3-Pyridinols and 5-pyrimidinols: Tailor-made for use in synergistic radical-trapping co-antioxidant systems

• Luca Valgimigli,
• Daniele Bartolomei,
• Riccardo Amorati,
• Evan Haidasz,
• Jason J. Hanthorn,
• Susheel J. Nara,
• Johan Brinkhorst and
• Derek A. Pratt

Beilstein J. Org. Chem. 2013, 9, 2781–2792, doi:10.3762/bjoc.9.313

• traces with numerical simulations based on Scheme 3 using Gepasi 3.0 software, as previously described [45]. FTIR spectroscopy. Spectra were recorded at 298 K in a Nicolet Protegé 460 FTIR spectrometer under nitrogen atmosphere using a sealed KBr cell with optical path of 0.5 mm. Solutions of the test

Structure elucidation of β-cyclodextrin–xylazine complex by a combination of quantitative ¹H–¹H ROESY and molecular dynamics studies

• Syed Mashhood Ali,
• Kehkeshan Fatma and
• Snehal Dhokale

Beilstein J. Org. Chem. 2013, 9, 1917–1924, doi:10.3762/bjoc.9.226

• mechanics and ROESY data recorded with 0.5 s mixing time, but intermolecular peaks on both sides of the diagonal were clear in that case. Molecular dynamics Molecular dynamics simulations for only aromatic ring were performed. All the calculations were performed using CS Chem3D Pro (Cambridge Soft Corp.) in

• Allinger’s force field. Simulations were performed by placing the aromatic ring of xylazine near the mouth of the β-CD cavity along the z-axis either on the narrow (N) or wide (W) side (Figure 6). The carbon skeleton of the β-CD was kept static but other atoms and the xylazine molecule were allowed to move

• then calculated the summed peak intensity ratio ΣΙH-1/ΣΙH-2 for two frames from the narrow side (Frame 105 and 118) and one frame from the wider side (Frame 132) obtained in molecular dynamics simulations. The interproton distances between aromatic protons of xylazine and cavity protons were obtained

Self-assembly of 2,3-dihydroxycholestane steroids into supramolecular organogels as a soft template for the in-situ generation of silicate nanomaterials

• Valeria C. Edelsztein,
• Andrea S. Mac Cormack,
• Matías Ciarlantini and
• Pablo H. Di Chenna

Beilstein J. Org. Chem. 2013, 9, 1826–1836, doi:10.3762/bjoc.9.213

• model of self-assembly through multiple intermolecular hydrogen bonds between the 1,2-dihydroxy system, which is based on experimental data and computational simulations revealing the importance of the di-axial orientation of the hydroxy groups for the one-dimensional self-assembly. Under controlled

True and masked three-coordinate T-shaped platinum(II) intermediates

• Manuel A. Ortuño,
• Salvador Conejero and
• Agustí Lledós

Beilstein J. Org. Chem. 2013, 9, 1352–1382, doi:10.3762/bjoc.9.153

• at work in solution. Recently, ab initio molecular dynamics (AIMD) simulations of some representative T-shaped Pt(II) complexes (T5b, A2b and A11a), performed in explicit dichloromethane solvent, have provided a detailed description of the mechanism by which the equivalence of signals takes place

• [106]. Simulations showed that the dynamics of the agostic interaction in solution strongly depends on the complex. Contingent upon the strength of the agostic interaction and the flexibility of the ligand, several events related with the occupation of the fourth coordination site by an agostic bond

Space filling of β-cyclodextrin and β-cyclodextrin derivatives by volatile hydrophobic guests

• Sophie Fourmentin,
• Anca Ciobanu,
• David Landy and
• Gerhard Wenz

Beilstein J. Org. Chem. 2013, 9, 1185–1191, doi:10.3762/bjoc.9.133

• by means of docking simulations. Measured binding free energies were plotted as a function of the simulated inclusion enthalpies (Figure 6), defined as the enthalpy differences between the inclusion compounds and the free species. A significant linear correlation was obtained, confirming that the

• for benzene derivatives and 7, 10, 12 and 15 mL for cyclohexane derivatives, respectively). Molecular modelling Simulations of inclusion compounds for each benzene derivative into the cavity of host 4 were realized by means of Macromodel [45] with MMFF force field and GB/SA simulation of water [46

