Chemical systems, chemical contiguity and the emergence of life

• Terrence P. Kee and
• Pierre-Alain Monnard

Beilstein J. Org. Chem. 2017, 13, 1551–1563, doi:10.3762/bjoc.13.155

• eutectic phase in water/ice [35][36][37], but computer modelling [38] and preliminary wet-chemistry experiments, which show a selective accumulation of long oligomers [39], already hint at the possibility of similar processes taking place in mineral formations. In the same environments, short peptides

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• ). Although this is based on the analysis of only two metal cations, studies using dynamic modelling have displayed similar, limited impact of different metal cations upon merocyanine ε values [34] so we have cautious confidence in the validity of this approach. All compounds, including control compound 9

Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• accurate modelling and has revealed fundamental features that would otherwise be too difficult to comprehend [24]. It is generally accepted that complex molecular networks, like electrical circuits, are constructed from simpler modules (network motifs) and control the regulatory functions as well as the

• lay out a general strategy for the design and implementation of CRNs that operate under out-of-equilibrium conditions and show complex behavior. We believe that new approaches are needed to build molecular networks, firmly rooted in (synthetic) chemistry but incorporating mathematical modelling and

• molecular level understanding of networks ultimately allows us to ask questions about the relationship between individual molecules or reactions and the robustness or resilience of the network that cannot otherwise be asked in other systems [97][98]. Mathematical modelling Our network is inherently

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• parameters (network weights) and minimizing overfitting. While deep learning is attracting much attention in fields like image and voice recognition, it may not be superior to three layer ‘shallow’ neural networks for modelling chemical, molecular and biological properties. An important mathematical theorem

• selection methods provide a valuable adjunct to molecular and materials modelling methods based on structure–activity/property regression and neural networks models. Such machine learning-based models have been used successfully in pharmaceutical discovery for several decades. More recently, they have been

• applied to modelling materials other than small, discrete, organic molecules, with considerable success. Many types of materials are considerably more complex than small organic molecules (e.g., with size and weight distributions, diverse shapes, variable degree of crosslinking, different degrees of

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• interaction with the protein led to the development of different molecular modelling methods. A somehow indirect application of the fine specificity of the binding of oligosaccharides to lectins has been elegantly developed to solve the phase problem in protein crystallography. Selenium-labelled carbohydrates

• number of reflections to permit structural determination based on the data alone. Such a lack of experimental data must be complemented by modelling techniques. As such, the process of structural elucidation combines the calculation of diffraction intensities from various low energy models with those

• domains of the two allomorphs of starch granules found in cereal and tubers had been established from a series of experimental observations (X-ray and electron crystallography) and molecular modelling. While displaying differences in their mode of interactions, both allomorphs are characterized by a

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• three dimensional conformation of the archazolids by NMR methods, molecular modelling and chemical derivatizations [59][60]. During these studies, they became aware that C2–C5 diene of acyclic analogs would be very labile towards isomerization. However, such processes would be suppressed in the

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

• Simon Drescher,
• Vasil M. Garamus,
• Christopher J. Garvey,
• Annette Meister and
• Alfred Blume

Beilstein J. Org. Chem. 2017, 13, 995–1007, doi:10.3762/bjoc.13.99

• 83 Å, and Nagg is about 121 ± 5 bolalipid molecules per micelle. Modelling of the scattering curves by ellipsoids of revolution yields values for the semi axes a = b = 22 Å and c = 47 Å. The results of SANS measurements are summarized in Table 1. Mixing behaviour with saturated phosphatidylcholines

The effect of cyclodextrin complexation on the solubility and photostability of nerolidol as pure compound and as main constituent of cabreuva essential oil

• Joyce Azzi,
• Pierre-Edouard Danjou,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2017, 13, 835–844, doi:10.3762/bjoc.13.84

• solid complexes was assessed by HPLC. The structural characterization of CD/trans-Ner inclusion complex was then conducted by NMR spectroscopy followed by molecular modelling studies. The effect of encapsulation on the Ner photostability was also carried out over time under UVB irradiation. AL-type

• modelling studies revealed the most stable structure for trans-Ner inside the CD cavity with the OH group oriented towards the wider rim of the CD. Finally, CD encapsulation of Ner as pure compound or as main component of the cabreuva EO, protected it from degradation. This effect was more pronounced as the

