Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• molecules along the a-axis. EPR measurements Figure 4 demonstrates the X-band CW EPR spectra of nitroxide 6 in water/glycerol solution at 180 K and at room temperature with simulations (red) using the parameters listed in the caption. The electron spin relaxation of nitroxides with different bulky

• experimental spectra and the red lines are simulations for hfi, g-factor and correlation times of A(N) = [0.71; 0.71; 3.71] mT, g = [2.0087; 2.0055; 2.0019], tcorr = 0.53 ns (at 298 K). Synthesis of compound 1. Possible mechanism for the formation of 1. Synthesis of nitroxide 6. A proposed mechanism for

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

• date, CotB2 represents the best studied bacterial diterpene synthase. Its reaction mechanism has been addressed by isoptope labeling, targeted mutagenesis and theoretical computations in the gas phase, as well as full enzyme molecular dynamic simulations. By X-ray crystallography different snapshots of

• ], density functional theory calculations [33] as well as QM/MM simulations [37]. Variants of CotB2 open the route to a novel product portfolio with altered cyclic carbon skeletons, which can be converted into bioactive compounds by chemo-enzymatic methodologies. Modification descriptions are composed

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• force field within 5 kcal/mol energy ranges. Further optimization was carried out at DFT level using the B3LYP functional and the Def2TZVP basis set in the Gaussian 09 [36]. Simulations of ECD spectra were carried out with TD-DFT methods for conformers found in the range of 2.5 kcal/mol. The B3LYP

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• ). The first round of simulations (1–10 ns) of compound 1 docking into SERCA cavity with compound 1 constrained as described (simulation 1) showed the presence of hydrophobic interactions of ligand side chains with Phe256, Val263, Ile829 and the hydrophobic part of Gln259 amino acid residues. Gln259 was

• the main residue involved in hydrophilic interaction. Interestingly, during the simulations in water environment, compound 1 had the tendency to escape from the SERCA cavity. In simulation 2 of compound 1 rotated by 180° with constrained positions (10 ns), interactions with Phe256 and hydrophobic

• and Figure 5). During simulations with SERCA positioned in a phospholipid membrane (simulation 4; 1 ns), the free space between individual phospholipids in the cell membrane was filled. SERCA remained stable and tightly embedded in the membrane and did not show any tendency to escape from it. Compound

Functional panchromatic BODIPY dyes with near-infrared absorption: design, synthesis, characterization and use in dye-sensitized solar cells

• Quentin Huaulmé,
• Cyril Aumaitre,
• Outi Vilhelmiina Kontkanen,
• David Beljonne,
• Alexandra Sutter,
• Gilles Ulrich,
• Renaud Demadrille and
• Nicolas Leclerc

Beilstein J. Org. Chem. 2019, 15, 1758–1768, doi:10.3762/bjoc.15.169

• also a reduced energy driving force for charge separation at the TiO2 surface. To check this hypothesis, we performed TD-DFT simulations of the optical absorption spectra of the 4 representative dyes. The results reported in Figure 3 are fully consistent with the predictions from the one-electron

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

• disordered and mobile, and that the OH groups of the host β-CD may rotate [17]. Studies with molecular dynamics simulations have found only four water molecules inside the host β-CD cavity [18]. The energetics of the CD hydration/dehydration have been investigated as well. Experimental studies have been able

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• into the ice lattice [12], others investigated the adsorption process on different surfaces via atomic force microscopy [10][13][14]. The antifreeze activity has been correlated with long-range perturbation of hydration dynamics [15]. Latest molecular dynamics simulations suggest that AFGP reversibly

Transient and intermediate carbocations in ruthenium tetroxide oxidation of saturated rings

• Manuel Pedrón,
• Laura Legnani,
• Maria-Assunta Chiacchio,
• Pierluigi Caramella,
• Tomás Tejero and
• Pedro Merino

Beilstein J. Org. Chem. 2019, 15, 1552–1562, doi:10.3762/bjoc.15.158

• , the proposed asynchronous concerted mechanism. A deeper analysis of the full path of the reaction using MD calculations [29] would be needed in order to assess the synchronicity and life time of transient species [30]. The recent use of MD simulations has demonstrated that a single transition state

• some chemical behavior. Indeed, further theoretical studies on MD simulations would be needed to elucidate the lifetime of the transient carbocation [34][35]. These results demonstrate the one-step-two-stage character [42] of the ruthenium oxidations of alkanes in which H transfer and O–C bond

