The hydrolysis of geminal ethers: a kinetic appraisal of orthoesters and ketals

• Sonia L. Repetto,
• James F. Costello,
• Craig P. Butts,
• Joseph K. W. Lam and
• Norman M. Ratcliffe

Beilstein J. Org. Chem. 2016, 12, 1467–1475, doi:10.3762/bjoc.12.143

• the anti rotamer 16c would lead to a more rapid elimination of methanol after protonation, consistent with an earlier transition state [29]. Compound 5, which does not have such an accessible flattened ring conformation cannot access this lower entropy trajectory and hence reacts more slowly

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

• a first order kinetics as anticipated in the absence of a base. An Eyring–Polanyi plot gives an activation enthalpy of ΔH‡ = 54.5 ± 10.4 kJ mol−1 and an activation entropy of ΔS‡ = –193 ± 30 J mol−1 K−1 (Supporting Information File 1, Figure S25). These values give a Gibbs free energy of activation

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

• MIA descriptors generated to build the model, a straightforward analysis would not be an easy task using the raw data. Thus, pre-filtration procedures were performed in order to reduce the number of variables. In this sense, the first approach was a measure of Shannon's entropy (SE), corresponding to

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• entropy paid by the hydrogen bonding is sufficient to allow the enthalpy of the aromatic stacking to be observed. However, there are other explanations for the high stability observed in the 8·9 complex. The aromatic cleft may serve to desolvate the carboxylic acid, thereby improving its hydrogen bonding

• context of analyzing the vancomycin complex with D–Ala–D–Ala containing peptides, suggested the cost of freezing a free rotation to be between 0.4 to 0.9 kcal/mol – a value that is also close to what we had measured [25]. In Williams’ case, the value was derived from the entropy of fusion within a

Versatile deprotonated NHC: C,N-bridged dinuclear iridium and rhodium complexes

• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 117–124, doi:10.3762/bjoc.12.13

• of Martin et al. [85] which consists of thermal corrections and entropy effects evaluated at 1354 atm [86][87][88][89], with the BP86-d3/TZVP method in the gas phase [90][91]. %VBur calculations: The buried volume calculations were performed with the SambVca package developed by Cavallo et al. [90

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

• configurational entropy. On the other hand, taken together the present results in water may provide some clues about the possible kinetics of aggregation: at first there is the fast formation of small clusters comprising few molecules, followed by the further aggregation of these cluster with may add individual

• the alkyl chains: their cooperative effect would then favour the micelle formation vs. the isolated molecules in spite of the entropy loss entailed by the clustering process. As a final remark, we point out that with atomistic MM and MD methods we can model the first nucleation steps which may take

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

• is successfully applied in other biological systems [29][34][35][48]. The non-polar contribution is calculated by the solvent-assessable surface area (SASA) as Where γ was set as 0.0072 kcal/(mol/A2) [49]. The TS term is a solute entropy contribution arising from changes in degrees of freedom

• 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

• inclusion complex, as seen by a reduction in ΔGsolv at high ethanol percentages. In contrast, the entropies of all systems were likely similar (−T∆S of ≈13 kcal/mol). After combining the interaction energy (1), solvation (2) and entropy (3) terms, the binding affinity of the α-MGS/β-CD complexation at 0–60

Synthesis, structure, and mechanical properties of silica nanocomposite polyrotaxane gels

• Kazuaki Kato,
• Daisuke Matsui,
• Koichi Mayumi and
• Kohzo Ito

Beilstein J. Org. Chem. 2015, 11, 2194–2201, doi:10.3762/bjoc.11.238

• polymer, their inhomogeneous distribution can generate entropic stress. Thus, the origin of elasticity is not the entropy of polymer chains but that of the CDs, and the abnormally small modulus of polyrotaxane gels can be explained by the characteristic elasticity. Similarly, the extremely low modulus of

• the nanocomposite polyrotaxane gels is attributable to the characteristic elasticity originated from the entropy of CDs. Since the infinite network was formed mainly by the covalent bonds between CDs and silica surface, the polymer chains are bound to neither CDs nor silica. If the polymer chains are

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

• between host (H) and guest (G) molecules. This is because, as Etter's rules [40] state, intramolecular hydrogen bonding is stronger than intermolecular one and more probable due to the entropy reasons. In order to construct a molecule capable to form intramolecular hydrogen bonds one should bear in mind

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

• and CO2 insertion occur simultaneously, whereby at a given time three molecules need to orientate themselves into a particular configuration to form the transition state (see Scheme 5). This is demanding with respect to the entropy effects. In both pathways, the CO2 addition to the epoxide was found

• and metal alkoxide. Formation of this associative complex is endergonic due to the entropy effects [45]. The transition state for the CO2 insertion into metal–oxygen bonds has been postulated to be a four-membered ring consisting of the metal, the carbon and two oxygen atoms (Scheme 9) [44]. For this

• 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

New palladium–oxazoline complexes: Synthesis and evaluation of the optical properties and the catalytic power during the oxidation of textile dyes

