Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier

• Kayoko Hayashida,
• Taishi Higashi,
• Daichi Kono,
• Keiichi Motoyama,
• Koki Wada and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2014, 10, 2756–2764, doi:10.3762/bjoc.10.292

• such as polyethylene glycol (PEG). On the other hand, PEGylated liposomes have been utilized as a representative anticancer drug carrier. However, little is known about the formation of CD PPRX with PEGylated liposome. In the present study, we first report the formation of CD PPRX with PEGylated

• liposome and evaluate it as a sustained release drug carrier. PEGylated liposome encapsulating doxorubicin was disrupted by the addition of α-CD. Meanwhile, γ-CD included two PEG chains and/or one bending PEG chain of PEGylated liposome and formed PPRX without the disruption of the membrane integrity of

• et al. have reported that a number of α-CDs spontaneously thread onto polyethylene glycol (PEG) and form necklace-like supramolecular assemblies [6][7]. The latter are referred to as polypseudorotaxanes (PPRXs), since the release of α-CD from the polymer chain can be achieved upon dissolution in

Synthesis of a resin monomer-soluble polyrotaxane crosslinker containing cleavable end groups

• Ji-Hun Seo,
• Shino Nakagawa,
• Koichiro Hirata and
• Nobuhiko Yui

Beilstein J. Org. Chem. 2014, 10, 2623–2629, doi:10.3762/bjoc.10.274

• , e.g., α-cyclodextrin (α-CD), threaded on a linear guest molecule, e.g., poly(ethylene glycol) (PEG) [1]. The threaded α-CD molecules are known to be reversibly disassembled when a cleavable end-capping group was introduced in the PEGs, and the cleavable reaction was triggered by proper signals [2][3

•  3 shows the results of the SEC analysis of the synthesized polymers. Although a slight degradation of PRX was observed (disassembled α-CD at 42 min), C12-Bu12 and C12-Bu12-MA12 show shorter elution times compared to PEG, which indicates that the molecular weight is increased due to the formation of

• an inclusion complex of PEG with ca. 50 α-CDs. The degradation nature of C12-Bu12-MA12 was confirmed after the treatment with DTT. As shown in Figure 3, the PRX SEC signal almost disappeared, and a large intensity of low molecular weight signals was observed within 40–50 min. The low molecular weight

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

• oven at 70 °C. DMF solutions of the samples (3 mg/mL) were filtered through 0.45 μm PTFE membrane filters. Calibration was obtained with PEG/PEO molecular weight standards. All Raman measurements were carried out on dried samples deposited on a glass slide in air and at room temperature. Spectra were

Synthesis of graft polyrotaxane by simultaneous capping of backbone and grafting from rings of pseudo-polyrotaxane

• Kazuaki Kato,
• Katsunari Inoue,
• Masabumi Kudo and
• Kohzo Ito

Beilstein J. Org. Chem. 2014, 10, 2573–2579, doi:10.3762/bjoc.10.269

• (PEG) and the formation of inclusion complexes with α-cyclodextrin (α-CD). PEG with multiple functional groups at each end was prepared by the condensation of PEG-amine and D-gluconic acid; the PEG derivative formed an inclusion complex with α-CD. The polymerization of multiple hydroxy groups at the

• backbone ends resulted in a star-shaped end group, which served as a bulky capping group to prevent dethreading. In contrast, PEG with only one hydroxy group at each end did not produce polyrotaxanes, indicating that single PCL chains were too thin to confine α-CDs to the complex. In addition, the grafting

• form an inclusion complex with α-CD, indicating that the PCL chains at the ends of PEG cannot prevent the dethreading of the CDs. We demonstrated the complexation between α-CD and PCL-PEG-PCL triblock copolymers. The triblock copolymer was synthesized by the ring-opening polymerization of ε

