Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• most reliable method, it was employed to optimize the geometry and compute frequencies (to derive Gibbs free energy) for the difluorinated pyrrolidines. These computations were conducted in both the gas phase and employing an implicit DMSO solvent using SMD [22]. Subsequently, a NBO [23] analysis was

• the gas phase and implicit DMSO (in parentheses), along with the MAE compared to the CCSD/DGTZVP level. Relative Gibbs free energy (kcal⋅mol−1) for the geometry-optimized difluorinated pyrrolidines. Relative electronic energy (ΔEfull = ΔELewis + ΔEnon-Lewis) in isodesmic relationships and significant

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• enthalpy (ΔH), and stoichiometry (n). Values for free energy change (ΔG) and entropy contributions (TΔS) were derived from the equation ΔG = ΔH − TΔS = − RT ln Kd (with T = 298.15 K and R = 8.314 J mol−1K−1). General procedure I for the O-alkylation with BrCH2CH2NHBoc: A solution of glycosyl azobenzene

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• anticipated that 1 would similarly undergo Cope rearrangement. However, when we heated 1 up to 200 °C for 5 h, we did not observe any Cope rearrangement products and we were able to recover >90% of 1. DFT calculations [mPW1PW91/6–31+G(d/p)/SMD(toluene)] on the Cope rearrangement of 2 revealed a free energy

• barrier through the chair–chair transition state of 28.1 kcal mol−1 and an overall ΔG from 2 to 10a/10b, which have the same predicted energy, of −2.0 kcal mol−1 (Figure 3B). The relative free energy barrier through the chair–boat transition state was calculated to be 36.9 kcal mol−1, but would require a

• , Supporting Information File 1). The lowest transition state for a Cope rearrangement, a chair–chair structure at 29.3 kcal mol−1, originates from a DD (down–down orientations of the methyl groups on the 10-membered ring) conformer that is 3.2 kcal mol−1 higher in free energy than the most dominant conformer

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• divided into three analogous sets. Below we will describe the free energy trends for the germacrene A and hedycaryol carbocations (Figure 2), while the corresponding electronic energy trends are presented in Supporting Information File 1 (Figure S1). Gibbs free energy of germacrene A–L carbocations For

• ring carbocation, E and F are 6.0 and 10.9 kcal/mol less stable than A, H is 16.0 kcal/mol above A, whereas G is the least stable (19.5 kcal/mol). For the remaining set (I–L), the free energy variation is smaller, with values ranging from 10.0 to 11.4 kcal/mol relative to A. To understand the reason

• for the difference in free energy, we analyzed the NCI plots for germacrene cations A–D. Despite being isomers, these carbocations possess quite different geometric arrangements. For instance, molecule A is more planar than the puckered B. It is clear from visual inspection of the NCI plots that B

Novel route to enhance the thermo-optical performance of bicyclic diene photoswitches for solar thermal batteries

• Akanksha Ashok Sangolkar,
• Rama Krishna Kadiyam and
• Ravinder Pawar

Beilstein J. Org. Chem. 2024, 20, 1053–1068, doi:10.3762/bjoc.20.93

• calculated employing the following equation: where Gdiene and Gphotoproduct indicate the Gibbs free energy of the bridged bicyclic diene molecule and the corresponding photoproduct. The ΔGstr was herein calculated by computing the Gibbs free energy of the diene and photoproduct using the M062X/6-311++G

• and photoproduct and ΔT is the difference in thermal contribution to the Gibbs free energy (M062X/6-311++G**) of the two photoisomers. The thermal back reaction (TBR) barrier is the energy barrier that the photoproduct must overcome to revert back into the parent isomer for continuing the

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• energy, with a difference of Gibbs free energy with oxocarbenium 7 (39.2 kcal/mol) and 7’ (35.8 kcal/mol) incompatible with the reaction conditions. We therefore ruled out this possibility and suggest that aldehyde 3 is the main intermediate in this transformation (Scheme 3). Interestingly, the 1

• dihydronaphthalene 4. One-pot conversion of substrate 1 into 1-aryltetraline structure 6, and the proposed mechanism for its formation. Free-energy profile of the hypothesized [1,5]-sigmatropic hydrogen shift between 7 and 7’, (IEFPCM(CH2Cl2)-M06/6-311++G(2d,2p)//M06/6-31G(d,p) level of theory). Scope of substrates

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• -order kinetics, indicating a bimolecular process. Furthermore, their findings elucidated a compelling linear free-energy relationship between the rate constants and electronic characteristics of the para-substituents of the DCV electrophiles, implying a dipolar, zwitterionic mechanism. The researchers

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• settings) is also predicted to be formed. Free energy difference between the two isomers, estimated in the gas phase, is somewhat reduced when increasing temperature (see Supporting Information File 1, Table S1). Therefore, the molar fraction of (1-Cs)•+@CNT would increase slightly at higher temperatures

