Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• methyl anthranilate structure from the ideal Lewis structure. The lone pair electron of nitrogen was donated to the non-Lewis orbital (i.e., LP*) of the adjacent carbon C(4) (see Figure 8), with a high interaction energy of 93.62 kcal⋅mol−1. Such an interaction was not found for aniline and o-anisidine

• . Instead, for o-anisidine and aniline, the lone pair electrons were delocalized into the antibonding NBO (i.e., BD*) with a smaller interaction energy of ≈26 kcal⋅mol−1. In other words, as shown in Scheme 8, the lone electron pair present at the nitrogen atom was delocalized into the π-conjugated system

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

• Computational methods). This significant amount of energy, which could be overestimated, comes from the π–π interactions between the C60 surface and the CNT wall and is modelled in a first approximation using Grimme’s corrections to the dispersion energy [16]. This interaction energy is comparable to those in

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

• simulations were set up. First, hybrid GAGs (Figure 1) were prepared and docked using RS-REMD to find the pose in the binding site with the lowest interaction energy. Then, the GAG was pulled away from the binding site until it was shifted 40 Å from the starting position. Afterwards, the GAG was pulled in

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• -mannosidase II (LManII) and JBMan). Finally, structural and physicochemical properties of inhibitor:enzyme complexes were investigated at the theoretical level using molecular docking, hybrid quantum mechanics/molecular mechanics (QM/MM) calculations and fragmented molecular orbital pair interaction energy

• /MM level (BP86/LACVP*:OPLS2005). The FMO-PIEDA results are compiled in Table 2 and visualized in Figure 3. Firstly, the results for the complex 29:dGMII were analyzed: the overall interaction energy (ΔEI-E) between 29 and the enzyme is −563.6 kcal mol−1, towards which the interaction energy between

• groups (with R-configuration in case of 28, 29 and DIM). The methyl group itself (in 10) contributes repulsively and decreases the overall interaction energy. Thus, only hydroxymethyl, (R)-1-hydroxyethyl and (R)-1,2-dihydroxyethyl are suitable substituents at the C-5 position of 1,4-imino-ᴅ-lyxitols. The

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• interact with BCR-Abl-1 at the same binding site as IMT but show differences in the binding modes and with higher values of interaction energy. Compound 2c presented a MolDock value of −152.993 a.u. For compound 2d, the value was −152.127 a.u., and for compound 2g, it was −167.520 a.u. (Table 2

• a.u.) and steric interactions with Glu301, Glu305, Val308, Met309, Leu373, Ile379, and Asp400 (steric interaction energy = −151.683 a.u.) (Figure 4b). Similarly, compound 2g showed a hydrogen-bonding interaction with Asp400 (hydrogen bonding energy = −2.62 a.u.) and steric interactions with Lys290

• , Glu305, Ile312, Leu317, Ile379, His380, Ala399, and Asp400 (steric interaction energy = −164,897 a.u.) (Figure 4d), presenting the best overlap with the co-crystalized IMT structure. However, compound 2d showed hydrogen-bonding interactions with Asp400, His380 and Ile379 (hydrogen bonding energy = −2.19

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

• should be noted that the essential property of an ideal mixture of liquids is not the exclusion of all interactions as it is assumed for the mixing of ideal gases. In an ideal solution, there are interactions between the components A and B, but the average interaction energy between A and B in the

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• approximation, to study the effect of these structural modification on the pharmacodynamics, we performed a molecular docking over two MPPs. In Table 4, the interaction energy value (MolDock Score) [38] of each compound with the two different MMPs obtained from the docking calculation is displayed. Also, the

• ligand efficiency (LE) of each bisphosphonate is shown; the ligand efficiency stands for the coefficient of the interaction energy by the number of atoms in the molecule (excluding hydrogen atoms). By the inspection of the results above, there is a correlation between the LE parameter in MMP-8 and the

• MolDock Score values, but nevertheless, its inhibition activity was the lowest (Table 2). It is important to note that a clear correlation between the predicted interaction energy of 3–6 with MMP-8 and the topical antiinflammatory activity was observed (TPA model), with the derivative 6 being the most

Anion-driven encapsulation of cationic guests inside pyridine[4]arene dimers

• Anniina Kiesilä,
• Jani O. Moilanen,
• Anneli Kruve,
• Christoph A. Schalley,
• Perdita Barran and
• Elina Kalenius

Beilstein J. Org. Chem. 2019, 15, 2486–2492, doi:10.3762/bjoc.15.241

• simultaneous complexation of anionic and cationic guests, resulting in a partial rupture of the hydrogen-bonding seam and a ≈100 kJ/mol weaker interaction energy compared to [12 + Me4Nendo + Iexo] (Figure S7 and Table S2, Supporting Information File 1). To illustrate the unsuitability of the lower rim for