• Rym Hassani,
• Mahjoub Jabli,
• Yakdhane Kacem,
• Jérôme Marrot,
• Damien Prim and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2015, 11, 1175–1186, doi:10.3762/bjoc.11.132

• . Thermodynamic parameters To better understand the degradation process, the pseudo first-order kinetic equation was used to determine the kinetic parameters. The Arrhenius law was used to calculate the activation energy (Ea). The determination of the entropy and the enthalpy of activations (ΔS* and ΔH*) were

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

• matched in order to balance enthalpic gain with entropic loss of the system. In such a setting, a rigid multivalent ligand binding to a flexible receptor can be expected to reduce the entropy of the system upon binding, and thus will result in a partial or complete loss of the multivalent affinity

• and almost negligible entropic contributions , all polyhydroxy-based peptide–polymer conjugates showed significantly stronger generation of heat through binding (enthalpy) together with a pronounced loss in entropy. Binding in all cases was driven mainly by enthalpy, which clearly outweighed the

• observed entropy loss. In the seven peptide–polymer conjugates investigated, increased loading density of ligands led consistently to increased affinity of the multivalent ligand (Table 1). The most significant difference between dextran and the two other polymer carriers was the stoichiometry of the

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

• receptors [1]. Each multivalent ligand consists of several monovalent ligands that are connected via a scaffold. The binding affinity of such a multivalent ligand is determined by the interplay between gain in binding energy and loss of entropy associated with conformational degrees of freedom. The more

• flexible the scaffold is, the better it can adapt to the geometry of the receptor, but the more pronounced on the other hand is the entropy penalty. This simple, qualitative argument shows that the careful choice of the ligand scaffold is essential, in order to benefit from multivalent enhancement. It is

• monovalent ligand binds better than the divalent ligand. In this case the loss in entropy of the spacer is larger than the gain in binding energy due to the multiple binding of ligand units. Inserting the effective concentration from Equation 13 and Equation 23 into Equation 41 and Equation 47, the RBA can

Impact of multivalent charge presentation on peptide–nanoparticle aggregation

• Daniel Schöne,
• Boris Schade,
• Christoph Böttcher and
• Beate Koksch

Beilstein J. Org. Chem. 2015, 11, 792–803, doi:10.3762/bjoc.11.89

• , and the enthalpy ΔH can be directly obtained from the measured data whereas the entropy ΔS is calculated. Due to very weak or absent interactions of R1A3 or R2A5 with Au/MUA nanoparticles it was not possible to determine thermodynamic parameters. Surprisingly, the obtained binding constants are not in

• energy. Nevertheless, all peptide–nanoparticle interactions are entropically favored processes as entropy increases with along with binding energy. Morphological studies of peptide-induced nanoparticle assemblies Cryo TEM was used to gain insight into the morphology of the peptide–nanoparticle aggregates

Probing multivalency in ligand–receptor-mediated adhesion of soft, biomimetic interfaces

• Stephan Schmidt,
• Hanqing Wang,
• Daniel Pussak,
• Simone Mosca and
• Laura Hartmann

Beilstein J. Org. Chem. 2015, 11, 720–729, doi:10.3762/bjoc.11.82

• generally low affinity between sugars and receptors and possibly also by the high flexibility of the polymeric mannose linkers [9]. High molecular flexibility causes a high degree of conformational entropy that negatively affects complex formation between ligands and receptors [23]. Also the design of the

Exploring monovalent and multivalent peptides for the inhibition of FBP21-tWW

• Lisa Maria Henning,
• Sumati Bhatia,
• Miriam Bertazzon,
• Michaela Marczynke,
• Oliver Seitz,
• Rudolf Volkmer,
• Rainer Haag and
• Christian Freund

Beilstein J. Org. Chem. 2015, 11, 701–706, doi:10.3762/bjoc.11.80

• peptides on the hPG particle are not engaged in the interaction with FBP21-tWW. The enthalpy of the interaction is twice as large for the hPG-peptide conjugate as for the monovalent ligand, while the entropy loss upon interaction (−19.5 cal/mol/deg for the interaction with the monovalent ligand and −45.9

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

• thermodynamically and kinetically favorable process for DDC with at least one electron-withdrawing acyl group. At higher temperatures, however, due to the entropy contribution, the dominating process becomes the 1,3-cyclization followed by desulfurization of the obtained thiiranes, which leads to the corresponding

Novel biphenyl-substituted 1,2,4-oxadiazole ferroelectric liquid crystals: synthesis and characterization

• Mahabaleshwara Subrao,
• Dakshina Murthy Potukuchi,
• Girish Sharada Ramachandra,
• Poornima Bhagavath,
• Sangeetha G. Bhat and
• Srinivasulu Maddasani

Beilstein J. Org. Chem. 2015, 11, 233–241, doi:10.3762/bjoc.11.26

• during the thermal studies at 5 °C/min are given in Supporting Information File 1. It is noticed that the mesomorphic thermal range is almost the same in both cases. The data of transition temperatures (TC), the enthalpy changes (∆H) across the transitions and entropy changes (∆S) of 13a (Ph.Ox.C*Cn) and