• simulations. The docking of each guest inside host 4 was realized by means of Monte Carlo searches, with the generation of 5000 conformations (Polak–Ribiere conjugate gradient minimization, convergence fixed to 0.05 kJ Å−1 mol−1). During the search, host 4 was kept rigid, while the guest was freely modified

High-spin intermediates of the photolysis of 2,4,6-triazido-3-chloro-5-fluoropyridine

• Sergei V. Chapyshev,
• Denis V. Korchagin,
• Patrik Neuhaus and
• Wolfram Sander

Beilstein J. Org. Chem. 2013, 9, 733–742, doi:10.3762/bjoc.9.83

• Abstract In contrast to theoretical expectations, the photolysis of 2,4,6-triazido-3-chloro-5-fluoropyridine in argon at 5 K gives rise to EPR peaks of just two triplet mononitrenes, two quintet dinitrenes, and a septet trinitrene. EPR spectral simulations in combination with DFT calculations show that

• -spin nitrenes. The intensities of these signals reached their maximum values after 45 min of irradiation and then gradually decayed upon further irradiation. The EPR spectrum recorded after 45 min of irradiation is shown in Figure 1b. The EPR spectral simulations show that the products of the reaction

• safely assigned to trinitrene 18 since only this trinitrene has a septet spin state. According to EPR spectral simulations (Figure 1a), this trinitrene is formed in ca. 2% yield. Due to different substituents in positions 3 and 5 of the pyridine ring, trinitrene 18 has different angles Θ1, Θ2, Θ3 between

Photoionisation of the tropyl radical

• Kathrin H. Fischer,
• Patrick Hemberger,
• Andras Bodi and
• Ingo Fischer

Beilstein J. Org. Chem. 2013, 9, 681–688, doi:10.3762/bjoc.9.77

• resonance geometry of the neutral, i.e., the dienylic 2A2 component, even though the geometries are somewhat different. The ground state can be described as a superposition of the 2A2 and 2B1 states, and it is reassuring that they both lead to very similar FC simulations. This also explains why the harmonic

• +, namely (+0.31 eV) and (+0.50 eV). An additional mode reported in the MPI spectrum at +1284 cm–1 is also predicted by the FC-simulations as visible in the stick spectrum in Figure 3. It is buried in the red edge of the +0.19 eV band. We assign it to the ν17+ C–H in-plane bend of e3’ symmetry, computed

• stretching mode with a spacing of 1530 cm−1 (0.19 eV), while the second progression is a combination of the ν2+ a1’ ring-breathing mode and ν16+. The simulations also indicate activity in the ν17+ C–H in-plane bending mode of e3’ symmetry. Moreover the first triplet and (possibly) singlet excited states of

A computational study of base-catalyzed reactions of cyclic 1,2-diones: cyclobutane-1,2-dione

• Nargis Sultana and
• Walter M. F. Fabian

Beilstein J. Org. Chem. 2013, 9, 594–601, doi:10.3762/bjoc.9.64

• rearrangements of biacetyl and benzil [11]. Car–Parrinello molecular dynamics simulations of the hydrolysis of formamide in basic solution indicated that the traditional view of attack by hydroxide anion rather than a first-solvation-shell water molecule is more likely; however, the more powerful electrophile

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39

The β-cyclodextrin/benzene complex and its hydrogen bonds – a theoretical study using molecular dynamics, quantum mechanics and COSMO-RS

• Jutta Erika Helga Köhler and
• Nicole Grczelschak-Mick

Beilstein J. Org. Chem. 2013, 9, 118–134, doi:10.3762/bjoc.9.15

• investigated by three different theoretical methods: classical quantum mechanics (QM) on AM1 and on the BP/TZVP-DISP3 level of approximation, and thirdly by classical molecular dynamics simulations (MD) at different temperatures (120 K and 273 to 300 K). The hydrogen bonds at the larger O2/O3 rim of empty β

• its O6 rim than on its O2/O3 side when all hydrogen bonds were arranged in a concerted mode. This static QM picture of the β-CD/benzene complex at 0 K was extended by MD simulations. At 120 K benzene was mobile but always stayed inside the cavity of β-CD. The trajectories at 273, 280, 290 and 300 K

• simulations displayed different hydrogen bond patterns of cyclodextrins in crystal and in solution and confirmed the experimental findings of soluble cyclodextrin complexes of cholesterol type versus precipitates of cis/trans-cyclohexadecenone//CDs [10][11][12]. MD with λ-dynamics and calculation of the

