Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates

• Souad Kachbi-Khelfallah,
• Maelle Monteil,
• Margery Cortes-Clerget,
• Evelyne Migianu-Griffoni,
• Jean-Luc Pirat,
• Olivier Gager,
• Julia Deschamp and
• Marc Lecouvey

Beilstein J. Org. Chem. 2016, 12, 1366–1371, doi:10.3762/bjoc.12.130

• is a procedure developed in our laboratory to introduce the bisphosphonate from acyl chloride and tris(trimethylsilyl)phosphite in one step. Keywords: bisphosphonate; Fe2O3 nanoparticle; polyethylene glycol derivatives; surface ligand synthesis; Introduction Numerous researchers are interested in

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• atom in the chain, and 10 possessing several ethylene glycol moieties were used to increase the solubility of modified polyamides in water. Selection of the target DNA and design of TFOs and MGBs The polypurine tract of the HIV-1 provirus is a valuable target for MGB-TFO conjugates [35]. It has a 16-bp

Artificial Diels–Alderase based on the transmembrane protein FhuA

• Hassan Osseili,
• Daniel F. Sauer,
• Klaus Beckerle,
• Marcus Arlt,
• Tomoki Himiyama,
• Tino Polen,
• Akira Onoda,
• Ulrich Schwaneberg,
• Takashi Hayashi and
• Jun Okuda

Beilstein J. Org. Chem. 2016, 12, 1314–1321, doi:10.3762/bjoc.12.124

• (polyethylene-polyethylene glycol), SDS (sodium dodecyl sulfate), TEV (Tobacco Etch Virus), MALDI–TOF–MS (matrix-assisted laser desorption/ionisation and time-of-flight mass spectrometry), FhuAΔCVFtev (FhuA Δ1-159_C545_V548_F501_tev), CD (circular dichroism), ESI-MS (electrospray ionization-mass spectrometry

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• alcohol 18 (15%) and diol 17 (20%). This result could not by improved using reverse addition conditions (Scheme 2). Therefore, selective monoprotection of the dialdehyde 5 was next attempted. Unfortunately, treatment of the latter either with ethylene glycol or 2,2-dimethylpropandiol gave a mixture of di

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• in 18 on reaction with KHF2 in ethylene glycol [48][49] furnished the 4-fluoro derivative 26 (Scheme 3). The moderate yield of 26 (40–60%) can be attributed to the formation of the 4-O-(2-hydroxyethyl) derivative 27 arising from solvent participation, and to a partial decomposition (indicated by TLC

Creating molecular macrocycles for anion recognition

• Amar H. Flood

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

• salt binding to an aryl–triazole–glycol macrocycle (Figure 2, 12–15, and Figure 10) and examined the cooperativity using theory. We investigated NaClO4 and NaI (Figure 10b) experimentally and NaI, NaBr, NaCl theoretically. Theory is able to do things that are impossible in experiment (Figure 10c). As a

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

• and repeating units (ethylene glycol or methylene). The target compounds were characterized by IR, MS and NMR spectra. A simple method for their complete conversion to the corresponding disulfides as well as a method for the reduction of the disulfides back to the thiols is presented. Both, thiols and

• of the commonly used method [18]. The modification consisted in the repeated recrystallization from 50% water–methanol which yielded a very pure product with no interfering impurities (di- or tri-Ts-β-CD) or unreacted β-CD. The terminal sulfanyl groups were introduced to the oligoethylene glycol

• linkers using standard chemical transformations (Scheme 1). Oligoethylene glycol ditosylates 2a–c [19] were converted to S-acetyl dithiols 3a–c [20] and deacetylated to the oligoethylene glycol dithiols 4a–c using a procedure published for similar thiols [21]. Compounds 4 can be easily oxidized to

Aggregation behavior of amphiphilic cyclodextrins in a nonpolar solvent: evidence of large-scale structures by atomistic molecular dynamics simulations and solution studies

• Giuseppina Raffaini,
• Fabio Ganazzoli and
• Antonino Mazzaglia

Beilstein J. Org. Chem. 2016, 12, 73–80, doi:10.3762/bjoc.12.8

• applications [1][2]. In particular, the modification with thioalkyl chains in the primary rim and oligoethylene glycol chains in the secondary rim and, consequently, their hydrophobic–hydrophilic balance (Scheme 1) modulates the formation of differently sized and shaped nanoconstructs as membrane models for