Loose-fit polypseudorotaxanes constructed from γ-CDs and PHEMA-PPG-PEG-PPG-PHEMA

• Tao Kong,
• Lin Ye,
• Ai-ying Zhang and
• Zeng-guo Feng

Beilstein J. Org. Chem. 2014, 10, 2461–2469, doi:10.3762/bjoc.10.257

• to not only small guest molecules, but also to linear polymeric guest molecules. They can self-assemble into novel inclusion complexes (ICs), or polypseudorotaxanes (PPRs) and polyrotaxanes (PRs) end-capped by bulky stoppers. For example, α-CDs typically include PEG, but not PPG, β-CDs contain PPG

• instead of PEG, and γ-CDs accommodate either single-chain PPG or double-chain PEG [1]. The driving force behind the self-assembly is mostly ascribed to a suitable fit between the cross-sectional area of the incoming polymer chain and the cavity size of the CDs [2]. However, the cavity shape and size of

• first PPRs (comprised of γ-CD and PEG) as early as the 1990s. The γ-CD-based PPRs with designated supramolecular structure have been seldom prepared as compared with the α-CD- or β-CD-based PPRs [5][6][7][8][9][10][11][12][13]. Besides the typical double-chain stranded PPR showing a characteristic

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• (BS(PEG)5) linker was used to rule out the interference of the spacer (details are reported in Supporting Information File 1). ELISA analysis using HSA conjugates as coating reagent demonstrated that the conjugated monomer 1 and the dimer 2 at the present dose elicited extremely low levels of

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• , each holding 10 µM of DNA (by UV spectroscopy at 260 nm prior to dilution). For the annealing step, aliquots (1 µL, containing each 10 pmol, ca. 125–250 ng of DNA) were combined from each of the stock solutions with 5× ISO buffer (8 μL, 25% PEG-6000, 500 mM Tris-HCl, pH 7.5, 50 mM MgCl2, 50 mM DTT, 5

• mM NAD+) and diluted with water (40 μL final volume; final concentrations: 250 nM each oligonucleotide, 5% PEG-6000, 100 mM Tris-HCl, pH 7.5, 10 mM MgCl2, 10 mM DTT, 1 mM NAD+). This mixture was then heated at 95 °C for 5 min, and then slowly cooled (0.1 °C/second) to 42 °C. Aliquots (5 μL) of the

End group functionalization of poly(ethylene glycol) with phenolphthalein: towards star-shaped polymers based on supramolecular interactions

• Carolin Fleischmann,
• Hendrik Wöhlk and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 2263–2269, doi:10.3762/bjoc.10.235

• formation occurred with bare eyes. For this, a molar excess of 16.7 DPE-CD equivalents, which equals 100 CD units per PP moiety, was added to a solution of 0.05 mg/mL PEG-PP at pH 12. In order to compare the complexation ability of DPE-CD to free β-CD, a sample containing the same number of equivalents of

• form, indeed resulted in a stronger decrease of the colorization. In addition to the qualitative evaluation of the complexation behavior of PEG-PP, UV–vis measurements were performed in order to get an insight into the quantitative complex analysis. For native phenolphthalein, the characteristic

• absorption maximum that refers to the pink color in basic solution can be found at 554 nm in corresponding UV–vis spectra. For the phenolphthalein-containing polymer PEG-PP, a slight bathochromic effect is observed, which shifts the maximum to 561 nm. Accordingly, the decrease of the absorption at 561 nm was

Efficient CO₂ capture by tertiary amine-functionalized ionic liquids through Li⁺-stabilized zwitterionic adduct formation

• Zhen-Zhen Yang and
• Liang-Nian He

Beilstein J. Org. Chem. 2014, 10, 1959–1966, doi:10.3762/bjoc.10.204

• through formation of zwitterionic adducts, combining synthetic strategies to ionic liquids (ILs) and coordination. The essence of our strategy is to make use of multidentate cation coordination between Li+ and an organic base. Also PEG-functionalized organic bases were employed to enhance the CO2

• ). Notably, equimolar CO2 absorption was obtained using task-specific ionic liquids (TSILs) with the phosphonium cation containing long alkyl chains and anions derived from AAs (prolinate and methioninate) [36], or AA salts with bulky N-substituents in polyethylene glycol (PEG) solution [37]. However

