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

• dialysis against SDS-solution, excess catalyst 10–12 was removed. Additional 3 days of dialysis against PE-PEG solution renatured the protein structure to give the expected β-barrel structure, as indicated by CD spectra (Figure 1). The CD spectra show a minimum at around 215 nm and a maximum at 195 nm, as

• SDS at 23 °C. After 3 days, the reaction showed 62% conversion with an endo to exo ratio of 70:30 (Table 1, entry 2). Since detergents such as SDS influences the reaction significantly, this value is in good agreement with previously reported results [32]. In PE-PEG at 4 °C the conversion was lower

• against 200 fold volume containing the refolding detergent PE-PEG (0.125 mM, average Mn = 2250 g/mol), sodium phosphate buffer (10 mM, pH 7.4), and water. The dialysis solution was changed every 12 h. The protein concentration was analyzed by BCA assay, the coupling efficiency was determined by ThioGlo

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• nanoparticles [10][11][12], inorganic solids [13][14], and different polystyrene derivatives [15][16][17][18][19][20]. Bifunctional thioureas were first supported on PEG [21], and later on different materials such as poly(methylhydrosiloxane) [16], polystyrene [18][19][20][21][22], and magnetic nanoparticles

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

• backbones Since the report of host–guest complexation between α-CD and poly(ethylene glycol) (PEG) by Harada and Kamachi in 1990 [82], a variety of pseudo-polyrotaxanes and polyrotaxanes formed through host–guest complexation between cyclodextrins and linear polymers have been reported [83], some of which

• form hydrogels [84][85]. In particular, hydrogels formed by PEG and cyclodextrins have been investigated intensively because of the biocompatibility of their components. Interestingly, local crystallization of the polyrotaxane threaded cyclodextrins, sometimes called molecular necklaces [86], may form

• cross-links and polymer networks in aqueous solution. In 1994, Li et al. reported the formation of hydrogels based on the host–guest complexation between α-CD and high molecular weight PEG [87]. They found the hydrogel melting temperature to increase with increase in PEG length and α-CD concentration

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

• multicomponent CuAAC reaction proceeded well in PEG-400 among various solvents, mainly due to the hydrophilic and hydrophobic character of the PEG-400. As shown in Scheme 12, the CuAAC gave the desired bistriazoles 31 in good to excellent yield when electron-withdrawing groups were present in the benzyl bromides

Smart molecules for imaging, sensing and health (SMITH)

• Bradley D. Smith

Beilstein J. Org. Chem. 2015, 11, 2540–2548, doi:10.3762/bjoc.11.274

• a remarkable self-assembly process that we call Synthavidin (synthetic avidin). A simple example is illustrated in Scheme 5 [44]. A water soluble tetralactam macrocycle with anthracene sidewalls is threaded by squaraine dyes that are flanked by long PEG chains to give highly stable complexes with

• nanomolar dissociation constants. The rate of macrocycle threading is insensitive to the length of the appended PEG chains. But the threading kinetics are greatly affected by the steric size of the second N-substituent at each end of the squaraine dye, and an N-propyl group produces a perfect mixture of

• -pairs. Trapping a macrocyclic receptor containing a reactive ion-pair produces an interlocked [2]rotaxane. (top) Basis of Synthavidin technology. A fluorescent squaraine dye that is flanked by PEG chains can rapidly thread a tetralactam macrocycle in water to produce a highly stable complex. (bottom

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

• modulates the formation of micelles, vesicles, nanospheres (or dense aggregates), and nanocapsules [1]. In particular, non-ionic aCD obtained from β-CD modified with hydrophobic thioalkyl chains (H groups in the following) at the primary rim and short polar PEG oligomers (P groups) at the secondary rim form

• recently reported [14], while analogue cationic aCD with terminal short amino-PEG at the secondary rim form nanoassemblies which entrap photosensitizers for photoactivated therapy [25] or DNA for gene delivery [26][27][28][29][30]. The potential of aCD is strengthened by their ability to selectively

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

• (amidoamine) (PAMAM) dendrimers, and a monovalent neutral Ad-PEG stopper is introduced at the surface for stabilization. The SNP size was increased by increasing the amount of multivalent guest molecules in the core, while keeping the host and stopper concentration constant and having an excess of stopper to

• 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

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

• single-chain-stranded with poly(methyl vinyl ether) (PMVE) [4] or poly(dimethylsiloxane) (PDMS) [5], but also double-chain-stranded with PEG and poly(ε-caprolactone) (PCL) [6]. Recently, Akashi et al. reported the single-chain-stranded inclusion complexation of γ-CDs with poly(methyl methacrylate) (PMMA

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

• components (CDs, in this study) and the nanoparticle surfaces (SiO2), hydroxy groups of the cyclic components of a polyrotaxane comprised of α-CD and PEG (PR) was modified as shown in Scheme 1. The polyrotaxane with triethoxysilylated CD (TES-PR) is suitable for the reaction with SiO2 in the presence of base

