielding a long-lived (Z)-isomer. Both isomers, E and Z, show excellent water solubility and were tested as inhibitors of mannoside-specific bacterial adhesion in solution. Their inhibitory potency was found to be equal and almost two orders of magnitude higher than

Asymmetric synthesis of host-directed inhibitors of myxoviruses

• Terry W. Moore,
• Kasinath Sana,
• Dan Yan,
• Pahk Thepchatri,
• John M. Ndungu,
• Manohar T. Saindane,
• Mark A. Lockwood,
• Michael G. Natchus,
• Dennis C. Liotta,
• Richard K. Plemper,
• James P. Snyder and
• Aiming Sun

Beilstein J. Org. Chem. 2013, 9, 197–203, doi:10.3762/bjoc.9.23

• -molecule antiviral hits resident in host cells [13]. One such molecule recently described is benzimidazole 1 [14] (Figure 1). Although the compound is active in vitro against a number of different para- and orthomyxoviruses, 1 has poor water solubility (<15 μg/mL), which may contribute to its low oral

A chemist and biologist talk to each other about caged neurotransmitters

• Graham C.R. Ellis-Davies

Beilstein J. Org. Chem. 2013, 9, 64–73, doi:10.3762/bjoc.9.8

• "? Chemist: It is well known in the pharmaceutical industry that water solubility is one of the true challenges for drug development. Often drugs are built up around rigid hydrocarbon scaffolds, such substances are inherently hydrophobic. The same issue applies to caged compounds, as in these we add aromatic

• rings to produce photosensitivity. The simplest type of caging chromophores are quite water soluble (Table 1), but even modest derivatives can lose water solubility precipitously! With drugs this is often counteracted by adding betacyclodextrin to the formulation, and with caged compounds, a small

• of an issue. It is important for chemists to know that we usually make up stock solutions that are at least 10 times higher than those used, therefore we would look for water solubility in the 50–100 mM range. Chemist: This can easily be achieved for caged transmitters with simple chromophores such

Theoretical study on β-cyclodextrin inclusion complexes with propiconazole and protonated propiconazole

• Adrian Fifere,
• Narcisa Marangoci,
• Stelian Maier,
• Adina Coroaba,
• Dan Maftei and
• Mariana Pinteala

Beilstein J. Org. Chem. 2012, 8, 2191–2201, doi:10.3762/bjoc.8.247

• increasingly large-scale expansion of this phenomenon [3]. Consequently, the development of new therapeutic conjugates able to combine new antifungal properties with water solubility of the drug has become a major direction of research in the field of antifungal therapy. In this respect, one of the expected

Cyclodextrin-based nanosponges as drug carriers

• Francesco Trotta,
• Marco Zanetti and
• Roberta Cavalli

Beilstein J. Org. Chem. 2012, 8, 2091–2099, doi:10.3762/bjoc.8.235

• low water solubility (1.85% w/v at 25 °C) and is toxic when injected intravenously. Consequently, many chemical modifications of cyclodextrins have been studied in an attempt to overcome their limitations and improve their technological characteristics. Well-structured molecules as well as random

• summarise their potential capacities by classifying nanosponges according to their main applications, and some examples are reported as case studies. Solubility enhancement One of the greatest limits to the development of various pharmaceuticals is the low water solubility of many drugs. About 40% of new

Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

• Nikolay T. Tzvetkov,
• Harald Euler and
• Christa E. Müller

Beilstein J. Org. Chem. 2012, 8, 1584–1593, doi:10.3762/bjoc.8.181

• the physicochemical properties of imidazo[5,1-c][1,2,4]triazine-3,6-dione derivatives we determined water-solubility, log P, and pKa values for compound 25 as a representative of this new class of heterocyclic compounds. Water solubility at physiological pH of 7.4 was found to be 47 µg/mL, which is a

Cyanoethylation of the glucans dextran and pullulan: Substitution pattern and formation of nanostructures and entrapment of magnetic nanoparticles

• Kathrin Fiege,
• Heinrich Lünsdorf,
• Sevil Atarijabarzadeh and
• Petra Mischnick

Beilstein J. Org. Chem. 2012, 8, 551–566, doi:10.3762/bjoc.8.63

• years their importance for special biochemical or pharmaceutical applications, such drug delivery or biosensor technology, has grown, due to their special properties such as water solubility, low viscosity and film formation [24][25][26][27]. Pullulan is a homopolysaccharide of D-glucose secreted by