A versatile route to polythiophenes with functional pendant groups using alkyne chemistry

• Xiao Huang,
• Li Yang,
• Rikard Emanuelsson,
• Jonas Bergquist,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 2682–2688, doi:10.3762/bjoc.12.265

• conditions leading to exomethylene-EDOT [19]. Therefore, the usage of basic nucleophiles is problematic. Moreover, these heteroatom-based linkers between the polymer backbone and the pendant group usually have limited tolerance to acidic or basic conditions promoting hydrolysis, and some of them are

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

• Arne Klinkebiel,
• Ole Beyer,
• Barbara Malawko and
• Ulrich Lüning

Beilstein J. Org. Chem. 2016, 12, 2267–2273, doi:10.3762/bjoc.12.219

• Arne Klinkebiel Ole Beyer Barbara Malawko Ulrich Luning Otto-Diels-Institut für Organische Chemie, Christian-Albrechts-Universität zu Kiel, Olshausenstr. 40, D-24098 Kiel, Germany 10.3762/bjoc.12.219 Abstract New triazine-based tricarboxylic acid linkers were prepared as elongated relatives of

• substituted) with two equivalents of an unsubstituted nitrile. Triple Suzuki coupling of the cores 3 with suitable phenyl- and biphenylboronic acid derivatives provided elongated tricarboxylic acid linkers as carboxylic acids 17 and 20 or their esters 16 and 19. Reduction of the nitro group and cleavage of

• the methoxy group gave the respective amino and hydroxy-substituted triazine linkers. Keywords: isoreticular; linker; MOF; Suzuki coupling; triazine; Introduction A typical building block for many metal–organic frameworks (MOFs) [1][2][3][4] carries two functional groups such as carboxylic acids or

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• generate libraries of molecules from simpler building blocks by reversible reactions under thermodynamic control. Here we focus on the chemical modification of DNA oligonucleotides with acyclic diol linkers and demonstrate their potential for the deoxyribonucleic acid functionalization and generation of

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

• synthesis of conjugates of pyrrole–imidazole polyamide minor groove binders (MGB) with fluorophores and with triplex-forming oligonucleotides (TFOs). Diverse bifunctional linkers were synthesized and used for the insertion of terminal azides or alkynes into TFOs and MGBs. The formation of stable triple

• part of the present article, we describe the synthesis of various linkers bearing different functional groups for simple and accessible introduction of azide and alkyne groups into biopolymers, fluorophores and ligands. Then, these linkers were introduced into the structure of MGBs and TFOs and used

• for the synthesis of MGB-fluorophore and MGB-TFO conjugates via CuAAC (Figure 2). Properties of the conjugates obtained are discussed. Results and Discussion Synthesis of bifunctional linkers Two components in MGB-TFO conjugates must be connected by a linker, which is at least 12 chemical bonds long

Creating molecular macrocycles for anion recognition

• Amar H. Flood

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

• microscopy (STM) imaging. Their shape persistence makes them ideal for the study of structure–property relationships to enable deep understanding of anion recognition phenomena. The identification of 1,2,3-triazoles as linkers, ligands and building blocks. The synthetic creation of macrocycles sets the scene

New synthetic strategies for xanthene-dye-appended cyclodextrins

• Milo Malanga,
• Andras Darcsi,
• Mihaly Balint,
• Gabor Benkovics,
• Tamas Sohajda and
• Szabolcs Beni

Beilstein J. Org. Chem. 2016, 12, 537–548, doi:10.3762/bjoc.12.53

• of the CD scaffold with two different linkers (both polyamines) and then on the coupling of the terminal amino group of the linkers with rhodamine B. The coupling conditions were slightly different from those reported by Harada [14]. The solvent was a mixture of pyridine and DMF, the activating

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

• Prague, Hlavova 8, 128 43, Prague 2, Czech Republic 10.3762/bjoc.12.38 Abstract A general high-yielding method for the preparation of monosubstituted β-cyclodextrin derivatives which have attached a thiol group in position 6 is described. The thiol group is attached through linkers of different lengths

• 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

• more hydrophilic and flexible oligoethylene glycol linker, which have been successfully applied in several studies to position the CD units at a sufficient distance from the solid surface. These linkers also have the advantage, compared to the aliphatic chain linkers, in a lower tendency to form an

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• intercalation sites only half occupied. Le Pecq and coworkers studied bisacridines such as 1 (Figure 2b) [7]. Consistent with the NEP, 1 formed a very tight bisintercalation complex with its spermine-derived linker chain spanning two base-pairs (Figure 2c). However, with shorter linkers that can only span a

• interested in linkers or spacers that minimally allowed or even forced the two chromophores to stack on one another. The DNA target in which we became interested was a repeating sequence (CTG)n in the DMPK gene on chromosome 19. The sequence becomes unstable when n > 50, undergoing progressive expansion to