A bisazobenzene crosslinker that isomerizes with visible light

• Subhas Samanta,
• Harris I. Qureshi and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2012, 8, 2184–2190, doi:10.3762/bjoc.8.246

• residues [24]. The end-to-end distance changes expected upon photoisomerization of the resulting crosslink were estimated by molecular dynamics methods. Figure 1 shows models of compound 2 in trans,trans, trans,cis, and cis,cis-isomeric states. These simulations indicate that the trans,trans and cis,cis

• simulations for each isomer. (a) Histograms showing the relative populations of conformations having the sulfur-to-sulfur distances indicated. (b) Examples of trans,trans, trans,cis and cis,cis conformations with the S–S distances indicated. (a) Normalized UV–vis absorption spectra of 2 in DMSO, acetonitrile

Peptides presenting the binding site of human CD4 for the HIV-1 envelope glycoprotein gp120

• Julia Meier,
• Kristin Kassler,
• Heinrich Sticht and
• Jutta Eichler

Beilstein J. Org. Chem. 2012, 8, 1858–1866, doi:10.3762/bjoc.8.214

• through cyclization, as evidenced by binding assays, as well as through molecular-dynamics simulations of peptide–gp120 complexes. The specificity of the peptide–gp120 interaction was demonstrated by using peptide variants, in which key residues for the interaction with gp120 were replaced by alanine or D

• binding properties of CD4-M1 and CD4-M2, molecular dynamics (MD) simulations of the peptides in complex with gp120 were carried out and compared to a simulation of the CD4–gp120 complex. Analysis confirmed that the linear peptide CD4-M1 is more flexible than the respective region in CD4 (Figure 5A

• the stable interactions with gp120 that are present in the gp120–CD4 complex (Figure 1), while R58 does not significantly contribute to binding in any of the simulations. The importance of F43 and R59 for peptide binding also supports the notion that both peptides bind specifically to the CD4 binding

Evaluation of a chiral cubane-based Schiff base ligand in asymmetric catalysis reactions

• Kyle F. Biegasiewicz,
• Michelle L. Ingalsbe,
• Jeffrey D. St. Denis,
• James L. Gleason,
• Junming Ho,
• Michelle L. Coote,
• G. Paul Savage and
• Ronny Priefer

Beilstein J. Org. Chem. 2012, 8, 1814–1818, doi:10.3762/bjoc.8.207

• increasing stereoselectivity. Appropriate crystals for X-ray analysis were not obtained, thus we decided to look into computational simulations. On the basis of earlier assessment studies [23][24], we chose the M06L [25] density functional theory method (and B3LYP [26] for comparison) to locate the global

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

Beilstein J. Org. Chem. 2012, 8, 915–929, doi:10.3762/bjoc.8.104

• adopt several conformations with different populations. The conformational space of a glycan can be analyzed by molecular dynamics (MD) simulations (see in the following) [100]. For this purpose the models generated by the GLYCAM Biomolecules Builder are convenient, as this tool already provides the

• input files for AMBER simulations. The list of residues that are available, however, is more limited than in Sweet-2. Sulfated residues, which frequently occur in glycosaminoglycans [101], for example, are only supported by Sweet-2 at the moment. GlycanReader [96] as part of the CHARMM-GUI [102] creates

• synthetic glycan mimetics [117][118][119]. Results can be improved by combinations of different modeling approaches, such as docking and MD simulations [101]. To run reliable MD simulations of carbohydrate 3D structures, force fields are necessary that contain parameters for carbohydrates. In the case of

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• [17]. Molecular dynamics simulations have shown that furans with two saccharides bound to hydroxymethyl groups show a nearly perfect alignment with each of the three terminal saccharides in Lewisy [15], another member of the Lewis histo blood group family, which is involved in tumor cell adhesion [18

• , 2H, CH2OSO3), 7.65 (s, 1H, H5), 7.68 (s, 1H, H2); 13C NMR (63 MHz, DMSO-d6) δ 58.4, 60.5, 60.6 (CH2OSO3, CH2OGal, C6´), 68.2, 70.6, 73.4, 75.2 (C2´, C3´, C4´, C5´), 102.6 (C1´), 121.3, 121.7 (C3, C4), 141.49, 141.52 (C2, C5). In silico blind-docking and molecular dynamics simulations A flexible

