Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• methods are used to characterise the protein complex and to confirm the presence of certain interactions. Biophysical approaches are important to determine binding affinities, enthalpy changes, entropy changes, and the on- and off-rates of binding, amongst others. Examples include surface plasmon

• thermodynamic properties, including the binding constant Kb, the reaction stoichiometry (n), the observed molar calorimetric enthalpy ΔHobs, the entropy ΔS, the heat capacity of the binding ΔCp,obs, and the change in the Gibbs free energy ΔG. As a result, ITC is used to provide a complete thermodynamic

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• rotamers in hand, an Eyring plot was generated, and the enthalpy and entropy of activation were derived (Table 2). The structural identification of the major and minor rotamers was not attempted by NMR, but in silico investigations of 3a supported the intuitive notion that the rotamer of lower energy was

• , the enhanced imbalance in the population of the rotamers of 6a is notable and consistent with the amino moiety imposing a greater steric hindrance. The differences among the other compounds are more modest. The small entropy of activation is consistent with a simple rotation over a steric barrier

• tetrakis(trifluoromethyl)-1,3-dithietane (1) with compounds 2–7. Reaction products, conditions, yield, ratio of isomers, and melting points for the new materials. Enthalpy and entropy of activation for the rotameric interconversion of a subset of hexafluoroisopropyl azoles. NMR and MS data for the

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• binding properties, isothermal titration calorimetry is an advantageous method as it yields the binding stoichiometry, the binding constant Ka and the binding enthalpy ΔH0 in one measurement. From these data, the Gibbs free binding energy ΔG0 and the binding entropy ΔS0 can be calculated. Pseudo[2

• the pseudorotaxane of NDIC8, and thus to a more favorable binding entropy compared to the pseudorotaxane of TTFC8. For TTFC8, the increased binding enthalpy can be explained by additional π–π-interactions between the naphthalene and TTF unit of the crown ether and the ammonium axle, resulting in a

• rather rigid crown ether conformation in the complex as compared to the free macrocycle. This loss of conformational flexibility rationalizes the increased entropic penalty. A similar trend is observed for the binding enthalpy and entropy of NDIC8 and TTFC8 with the axles A2·PF6 (Table 1, entries 7 and 8

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• calorimetry experiments (ITC), which allowed us to determine all thermodynamic components simultaneously in a single experiment (the equilibrium binding constant (Ka), reaction Gibbs free energy of binding (ΔrG), reaction enthalpy (ΔrH), reaction entropy (ΔrS), and the stoichiometry (n) of the complex formed

• reaction entropy change, indicating favourable enthalpic (exothermic) and entropic contribution to the reaction Gibbs free energy change. This means that the reaction is both enthalpically and entropically driven. However, secondary binding site (n > 0.4; excess of 4 over DNA primarily binding site) is

• energetically favourable non-covalent interactions, hydrogen bonds, and van der Waals interactions formed between the DNA/RNA and solvent, and between the compound 4 and solvent. The large positive entropy changes suggest solvent release upon binding, which makes a favourable contribution to the reaction Gibbs

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• enthalpy (ΔH [kcal/mol]) and positive entropy (ΔS [cal/mol/K]) values, pointing out that the complexation processes are enthalpy-driven and characterised by the same type of binding mode, i.e., intercalation [17][44]. The relatively large entropy contribution might be attributed to the displacement of

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• therefore be met with some caution. FF seems to bind stronger to a(CFC)2 than to p(CFC)2, though again the values show some uncertainty and real values of the binding constants are likely in the same order of magnitude as for YY. Unlike for the interaction with FF, the entropy change of interaction with YY

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• compensated by the dimerization entropy (ca. 128 J mol−1 K−1) due to the fact that the entropy obtained in vacuo calculations are not realistic in condensed phase. Computed reaction mechanism of the 3-phospholene oxide (1) 2-phospholene oxide (4) isomerization under acidic conditions at MP2/6-311++G(2d,2p