Supramolecular polymer assembly in aqueous solution arising from cyclodextrin host–guest complexation

• Jie Wang,
• Zhiqiang Qiu,
• Yiming Wang,
• Li Li,
• Xuhong Guo,
• Duc-Truc Pham,
• Stephen F. Lincoln and
• Robert K. Prud’homme

Beilstein J. Org. Chem. 2016, 12, 50–72, doi:10.3762/bjoc.12.7

• , may be disrupted by cyclodextrin host–guest complexation of these substituents (Figure 2) [41][42][43][44][45][46][47][48][49]. Thus, in 1998, Zhang et al. reported that the viscosity of an aqueous solution of perfluorocarbon-substituted poly(ethylene glycol) was decreased through the addition of β-CD

• permeation chromatography and light scattering methods [48]. In 2002, Karlson et al. found that hydrophobic association among the hydrophobic substituents of substituted poly(ethylene glycol) was disrupted by host–guest complexation by methylated α-CD [42]; as was a similar association by the hydrophobic

• surfactants based on poly(ethylene glycol) to recover the hydrophobic associations in hydrophobically substituted alkali-soluble emulsion (HASE) polymers complexed by α-CD and β-CD [41]. (It should be noted that association occurs between hydrophobically substituted polymers in aqueous solution and that this

Recent advances in metathesis-derived polymers containing transition metals in the side chain

• Ileana Dragutan,
• Valerian Dragutan,
• Bogdan C. Simionescu,
• Albert Demonceau and
• Helmut Fischer

Beilstein J. Org. Chem. 2015, 11, 2747–2762, doi:10.3762/bjoc.11.296

• biologically relevant type of new homopolymers (e.g., 2, Scheme 1) and block copolymers provided with amidoferrocenyl groups linked through a tetraethylene glycol side chain. These interesting metallopolymers were readily prepared through living ROMP initiated by the Grubbs 3rd generation catalyst which proved

• used to prepare modified Pt electrodes with high stability and good qualitative sensing of ATP2− anions. It was supposed that the triethylene glycol domains in the block copolymers favor the amidoferrocene–ATP interactions by encapsulation. Astruc assumed that during the recognition process different H

• corresponding monomers, appended to Ir bipyridine complexes, oligoethylene glycol and biotin entities, have been examined by fluorescence spectroscopy for their self-assembling behavior and biodetection capability (Scheme 15). In a very interesting work, Blechert, Buchmeiser and coworkers [61] copolymerized

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

• ). The formation of triazole functional groups can work as a powerful auxochrome. In 2010, Bunz and co-workers used the TMS-protected diethynylbenzothiadiazoles 48 and 50 as the source of dialkynes. The CuAAC reaction was carried out with ethylene-glycol-functionalized azide 47 in the presence of CuSO4

• 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

• report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics

• atoms) as a function of their distance from the atoms belonging to each of the two clusters of three molecules (see Figure 10). Structure of an aCD functionalized with hydrophobic thioalkyl C2 (R = C2H5) or C6 (R = C6H13) chains at the primary rim (hydrophobic H groups) and polar oligoethylene glycol

Size-controlled and redox-responsive supramolecular nanoparticles

• Raquel Mejia-Ariza,
• Gavin A. Kronig and
• Jurriaan Huskens

Beilstein J. Org. Chem. 2015, 11, 2388–2399, doi:10.3762/bjoc.11.260

• . Davis et al. showed the formation of SNPs using attractive electrostatic interactions between positively charged β-cyclodextrin (CD)-containing polymers and negatively charged siRNA at the core [8]. Neutral adamantyl-grafted poly(ethylene glycol) (Ad-PEG) was incorporated at the surface to stabilize

• PAMAM (Fc8-PAMAM) dendrimer as the multivalent guest and a monovalent stabilizer. Different stabilizers were used such as: Ad-PEG, Fc-terminated poly(ethylene glycol) (Fc-PEG), methoxypoly(ethylene glycol) (mPEG), and Ad-tetraethylene glycol (Ad-TEG). The effect of the following parameters on the