• changes (kJ/mol) and entropy changes (J/mol/K) of the 13a (Ph.Ox.C*Cn) series. Phase transition temperatures (°C), enthalpy changes (kJ/mol) and entropy changes (J/mol/K) of the 13b (C12Ox.C*Cn) series. Supporting Information The experimental procedure for the synthesis of 13ap–13as and 13bp–13bs with

Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• formation is enthalpy driven in the case of D10GP-CPT1, but mainly entropy driven (|TΔS| > |ΔH|) in the case of D70GP-CPT2. This high positive entropy variation shows a cooperative inclusion of the polymers. No binding between native β-CD and D70GP-CPT2 could be measured by ITC. Figure 1 shows the heat flow

Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs

• Lisa F. Becker,
• Dennis H. Schwarz and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 2920–2927, doi:10.3762/bjoc.10.310

• . This fact was attributed to an increasing loss of entropy upon complexation of the guests. The longer the substituents the higher the conformational freedom of the host leading to higher intrinsic entropy. Also the two statistical derivatives, 2b1 and 2b2 showed somewhat lower binding constants than

Synthesis and characterization of a new photoinduced switchable β-cyclodextrin dimer

• Florian Hamon,
• Claire Blaszkiewicz,
• Marie Buchotte,
• Estelle Banaszak-Léonard,
• Hervé Bricout,
• Sébastien Tilloy,
• Eric Monflier,
• Christine Cézard,
• Laurent Bouteiller,
• Christophe Len and
• Florence Djedaini-Pilard

Beilstein J. Org. Chem. 2014, 10, 2874–2885, doi:10.3762/bjoc.10.304

• characterize the interaction of CDs with guests in solution [37][38]. It enables the enthalpy, entropy and equilibrium constants involved in complexation processes to be determined in a single experiment. Moreover, the guest:host molar ratio (i.e., the stoichiometry of the complex) can be measured. First

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

• (ΔG) can be calculated from enthalpy (ΔH) and entropy terms with constant temperature (TΔS). In solution, the ΔH term was divided into enthalpy energy in gas phase upon formation of complex (ΔEMM) and the free energy of solvation (ΔGsol), while the entropy term, T∆S, for conformational entropy change

• is worth to note that in comparison to the QM energy (∆EQM) the MM method was likely found to overestimate the binding interaction by ca. 10 kcal/mol for all snapshots in the three forms of complex (Figure 7). Our results also suggested that for binding free energy prediction, the entropy and

Improving ITC studies of cyclodextrin inclusion compounds by global analysis of conventional and non-conventional experiments

• Eléonore Bertaut and
• David Landy

Beilstein J. Org. Chem. 2014, 10, 2630–2641, doi:10.3762/bjoc.10.275

• enthalpy ΔH, inclusion entropy ΔS, heat capacity variation ΔCp ) [5][6][7][8][9][10][11]. On a methodological point of view, most ITC studies are based on the classical titration protocol. While one partner of the studied phenomenon, called titrand, is placed inside the cell, the second partner, called

Microsolvation and sp²-stereoinversion of monomeric α-(2,6-di-tert-butylphenyl)vinyllithium as measured by NMR

• Rudolf Knorr,
• Monika Knittl and
• Eva C. Rossmann

Beilstein J. Org. Chem. 2014, 10, 2521–2530, doi:10.3762/bjoc.10.263

• immoblization of additional ligands by its less negative entropy contribution. If so, this disolvation of monomeric 4 implies that TMEDA did not admit the solvent t-BuOMe to participate in direct microsolvation. After final quenching with DOCH3 (6 equiv), the in situ 1H and 13C NMR spectra showed the

• -stereoinversion through limiting the negative entropy contribution of ligand immoblization: Since 4&3THF needs only one further THF ligand to generate the SSIPs 12 and 13 from 11, this immobilization costs only a one-particle entropy contribution of ca. −11 cal mol−1 K−1 [10], as also known [11] for the

• expense of doubled entropy contributions (ca. −22 cal mol−1 K−1) if generating SSIPs (like 12) with tetrasolvated Li+, which explains why their diastereotopomerization rates remained below our NMR time scales even though the doubled THF fixation would provide an increased negative contribution to ΔHψ

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• constant between 17 and β-CD, caused by the symmetry effect of the interaction between two homodivalent systems [1]. The intrinsic complexation enthalpy and entropy show that both complexations are enthalpically as well as entropically driven. The interaction of 8 with the non-complementary CD dimer 1

• higher than the binding constant between 17 and α-CD due to the symmetry effect. The complexation enthalpy and entropy differ from the monovalent interaction α-CD/17 because of the bridging of the host and the guest molecules (Figure 8C). In summary, for none of the divalent strands sequence-specific

• indicate that every inclusion process is mainly driven by the complexation entropy although four molecules are combined in one aggregate. The analysis of the ITC data of the system 7/12 was done with a 1:3 binding model where only the interaction between the adamantane moiety of 12 and the β-CD of 7 was