• simulation technique that allowed us to explore the free energy surface in a fast and efficient way. In particular, we performed Car–Parrinello metadynamics simulations by choosing collective variables (CVs) that describe the formation and breaking of C–C bonds in the interdimer region (see Computational

• carbon atoms of one C60 molecule (those of contiguous hexagon and pentagon) with respect to nine carbon atoms in the other C60, all of them in the interdimer region (see Supporting Information File 1). Choosing this single CV, we aim to rapidly and efficiently explore the region of the free energy

Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling

• Mateusz Marcisz,
• Sebastian Anila,
• Margrethe Gaardløs,
• Martin Zacharias and
• Sergey A. Samsonov

Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144

• GAG properties, especially protein recognition specificity and multipose binding. We found that the binding free energy landscape in the proximity of the GAG native binding pose is complex and implies the co-existence of several binding poses. The sliding of a GAG chain along a protein surface could

• multipose character of GAG binding and the polarity of the binding poses of these periodic molecules. In the present work, all-atom MD simulations are conducted to study the dynamics of the protein–GAG complexes, and are complemented by free energy analysis. The free energy analysis of the protein–GAG

• analysis of the contacts between protein and GAG molecules established in the course of the simulation. Binding free energy calculations MM/GBSA (molecular mechanics generalized born surface area) model igb = 2 [48] from AMBER20 was used for free energy calculations on the trajectories obtained from RS

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• (С-6), 143.51 (С-4), 129.63 (С-3), 103.54 (С-3a), 38.35 (NСH3), 22.65 (CH3 in Ac); HRESIMS–TOF ( m/z): [M + Na]+ calcd for C8H10N6ONa, 229.0808; found, 229.0815; Anal. calcd for C8H10N6O: C, 46.60; H, 4.89; N, 40.76; found, C, 46.65; H, 4.85; N, 40.86. Gibbs free energy diagram (B3LYP/6-311++G(d,p

Benzoimidazolium-derived dimeric and hydride n-dopants for organic electron-transport materials: impact of substitution on structures, electrochemistry, and reactivity

• Swagat K. Mohapatra,
• Khaled Al Kurdi,
• Samik Jhulki,
• Georgii Bogdanov,
• John Bacsa,
• Maxwell Conte,
• Tatiana V. Timofeeva,
• Seth R. Marder and
• Stephen Barlow

Beilstein J. Org. Chem. 2023, 19, 1651–1663, doi:10.3762/bjoc.19.121

• according to: where ΔGdiss(12) is the free-energy change for dissociation of 12 to 1• (dissociation energetics are not estimated in the present work, but have been estimated using DFT calculations for 1b–e2 in previous works [8][14] and, in favorable cases, can be experimentally estimated using electron

• of 1H dopants is given by: where ΔGdiss(1H) is the free-energy change for dissociation of 1H to 1• and H• (again, not discussed in this work), and ΔGdiss(H2) the free-energy change for dissociation of dihydrogen. The values of E(1+/1•) are also relevant to the kinetics of steps in doping reactions

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• ′, and 24 conformers for 3. The geometry of each conformer was optimized using DFT calculations at the B3LYP/6-31G(d) level of theory [20][21] with the conductor-like polarizable continuum model (CPCM) solvent model (MeOH) and Gibbs free energy was calculated subsequent frequency calculations. Time

• -dependent (TD)-DFT calculations at the B3LYP/6-31+G(d,p) level with CPCM solvent model (MeOH) [22] were performed for the optimized conformers. The resulting ECD spectra calculated for each conformer were averaged using Boltzmann populations evaluated at 300 K from Gibbs free energy calculated from the

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• negative free energy of polymerization and the latter an adequate reactivity of the monomer, stability of the derived free radical, and a low proportion of side reactions. A slow rate of chain initiation, a fast rate of chain propagation, and a rapid rate of chain termination are key features of

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• regeneration to occur. As shown in Figure 1, the scale of electrochemical potential measured in volts is an inverted scale of free energy. Therefore, it is thermodynamically favorable for electrons to be transferred from higher energy sacrificial donor orbitals with less positive oxidation potentials to lower

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

The effect of dark states on the intersystem crossing and thermally activated delayed fluorescence of naphthalimide-phenothiazine dyads

• Liyuan Cao,
• Xi Liu,
• Xue Zhang,
• Jianzhang Zhao,
• Fabiao Yu and
• Yan Wan

Beilstein J. Org. Chem. 2023, 19, 1028–1046, doi:10.3762/bjoc.19.79

• . The Gibbs free energy changes (ΔGCS) for charge separation (CS) as well as the energy of the charge transfer states (ECS) were calculated using the Rehm–Weller equation (Equations 1–3) and the obtained values are listed in Table 4 [62][63][64]. It should be noted that the E00 values used in the