• employed using a competition method. The solubility of cabreuva EO rich in trans-Ner was also assessed with HP-β-CD using the total organic carbon method developed in our laboratory [17]. In addition, 1H and 2D ROESY NMR experiments and molecular modelling were performed to investigate the orientations of

Synthesis and optical properties of new 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles

• Anastasia S. Kostyuchenko,
• Tatyana Yu. Zheleznova,
• Anton J. Stasyuk,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2017, 13, 313–322, doi:10.3762/bjoc.13.34

• -04313-Sibiria-a; 16-33-00340 mol_a) and the Ministry of Education and Science of the Russian Federation (the Agreement number 02.a03.21.0008). A. J. S. gratefully acknowledges The Interdisciplinary Centre for Mathematical and Molecular Modelling of the University of Warsaw (ICM) for computational

Self-optimisation and model-based design of experiments for developing a C–H activation flow process

• Alexander Echtermeyer,
• Yehia Amar,
• Jacek Zakrzewski and
• Alexei Lapkin

Beilstein J. Org. Chem. 2017, 13, 150–163, doi:10.3762/bjoc.13.18

• ; flow chemistry; process modelling; self-optimisation; Introduction The development of manufacturing processes to produce functional molecules, such as pharmaceuticals or fine chemicals, often relies on experience and trial-and-error, rather than on mechanistic process models [1]. The only reason for

• ]. Performing MBDoE in the process modelling software gPROMS [22] resulted in a design indicating the experimental conditions, the reaction times and the number of samples required in each experiment for the estimation of a particular parameter or the combination of parameters. Table 2 shows the different

3D printed fluidics with embedded analytic functionality for automated reaction optimisation

• Andrew J. Capel,
• Andrew Wright,
• Matthew J. Harding,
• George W. Weaver,
• Yuqi Li,
• Russell A. Harris,
• Steve Edmondson,
• Ruth D. Goodridge and
• Steven D. R. Christie

Beilstein J. Org. Chem. 2017, 13, 111–119, doi:10.3762/bjoc.13.14

• systems destructive to the majority of devices manufactured via stereolithography, polymer jetting and fused deposition modelling processes previously utilised for this application. These devices were integrated with commercially available flow chemistry, chromatographic and spectroscopic analysis

• of using 3D printing to produce microfluidic devices using AM techniques such as stereolithography (SL) [11], polymer jetting and fused deposition modelling (FDM) [12][13]. There is therefore considerable interest in the optimisation of chemical systems using this type of multifunctional continuous

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• modelling and chemical lead optimization. Examples of successful inhibitors are represented by the scaffolds of various 2-benzamidobenzoic acids [11][25][26], 2-nitrophenyl derivatives [27][28][29], ureidothiophene-2-carboxylic acids [24][30], and catechol-based compounds [31]. Many promising in vitro

• decrease in the production of the virulence factors pyocyanine and pyoverdine [32]. So far only laborious enzyme-based assays, docking studies or modelling resulted in new scaffolds. We were thus interested, if our probes could be applied as a simple tool to discover novel scaffolds or chemical PqsD

The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot

• Philip J. Kitson,
• Stefan Glatzel and
• Leroy Cronin

Beilstein J. Org. Chem. 2016, 12, 2776–2783, doi:10.3762/bjoc.12.276

• prusa i3 model (see Figure 1). This is a fused deposition modelling (FDM)-type 3D printer, meaning it works on the principle of using a movable heated print head which extrudes molten or semi-molten material in pre-defined patterns onto a print bed by moving the heated extruder in the x and y directions

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• (cN-II), an enzyme involved in the regulation of purine nucleotide pools. NMR and molecular modelling studies showed that a few derivatives adopted similar structural features to IMP or GMP. Five derivatives were identified as modest inhibitors with 53 to 64% of cN-II inhibition at 1 mM. Keywords

• inhibition and molecular modelling studies All derivatives were assayed for their ability to inhibit the human 5’-nucleotidase activity in comparison to previously published derivative (UA1776), using a rapid in vitro assay. Briefly, the enzyme catalyzes the hydrolysis of IMP into inosine and inorganic

• synthesis of derivatives 1a–q. Summary of the in vitro inhibition assays performed on human recombinant cN-II in the presence of the various derivatives and docking scores obtained from molecular modelling calculation. Supporting Information Supporting Information File 207: Description of the materials and

On the mechanism of imine elimination from Fischer tungsten carbene complexes

• Philipp Veit,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2016, 12, 1322–1333, doi:10.3762/bjoc.12.125