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• (TS) is reflected in the low value of the activation entropy, ΔS≠ = 0.474 cal/mol∙K, which means that there is a very small disorganization in the transition state as compared to the reactant in the T1 minimum state. The length of the bond N–O in the transition state is equal to 1.629 Å. The

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• conformational entropy penalty upon binding to a protein target, and the approach of constraining the ligand conformation with a ring is widely used in drug design [2]. Accordingly, with increasing interest for sp3-rich molecules, spirocyclic compounds are being considered valuable as molecular platforms for the

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds

• Itamar L. Gonçalves,
• Rafaela R. da Rosa,
• Vera L. Eifler-Lima and
• Aloir A. Merlo

Beilstein J. Org. Chem. 2020, 16, 175–184, doi:10.3762/bjoc.16.20

• properties Mesomorphic properties of thioureas 17a–c, and 18a–c and amides 19–22 and 24 were investigated by POM and DSC. The DSC results for all compounds are summarized in Table 1. Transition temperatures, as well as the enthalpy and entropy values of each compound were acquired by differential scanning

• temperatures (°C), enthalpy/entropy for thioureas 17a–c, 18a–c and amides 19–22 and 24 upon heating.a Supporting Information Supporting Information File 255: Experimental descriptions for the preparation of compounds and characterization data. Supporting Information File 256: Differential scanning calorimetry

Effect of ring size on photoisomerization properties of stiff stilbene macrocycles

• Sandra Olsson,
• Óscar Benito Pérez,
• Magnus Blom and
• Adolf Gogoll

Beilstein J. Org. Chem. 2019, 15, 2408–2418, doi:10.3762/bjoc.15.233

• conformations. This will add an entropy penalty for the E-isomers. Interatomic distances from NOE buildup rates Interatomic distances, derived from NOE buildup rates, are summarized in Figure 7. Signal overlap prevented an analysis accounting for the presence of an ensemble of conformers such as NAMFIS [39][40

Halide metathesis in overdrive: mechanochemical synthesis of a heterometallic group 1 allyl complex

• Ross F. Koby,
• Nicholas R. Rightmire,
• Nathan D. Schley,
• Timothy P. Hanusa and
• William W. Brennessel

Beilstein J. Org. Chem. 2019, 15, 1856–1863, doi:10.3762/bjoc.15.181

• ]∞, enable an otherwise unfavorable halide metathesis to proceed with mechanochemical assistance. From this result, we demonstrate that ball milling and unexpected solid-state effects can permit seemingly unfavored reactions to occur. Keywords: caesium; entropy; intermolecular forces; mechanochemistry

• additional entropy provided by the two metal ions and the site disorder in the solid. Using a standard formula for the entropy of mixing two species (configurational entropy, ∆Smix = −nR(XA ln XA + XB ln XB) [31], and with 3 atoms distributed randomly over the three crystallographically identified metal

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

• 0.15 eV (neglecting entropy changes during the light absorption) is required to efficiently inject photo excited electrons from the LUMO of the dyes in the CB of the oxide [34]. Usually iodine-based liquid electrolytes are comprising additives such as tert-butylpyridine (tBP) which is known to shift

Host–guest interactions in nor-seco-cucurbit[10]uril: novel guest-dependent molecular recognition and stereoisomerism

• Xiaodong Zhang,
• Wei Wu,
• Zhu Tao and
• Xin-Long Ni

Beilstein J. Org. Chem. 2019, 15, 1705–1711, doi:10.3762/bjoc.15.166

• driven by both enthalpy and entropy (ΔH = −30.96 kJ·mol−1 and TΔS = 9.46 kJ·mol−1). Evidently, the high enthalpy gain for host-1 with G1 and G2, host-2 with G1 may be attributed to the strong ion–dipole interactions between the guest and host. However, the host–guest interactions in the case of complexes