• synthesized by a reaction of 1-(chlorocarbonyl)ferrocene with the terminal amino group of methoxypoly(ethylene glycol)amine (Mw = 5000 g/mol) in dichloromethane, using an excess of triethylamine as a base, followed by precipitation from diethyl ether. To evaluate the association constant of the Fc moiety with

Self-assemblies of γ-CDs with pentablock copolymers PMA-PPO-PEO-PPO-PMA and endcapping via atom transfer radical polymerization of 2-methacryloyloxyethyl phosphorylcholine

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

Beilstein J. Org. Chem. 2015, 11, 2267–2277, doi:10.3762/bjoc.11.247

• inclusion complexation of α-CDs with poly(ethylene glycol) (PEG) [1], a great variety of polymers with different cross-sectional areas have been shown to thread CDs to create PPRs. For example, β-CDs are single-chain-stranded with poly(propylene glycol) (PPG) but not with PEG [2][3], and γ-CDs are not only

Synthesis, structure, and mechanical properties of silica nanocomposite polyrotaxane gels

• Kazuaki Kato,
• Daisuke Matsui,
• Koichi Mayumi and
• Kohzo Ito

Beilstein J. Org. Chem. 2015, 11, 2194–2201, doi:10.3762/bjoc.11.238

• progress. Experimental Materials Crude polyrotaxane consisting of polyethylene glycol (PEG, Mn = 32,000) and α-cyclodextrin (CD) were purchased from Advanced Softmaterials, Inc. The crude polyrotaxane was purified by repeated reprecipitation from its DMSO solution into deionized water. The obtained

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• methylketones 75 in the presence of molecular iodine, respectively. The tandem transformation of a carbonyl acetalization and a iodination in sustainable ethylene glycol under mild heating provided a practical approach in the synthesis of useful protected α-haloketones (Scheme 25). Recently, Kakiuchi and co

A new approach to ferrocene derived alkenes via copper-catalyzed olefination

• Vasily M. Muzalevskiy,
• Aleksei V. Shastin,
• Alexandra D. Demidovich,
• Namiq G. Shikhaliev,
• Abel M. Magerramov,
• Victor N. Khrustalev,
• Rustem D. Rakhimov,
• Sergey Z. Vatsadze and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2015, 11, 2072–2078, doi:10.3762/bjoc.11.223

• N2H4·H2O, DMSO or EtOH as a solvent) the yields of the desired alkenes were not good enough. Better results were obtained in ethylene glycol with a 4-fold excess of N2H4·H2O (novel media just reported for COR [37]). In this case, target alkenes were isolated in up to 62% yield. Using C2-freons

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• acetonitrile. The stability of the complexes increased with the elongation of the ethylene glycol chains. Aromatic amide oligomers: extended secondary structures. Our students also tried to make use of hydrogen bonding to control the conformation of aromatic amide backbones. Previously, Hamilton [26], Gong [27

Hexacoordinate Ru-based olefin metathesis catalysts with pH-responsive N-heterocyclic carbene (NHC) and N-donor ligands for ROMP reactions in non-aqueous, aqueous and emulsion conditions

• Shawna L. Balof,
• K. Owen Nix,
• Matthew S. Olliff,
• Sarah E. Roessler,
• Arpita Saha,
• Kevin B. Müller,
• Ulrich Behrens,
• Edward J. Valente and
• Hans-Jörg Schanz

Beilstein J. Org. Chem. 2015, 11, 1960–1972, doi:10.3762/bjoc.11.212

• monomer liquidity and polyethylene glycol (PEG) based Emulgin® B3 as surfactant which was previously vigorously stirred for 1 h and then further emulsified using a sonication probe for another 5 min establishing the microemulsion. The emulsion polymerization reactions were conducted at less favorable

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

• . The formed diol was mixed with an equal molar amount of divinyl sebacate and lipase as a catalyst, after some time methoxypoly(ethylene glycol) was added to react with the remaining vinyl carboxylates to give an amphiphilic polymer. This product self-assembled into nanometer-scale-sized particles in

