Synthesis, liquid crystalline behaviour and structure–property relationships of 1,3-bis(5-substituted-1,3,4-oxadiazol-2-yl)benzenes

• Afef Mabrouki,
• Malek Fouzai,
• Armand Soldera,
• Abdelkader Kriaa and
• Ahmed Hedhli

Beilstein J. Org. Chem. 2020, 16, 149–158, doi:10.3762/bjoc.16.17

• focal conic texture with unusually narrow ellipses of a SmA phase. Compound 4a presents a mosaic SmB phase where the molecules are organized in a hexagonal network as shown in Figure 2b. The low average of enthalpy value (1.89 J/g) given in Table 2 is due to the first order phase transition marked by

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• photopharmaceutical antimitotics in a series of cell-free and cellular assays, and allowed robust photocontrol over tubulin polymerisation, microtubule (MT) network structure, cell cycle, and cell survival. Conclusions: HITubs represent a powerful addition to the growing toolbox of photopharmaceutical reagents for MT

• . This suggests that the same specific direct action can be reproduced in cellulo, and that effects on auxiliary cellular systems dependent upon the MT cytoskeleton can likely be downstream effects of MT depolymerisation. We next investigated the HITubs’ isomer-dependent effects on the MT network inside

• cells, focusing on the active analogues HITub-4 and HITub-2 in comparison with inactive HITub-5 as a control (Figure 5). By reducing tubulin polymerisation dynamics, CDI treatment should first disorganise and then depolymerise the cellular MT network. We performed immunofluorescence staining of the MT

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• Information File 528: Experimental procedures, compound characterization data and NMR spectra. Acknowledgements KRB thanks the National Research Foundation (South Africa) and the SABINA network for funding. DP and DB gratefully acknowledge the Department of Science and Technology Biocatalysis Initiative

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• : mutations. Engineering of terpenoid pathways. a) Metabolic network of terpenoid biosynthesis. Toxic intermediates are labeled with skull signs and known enzyme inhibition by intermediates is indicated. Bottleneck enzymes that have been subjected to optimization/engineering are highlighted in bold. Two novel

Influence of the cis/trans configuration on the supramolecular aggregation of aryltriazoles

• Sara Tejera,
• Giada Caniglia,
• Rosa L. Dorta,
• Andrea Favero,
• Javier González-Platas and
• Jesús T. Vázquez

Beilstein J. Org. Chem. 2019, 15, 2881–2888, doi:10.3762/bjoc.15.282

• , and 14 were obtained by SEM (Figure 2). Analyses of these images revealed typically fibrous networks for all except 10. Compound 7f (trans) showed a dense, thin, short, and interlaced/tangled fiber network. The corresponding α-anomer 8f (cis) exhibited an irregular, porous, and dense structure having

• thin and short fibers. The xerogel of compound 12 showed long, thin, and relatively straight fibers, with lack of torsion, as well as regularity of the network. Its cis stereoisomer 14 showed a fibrous network, but of much shorter length. However, the gel of compound 10 showed a different morphology

Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum

• Xinlu Chen,
• Tobias G. Köllner,
• Wangdan Xiong,
• Guo Wei and
• Feng Chen

Beilstein J. Org. Chem. 2019, 15, 2872–2880, doi:10.3762/bjoc.15.281

• lineage-specific functions. P. polycephalum has a unique biology. It sends information in the form of nutrient concentrations through the tubular network using the streaming cytoplasm [30]. It will be interesting to test whether volatile terpenoids function in internal communication of P. polycephalum

Carbazole-functionalized hyper-cross-linked polymers for CO₂ uptake based on Friedel–Crafts polymerization on 9-phenylcarbazole

• Dandan Fang,
• Xiaodong Li,
• Meishuai Zou,
• Xiaoyan Guo and
• Aijuan Zhang

Beilstein J. Org. Chem. 2019, 15, 2856–2863, doi:10.3762/bjoc.15.279

• , 0.6 cm3 g−1) [20][33]. This may be the result of that excessive temperature caused excessive crosslink at the beginning of the reaction, the plethora network cocooned a part of the reaction center, and prevented it from further cross-linking (micropores), hence it formed macropores. All that indicated

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• . DFT computations with inclusion of implicit solvation support a complex network of phenyl and biphenyl shifts, with barriers to rearrangement in the range of 10–21 kcal/mol. Consistent with experiments, the lowest energy arenium ion located on this surface is due to protonation of m,p'-quaterphenyl

• through 1,2-biphenyl migration, with a similar network of interconversions. Based on the behavior of terphenyl which favors meta substitution at equilibrium, we initially hypothesized that m,m'-quaterphenyl (14) would likely be the major isomer at equilibrium. Only brief exploration of quaterphenyl