The activity of indenylidene derivatives in olefin metathesis catalysts

• Maria Voccia,
• Steven P. Nolan,
• Luigi Cavallo and
• Albert Poater

Beilstein J. Org. Chem. 2018, 14, 2956–2963, doi:10.3762/bjoc.14.275

• , apart from calculating the unscaled zero-point energies (ZPEs) and the thermal corrections and entropy effects at 298 K, and all values at a pressure of 1354 atm using the approach of Martin and co-workers [61], excluding the potential overestimation of the entropy contribution [38][62][63]. Energies

• include energies obtained at the M06/TZVPsdd level of theory corrected with zero-point energies, thermal corrections, and entropy effects evaluated at 298 K, achieved at the BP86/SVPsdd level. This computational approach for olefin metathesis with Ru based catalysts turned out to display errors of less

The influence of the cationic carbenes on the initiation kinetics of ruthenium-based metathesis catalysts; a DFT study

• Magdalena Jawiczuk,
• Angelika Janaszkiewicz and
• Bartosz Trzaskowski

Beilstein J. Org. Chem. 2018, 14, 2872–2880, doi:10.3762/bjoc.14.266

• -point LACV3P++** calculations), solvation energy, zero-point energy correction, thermal correction to enthalpy, and the negative product of temperature and entropy (at 298 K). All final estimates of Gibbs free energies include the counterpoise correction [69]. To further validate our results we used the

Dynamic light scattering studies of the effects of salts on the diffusivity of cationic and anionic cavitands

• Anthony Wishard and
• Bruce C. Gibb

Beilstein J. Org. Chem. 2018, 14, 2212–2219, doi:10.3762/bjoc.14.195

• therefore LiI should be the greatest aggregator of 2. As Table 1 reveals, this is not the case; it is NaI that has the strongest influence on the host. A straightforward answer for this may be that entropy is a part of the aggregation of 2, whereas the LMWA is purely enthalpically based. Additionally

A conformationally adaptive macrocycle: conformational complexity and host–guest chemistry of zorb[4]arene

• Liu-Pan Yang,
• Song-Bo Lu,
• Arto Valkonen,
• Fangfang Pan,
• Kari Rissanen and
• Wei Jiang

Beilstein J. Org. Chem. 2018, 14, 1570–1577, doi:10.3762/bjoc.14.134

• based on the information obtained from four representative crystal structures. In addition, heat capacity changes (ΔCp) and enthalpy–entropy compensation phenomena both indicate that solvent reorganization is also involved during the binding. This research further deepens our understanding on the

• [12] is crucial for minimizing the entropy cost in molecular recognition. In contrast, bioreceptors often possess flexible backbone structures and even undergo large amplitude conformational changes upon binding substrates [13][14]. This conformational adaptivity is the basis of the allosteric effects

• formation of 18+@ZB4 complex over the temperature range 283–313 K is very small (0.31 kJ mol−1), while the changes in ΔH and −TΔS are much larger (ca. 4–4.3 kJ mol−1). The changes in ΔH and −TΔS are opposite in signs and perfectly compensate each other. The enthalpy–entropy compensation phenomenon may be

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• -phenylsydnone and DMAD was first studied by Huisgen and Gotthardt [54] in p-cymene at 90–110 °C. They found the cycloaddition to be overall second order and its activation entropy ΔS≠ = −130 J·mol−1·K−1 showed association character of the rate-limiting step with a relatively tight transition state. Moreover

• ≈ +0.3 to +0.4) was described [55] for reactions of 3-(4-substituted phenyl)sydnones with more reactive DMAD while the activation entropy (ΔS≠ = −106 to −121 J·mol−1·K−1) remained similar. The reaction mechanism (Scheme 5) consistent with these kinetic measurements involves rate-limiting formation of a

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• calculated by GB model and nonpolar contribution to the solvation free energy calculated using 'LCPO' surface areas) ΔGGB = ΔGgas + ΔGsolv as described by Miller et al. [50]. The entropy term T∙ΔS was also calculated from normal mode analysis with constant temperature using the respective module of the Amber