• method combining the formation of ILs and coordination to achieve equimolar CO2 capture through zwitterionic adduct formation. The essence of our strategy is to make use of the multisite coordination interaction between Li+ and organic bases or PEG-functionalized organic bases. The readily prepared ILs

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• allow to study the effect of substitution on the activity of the complexes. The ether tether in B serves as a model for PEG. The titanocene carboxylates 1–3 were transformed into the corresponding acid chlorides and then reacted with amino azides A–D in the presence of NaH without purification of the

• bulkiness of the ligand’s substituents. It should be noted that polyether groups can be readily incorporated into cationic titanocenes. This suggests that the cationic titanocenes can be readily immobilized by covalent binding to PEG. In general, our results clearly demonstrate that the azide group is

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

• polyethylene glycol (PEG), known as PEGylation, has been widely used to improve the bioavailability of proteins and low molecular weight drugs. The covalent conjugation of PEG to the carbohydrate moiety of a protein has been mainly used to enhance the pharmacokinetic properties of the attached protein while

• and viral infections and are consequently candidates for chemotherapy. The short in vivo half-life of low molecular weight glycans hampered their use but methods for the covalent attachment of PEG have been less exploited. In this review, information on the preparation and application of PEG

• -carbohydrates, in particular multiarm PEGylation, is presented. Keywords: bioavailability; carbohydrates; conjugates; glycoPEGylation; multivalent glycosystems; multivalent PEGylation; Introduction In recent years, the modification of biotherapeutics by covalent conjugation with polyethyleneglycol (PEG) known

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• polymerization of functional lactide monomers, post-polymerization modification, or a combination of these two approaches. The appending hydroxy [9], carboxyl [10], poly(ethylene glycol) (PEG) [11][12][13][14], allyl [15], azido [16] and acetylene [17] functionalities on PLA backbones have been reported and

• family of water-soluble and temperature responsive biodegradable PLA material with tunable lower critical solution temperature (LCST) in a range from 25 to 65 °C was obtained after ‘click’ grafting with a mixture of alkyl and PEG azides. Starting from the same precursor 1 [18], Yu and coworkers have

• clinical application. More recently, Coumes and coworkers have prepared acetylene functionalized PLAs from precursor 1 and ‘click’ modification of the resulting PLAs with PEG azides provided amphiphilic graft copolymers which form nanorod aggregates in water [19]. The results discussed above indicate the

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• epoxide ring opening reaction with amines is much faster at elevated temperatures, the surface of oxidized, patterned PDMS stamps was coated with 2-[methoxy(polyethyleneoxy)propyl]trimethylsilane (PEG silane) [51]. The PEG coated stamps provided optimal wetting of the stamp by the carbohydrate ink

• solution, while preventing contamination of the substrate by PDMS residues. Moreover, it was observed that oxidized stamps without such a PEG coating adhered irreversibly to the epoxide substrates, possible due to reaction of the epoxide substrate with the oxidized PDMS surface. In the optimized µCP

• protocol, the PEG coated stamps were wetted with a 20 mM ethanolic solution of carbohydrate inks (NANA, Glc, Gal or Man) and triethylamine, and dried after 1 min incubation time. After placing the stamps on the epoxide-terminated SAMs on cleaned and activated glass or silicon substrates, the substrate and

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

• styrene and cross-linked divinylbenzene [20]. At present, there are mainly three classes of solid carriers: traditional polystyrene (PS), polyethylene glycol (PEG)-functionalized PS (such as TentaGel-supports [47]) and pure PEG-based resins such as PEGA resin [48] and ChemMatrix [49]. Shelton et al

• . recently published a collection of commonly used resins, together with their individual swelling and loading (is defined by the equivalents of amino acid in mmol/g, which can be attached to the resin) properties [50]. With respect to PEG-functionalized linkers, peptide synthesis yields can be improved by