• interested in bisintercalators and the question of rigid vs flexible linkers? The triaminotriazine unit was designed to provide selective recognition of U–U or T–T mismatches, but on its own was viewed as unlikely to provide significant binding affinity because the hydrogen bonding simply involves replacing

Hydroquinone–pyrrole dyads with varied linkers

• Hao Huang,
• Christoffer Karlsson,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 89–96, doi:10.3762/bjoc.12.10

• , Box 576, SE-751 23 Uppsala, Sweden 10.3762/bjoc.12.10 Abstract A series of pyrroles functionalized in the 3-position with p-dimethoxybenzene via various linkers (CH2, CH2CH2, CH=CH, C≡C) has been synthesized. Their electronic properties have been deduced from 1H NMR, 13C NMR, and UV–vis spectra to

• detect possible interactions between the two aromatic subunits. The extent of conjugation between the subunits is largely controlled by the nature of the linker, with the largest conjugation found with the trans-ethene linker and the weakest with the aliphatic linkers. DFT calculations revealed

• different linkers between the pyrrole and hydroquinone subunits was designed [6]. Although it is known that N-protected pyrrole (Py) can be selectively functionalized at the β-position [7], we found the published procedures to be unsuitable for our purpose (vide infra). Therefore, we have developed improved

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

• [76]. (The 66 prefix in 66β-CD2su and 66β-CD2ur indicates that the succinamide and urea linkers are attached to the C6 carbon in a D-glucopyranose subunit of each β-CD.) The increasing length of the adamantyl tether from amido to hexylamido in PAAAD and PAAADhn progressively decreases steric hindrance

• M−1 in aqueous solution at 298.2 K for β-CD and the β-CD dimer b and the β-CD dimer c, respectively, where the greater β-CD dimer c complex stability was attributed to the greater hydrophobicity arising from the two octamethylene linkers. Rheological studies of aqueous solutions of adamantyl

• . A much greater increase in viscosity was observed when the β-CD dimer c was employed consistent with its greater rigidity derived from the twin octamethylene linkers enhancing interchain cross-link formation. Interesting variations on the above complexation studies are those relating to β-CD

Effective immobilisation of a metathesis catalyst bearing an ammonium-tagged NHC ligand on various solid supports

• Krzysztof Skowerski,
• Jacek Białecki,
• Stefan J. Czarnocki,
• Karolina Żukowska and
• Karol Grela

Beilstein J. Org. Chem. 2016, 12, 5–15, doi:10.3762/bjoc.12.2

• the need for sophisticated linkers and tags, is significantly more complicated. Several protocols were developed for heterogenisation of ruthenium catalysts and this topic has been thoroughly reviewed [8][9][10][11][12][13][14][15][16][17][18]. The implementation of such concepts requires the presence

Polydisperse methyl β-cyclodextrin–epichlorohydrin polymers: variable contact time ¹³C CP-MAS solid-state NMR characterization

• Isabelle Mallard,
• Davy Baudelet,
• Franca Castiglione,
• Monica Ferro,
• Walter Panzeri,
• Enzio Ragg and
• Andrea Mele

Beilstein J. Org. Chem. 2015, 11, 2785–2794, doi:10.3762/bjoc.11.299

• remove organic pollutants [6][11][12][13] and heavy metals [14] from water. The most efficient method for the synthesis of insoluble polymers is to use di- or polyfunctional linkers with monomers of cyclodextrins. Different effective crosslinkers have been reported in the literature such as

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

• not occur without silica. This suggests that the silica nanoparticles behave as cross-linkers. Viscoelastic measurements of the nanocomposite gels showed no stress relaxation regardless of the silica content for <20% compression strain, indicating an infinite stable network without physical cross

• polymer chains were not directly bonded but rather mechanically interlocked to the silica surfaces. The silica nanoparticles were homogeneously distributed in the gel and worked as cross-linkers to immobilize the cyclic components of the polyrotaxanes on the silica surfaces. As the backbone polymer chains

Ru complexes of Hoveyda–Grubbs type immobilized on lamellar zeolites: activity in olefin metathesis reactions

• Hynek Balcar,
• Naděžda Žilková,
• Martin Kubů,
• Michal Mazur,
• Zdeněk Bastl and
• Jiří Čejka

Beilstein J. Org. Chem. 2015, 11, 2087–2096, doi:10.3762/bjoc.11.225

• developed [1][5][13]; most of them are based on surface modification by specially designed linkers providing covalent bond linkage between the support and Ru complex. Hoveyda–Grubbs type catalysts are also capable of direct (linker-free) immobilization by means of non-covalent interactions [8][14][15][16

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

• ]). Ethynylferrocenes are one of the most popular and extremely effective starting compounds in the creation of ferrocenyl polymers. They are widely used for making both polyferrocenylvinylenes (double bond linkers) [17][18][19][20][21] and polyethynylferrocenes (triple bond linkers) [22][23][24][25]. There are several