• 12 suite and added to the ΔGGB term according to: ΔGbind = ΔGGB − T∙ΔS. The entropy term was calculated by taking snapshots every 100 frames for as long as the equilibrated system of the inclusion complex was subjected to MD simulations. However, it should be noted that the estimation of the entropy

• term is often problematic as the normal mode lacks information of the conformational entropy and alternative methods do not give converged results [51]. Thus, this term is usually omitted and the comparison between similar complexes is based on the ΔGGB solely. Schematic representation of (a) the

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• consequent unfavourable effect on the complex formation entropy [43][50]. A further unfavourable contribution may also come from the increasingly difficult desolvation of the charged host. These combined effects cause the observed decrease of K values for the neutral guest 1. By contrast, for the anionic

• that the ancillary chain of 3 is unable to give multiple hydrogen bonding with the host cavity, due to the methyl group placed on the amino N atom. According to literature, this peculiar structural feature is able to enhance largely the outcome of entropy-unfavourable stiffening effects [50][52]. On

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2698–2709, doi:10.3762/bjoc.13.268

• interactions, π–π interactions, desolvation effects and entropy-unfavorable conformational dynamic restraints. Polarimetry is confirmed as a very useful and versatile tool for the investigation of supramolecular interactions with chiral hosts, even in complex systems involving multiple equilibria. Keywords

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• water molecule does not lead to an additional entropy penalty upon H-bonding to the ligand. As a result, the interaction benefits from an enthalpic gain without suffering from an entropic penalty [58]. Examples of such highly conserved water molecules are found in both, L-arabinose binding protein (ABP

• ). With the entropically driven sLex interaction, surface waters are displaced to the bulk and penalized by a positive enthalpy term resulting from a desolvation penalty that is not compensated by the newly formed electrostatic interactions (Figure 6) [67]. According to Dunitz [68], the entropy that can

• overall enthalpic benefit by forming additional interactions at a reduced cost. In addition, the entropy gained by releasing three water molecules into bulk, as compared to only two, should also be taken into account. The formation of multiple H-bonds in rigid, buried binding sites is an alternative way

One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni’s reagent

• Azim Ziyaei Halimehjani,
• Martin Dračínský and
• Petr Beier

Beilstein J. Org. Chem. 2017, 13, 2502–2508, doi:10.3762/bjoc.13.247

• ) provided the rates of rotation around the N–C bond at all temperatures and the Eyring plot (Figure 2) allowed to determine the enthalpy and entropy of activation. The entropy of activation is small (−4.2 cal/K) and the free energy of activation (15.8 kcal/mol at 300 K) is dominated by the enthalpic term

β-Cyclodextrin- and adamantyl-substituted poly(acrylate) self-assembling aqueous networks designed for controlled complexation and release of small molecules

• Liang Yan,
• Duc-Truc Pham,
• Philip Clements,
• Stephen F. Lincoln,
• Jie Wang,
• Xuhong Guo and
• Christopher J. Easton

Beilstein J. Org. Chem. 2017, 13, 1879–1892, doi:10.3762/bjoc.13.183

• adamantyl group and its dodecyl tether as is discussed below. The large K for the PAAβ-CDen/PAAADen and PAAβ-CDen/PAAADhn systems are mainly due to substantial ΔH contributions (Table 1). The negative TΔS for the PAAβ-CDen/PAAADen system is attributable to the entropy loss arising from the combination of

• the β-CDen and ADen substituents into a single complex and network formation outweighing the entropy gain [49][50] anticipated for the displacement of water from the β-CDen annulus by the ADen substituent. This offset is smaller for the PAAβ-CDen/PAAADhn system possibly because the ADhn substituent

• hexyl tether allows more network flexibility. The K for the PAAβ-CDen/PAAADddn system is the largest observed as a consequence of a smaller ΔH being offset by a positive TΔS. This probably arises from the entropy loss expected for complexation of the adamantyl group and the dodecyl tether of the ADddn