• appropriate PEG units, loading and cross linking leading to elevated solubility and decreased intra- and intermolecular aggregation of the growing polypeptide [50]. The linker represents the reversible connection between the solid support and the assembling peptide. It determines the loading of the resin, the

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• , both for aromatic and aliphatic amines. We restrained the reaction to using PEG–OSO3H as a Brønsted acid–surfactant combined catalyst in aqeous solution under refluxing conditions as well as under solvent-free conditions (Table 1, entries 7 and 8). Although under solvent-free conditions the required

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• in flow previously as a route to densely functionalized heterocycles using HBr generated in a prior step as the catalyst for the reaction [51]. Copper catalysis has also been used in flow mode for preparing PEG-immobilized dihydropyrimidines [52]. We decided to screen a set of conditions for the

Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide

• Lena Möller,
• Christian Hess,
• Jiří Paleček,
• Yi Su,
• Axel Haverich,
• Andreas Kirschning and
• Gerald Dräger

Beilstein J. Org. Chem. 2013, 9, 270–277, doi:10.3762/bjoc.9.33

• ° + 2° within two months, making plasma-treated TPX 2 not suited for biomedical applications. Once the TPX-membrane was functionalized with the PEG unit, a significant reduction of the number of adhered cells was encountered (Figure 5c). This effect was even more pronounced on TPX membranes 7a and 7b

• response for a given mode of chemical modification. Finally, we also repeated the whole synthetic sequence, but this time using a PEG unit with a molar-mass distribution of 3000 g/mol instead of the defined PEG linker 3. This modified material should reveal the impact of linker length on the effectivity to

• seeding onto TPX derivatives (scale bar equals 500 µm) (a) 2 as control with heparin/albumin dip coating; (b) 2 treated with forming-gas plasma; (c) functionalized TPX 4 with PEG; (d) functionalized TPX 7a with PEG and alkyne group; (e) functionalized TPX 8a with cRGD (copper-catalyzed approach); (f

Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

• Francesca Pertici,
• Norbert Varga,
• Arnoud van Duijn,
• Matias Rey-Carrizo,
• Anna Bernardi and
• Roland J. Pieters

Beilstein J. Org. Chem. 2013, 9, 215–222, doi:10.3762/bjoc.9.25

• aqueous environment is notoriously poor, and therefore PEG attachments have been employed. Such PEG units were also incorporated in glycopolymers based on the phenylene-ethynylene repeating units by Seeberger and co-workers (see schematically in Figure 1a), who used them for the detection of bacteria [25

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• glycol (PEG) chains [31], resulting in solid supports such as Tentagel, Hypogel or Argogel. These resins were successfully used for the synthesis of peptides [31]. Meldal and co-workers developed PEGA resins [32] with good swelling behavior in water and polar solvents. Since the amide bonds of this solid

• support mimic peptides, the degree of aggregation of peptide chains during solid-phase synthesis is decreased, which facilitates the synthesis of peptides and glycopeptides [33]. Since amides are incompatible with many organic reactions, pure PEG resins, such as SPOCC [34], ChemMatrix [35] or NovaPEG

• conditions, such as Tentagel, were employed, glycosylation reactions proved to be ineffective and resulted in nonglycosylated linker 36 as the major product (Figure 2, A). A possible explanation for the low conversion to 37 is the long PEG chains contained in the resin structure that can either trap water to

An improved synthesis of a fluorophosphonate–polyethylene glycol–biotin probe and its use against competitive substrates

• Hao Xu,
• Hairat Sabit,
• Gordon L. Amidon and
• H. D. Hollis Showalter

Beilstein J. Org. Chem. 2013, 9, 89–96, doi:10.3762/bjoc.9.12

• ). In this study we have designed a novel synthetic route to a known FP probe linked by polyethylene glycol to a biotin tag (FP–PEG–biotin). Our route markedly increases the efficiency of the probe synthesis and overcomes several problems of a prior synthesis. As a proof of principle, FP–PEG–biotin was

• evaluated against isolated protein mixtures and different rat-tissue homogenates, showing its ability to specifically target serine hydrolases. We also assessed the ability of FP–PEG–biotin to compete with substrates that have high enzyme turnover rates. The reduced protein-band intensities resulting in

