Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

• Giuseppina Raffaini,
• Antonino Mazzaglia and
• Fabio Ganazzoli

Beilstein J. Org. Chem. 2015, 11, 2459–2473, doi:10.3762/bjoc.11.267

• cannot be ruled out: in fact, in view of the small size of these aggregates and of the simulations carried out in vacuo with four and eight molecules, the present results only describe the embryonic stage of aggregation, separated from later stages by some free energy barrier, mainly due to

Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex

• Chompoonut Rungnim,
• Sarunya Phunpee,
• Manaschai Kunaseth,
• Supawadee Namuangruk,
• Kanin Rungsardthong,
• Thanyada Rungrotmongkol and
• Uracha Ruktanonchai

Beilstein J. Org. Chem. 2015, 11, 2306–2317, doi:10.3762/bjoc.11.251

• between the hydrogen donor and acceptor atoms being ≤3.5 Å; and (ii) the angle of the donor-hydrogen-acceptor being ≥120° [36]. Binding free energy calculations Herein, the binding free energies of α-MGS/β-CD complex were calculated as follows. The ΔG is defined by where each free energy is estimated from

• The gas phase energy, ΔEMM, is a summation of bonded and non-bonded (electrostatic and van der Waals (vdW)) energies obtained from molecular mechanics calculation. The ΔGsolv is solvation free energy. In general, there are several methods for ΔGsolv prediction. Some methods calculate the ΔGsolv using

• higher than for electrostatic interactions (ΔEele). Through summation of the solvation free energy (ΔGsolv) and the entropy term (TΔS), the predicted binding free energies (ΔGbind) of the inclusion complexes I and II are similar with values of –8.86 ± 3.25 and –9.06 ± 2.87 kcal/mol, respectively. Thus

Computational study of productive and non-productive cycles in fluoroalkene metathesis

• Markéta Rybáčková,
• Jan Hošek,
• Ondřej Šimůnek,
• Viola Kolaříková and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2015, 11, 2150–2157, doi:10.3762/bjoc.11.232

• decoordination of alkoxybenzylidene oxygen (structures 1c and 2c). For ethene (1c) and the anti-coordinated 1,1-difluoroethene (a2c), shallow minima were observed in the Gibbs free energy profile, while for the syn structure (s2c), the minimum obtained by the calculation of electronic energy changed just to

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• temperatures below −25 °C the equilibrium is slow enough to observe an asymmetric complex. It is important to keep in mind that these spectra are recorded for a 1:0.1 molar ratio of 1 and 10 to be sure that most of 10 is associated. From VT 1H NMR measurements the Gibb's free energy equal to 66.6 kJ/mol was

Mechanism, kinetics and selectivity of selenocyclization of 5-alkenylhydantoins: an experimental and computational study

• Biljana M. Šmit,
• Radoslav Z. Pavlović,
• Dejan A. Milenković and
• Zoran S. Marković

Beilstein J. Org. Chem. 2015, 11, 1865–1875, doi:10.3762/bjoc.11.200

• , whereas that for the formation of (S,S)-INT3’ and (S,S)-INT3 (cis-diastereoisomers) are significantly lower (Table 2). But the free energy of both six-membered imidazolinium cations INT3’ are very similar and match higher than those for five-membered INT3. The facts that six-membered imidazolinium cations

• (Gibbs free energy) difference between transition states and reactants. The 1H NMR spectra of the intermediates and products in acetonitrile were simulated. The geometry of TMS in acetonitrile was optimized using the B3LYP/6-311+G(d,p) and SMD models. We chose to use the B3LYP functional based on

• substrate 1, with relative free energy values indicated in kJ/mol. The crucial bond lengths are given in pm. Energy profile for the proposed mechanism of selenocyclization of model substrate 1. Relative energies are given in kJ/mol. Optimized geometries for seleniranium cations and corresponding transition

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

• each L, the precursor state (preS) was 10–20 kJ·mol−1 more stable than the reactant state (RS). Thus, the change in energy was small with respect to the reactant state. Consistent with an associative step, the entropy change was negative and the change in free energy was positive. Consistent with the

Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• bivalent binding modes are strongly favoured through enthalpic gain, the free energy gain is limited by the entropy loss, most likely caused by the flexibility of the linker and thus a larger number of alternative conformational states of the protein receptor. Conclusion All three investigated