• solvation support a complex network of phenyl and biphenyl shifts, with barriers to rearrangement in the range of 10–21 kcal/mol. Consistent with experiments, the lowest energy arenium ion located on this surface is due to protonation of m,p'-quaterphenyl. This supports thermodynamic control based on

Anion-driven encapsulation of cationic guests inside pyridine[4]arene dimers

• Anniina Kiesilä,
• Jani O. Moilanen,
• Anneli Kruve,
• Christoph A. Schalley,
• Perdita Barran and
• Elina Kalenius

Beilstein J. Org. Chem. 2019, 15, 2486–2492, doi:10.3762/bjoc.15.241

• the coordination of the Me4N+ cation at the lower rim has only a minor effect on the hydrogen-bond network of 12. To verify complexation of separate ion pairs, the geometry optimization was carried out also for [12 + Me4Nendo + Iendo] , which showed that the cavity of 12 is too small for the

• absence of the dispersion force, the positively charged Me4N+ cation, therefore, prefers interactions with the electron-rich oxygen atoms of the hydrogen-bond network to the positively charged lower rim isobutyl groups. The calculated interaction energies are listed in Table S2 (Supporting Information

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• involved in coordination of water molecules in the water network around the catalytic Mg2+ ions. The pyrophosphate sensor motif In a recent review, the presence of a “pyrophosphate sensor”, an arginine 46 amino acid residues upstream of the NSE motif, was discussed as a universal feature of bacterial TPSs

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• incubated for 0.5 h with 1 µM of dye 15 and 100 nM of MitoTracker® Green FM, washed and imaged with excitation at 470 nm (380 µW) and 652 nm (7.5 µW). Confocal images are color shift and background corrected, scale bar 5 µm. STED and confocal images of the mitochondrial network in living HeLa cells stained

1,2,3,4-Tetrahydro-1,4,5,8-tetraazaanthracene revisited: properties and structural evidence of aromaticity loss

• Arnault Heynderickx,
• Sébastien Nénon,
• Olivier Siri,
• Vladimir Lokshin and
• Vladimir Khodorkovsky

Beilstein J. Org. Chem. 2019, 15, 2059–2068, doi:10.3762/bjoc.15.203

• , 6a forms a 2D supramolecular network involving the chloride anion Cl1 as an intermolecular connector between the molecules. Each anion interacts with the two N–H protons of the associated dications (Figure 10). In spite of the asymmetrical structure, the X-ray structure of 7a exhibits the same trend

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• cross-talk network amongst these targets and signaling pathways are considered to be responsible for the multiple anticancer activities of triptolide [18][19][20][21][22][23][24]. Triptolide could also suppress inflammation and stimulate cytoprotection by regulating pro-inflammatory cytokines and

Halide metathesis in overdrive: mechanochemical synthesis of a heterometallic group 1 allyl complex

• Ross F. Koby,
• Nicholas R. Rightmire,
• Nathan D. Schley,
• Timothy P. Hanusa and
• William W. Brennessel

Beilstein J. Org. Chem. 2019, 15, 1856–1863, doi:10.3762/bjoc.15.181

• network structure [34]. Intermolecular Cs…CH3 distances below 3.5 Å, however, do not appear to have been previously reported [35]. The shortest distance in [CsKA'2], at 3.44 Å, is 2.0 Å less than the sum of the appropriate van der Waal’s radii (although less precisely located, the corresponding Cs…H

Water inside β-cyclodextrin cavity: amount, stability and mechanism of binding

• Stiliyana Pereva,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2019, 15, 1592–1600, doi:10.3762/bjoc.15.163

• rim is the preferred mode of coordination (n = 2; Figure 2, structure a). In this construct the water dimer not only connects two oppositely located OH groups from the rim, but additionally interacts with four other OH groups and forms an elaborate hydrogen-bond network that almost occludes the

• evaluated at the M062X/6-311++G(d,p)//M062X/6-31G(d,p) level of theory (Supporting Information File 1, Table S1). As a general trend, it was observed that expanding the intramolecular hydrogen bond network upon each H2O addition (comprising the water–water and water–cyclodextrin interactions) enhances the

• location. Inside the β-CD cavern a water cluster is formed by a stepwise consecutive coordination of water guests. The cluster is stabilized by a network of hydrogen bonds mostly between the water molecules themselves and interactions between water ligands and cyclodextrin walls. The general trends

Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration

• Sora Park and
• Jeung Gon Kim

Beilstein J. Org. Chem. 2019, 15, 963–970, doi:10.3762/bjoc.15.93

• showed that poly(ethylene oxide) end group modification is facile under ball-mill conditions [16]. Network polymeric material fabrications were also realized using ball milling [17][18][19]. As mentioned, many mechanochemical reactions realized exceptional efficiencies that solution synthesis cannot