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• adds to the diazo compound 5 under formation of zwitterionic Int1 (ΔG = 5.2 kcal/mol). Afterwards, copper carbene complex Int2 is formed after extrusion of nitrogen. The transition state of this metal carbene formation TS1 was calculated with an activation free energy of 16.4 kcal/mol (Scheme 5). Int2

• Int2 yielding Int4_3 and Int4_4 without further intermediates. Formation of the products Pr1 to Pr4. Optimization of the reaction conditionsa. Change in Gibbs free energy ΔG (kcal∙mol−1) from the CuI-catalyzed cyclopropanation of the diazo compound with styrene for possible stereoisomers Pr1 to Pr4

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• kinetic and computational analyses, the B‒C(sp2)/B‒H transborylation transition state was determined to have a free energy barrier of approximately 20 kcal mol−1 (ΔG‡calc = 19.7 kcal mol−1; ΔG‡exp = 20.3 kcal mol−1) (Scheme 2). The borane-catalysed hydroboration of alkenes has been less explored, with

• experimentally determined free energy barrier of 28 kcal mol−1 for the second transborylation reaction (Scheme 3b) [60]. The seminal work from Fontaine reported that [1-(N-2,2,6,6-tetramethylpiperidinyl)-2-BH2-C6H4]2 catalysed the C–H borylation of heterocycles with HBpin [61], the first example of a catalytic

• discovered, leaving an exciting future for main group catalysis underpinned by group 13 exchange and transborylation reactions (Figure 1). a) The number of reports for a given group 13 exchange in catalysis. b) Average free energy barrier to group 13 exchange in catalysis (blank where no free energy value

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• process was explained by the unusual feature in the reactivity of the HSPyf/(SPyf)2 pair compared to other thiols and disulfides revealed by DFT calculations. In the case of the SPyf moiety the free-energy barrier for HAT between C-centered radicals and HSPyf is higher than the barrier for an SPyf group

• high hydrogen binding energy and low deprotonation free energy. N-Ammonium ylides were used for the electrochemical oxidation of unactivated C–H bonds (Scheme 37). Ylides showed good selectivity and an unusual reactivity pattern in comparison with known mediators for CH-oxidation. For example, a

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

• , 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

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• , ΦΔ are much larger, up to 100% in dichloromethane (DCM) and ACN, likely due to the heavy-atom effect. Electrochemistry study The redox potentials of the dyads were studied with cyclovoltammetry (Figure 6, Table 3), and the Gibbs free energy changes of the charge separation (ΔGCS) and charge

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• 9H-purine structure. B3LYP/6-31+G(d)/SDD optimized transition state structures for N7- (6-TSN7) and N9-ferrocenoylation (6-TSN9) of the adenine anion 6. Two bulky tert-butyloxycarbonyl groups are displayed in the tube mode for clarity. Relation between the Gibbs free energy barrier (ΔG‡) for the N7

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• reactants, intermediates, transition states, and products were optimized and are illustrated in Figure S7 in Supporting Information File 1. The relative free energy (ΔG, ΔG#) values for all species are presented in Figure 4, the reaction potential energy surface. This figure is a detailed reaction mechanism

• bond to N atom (Scheme 4). This process is thermodynamically favorable by a Gibbs free energy (ΔG) of −6.5 kcal·mol−1. In addition, a second way from 4a, through the TS5 transition state, to form the IS3 intermediate requires an activation energy of ca. 33.7 kcal·mol−1. IS3 could release one H2O

• favorable than from –OH and –NH groups. Moreover, the reaction mechanism in the chloroform and DMSO solvent model is also considered to confirm the main reaction pathway (Table S3 in Supporting Information File 1). The results indicate that the same trends and slight differences of free energy values are

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• the 2 kJ/mol energy window were generated and optimized using DFT calculations at the B3LYP/6-31+G (d,p) level. Frequency calculations were performed at the same level to confirm that each optimized conformer was true minimum and to estimate the relative thermal free energy (ΔG) at 298.15 K. The two

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• ). We studied the inherent chemistry of the reaction leading to HP and IE using gas-phase calculations. This provided the free energy of distinct carbocation intermediates and transition states along the proposed reaction path leading to products in the gas phase. The gas phase is a natural choice as a

• reference environment for terpene synthases [10][11][12][15][16][21][22][23][24][25]. The proposed reaction mechanisms yielding HP and IE and are presented in Scheme 1, while the reaction free energy profile is presented in Figure 2. Here, we modeled the transformations A→I (HP) and A’→E’ (IE). The gas

• any free energy barrier. The deprotonation and re-protonation steps are not included in our calculations. The overall exergonicity of this process which transforms four π-bonds to σ-bonds, with accompanying gains in intramolecular dispersion interactions, is −62.8 kcal/mol. IE pathway As described