Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• multiple bonds (10 and 12). However, in the case of shorter (from 2-bromoethanol) and longer (compound 24) chain intermediates, the cyclization is retarded due to the disadvantage of forming a strained four-membered ring in the former case and a significant loss of entropy during the formation of a seven

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• mechanism to a <1st-order dependence on catalyst, which could indicate a competing alcohol or H-bonding driven mechanism. In CD3OD, first-order-catalyst dependence is maintained. The entropy of activation reveals an organized transition state (−42.1 cal/mol·K) which would be consistent with the mechanism in

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• (Figure 1C). Elongation of the tether in fullerenes 10 and 11 reduced product ratios to still significant A/D10/9 ~ A/D11/9 = 2.1. The origin of this decrease in anion–π catalysis is likely to include increasing entropy losses in pseudo-macrocyclic transition states. Normalized against the fullerene-free

• ammonium cation. Normalized against the fullerene-free control 18, an electron-withdrawing cyano group on the cyclopropane in 19 gave similarly poor A/D19/18 = 1.5. At constant tether length as short as possible, strong increases in anion–π catalysis were found by further minimizing entropy losses in

GlAIcomics: a deep neural network classifier for spectroscopy-augmented mass spectrometric glycans data

• Thomas Barillot,
• Baptiste Schindler,
• Baptiste Moge,
• Elisa Fadda,
• Franck Lépine and
• Isabelle Compagnon

Beilstein J. Org. Chem. 2023, 19, 1825–1831, doi:10.3762/bjoc.19.134

• ) activation functions for each layer. Two dropout layers are interleaved after the first and second hidden layers with a dropout setting of 25% to avoid over-fitting issues. The training objective is a classification task between the 4 monomer categories with a cross-entropy loss function. To account for the

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• -site binding model (Figure 7, Table 3). ITC experiments confirmed the binding of the ligand with human DPP III mutant E451A. The experiment resulted in positive peaks as a result of an endothermic reaction, which took place with an increase in entropy (Figure 7C, Table 3). This means that the binding

• -Py-1: endothermic reaction with an increase of entropy. The analogous guanidiniocarbonylpyrrole–pyrene conjugate showed a negative enthalpy change and an increase of entropy [17]. Conclusion Two novel phenanthridine–pyrene conjugates Phen-Py-1 and Phen-Py-2 were prepared by the condensation of

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• by the tethers, the entropy effects caused by them has also been studied. The analysis of the evolution of the electron localization function along the reaction revealed the highly concerted character of the reaction. Keywords: DFT; distortion model; hydrazones; transannular cycloadditions

Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements

• Robert N. Goldberg,
• Robert T. Giessmann,
• Peter J. Halling,
• Carsten Kettner and
• Hans V. Westerhoff

Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26

• temperature. But, if K′ is measured at different temperatures one can also calculate the standard transformed molar enthalpy of reaction ΔrH′° and then the standard transformed molar entropy of reaction ΔrS′°. Using ΔrH′° one may then calculate ΔrG′° and K′ at different temperatures. Additionally, a

• in the scientific literature. Thus, comparisons with previously measured values of K or K′ of the same or highly similar reactions should be made and reported. In thermodynamics, the measured quantities are frequently related to the Gibbs energy G, the enthalpy H, and the entropy S. The

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• partially methylated CDs with the admixture of water in DMSO. All CDs interactions with tetracene were accompanied by sufficient entropy gain, which points to the desolvation of interacting molecules. The interaction of CD "monomers" 13 and 16 with tetracene is weakly endothermic and, therefore, understood

• as an entropy-driven process with the potential formation of a complex in 1:1 stoichiometry. All CD dimers interacted with tetracene exothermically. Since the overall amount of water in the system is one order lower than the amount of hydroxy groups in CDs, they preserve the capacity for hydrogen

• , USA), to the two independent binding sites model. From the fit, the stoichiometry (n), binding enthalpy change (ΔH, kJ·mol−1), affinity constant (Ka, M−1), binding free energy change (ΔG, kJ·mol−1), and binding entropy change (ΔS, J·mol–1·K−1) for the first binding site were calculated. The

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• hydroxy groups pointing towards the sides [1]. This makes the ‘hole’ in the donut a lipophilic cavity that in water can form complexes with small hydrophobic molecules [2] driven by the entropy increase by expulsion of water [3]. Compound 1 has a wide range of applications where the complexation of

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• proceed in an alcoholysis reaction through a cyclic structure involving three molecules of the alcohol and the sulfur of the sulfonyl chloride present in the ring [52]. One would predict that such an extremely ordered pathway would have a very negative entropy of activation, but the required studies with

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• solvation of the polymer chains (T > UCST). Compared to an entropy-driven LCST behavior of polymers, the enthalpy-driven UCST thermoresponse is based on spatially highly directed forces between polymer segments [51][52][54][55]. Understanding the molecular mechanism and thus precisely controlling the

• processes in general, and the mixing processes discussed here, has been thermodynamically formulated. Mathematically, this description results in the Gibbs energy of mixing ΔmG, which is linked to the enthalpy of mixing ∆mH and the entropy of mixing ∆mS via the following well-known connection: This means

• obtain for the entropy of mixing: Thus, the driving force of the mixing process is the increase in disorder due to the mixing of the particles of both species. ∆mG is therefore always negative for ideal mixtures of any composition with a minimum at a certain ratio A–B and is always smaller than the Gibbs

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• involving PNA usually follow the order PNA–PNA > PNA–RNA > PNA–DNA [20][21]. Hybridization of PNA with complementary nucleic acids is enthalpy driven, involving large favorable gains in enthalpy compensated by significant unfavorable entropy, as typically observed for nucleic acid complexes [22]. The

• (Figure 2B). An innovative design links the two ends together with an ethylene glycol linker (Figure 2C), which reduced the unfavorable loss of entropy by converting the binding event from a trimolecular to a bimolecular process [34][35][36]. The new bis-PNAs (Figure 2C) showed about two orders of

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• + modifications led to the formation of duplexes with a thermal stability that was less dependent on the ionic strength than native DNA duplexes. The thermodynamic analysis of the melting curves revealed that it is the reduction in unfavourable entropy, despite the decrease in favourable enthalpy, which is

• deprived by an even higher entropy penalty leading to a loss in ΔG (ΔΔG298 = 33 kJ/mol), thus lowering the Tm value at 25 mM NaCl. For the unmodified RNA duplex (ON1/ON19), ΔΔH between 25 mM and 100 mM NaCl is 84 kJ/mol, and the corresponding entopic factor Δ(TΔS) is 84 kJ/mol. As a result, changes in

• was more favourable. According to Kuo et al. [37], an increase in the salt concentration stabilises the DNA duplex by reducing the entropy costs of duplex formation rather than by reducing the strand charge repulsion. This reduction of entropy costs for duplex formation is due to the endothermic

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• interactions and secondary interactions such as π–π stacking [34][35][36][37][38][39][40]. The size and shape could be tuned through the free energy and the enthalpy/entropy interplay in the assembly process, which again are encoded in the molecular building block structure [31][37]. Supramolecular structures

• binding constants Kx, which are related to the free energy change ΔG and thus due to ΔG = ΔH − TΔS, also the entropy change ΔS is revealed. Table 5 summarizes the results from the full titration curve fitting. The values correlate to the binding of one monomer of the polymer to Flavy and/or photoacid. For

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• various main factors, such as the percentage of the host occupancy, the temperature, and the solvent but not on the entropy of the system. In continuation of their previous work, Inoue, Yang, et al. reported an alternative approach so that the chiral slipped 5,8:9',10'-cyclodimers 14 and 15 were

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