• upon injection of peptide–polymer conjugates into the protein; bottom part shows integrated and normalized heat of reaction plotted against peptide/protein molar ratio; binding isotherms are fitted with a 1:1 binding model. Enthalpic and entropic contributions to the free energy of binding processes of

• multivalent peptide–polymer conjugate to the tandem WW domain Binding studies with peptide–polymer conjugates were conducted employing isothermal titration calorimetry (ITC). This method enables the determination of the binding affinity of the multivalent ligands and elucidates the composition of the free

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

• up/lying down” mechanism [25] or even more likely via “rolling” into minima of the free energy [26]. We anticipate that these results will help improve catecholic hPGs as stable surface coatings in aqueous buffer [22]. Experimental hPGs Hyperbranched polyglycerol (hPG) with Mn ≈5000 g/mol and Mw

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

• spacer is on average extended to almost its full length. The fluctuations around its most probable end-to-end distance r0 are assumed to be much smaller than the contour length L. We approximate the free energy F, similar to a harmonic spring, as with k the effective spring constant and d the end-to-end

• relevant average end-to-end distance rete and the variance Δr, we first have to determine the relation between rete and Δr on the one side and k and r0 on the other side. From the free energy F in Equation 4 the average end-to-end distance rete and the variance Δr are obtained as: Note that according to

• effective concentration of flexible polymers is often modeled by a Gaussian chain [11][20][24] with the free energy: using the mean squared end-to-end distance . The end-to-end distance rete and the variance Δr can be expressed in terms of the mean squared end-to-end distance: As a consequence the end-to

On the strong difference in reactivity of acyclic and cyclic diazodiketones with thioketones: experimental results and quantum-chemical interpretation

• Andrey S. Mereshchenko,
• Alexey V. Ivanov,
• Viktor I. Baranovskii,
• Grzegorz Mloston,
• Ludmila L. Rodina and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2015, 11, 504–513, doi:10.3762/bjoc.11.57

• , carbocyclic diazodiketones are much less reactive under similar conditions due to the locked cyclic structure and are unfavorable for the 1,3-dipolar cycloaddition due to the Z,Z-conformation of the diazo molecule. This structure results in high, positive values of the Gibbs free energy change for the first

• structural formulas and the corresponding, optimized geometry energy for the first and the second reaction steps (cycloaddition of 1 with 2a and decomposition of 1,3,4-thiadiazolines 6) are given in Table 1. The positive values of the Gibbs free energy change for the first stage of the process (Table 1; ΔG1

• ) demonstrate that formation of thiadiazolines 6 from 1a–d and 2a is thermodynamically unfavorable. However, the total value of the Gibbs free energy change for the formation of molecular nitrogen and thiocarbonyl ylide 7 from 1a–d and 2a, ΔG1–7 = ΔG1 + ΔG2, is negative. Therefore, the formation of the

A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives

• Debabrata Samanta,
• Anup Rana,
• Jan W. Bats and
• Michael Schmittel

Beilstein J. Org. Chem. 2014, 10, 2989–2996, doi:10.3762/bjoc.10.317

• 14‡. Distances are shown in angstrom (italics). Synthesis of tricyclic 1,2,4-thiadiazoles 2a–c. Possible mechanistic scenarios. DMAP assisted cyclization-I and IIa. Free energies are reported in kcal mol−1 at 25 °C referenced to 8 for cyclization-I and 13 for cyclization-IIa. Free energy values

Binding mode and free energy prediction of fisetin/β-cyclodextrin inclusion complexes

• Bodee Nutho,
• Wasinee Khuntawee,
• Chompoonut Rungnim,
• Piamsook Pongsawasdi,
• Peter Wolschann,
• Alfred Karpfen,
• Nawee Kungwan and
• Thanyada Rungrotmongkol

Beilstein J. Org. Chem. 2014, 10, 2789–2799, doi:10.3762/bjoc.10.296

• to investigate the preferential binding mode and encapsulation of the flavonoid fisetin in the nano-pore of β-cyclodextrin (β-CD) at the molecular level using various theoretical approaches: molecular docking, molecular dynamics (MD) simulations and binding free energy calculations. The molecular

• binding or even unbinding preference was observed in the complexes where the larger chromone ring is located in the cavity. All MM- and QM-PBSA/GBSA free energy predictions supported the more stable fisetin/β-CD complex of the bound phenyl ring. Van der Waals interaction is the key force in forming the