• . The FP–PEG–biotin compound 1, shown in Figure 1, was first synthesized by the Cravatt group and utilized for affinity isolation of enzymes by pull-down with avidin beads followed by mass-spectrometry analysis [6]. Our interest in generating 1 on a larger scale to use in our research led us to consider

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• modification of DSP-phalloidin and DSS-phalloidin with methoxypolyethyleneglycolamine, monomethoxypolyethyleneglycol was tosylated and reacted with ammonia to yield monomethoxy-PEG with a reactive amino group: 100 mg monomethoxy-PEG 810, 5,200 and 22,600 were dissolved in 1.0 mL of dry pyridine in a round

• was evaporated in vacuo and the aminomonomethoxy-PEG purified by Sephadex-LH20 chromatography. Ten milligrams DSP- or DSS-aminophalloidin were dissolved in 0.5 mL N,N-dimethylformamide and added to 1 equiv dry aminomonomethoxy-PEG. After reaction for 16 h at rt, phalloidin PEG 22,600 and phalloidin

• PEG 5,200 were purified on a Sephadex G25 column by using 0.1% NaCl as solvent, and phalloidin PEG 810 was purified on a Sephadex-LH20 column developed with methanol. The yield was 37% for phalloidin PEG 22,600, 34% for phalloidin PEG 5,200 and 45% for phalloidin PEG 810. Affinity to rabbit muscle

Supramolecular hydrogels formed from poly(viologen) cross-linked with cyclodextrin dimers and their physical properties

• Yoshinori Takashima,
• Yang Yuting,
• Miyuki Otsubo,
• Hiroyasu Yamaguchi and
• Akira Harada

Beilstein J. Org. Chem. 2012, 8, 1594–1600, doi:10.3762/bjoc.8.182

• adding selenium or platinum complexes yields supramolecular assemblies of bis(molecular tube)s cross-linked with the β-CD dimer, which form nanofibers [12][13][14][15]. Moreover, mechanically linked polyrotaxane with the α-CD and poly(ethylene glycol) (PEG) produces a hydrogel material, which exhibits

• unique physical properties [10]. Previously, we have prepared a polyrotaxane using α-CD and PEG [16][17]. The α-CD/PEG polyrotaxane forms a hydrogel material in high concentrations [18]. Using polyelectrolytes as threading molecules results in complexation between the polyelectrolyte and α-CD within the

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• dithiol 5 was easily obtained from esterification of 3-mercaptopropionic acid and propane-1,3-diol [14]. Trivinyl ether 6, polyethylene glycol (PEG) dimethacrylate 7, diacrylate 8 and diallyl ether 9 are all commercially available compounds. For thiol–ene additions via the radical pathway, the order of

A novel and facile synthesis of 3-(2-benzofuroyl)- and 3,6-bis(2-benzofuroyl)carbazole derivatives

• Wentao Gao,
• Meiru Zheng and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 1533–1540, doi:10.3762/bjoc.7.180

• described. The synthesis mainly relies on the ultrasound-assisted Rap–Stoermer reaction of 3-chloroacetyl- (1) or 3,6-dichloroacetyl-9-ethyl-9H-carbazole (4) with various salicylaldehydes 2a–k as well as 2-hydroxy-1-naphthaldehyde (2l) in CH3CN with the presence of PEG-400 as catalyst. The procedure offers

• easy access to benzofuroylcarbazoles in short reaction times and the products are obtained in moderate to good yields. Keywords: 2-benzofuroyl; carbazole; PEG-400; Rap–Stoermer reaction; salicylaldehydes; ultrasound-assisted; Introduction Carbazole, and especially heterocycle-containing carbazole

• impressive, our attempts to follow the route to synthesize 3a were also frustrated by the very complex mixture of the resulting products, from which we could not separate any desired products in appreciable yields. After many trials, we found that when the Rap–Stoermer reaction was carried out with PEG-400