Host–guest interactions between p-sulfonatocalix[4]arene and p-sulfonatothiacalix[4]arene and group IA, IIA and f-block metal cations: a DFT/SMD study

• Valya K. Nikolova,
• Cristina V. Kirkova,
• Silvia E. Angelova and
• Todor M. Dudev

Beilstein J. Org. Chem. 2019, 15, 1321–1330, doi:10.3762/bjoc.15.131

• anchoring points for the positively charged guests. Cation–π interactions between the monoatomic cations and p-sulfonatocalix[4]arene in water are supposed (but not proven) to take part in the inclusion complex formation [31]. Mendes et al. have carried out molecular dynamics (MD) simulations of association

• upon binding has been noted [31]. A model of hydrated, by an average number of 10 water molecules, La3+ cation has already been used by Mendes et al. in the MD simulations of p-sulfonatocalix[4]arene association with rare-earth metal cations and organic cations in aqueous solutions [32]. The effect of

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• galectin-1 (pdb id 1GZW) and galectin-3 (pdb id 1KJL), respectively, and with the 4-fluorophenyltriazol ring protruding away from the protein. The simulations with 1b and galectin-1 converged toward a complex geometry in which the 4-fluorophenyltriazole extended along a shallow groove formed by Trp68-Gly69

• the weaker affinity by the corresponding 2-fluorophenyltriazole analogue 1d, because in the favored complex geometry of 1b introduction of a 2-fluoro atom would lead to this atom being close to either the Glu71 carboxylate or the triazole N3 lone pair. MD simulations with 1b positioned in a similar

Influence of per-O-sulfation upon the conformational behaviour of common furanosides

• Alexey G. Gerbst,
• Vadim B. Krylov,
• Dmitry A. Argunov,
• Maksim I. Petruk,
• Arsenii S. Solovev,
• Andrey S. Dmitrenok and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2019, 15, 685–694, doi:10.3762/bjoc.15.63

• overlapping signals J coupling constants were extracted from 2nd order spectra simulations using Bruker TopSpin software (DAISY). The obtained results (see Tables 1–3) showed good coincidence with previously published data for related monosaccharides [15][26][27]. As can be seen from Table 3, J coupling

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

• the 2:1:1 ratio expected on the grounds of numerical simulations. The separation of such a mixture would be unsuitable in view of a possible large-scale synthesis and application of the relevant nanosponge polymeric materials, because it should involve undesirable waste of time and materials. However

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• chains hinders their ordering [19] so that the only interesting are regular multiblock copolymers that can form structures with more than one periodicity [20]. Meanwhile, theoretical investigations [21][22][23] and computer simulations [24][25][26][27] gradually revealed the high potential of random

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, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• as the 6’F-bc4,3-DNA. Furthermore, duplexes of a 6’F-bc4,3-modified strand paired to RNA unveiled in the MD simulations a flexible minor groove distance [37]. This flexibility is thought to play a crucial role for the fitting of the duplex into the DNA-binding channel and the phosphate-binding pocket

• of the enzyme. Furthermore, the phosphate-binding pocket requires a large distortion of the backbone angle α in order that the phosphate group of the AON can be positioned in it [50][51]. The 6’F-bc4,3-DNA containing strand also complied with this requirement according to the MD simulations [37

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• modification might be a substrate for RNase H. Keywords: DNA/RNA affinity; fluorinated cyclopropanes; fluorinated nucleic acids; molecular dynamics simulations; sugar modified nucleosides; Introduction A powerful strategy for the treatment of various disorders like cancer, viral and inherited diseases is the

• unit and possibly positively impact the duplex stability. Here we report on the synthesis of the two 6’F-bc4,3 pyrimidine analogs with the base T and C, their incorporation into DNA, their biophysical properties, as well as a structural analysis by molecular dynamics simulations of hybrid DNA and RNA

• structure, giving evidence of mixed A/B-type helices. Molecular modeling To gain more information on the structural features of the 6’F-bc4,3 modification, we performed molecular dynamics simulations of the modified duplexes. We first calculated the potential energy profile versus pseudorotation phase angle

Dispersion-mediated steering of organic adsorbates on a precovered silicon surface

• Lisa Pecher,
• Sebastian Schmidt and
• Ralf Tonner

Beilstein J. Org. Chem. 2018, 14, 2715–2721, doi:10.3762/bjoc.14.249

• dispersion or covalent interactions. At very short distances, Pauli repulsion creates the repulsive potential wall. Experimental studies in combination with Monte Carlo simulations have shown that growth of 1 on Si(001) results in non-statistical formation of chains with an average distance of 1.5 to 2