• calculations. The calculated transition states exhibit a single imaginary frequency and they were additionally verified by intrinsic reaction coordinate (IRC) calculations. Solvent modelling was done employing the integral equation formalism polarizable continuum model (IEFPCM, toluene). The approximate free

Is conformation a fundamental descriptor in QSAR? A case for halogenated anesthetics

• Maria C. Guimarães,
• Mariene H. Duarte,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2016, 12, 760–768, doi:10.3762/bjoc.12.76

• high level calculations (in a receptor-free environment) in QSAR modelling was evaluated using a comparative study of the optimized and bioactive conformations of the fluorinated anesthetic isoflurane, which binds to a 4-helix bundle protein (apoferritin) [12] and to the integrin LFA1 enzyme [13

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• to these characterization methods, molecular modelling analysis can afford further clues to select the suitable CD derivative for one specific pesticide. This could also support the rational design of new macrocyclic compounds able to strongly interact with organophosphates. The structure of the

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

• ], where the local details of the interaction among a few molecules were investigated. Here the atomistic modelling study takes in account an increasingly large number of molecules in vacuo, taken as an approximation of a nonpolar and weakly interacting solvent, modelled in a cell with periodic boundary

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

• Mino R. Caira,
• Susan A. Bourne,
• Halima Samsodien and
• Vincent J. Smith

Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281

• host molecule. This necessitated reduction of the s.o.f. of the latter methyl group from 1.0 to 0.5. The net effect was that despite partial methylation of O3–H on G1, appropriate modelling of disordered residues resulted in retention of the nominal formula for the DIMEB molecule, namely C56H98O35. The

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• widely studied by both modelling and experiment [28][29]. The rate of reaction of NaOCl and amines at high pH is very fast with a second order rate constant, kobs of 1.52 × 105 L·mol−1·min−1 reported for dimethylamine [30]. In this case it is the rate of mass transfer of the reagents, partitioned between

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• recent literature. Applications span all aspects of enzyme technology including isolated biocatalysts, immobilised biocatalysts, whole-cell catalysts and bioelectrocatalytic systems. Theoretical studies modelling potential formatotrophic organisms showed significant promise for such systems [112

2-Hetaryl-1,3-tropolones based on five-membered nitrogen heterocycles: synthesis, structure and properties

• Yury A. Sayapin,
• Inna O. Tupaeva,
• Alexandra A. Kolodina,
• Eugeny A. Gusakov,
• Vitaly N. Komissarov,
• Igor V. Dorogan,
• Nadezhda I. Makarova,
• Anatoly V. Metelitsa,
• Valery V. Tkachev,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2015, 11, 2179–2188, doi:10.3762/bjoc.11.236

• solution (method B) is similar to that considered previously for the reaction of o-chloranil with 2-methylquinolines [19] which has been studied by means of DFT PBE0/6-311+G** modelling (Scheme 3, Table 1). At the initial stage, the aldol condensation of the methylene-active heterocyclic compounds with o

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• spectroscopy and molecular modelling. The reaction kinetics and mechanistic aspects of this transformation are discussed. These rearrangements provide a facile synthesis of novel macrolide scaffolds. Keywords: configuration; conformation; 6-O-methyl-9(E)-hydroxyiminoerythronolide A; reaction mechanism

• antibiotic. This 14-membered macrolide contains a [4.4]spiroketal unit connecting 6-C–O–9-C–O–12-C. Stereochemistry at position 9-C of this spiroketal was determined by combination of NMR spectroscopy and molecular modelling [42]. The kinetics of its formation has also been extensively studied [43][44][45

• less stable nonanomeric form [23]. To determine the configuration at 9-C and elucidate the conformation of 2, nOe analysis was performed (Tables SI1 and SI2, in Supporting Information File 1), followed by molecular modelling. Very strong nOe correlations between 2-H, 5-H and 10-H observed in both DMSO

Surprisingly facile CO₂ insertion into cobalt alkoxide bonds: A theoretical investigation

• Willem K. Offermans,
• Claudia Bizzarri,
• Walter Leitner and
• Thomas E. Müller

Beilstein J. Org. Chem. 2015, 11, 1340–1351, doi:10.3762/bjoc.11.144

• further study was limited to models with mer,mer-configuration. Here, the salen ligand coordinates the central cobalt atom in a square-planar fashion, whereby the trans-ligand L is located in the lower and 2-hydroxyethoxide in the upper hemisphere, respectively. The modelling of the insertion reaction