• 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

• precipitate was freeze-dried and the refined polyrotaxane (PR) obtained as a white powder. The coverage, which is a measure how densely the backbone PEG is covered with CDs, was calculated to be 25% based on the 1H NMR spectrum. Standard polymers for the calibration of the molecular weights by size-exclusion

Olefin metathesis in air

• Lorenzo Piola,
• Fady Nahra and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 2038–2056, doi:10.3762/bjoc.11.221

• ]. Conversions were found to be as low as 10% in DCM and <20% in toluene. In 2009, Abell and Zaman reported the use of a Hoveyda–Grubbs 2nd generation ruthenium-based catalyst immobilized on PEG (61, Figure 7) [65]. This catalyst was soluble in dichloromethane but could be retrieved and recycled by simple

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

• after 30 min. General procedure for the preparation of the polymer dispersions using DCPD or DCPD/COE mixtures with complexes 11 and 12. A mixture of 73.1 g of water, 8.3 g of a 10% (by strength) solution of PEG-30 cetyl stearyl ether (Emulgin® B3) as charge-neutral surfactant, 0.75 g of n-hexadecane

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

• weight (12–18000 Dalton) were obtained (Figure 6). Nano particles of the polymer were used for a controlled slow release of the drug doxorubicin (29) trapped in this material. Bhatia et al. used Novozyme 435 to make polymers from functionalized pentofuranose derivatives (i.e, 30) and PEG-600 dicarboxylic

• ´-dithiodipropionic acid dimethyl ester in combination with pentadecalactone and 1,4-butandiol (Figure 8) [57]. When MeO-PEG-OH was used as chain terminator amphiphilic copolymers were formed. The hydrophobicity of the polymer could easily be changed by the content of the lactone. The copolymers had low toxicity and

• diester using ethyl α-bromoacetate. The formed diester was copolymerized with PEG using CAL-B (Figure 14). The final product was an effective activator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) several times better than the free curcumin [66]. The curcumin diester was used in a second polymer

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• , hydrothermal cyclization, H2SO4 in acetic acid, PEG-600, silica supported TaCl5, esterification using inorganic base and alkylating agent followed by heating in the presence of tetrabutylammonium bromide, diphenyl 2-oxo-3-oxazolinylphosphonate and Et3N as well as several other conditions have been reported in

Adsorption mechanism and valency of catechol-functionalized hyperbranched polyglycerols

• Stefanie Krysiak,
• Qiang Wei,
• Klaus Rischka,
• Andreas Hartwig,
• Rainer Haag and
• Thorsten Hugel

Beilstein J. Org. Chem. 2015, 11, 828–836, doi:10.3762/bjoc.11.92

• with dopamine. Dopamine is derived from L-DOPA by removing the carboxyl group. This leaves an amine group that was used to covalently couple the probe molecule to the tip through a PEG linker using NHS-ester chemistry, as illustrated in the inset of Figure 1B. A sample force–distance trace showing the

• groups of one molecule or two molecules with catechol groups. The fact that only two of the five measurements showed high force peak interactions could be explained by geometrical constraints. The molecule was covalently attached to the tip by a PEG tether, which limits the ability of the molecule to

• catechol anchor and the second with two catecholic anchors. Note that in the last case, two catechols with two PEG linkers were involved that shared the applied force. Therefore, the triple maximum force peak with forces of up to 2 nN could be measured despite rupture forces of 1.4 nN for the Si–O bond

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

• bifunctional PEG as written above. Figure 1 shows the expected coordination complexes of our mono- and bivalent model systems with Cu2+ in aqueous solution. In the present work, we analyzed the bivalent systems 2b and 2c by DFS, similarly as for the recently published reference case of 2a [27]. We modified

• ) cantilever tip, there is also a certain possibility of simultaneous bond formation as shown in Figure 2b, or non-specific interactions directly between tip and surface. For a proper detection of single-molecular events, we utilized PEG chains with a well characterized force-extension behavior [40][41

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

• surface (P′(ρ,z = 0,N) = 0). To obtain the parameter α, P′ has to be integrated over one half space: In the limit of a long chain (N >> 1), Equation 28 can be approximated as: A PEG spacer with b = 0.38 nm requires 30–800 segments to adopt an average end-to-end distance of 2 to 10 nm. In this range α

• also the maximum and width of the RBA are in this case determined by the binding range σ. In Figure 5b we assume a DNA spacer that is decorated with flexible PEG linkers at both ends. The PEG linkers consist of four monomers each. Assuming Gaussian-chain behavior with a segment length of b = 0.38 nm

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• and BMP-2s are integrated in matrix metalloproteinase (MMP)-degradable PEG-maleimide hydrogels. The peptide ligands successfully host stem cells in vivo, and the sustained release of low doses of BMP-2 direct endogenous stem cell differentiation and promote bone healing [87]. Furthermore, the signal

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• and various families of branched polymers such as dendrimers, dendritic-hybrid and hyperbranched polymers are used as macromolecular support for catalysis [10][11][12]. Linear polymers such as poly(ethylene glycol) (PEG) [13] or non-cross-linked polystyrene (NCPS) [14] are readily available but suffer