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• not been reported in the literature, with the exception of electrocatalytic systems [26][27]. To achieve functional simulations of B12 enzymes under non-enzymatic conditions, our strategy is to fabricate the artificial enzymes by combining a functional equivalent of B12 and that of an apoenzyme

• catalytic reactions We deeply investigated the electrochemical catalytic reactions mediated by 1 and related complexes and succeeded in the functional simulations of MMCM-type 1,2-migration reactions [42]. For example, when 2,2-bis(ethoxycarbonyl)-1-bromopropane was selected as a model substrate, the 1,2

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• hydrogen bonding. Detailed electrochemical measurements and digital simulations revealed the ring still to be bound to the ammonium station in the TTF●+ state. However, after double oxidation a wheel distribution of 1:1 between the ammonium and the isoxazole station was found indicating a dynamic motion

Coordination-driven self-assembly vs dynamic covalent chemistry: versatile methods for the synthesis of molecular metallarectangles

• Li-Li Ma,
• Jia-Qin Han,
• Wei-Guo Jia and
• Ying-Feng Han

Beilstein J. Org. Chem. 2018, 14, 2027–2034, doi:10.3762/bjoc.14.178

• ). Notably, the isolated yields of the metallarectangles are higher than the overall yields of the two-step method. Since attempts to obtain X-ray quality single crystals of the target metallarectangles were unsuccessful, molecular simulations were performed to gain further insight into the structures of the

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• attributed to [9 + H]3+, [9 + 2H]4+ and [9 + 3H]5+ by comparison between the experimental and theoretical isotope distributions (see Supporting Information File 1). Molecular modeling simulations were carried out to provide insights into the size and morphology of conjugate 9. An optimized geometry is

• presented in Figure 2, as issued from a molecular dynamics (MD) simulations. The ruthenium complex and the RGD units are spatially well-separated thanks to their grafting on opposite faces of the rigid calixarene-based platform. In this conformation, the distances between the Ru atom and each of the nearest

• carbon atoms of RGDfK units exceed 30 Å. Along the MD simulations, we noticed that the Ru complex remained far from the cyclic pentapeptides. This is due to the fact that the linkers of each arm are smaller than the size of the calixarene platform, preventing contacts between the Ru complex and the RGDfK

Host–guest complexes of conformationally flexible C-hexyl-2-bromoresorcinarene and aromatic N-oxides: solid-state, solution and computational studies

• Rakesh Puttreddy,
• Ngong Kodiah Beyeh,
• S. Maryamdokht Taimoory,
• Daniel Meister,
• John F. Trant and
• Kari Rissanen

Beilstein J. Org. Chem. 2018, 14, 1723–1733, doi:10.3762/bjoc.14.146

• conformer space in these simulations, no constraints were enforced on either N-oxide or acetone molecules. The low energy structures obtained from these OPLS-2005 searches were then further analysed using DFT-based techniques [45][46][47]. The resulting optimised geometries of the 3@BrC2, 3@BrC3 and 3@BrC6

The phenyl vinyl ether–methanol complex: a model system for quantum chemistry benchmarking

• Dominic Bernhard,
• Fabian Dietrich,
• Mariyam Fatima,
• Cristóbal Pérez,
• Hannes C. Gottschalk,
• Axel Wuttke,
• Ricardo A. Mata,
• Martin A. Suhm,
• Melanie Schnell and
• Markus Gerhards

Beilstein J. Org. Chem. 2018, 14, 1642–1654, doi:10.3762/bjoc.14.140

• in black is compared with simulations, based on fitted parameters that can be assigned to the OH–O’ isomer (complex 1, red) for the PVE–MeOHcomplex. The observed complex has a clear splitting pattern due to the internal rotation of the methyl group of methanol, labeled with A and E. The experimental

Are dispersion corrections accurate outside equilibrium? A case study on benzene

• Tim Gould,
• Erin R. Johnson and
• Sherif Abdulkader Tawfik

Beilstein J. Org. Chem. 2018, 14, 1181–1191, doi:10.3762/bjoc.14.99

• interest in how to accurately model them. Multiple families of approaches for including dispersion forces in quantum chemical simulations now exist, mostly based around the principle of improving density functional theory (DFT) calculations (see, e.g., some key and recent summaries [3][5][13][14]) through

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93