• by using AMBER [53]. The atomic partial charges and the topology files for GSF were prepared with antechamber. The final input files for sander were built with tleap. The MD simulations were run at 300 K in explicit water, by using periodic boundary conditions and following established standard

Enantioselective supramolecular devices in the gas phase. Resorcin[4]arene as a model system

• Caterina Fraschetti,
• Matthias C. Letzel,
• Antonello Filippi,
• Maurizio Speranza and
• Jochen Mattay

Beilstein J. Org. Chem. 2012, 8, 539–550, doi:10.3762/bjoc.8.62

• well as in water: The skew-boat conformation of catharanthine is about 1 kcal mol−1 more stable than the chair conformation (Figure 5). The skew-boat structure of both T and TH+ is persistent during all the MD simulations, while the chair→skew-boat interconversion very easily occurs in aqueous TH

• +. Furthermore, in all simulations the position of the CO2Me function oscillates between two orientations differing by 180°, except for TH+ in vacuum, while the ethyl group is invariably free to rotate in the three-dimensional space [49]. The computational results indicated that the chair conformation is better

On the mechanism of action of gated molecular baskets: The synchronicity of the revolving motion of gates and in/out trafficking of guests

• Keith Hermann,
• Stephen Rieth,
• Hashem A. Taha,
• Bao-Yu Wang,
• Christopher M. Hadad and
• Jovica D. Badjić

Beilstein J. Org. Chem. 2012, 8, 90–99, doi:10.3762/bjoc.8.9

• steered molecular dynamics (SMD) simulations using the AMBER 10.0 suite of programs [29][30][31][32]. Without applying any external force on the entrapped CH3CCl3, we first found that this guest would, within 10 ns, adopt many positions inside host 1, although the one depicted in Figure 6A is obtained

(How) does 1,3,5-triethylbenzene scaffolding work? Analyzing the abilities of 1,3,5-triethylbenzene- and 1,3,5-trimethylbenzene-based scaffolds to preorganize the binding elements of supramolecular hosts and to improve binding of targets

• Xing Wang and
• Fraser Hof

Beilstein J. Org. Chem. 2012, 8, 1–10, doi:10.3762/bjoc.8.1

• rotational barriers Although kinetics has no bearing on binding thermodynamics, we sought also to understand computationally the dynamics of these different hosts. Molecular-dynamics simulations carried out at 300 K showed little or no dynamic exchange of conformations. Simulations carried out at the

• period. Faced with evidence that the barriers to exchange of “up” and “down” conformers in the sterically congested 1,3,5-triethylbenzene and 1,3,5-trimethylbenzene systems are too high to examine conveniently by MD simulations, we turned instead to a calculation of the barriers to bond rotation for a

•  7. The calculated rotation barriers for ethyl directed hosts are in the same range as previously reported values for related systems, which were determined by variable temperature NMR to be 9.3–11.8 kcal/mol [6][20]. As with the MD simulations, these results indicate that both ethyl and methyl ortho

Catalysis: transition-state molecular recognition?

• Ian H. Williams

Beilstein J. Org. Chem. 2010, 6, 1026–1034, doi:10.3762/bjoc.6.117

• transferase are described and compared with those for a model reaction in water, as computed by hybrid quantum-mechanical/molecular-mechanical molecular dynamics simulations. The case is discussed of molecular recognition in a xylanase enzyme that stabilises its sugar substrate in a (normally unfavourable

• AM1/OPLS/TIP3P simulations [19] with ensemble averaging to include the effect of thermal fluctuations in the enzyme and solvent environments to obtain a value for the α-D3 KIE = 0.82 ± 0.05, which is in excellent accord with the experimental value [11] of VCH3 /VCD3 = 0.83 ± 0.05 for methylation of

• for the COMT-catalysed reaction were computed as 2.06 ± 0.02 Å and 2.11 ± 0.01 Å, the sum of which is scarcely different from the sum of the corresponding average bond lengths, 2.18 ± 0.04 Å and 2.00 ± 0.04 Å, for the uncatalysed reaction. Thus the simulations did not provide any structural evidence

Oxalyl retro-peptide gelators. Synthesis, gelation properties and stereochemical effects

• Janja Makarević,
• Milan Jokić,
• Leo Frkanec,
• Vesna Čaplar,
• Nataša Šijaković Vujičić and
• Mladen Žinić