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

• . Under low temperature, this dynamic [2]catenane could be quantitatively generated. The intramolecular hydrogen bonds formed by the aromatic amide linkers remarkably enhanced the complexation of the porphyrin units towards the fullerene and the bipyridine ligand. Jiang further introduced amide subunits

• folding of the same series of benzene/triazole oligomers [10]. Recently, Jiang and co-workers reported that when fluorine or chlorine was introduced to the 2-position of the meta-substituted benzene linkers, the corresponding triazole oligomers folded to give new foldamers, which were stabilized by

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

• polymerization of tubulin in vitro. The same methodology might be applied to direct a drug by conjugation to a molecule binding to a specific receptor on cancer cells. Moreover, by using dicarboxylated linkers with a disulfide bridge, it was possible to generate dynamic libraries of dimeric hybrids based on

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• methylene linker, gave doubly reduced 42a as the major product. Pleasingly, however, the dioxadibenzenacyclododecaphane 41a was also obtained in a modest yield (13%). Diacids 40b and 40c were designed with rigid, planar phenyl ring linkers. TiO2 SCPC of the ortho-analogue 40b was more successful with the

Interactions between tetrathiafulvalene units in dimeric structures – the influence of cyclic cores

• Huixin Jiang,
• Virginia Mazzanti,
• Christian R. Parker,
• Søren Lindbæk Broman,
• Jens Heide Wallberg,
• Karol Lušpai,
• Adam Brincko,
• Henrik G. Kjaergaard,
• Anders Kadziola,
• Peter Rapta,
• Ole Hammerich and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2015, 11, 930–948, doi:10.3762/bjoc.11.104

• -ethynylpyridine linkers. When two TTFs are closer together via an ethyne spacer (4), the two waves are rather broad. In fact, a shoulder can be seen for each wave, which indicates weak interactions between the two units, not only for generating two TTF radical cation units, but also for the final generation of

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

• 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

• linkers. A) Force–distance curves where the rupture is not smooth but rather interrupted by a cluster of measurement points. This inter-rupture force is indicated by a red arrow. B) Same curve as in A) depicted as force vs time. C) Histograms of inter-rupture forces for the different dwell times

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

• 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

• [29], the fluctuations of the PEG linkers and hence the fluctuations of the whole ligand sum up to Δr = 0.5 nm. The shape of the RBA now is much broader, showing that the ligand is less affected by a mismatch between spacer length and distance between the binding pockets. Additionally, we obtain = 5

• attached via two PEG linkers. Linker length and binding range are set to be identical to the example presented in Figure 5b. The average end-to-end distance of the DNA spacer is either chosen to be equal to d (black, continuous line), or is chosen to be too short by 0.7 nm, which mimics the length of two

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

• generally low affinity between sugars and receptors and possibly also by the high flexibility of the polymeric mannose linkers [9]. High molecular flexibility causes a high degree of conformational entropy that negatively affects complex formation between ligands and receptors [23]. Also the design of the

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• diverse glycans could be iteratively introduced on amino acid linkers. Inspired by Shoda’s activation [40] which provides facile access to complex glycosyl azides from native carbohydrates, we subsequently applied reiterative CuAAC conjugation of glycans on propargyl glycine residues within a peptide [41

• instructions. To this end a pilot library of fourteen PNA-tagged glycoconjugates that included mannose disaccharides joined by linkers of different lengths were paired through hybridization, varying the ligand combinations and interligand distances. Measuring the affinity of 32 different assemblies against

• between the glycan units and the distinct spatial arrangement conferred by the different linkers. This library represents the largest array of heteroglycan conjugates reported to date. Based on the results obtained with the screen for LecA, a lectin intimately involved in the pathogenicity of P

First principle investigation of the linker length effects on the thermodynamics of divalent pseudorotaxanes

• Andreas J. Achazi,
• Doreen Mollenhauer and
• Beate Paulus

Beilstein J. Org. Chem. 2015, 11, 687–692, doi:10.3762/bjoc.11.78

• energies of association (Gibbs free (binding) energies) for divalent crown-8/ammonium pseudorotaxanes are determined by investigating the influence of different linkers onto the binding. Calculations are performed with density functional theory including dispersion corrections. The translational

• linker shows an enhanced binding strength due to electronic effects, namely the dispersion interaction between the linkers from the guest and the host. For the longer linkers this ideal packing is not possible due to steric hindrance. Keywords: density functional theory (DFT); dispersion correction

• different linkers. The shortest linker shows a much larger chelate cooperativity than the longer linkers due to non-innocent linkers that contribute to the binding. To analyze the individual contributions to the binding, we perform first principle calculations of the model system shown in Figure 1, which is

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

• per DNJ unit) [11][12]. In the following years, an impressive ever-growing number of multivalent iminosugars based on various scaffolds, ligands and linkers have been synthesized to further investigate the impact of multivalency on glycosidase inhibition [9][10][11][12][13][14][15][16][17][18][19][20