• inclusion complex. The ligand binding mode and water accessibility, host–guest interaction, and binding free energy of the inclusion complex were analyzed. The MM-PBSA/GBSA and M06-2X/6-31G(d,p)//MM-PBSA/GBSA approaches were used to predict the binding affinity of fisetin/β-CD complexes. The M06-2X/6-31G(d

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• , exchanging two-site 31P system (Figure 9). This enabled us to obtain the rate constants of the exchange at different temperatures and estimate the activation parameters of the interconversion such as the Gibbs free energy of activation ΔG‡298 = 80.7 kJ/mol; the enthalpy of activation ΔH‡ = 23.8 kJ/mol; and

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• isolated) – the corresponding changes in Gibbs free energy were evaluated from isodesmic reactions 1–4 (Scheme 4). These calculations were based on the Gibbs free energy of the compounds, which were obtained by DFT B3LYP/6-31G(d) calculations (ΔΔG298 K, kcal/mol). Although the substitution of the Ph group

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• this a gain in the free energy of duplex formation and, hence, more stable duplexes are expected [24]. Over the years we became interested in determining the structure/RNA affinity relationship of the underlying sugar scaffold and to develop them into a molecular platform for oligonucleotide

Why a diaminopyrrolic tripodal receptor binds mannosides in acetonitrile but not in water?

• Diogo Vila-Viçosa,
• Oscar Francesconi and
• Miguel Machuqueiro

Beilstein J. Org. Chem. 2014, 10, 1513–1523, doi:10.3762/bjoc.10.156

• titrable protons (n) present in the molecule. Radius of gyration (Rg) histograms for the receptor in water at pH 1.0, 3.0, 6.0, 10.0 and in ACN. The Rg curves at the pH values not shown are well behaved and respect the observed trend. Free energy profiles for the receptor at pH 1.0 (a), 6.0 (b), 10.0 (c

• with the population of each microstate, histograms of Rg, free energy profiles and schematic representation of the position of the arms at all pH values. Acknowledgments The authors thank Cristina Nativi and Stefano Roelens for the NMR derived structure and useful discussions. We also thank António M

Substitution effect and effect of axle’s flexibility at (pseudo-)rotaxanes

• Friedrich Malberg,
• Jan Gerit Brandenburg,
• Werner Reckien,
• Oldamur Hollóczki,
• Stefan Grimme and
• Barbara Kirchner

Beilstein J. Org. Chem. 2014, 10, 1299–1307, doi:10.3762/bjoc.10.131

• computational energy profile [22]. The formation of α-cyclodextrin-based [3]pseudorotaxanes in the gas phase was studied by means of density functional calculations [23]. Molecular mechanics calculations were used for a free energy calculation of an α-cyclodextrin rotaxane system and for the investigation of

Theoretical studies on the intramolecular cyclization of 2,4,6-t-Bu₃C₆H₂P=C: and effects of conjugation between the P=C and aromatic moieties

• Masaaki Yoshifuji and
• Shigekazu Ito

Beilstein J. Org. Chem. 2014, 10, 1032–1036, doi:10.3762/bjoc.10.103

• activation energy (ΔEa) was 12.3 kcal/mol, and the Gibbs free energy ΔG was estimated as 11.6 kcal/mol. Such energy profile indicates a sharp contrast to the modeled FBW rearrangement of phosphanylidenecarbene requiring no activation energy [20], and would be partially explicable for the experimental result

• that the phosphanylidenecarbenoid [Mes*P=C(Br)Li] afforded both phosphaalkyne [Mes*C≡P] and 2 [15]. The single imaginary frequency was optimized for the transition state (Figure 3). Figure 4 displays the optimized structure of 2 [MP2(full)/6-31G(d)]. Relative energy (Erel) and Gibbs free energy (G) of

The Ugi four-component reaction as a concise modular synthetic tool for photo-induced electron transfer donor-anthraquinone dyads

• Sarah Bay,
• Gamall Makhloufi,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 1006–1016, doi:10.3762/bjoc.10.100

• to a charge-separated state that is responsible for the observed fluorescence quenching can be calculated from the measured electrochemical and spectroscopic data. Among several representations for calculating the Gibbs free energy of the electron transfer [88][89] can be described by Equation 1 [90