Probing multivalency in ligand–receptor-mediated adhesion of soft, biomimetic interfaces

• Stephan Schmidt,
• Hanqing Wang,
• Daniel Pussak,
• Simone Mosca and
• Laura Hartmann

Beilstein J. Org. Chem. 2015, 11, 720–729, doi:10.3762/bjoc.11.82

• a concanavalin A (ConA) layer via poly(ethylene glycol)-(PEG)-based soft colloidal probes (SCPs). Special emphasis is on the dependence of multivalent presentation and density of carbohydrate units on specific adhesion. Consequently, we first present a synthetic strategy that allows for controlled

• density variation of functional groups on the PEG scaffold using unsaturated carboxylic acids (crotonic acid, acrylic acid, methacrylic acid) as grafting units for mannose conjugation. We showed by a range of analytic techniques (ATR–FTIR, Raman microscopy, zeta potential and titration) that this

• synthetic strategy allows for straightforward variation in grafting density and grafting length enabling the controlled presentation of mannose units on the PEG network. Finally we determined the specific adhesion of PEG-network-conjugated mannose units on ConA surfaces as a function of density and grafting

Synthesis of tripodal catecholates and their immobilization on zinc oxide nanoparticles

• Franziska Klitsche,
• Julian Ramcke,
• Julia Migenda,
• Andreas Hensel,
• Tobias Vossmeyer,
• Horst Weller,
• Silvia Gross and
• Wolfgang Maison

Beilstein J. Org. Chem. 2015, 11, 678–686, doi:10.3762/bjoc.11.77

• PEG, a sulfobetaine and an adamantyl group. The potential of these conjugates has been demonstrated with the immobilization of tripodal catecholates on ZnO NPs. The results confirmed a high loading of tripodal PEG-catecholates on the particles and the formation of stable PEG layers in aqueous solution

• derivatives bearing an additional effector moiety may be used to generate stable particles with tailored properties, good solubility and biocompatibility. Suitable effectors in this context are PEG [31][32][33], zwitterions [34][35] or polyglycerols [36][37] which, when immobilized on NPs, may be used to tune

• as a cheap starting material [43]. Amine 1 was coupled to a commercially available PEG-carboxylate (5 kDa) with EDC/DMAP. The resulting PEG-conjugate was treated with KOTMS to remove the methyl esters to give tricarboxylic acid 2 in good 57% yield for the two-step procedure. In a last step, dopamine

The preparation of new functionalized [2.2]paracyclophane derivatives with N-containing functional groups

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 437–445, doi:10.3762/bjoc.11.50

• bridging and the strain of the desired 17 would be too high for a successful ring closure. Reacting 16 with tetraethylene glycol (TEG) under high dilution conditions (toluene, reflux, 7 d) provides the crownophane 18 in 68% yield (Scheme 2). Likewise, replacement of TEG by pentaethylene glycol (PEG

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts

• Bin Yin,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2015, 11, 85–91, doi:10.3762/bjoc.11.12

• was achieved by direct and indirect anodic oxidation in the presence of the poly(HF) salts [12][13][14][15][16][23][24][25] or alkali-metal fluorides like KF and CsF with PEG 200 [17]. The anodic fluorination of a dithioacetal derived from an aliphatic aldehyde provided the fluorodesulfurization

Modification of physical properties of poly(L-lactic acid) by addition of methyl-β-cyclodextrin

• Toshiyuki Suzuki,
• Ayaka Ei,
• Yoshihisa Takada,
• Hiroki Uehara,
• Takeshi Yamanobe and
• Keiko Takahashi

Beilstein J. Org. Chem. 2014, 10, 2997–3006, doi:10.3762/bjoc.10.318

• . It has been reported that the unmodified α-CD accelerates the crystallization of PCL, PEG, PBS and P3HB during cooling from melts. Cooling measurements by DSC were carried out for PLLA, PL-MCD50, 67 and 83 to confirm the similar effects. However, the crystallization was not observed for PLLA, PL

A novel 4-aminoantipyrine-Pd(II) complex catalyzes Suzuki–Miyaura cross-coupling reactions of aryl halides

• Claudia A. Contreras-Celedón,
• Darío Mendoza-Rayo,
• José A. Rincón-Medina and
• Luis Chacón-García

Beilstein J. Org. Chem. 2014, 10, 2821–2826, doi:10.3762/bjoc.10.299

• are summarized in Table 2. The reaction proceeded in both protic and aprotic solvents, but with significantly varying yields of the product. In the cases of H2O, THF, DMF, toluene, benzene and PEG 600 solvents, the yields were between 29–67% (Table 2, entries 1–6), all lower than the product yield

• was carried out at room temperature for 22 hours. However, the yield of 3q was low when 1:1.5 PEG 600/H2O was used at 80 °C (Table 2, entry 7) and moderate yield when 1:1 EtOH/H2O when was used as solvent at room temperature (rt) or at 80 °C (Table 2, entries 11 and 12). Different bases were screened