Polyaminoazide mixtures for the synthesis of pH-responsive calixarene nanosponges

• Antonella Di Vincenzo,
• Antonio Palumbo Piccionello,
• Alberto Spinella,
• Delia Chillura Martino,
• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2019, 15, 633–641, doi:10.3762/bjoc.15.59

• with CyCaNSs. This fact was explained assuming that a diazidoalkane is a less effective reticulating agent than a heptakisazido-β-cyclodextrin, simply because of the lesser number of reactive azide groups present. Hence, we reasoned that the polymer network formation process could have been improved by

• the accomplishment of the reticulation reaction and the formation of the polymeric network. In particular, the IR spectrum (Figure 2) shows the disappearance of the signals in the range of 3310–3260 cm−1 and of the intense signal at 2103 cm−1, attributable to the Csp–H stretching of Ca and to the

• decreases on increasing the pH, clearly indicating that inclusion is favorably affected by the presence of positive charges on the polymer network due to protonation of amine basic sites. Consistently, the behavior of the diamine derivative 10 is reversed (inclusion decreases on decreasing the pH). A

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• feasible metabolic intermediates [13][14][15][16]. In a subsequent realization phase, the corresponding enzymes to realize the theoretical network are identified and/or engineered and a first version of the synthetic network is reconstructed. The network is further optimized or evolved in following rounds

• synthetic metabolic networks From above examples it becomes evident that for building completely novel pathways and/or complex reaction cascades, resources are required that provide synthetic biologists with the information to find individual enzymes for a given synthetic metabolic network. More than 116

• synthetic network, most likely because they lack a common evolutionary history that selects for stringent substrate specificity [57]. These unwanted side reactivities are able to compete with the wanted reactions of the synthetic network and can lead to the accumulation of dead-end products, thus decreasing

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• available (+)-fenchone has 98% enantiomeric purity, BIFOXSi(OH)2 can be further purified. rac-BIFOXSi(OH)2 crystallizes as a dimer from toluene (Figure 14). BIFOXSi(OH)2 (9) crystallizes as a tetramer from n-hexane (Figure 15), where six OH groups build a network of hydrogen bonds. Thus the polar core is

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• interchangeable (Table 1). Model E: active site of BFDC with (R)-mandelate bound In model E, in which the active site of BFDC contains the inhibitor (R)-mandelate, the hydrogen-bonding network is very similar to that of benzoylformate in model D. However, as shown in Figure 6, the benzylic hydroxy group provides

Adhesion, forces and the stability of interfaces

• Robin Guttmann,
• Johannes Hoja,
• Christoph Lechner,
• Reinhard J. Maurer and
• Alexander F. Sax

Beilstein J. Org. Chem. 2019, 15, 106–129, doi:10.3762/bjoc.15.12

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• (Figure 1) [44][45][46]. Tubulysins were originally discovered and isolated from myxobacteria [47][48], with picomolar in vitro activities [45][46][49][50][51][52][53][54], that are caused by a destabilization and degradation of the microtubuli network undermining its function in mitosis of eukaryotic

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• are generally regarded to be more rigid than disordered or α-helix structures [30][31]. β-Barrels are structural motifs found in numerous proteins in which (mostly) antiparallel β-strands twist and coil to form closed, quasi-cylindrical structures held together by a network of hydrogen bonds [32

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• coordinate population-wide group behaviours in the infection process like concerted secretion of virulence factors. One very important signalling network is the Pseudomonas quinolone signal (PQS) QS. With the aim to devise novel and innovative anti-infectives, inhibitors have been designed to address the

• network with compensatory mechanisms ensuring environmental adaptability and fine-tuned control of associated virulence genes (Figure 1). All four have been studied in the pursuit of quorum sensing inhibitors (QSI) to be used as blockers of P. aeruginosa pathogenicity [11][23]. Typically, a QS system of

• complex network of biosynthetic pathways and effector molecules renders selection of the perfect point for intervention difficult. Due to their rather peripheral role in AQ synthesis, PqsH and PqsL, have not been of significant interest for QSI discovery to date. However, all enzymes of the primary

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• -dimensional network consisting of a linear unit connected by hydrogen bonds between N3–H and the triazole N3’’ of a second molecule (Figure 3, Supporting Information File 1, Figures S3 and S4). Additionally, the molecules are bridged by water molecules connecting O2 of the base moiety and N2’’ of the triazole

• ellipsoids are drawn at the 50% probability level and H-atoms are shown as small spheres of arbitrary size. Hydrogen bonds are shown as dashed lines. The crystal packing of 8 shows the intramolecular hydrogen-bonding network (projection parallel to the x-axis). N- and S-conformation for cyclonucleoside 8. B