• electrochemical measurements are performed in the same solvent. Therefore, Equation 1 simplifies to Equation 2 for calculating Where the first two terms indicate the free energy of the charge-separated state calculated from the spectroscopic and electrochemical measurements (in eV) and represents the correction

Tailoring of organic dyes with oxidoreductive compounds to obtain photocyclic radical generator systems exhibiting photocatalytic behavior

• Christian Ley,
• Julien Christmann,
• Ahmad Ibrahim,
• Luciano H. Di Stefano and
• Xavier Allonas

Beilstein J. Org. Chem. 2014, 10, 936–947, doi:10.3762/bjoc.10.92

• is the electron transfer reaction between the dye ground state and the coinitiator. Its reactivity is governed by the corresponding Gibbs free energy change where Eox and Ered are the half-wave oxidation and reduction potentials for the donor and the acceptor, respectively. must be as high as

• possible. The values of the Gibbs free energy change for photoinduced electron transfer is given by the Rehm–Weller equation [56]: , where E* stands for the energy of the excited state. The Coulombic term C is usually neglected in polar solvent. will determine the rate of electron transfer and the dye

• ]. The last important step is the dye regeneration. In order for the cycle and for the catalytic behavior to occur, the corresponding Gibbs free energy change should be negative. If one assumes that the reduction potential of PS•+ is given by the oxidation potential of PS, then . Thus, in order to

Metal and metal-free photocatalysts: mechanistic approach and application as photoinitiators of photopolymerization

• Jacques Lalevée,
• Sofia Telitel,
• Pu Xiao,
• Marc Lepeltier,
• Frédéric Dumur,
• Fabrice Morlet-Savary,
• Didier Gigmes and
• Jean-Pierre Fouassier

Beilstein J. Org. Chem. 2014, 10, 863–876, doi:10.3762/bjoc.10.83

• /luminescence experiments (Figure 7B). From these data, a favorable 3Ir(piq)2(tmd)/Ph2I+ oxidation process can be expected, i.e., the free energy change ΔG for the corresponding electron transfer is negative (ΔG = −1.2 eV as calculated from the classical Rehm–Weller ΔG = Eox – Ered – ET + C where Eox, Ered, ET

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• that pseudo-cross-conjugated mesomeric betaines decarboxylate readily in the absence of stabilizing effects such as hydrogen bonds to protic solvents or water of crystallization [18][19]. Thus, the Gibbs free energy difference for the decarboxylation of 1,2-dimethylindazolium-3-carboxylate under

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• considered as dimers of azomethine ylides have been published, though concerted thermal dimerization of azomethine ylides is a forbidden process [33]. According to our calculations the free energy barriers to formation of the azomethine ylides 10a–c from compounds 8a–c are 34.1, 34.7, 32.2 kcal·mol−1 (353 K

• free energy barriers for the interaction of 2,5-dihydropyrazine with acylketenes the calculations of the reaction of dihydropyrazine 11a with ketene 6a, leading to adduct 12a, and the reaction of the latter with ketene 6a, leading to adducts 4a and 5a, were performed at the DFT B3LYP/6-31G(d) level

• compounds as 2H-azirines needs to overcome a quite high energy barrier. According to calculations at the DFT B3LYP/6-31G(d) level the free energy barriers to formation of nitrile ylides 13a–c from azirines 2a–c are 48.4, 47.6, 47.9 kcal·mol−1 (353 K, benzene (PCM)), respectively. Therefore the process of

Chromatographically separable rotamers of an unhindered amide

• Mario Geffe,
• Lars Andernach,
• Oliver Trapp and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 701–706, doi:10.3762/bjoc.10.63

• , the free energy of activation for the rotation of 4 is overestimated by at least 10 kJ/mol. A possible explanation for this difference could be the high basicity of the pyramidal nitrogen in both transition states which may favor the formation of hydrogen bonds lowering the total energy. Other reasons

• , quant. Relative Gibbs free energy (kJ/mol) for E-4, Z-4, TS1, TS2, GSDMF, TS1DMF and TS2DMF in the gas phase and with COSMO solvation for hexane, ethanol and DMSO at 298 K (BP-D3/def2-SVP). Supporting Information Supporting Information File 168: Experimental procedures, HPLC chromatograms, copies of 1D

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308