• calculated dispersion-corrected interaction energy of [12 + Me4Nexo1]+ (−37 kJ/mol) is roughly two fifth of the interaction energy of [12 + Me4Nexo2]+ (−98 kJ/mol) because there is no favorable ion–dipole interaction between 12 and Me4N+ in [12 + Me4Nexo1]+. Even though the encapsulation of the Me4N+ cation

Adhesion, forces and the stability of interfaces

• Robin Guttmann,
• Johannes Hoja,
• Christoph Lechner,
• Reinhard J. Maurer and
• Alexander F. Sax

Beilstein J. Org. Chem. 2019, 15, 106–129, doi:10.3762/bjoc.15.12

• Lennard-Jones potential or the Morse potential, see Figure 1. Because of the asymptotic boundary conditions, the constant interaction energy for large r is chosen as zero. Any system geometry Rdiss with V int(Rdiss) = 0 represents the dissociated system, and the energy difference ΔV = V int(Rdiss) − V int

• distortions are called rigid or stiff, the resistance of electron distributions against distortion is called its hardness. By freezing the geometries of the interacting subsystems the interaction energy is calculated as if the interacting subsystems were ideally rigid. The intermolecular contributions to the

• interaction energy can be calculated in different ways. In the supermolecule approach, the interacting system is treated as a large molecule and the stabilization energy is simply the difference between the energy of supermolecule EAB and the sum of the energies of the isolated molecules EA and EB: The mutual

Dispersion-mediated steering of organic adsorbates on a precovered silicon surface

• Lisa Pecher,
• Sebastian Schmidt and
• Ralf Tonner

Beilstein J. Org. Chem. 2018, 14, 2715–2721, doi:10.3762/bjoc.14.249

• the precovered surface as the major, albeit small, contribution to the slightly larger interaction energy thus confirming the finding above. Thus, the changes in the pEDA energy terms are rather small but the most important observation is that Pauli repulsion does not significantly rise as is often

Evaluation of dispersion type metal···π arene interaction in arylbismuth compounds – an experimental and theoretical study

• Ana-Maria Preda,
• Małgorzata Krasowska,
• Lydia Wrobel,
• Philipp Kitschke,
• Phil C. Andrews,
• Jonathan G. MacLellan,
• Lutz Mertens,
• Marcus Korb,
• Tobias Rüffer,
• Heinrich Lang,
• Alexander A. Auer and
• Michael Mehring

Beilstein J. Org. Chem. 2018, 14, 2125–2145, doi:10.3762/bjoc.14.187

• longer than for 1b (see Table 1). The curve for the interaction energy without dispersion contribution (Figure 9, E(int-disp)) is slightly attractive. The interaction energy of the BiPh3 complex is higher than the interaction energy obtained for BiMe3 but smaller than for Bi(OMe)3 (see Figure 10a

• ), however, the dispersion contribution to the interaction energy in the BiPh3 complex (see Figure 10b) is comparable to the dispersion contributions in other BiR3–benzene complexes. This implies that the character of the interaction in the BiPh3–benzene complex is closer to that of BiMe3 rather than to Bi

• 1a In case of polymorph 1a three different tetramers were chosen that are shown in Figure 11. The simplest tetramer 1a-1 consists of linear chains of BiPh3 molecules belonging to one layer. It is built from three equivalent Bi···phenyl dimers with an interaction energy of −46 kJ mol−1 (computed at

Cobalt-catalyzed C–H cyanations: Insights into the reaction mechanism and the role of London dispersion

• Eric Detmar,
• Valentin Müller,
• Daniel Zell,
• Lutz Ackermann and
• Martin Breugst

Beilstein J. Org. Chem. 2018, 14, 1537–1545, doi:10.3762/bjoc.14.130

• (blue) to +0.05 (red). Projected dispersion interaction density (DID) plots for selected intermediates and transition states. The molecular density isosurfaces (0.1 e/Bohr3) are colored from zero interaction energy (blue) to the strongest dispersion interaction (red). Cycloaddition reaction of in situ

Steric “attraction”: not by dispersion alone

• Ganna Gryn’ova and
• Clémence Corminboeuf

Beilstein J. Org. Chem. 2018, 14, 1482–1490, doi:10.3762/bjoc.14.125

• electrostatics is not the largest stabilizing energetic contribution, it is nonetheless the one that defines the trend in the total interaction energy for a range of investigated dimers. Electrostatic stabilization in graphane and graphene dimers has been attributed to the charge transfer (σCH → σHC