Beilstein J. Org. Chem. 2010, 6, 945–959, doi:10.3762/bjoc.6.106

• promising biomedicinal properties, very little is known about the self-assembly potential of this class of compounds in solution. Computer simulations of some malonamide retro-peptides have shown that the extended conformations are less stable than the helical ones [48][49]. Nevertheless, the crystal

EPR and pulsed ENDOR study of intermediates from reactions of aromatic azides with group 13 metal trichlorides

• Giorgio Bencivenni,
• Riccardo Cesari,
• Daniele Nanni,
• Hassane El Mkami and
• John C. Walton

Beilstein J. Org. Chem. 2010, 6, 713–725, doi:10.3762/bjoc.6.84

• appear different at first sight, the hfs derived from the simulations (Table 1) are actually quite similar. The contrasts in the spectral appearances are mainly the result of different line widths with consequently different resolutions. It is evident that the main species in each case is the radical

• , gave essentially the same strong spectrum, see Figure 5a and Supporting Information. The hfs derived from the simulations (Table 1) suggest that this is also a dimer type radical cation 17b+•. However, with the passage of time a central peak began to appear in this spectrum. When 5 was treated with

• intensity were obtained at around 300 K. Most of the EPR spectra were recorded with 2.0 mW power, 1.0–0.2 Gpp modulation intensity and a gain of ~106. In all cases where spectra were obtained, hfs were assigned with the aid of computer simulations using the Bruker SimFonia and NIEHS Winsim2002 software

Symmetry breaking and structure of a mixture of nematic liquid crystals and anisotropic nanoparticles

• Marjan Krasna,
• Matej Cvetko and
• Milan Ambrožič

Beilstein J. Org. Chem. 2010, 6, No. 74, doi:10.3762/bjoc.6.74

• align parallel. By contrast, we set JLC–NP < 0, tending to orient LC molecules and NP perpendicularly. In the simulations we take JLC–LC = JNP–NP = 1, and JLC–NP is either set to −1, −2 or −4. The exponent a is equal to 1 for magnetic–magnetic coupling while for nematic–nematic or nematic–magnetic

• results of numerical simulations, we find that G is indeed equal in cases with the same r, except for small unimportant statistical variations which are subsequently annulled by averaging G for data pairs (r, G) with the same r. To extract structural details from a calculated G(r) dependence, we fit it

• finite value of s. However, with increasing x the value of s decreases monotonously. Our numerical simulations suggest, that above a threshold value x = xc long range ordering is replaced by short range ordering. Therefore, for a sufficiently large concentration the degree of disorder introduced by

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• , temperature coefficient (Δδ/ΔT) measurements of amide protons and constrained MD simulations revealed that all the cyclic oligomers had symmetrical structures, although none of the unprotected cyclic oligomers displayed any ability to transport ions across model membranes according to ion flux studies. Cyclic

Competition between local disordering and global ordering fields in nematic liquid crystals

• Matej Cvetko,
• Milan Ambrožič and
• Samo Kralj

Beilstein J. Org. Chem. 2010, 6, No. 2, doi:10.3762/bjoc.6.2

• temperature). In simulations we either originate from randomly distributed orientations of directors, or from homogeneously aligned samples along a symmetry breaking direction. In the latter case the directors are initially homogeneously aligned along ex. We henceforth refer to these cases as the i) random

• . The ii) homogeneous case can be realized by applying first a strong homogeneous external field B along a symmetry breaking direction. After a well enough alignment is achieved the field is switched off. In order to diminish the influence of statistical variations we carry out several simulations

• simulations for 2D systems which demand less computational time. A typical G(r) dependence in 2D and 3D is shown in Figure 1a and Figure 1b, respectively. We plot G(r) for both homogeneous and random initial configuration in the presence of external field and without it. For B = 0 it holds ξ(hom) > ξ(ran

Chiral amplification in a cyanobiphenyl nematic liquid crystal doped with helicene-like derivatives

• Alberta Ferrarini,
• Silvia Pieraccini,
• Stefano Masiero and
• Gian Piero Spada

Beilstein J. Org. Chem. 2009, 5, No. 50, doi:10.3762/bjoc.5.50

• intermolecular interactions and opposes director distortions [24]. Different theories [25][26][27] have contributed to elucidate the molecular mechanism behind cholesteric induction, as well as Molecular Dynamics simulations [28][29][30]; for the connection between structure of the chiral dopant and cholesteric