• telechelics in a one-pot polycondensation. The backbone of the telechelics was built from ethylene glycol and divinyl adipate. Specific degrees of polymerisation (4, 8 and 13) were reached by terminating the process with the addition of 2-hydroxyethyl methacrylate. Well-defined telechelics with more than 90

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

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• functionalised with thioethers, exemplified by a series of ethylene glycol derivatives. Additionally, the merits of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as an alternative to the most common deprotecting agent, CsOH·H2O are discussed. Finally, we show how a copper-mediated Ullman-type reaction can be applied

• complex alkylating agents can be successfully used in place of methyl iodide. For example, functionalised ethylene glycol oligomers have been used in the preparation of rotaxanes and pseudorotaxanes [28][41][42][45]. Although CsOH·H2O is most commonly used, other bases are also known to remove the

• thioether-functionalised MPTTFs to be prepared, including the addition of large ethylene glycol-based substituents utilised in the preparation of rotaxanes and pseudorotaxanes. N-Arylation of MPTTFs is an area of increasing interest and can be achieved using a copper-mediated reaction. We have applied this

Synthesis of photoresponsive cholesterol-based azobenzene organogels: dependence on different spacer lengths

• Yuchun Ren,
• Bin Wang and
• Xiuqing Zhang

Beilstein J. Org. Chem. 2015, 11, 1089–1095, doi:10.3762/bjoc.11.122

• gel formation modes. Experimental Materials The starting materials, thylene glycol, 1,3-propanediol, 1,5-pentadiol, 1,6-hexanediol, 1,10-decanediol, 1,12-dodecanediol, cholesterol, 4-toluene sulfonyl chloride, phenol, 4-aminobenzoic acid, iodomethane, sodium nitrite, hydrochloric acid, sodium

• anhydrous dioxane (60 mL) and dry ethylene glycol (20 g, 0.32 mol) was added. The mixture was refluxed at 110 °C for 4 h. The solution was cooled and solvent was removed under vacuum. The white residue was dissolved in chloroform. The organic layer washed with NaHCO3, water, and brine; and dried over

Mechanical stability of bivalent transition metal complexes analyzed by single-molecule force spectroscopy

• Manuel Gensler,
• Christian Eidamshaus,
• Maurice Taszarek,
• Hans-Ulrich Reissig and
• Jürgen P. Rabe

Beilstein J. Org. Chem. 2015, 11, 817–827, doi:10.3762/bjoc.11.91

• rupture. Results and Discussion Regarding the synthesis, pyridine nanorod 3, which was also precursor for the synthesis of complex 2a [27], was hydrogenated to receive intermediate 4 (Scheme 1). Subsequent coupling with bifunctional poly(ethylene glycol) (PEG) and purification by dialysis gave compound 5

• (ethylene glycol) (R in Figure 1, H-terminated, 81.0 mg, 0.0081 mmol) and 4 (29.0 mg, 0.113 mmol) in anhydrous CH2Cl2 (0.6 mL) was added EDAC (6.5 mg, 0.034 mmol) and the resulting mixture was stirred at room temperature under an atmosphere of argon for 5 days. The solvent was evaporated and the residue was

• , 6.02; N, 11.96; found: C, 68.02; H, 6.00; N, 11.93. Synthesis of pyridine-PEG conjugate 10, ligand of 2c: To a solution of the bifunctional poly(ethylene glycol) (R in Figure 1, H-terminated, 117 mg, 0.0117 mmol) and compound 8 (32.0 mg, 0.116 mmol) in anhydrous CH2Cl2 (0.6 mL) was added EDAC (7 mg

Influence of length and flexibility of spacers on the binding affinity of divalent ligands

• Susanne Liese and
• Roland R. Netz

Beilstein J. Org. Chem. 2015, 11, 804–816, doi:10.3762/bjoc.11.90

• ratio lp/L ≈ 10 and thus correspond to the very stiff limit. Polyethylene glycol (PEG) with a persistence length of about lp = 0.38 nm on the other hand is characterized by a ratio smaller than lp/L = 0.08 and thus correspond to the flexible limit [23]. Effective concentration – harmonic spring and