• * hyperconjugative interaction) [17], and a similar argument was used to suggest the possibility of manipulating the band gap of patterned hydrogenated graphene C4H bilayer by an external electric field [27]. Furthermore, Schreiner et al. showed that approx. 10% of the total interaction energy in the tris(3,5-di

• -tert-butylphenyl)methane dimer (the system mentioned above for its shortest intermolecular H···H contacts) comes from stabilizing electrostatics [9]. Similarly, the interaction energy difference between the all-meta-tert-butyl-hexaphenylethane and the bare hexaphenylethane features ≈14% electrostatic

A three-armed cryptand with triazine and pyridine units: synthesis, structure and complexation with polycyclic aromatic compounds

• Claudia Lar,
• Adrian Woiczechowski-Pop,
• Attila Bende,
• Ioana Georgeta Grosu,
• Natalia Miklášová,
• Elena Bogdan,
• Niculina Daniela Hădade,
• Anamaria Terec and
• Ion Grosu

Beilstein J. Org. Chem. 2018, 14, 1370–1377, doi:10.3762/bjoc.14.115

• , the O–H···N fragment did not preserve its hydrogen-bond arrangement, as the aromatic fragment rather preferred the so-called “antiparallel-displaced” configuration [40][41] (see Figure 6). The intermolecular interaction energy between 1,5-dihydroxynaphthalene and cryptand 2 is −29.28 kcal/mol, while

Are dispersion corrections accurate outside equilibrium? A case study on benzene

• Tim Gould,
• Erin R. Johnson and
• Sherif Abdulkader Tawfik

Beilstein J. Org. Chem. 2018, 14, 1181–1191, doi:10.3762/bjoc.14.99

• ) = E(R) − E∞. We plot U(R) in Figure 1 and Figure 2, and use the minimum-energy values directly in Table 1 – Figure 3 shows U(R) = E(R) − E(0). Secondly, we obtain all forces by fitting cubic splines through the energy data, and taking the derivative of the splines. Figure 1 shows the interaction

• energy for the parallel configuration of the benzene dimer (labelled P – with D6h symmetry). Despite having a minimum as a function of distance between the two centres, this arrangement is unstable as the dimers wish to slide apart sideways (see later discussion on Figure 3) to reduce electrostatic

Correlation effects and many-body interactions in water clusters

• Andreas Heßelmann

Beilstein J. Org. Chem. 2018, 14, 979–991, doi:10.3762/bjoc.14.83

• methods on an adequate level, e.g., random-phase approximation electron correlation methods. The relative magnitudes of the different interaction energy contributions obtained by accurate ab initio calculations can therefore provide useful insights that can be exploited to develop enhanced force field

• structures optimized on an uncorrelated level. Overall, the many-body interactions amount to about 13% of the total interaction energy, irrespective of the cluster size. The electron correlation contribution to these, however, amounts to only about 30% to the total many-body interactions for the largest

• other force field exist that aim at a more physically sound decomposition of the interaction energy into distinct contributions. Examples for such force fields are the sum of interaction between fragments (SIBFA) [18][19][20] and the effective fragment potential (EFP) [21] method. The most recent

Local energy decomposition analysis of hydrogen-bonded dimers within a domain-based pair natural orbital coupled cluster study

• Ahmet Altun,
• Frank Neese and
• Giovanni Bistoni

Beilstein J. Org. Chem. 2018, 14, 919–929, doi:10.3762/bjoc.14.79

• . This information is used to rationalize the trend of stability of various conformers of the water and hydrogen fluoride dimers. Keywords: DLPNO-CCSD(T); hydrogen-bond interaction; interaction energy; local energy decomposition; London dispersion; Introduction Hydrogen bonds are of fundamental

• have been instrumental in providing insights into the nature of these interactions, by partitioning the total interaction energy of two (or more) interacting fragments into several chemically meaningful contributions [8][9][10]. EDA methods are mainly based on an early variational study of Morokuma [11

• ]. They are typically carried out at the Hartree–Fock (HF) or density functional theory (DFT) level. In these schemes, the interacting system is treated as a supermolecule and the overall interaction energy is decomposed into various terms such as electrostatic interaction, charge transfer, polarization

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• -based methods [90]. In Q-SiteFinder a van der Waals probe is used and the interaction energy between the probe and the protein is found in order to identify binding sites of the protein [91]. The SiteHound program is another energy-based method that uses two kinds of probes; a carbon probe and a

• mechanics. Electrostatic (coulombic) interactions and van der Waals interactions (Lennard-Jones potential) contribute to the interaction energy between a target–ligand complex. Two of the most widely used molecular mechanical force-fields are CHARMM [119] (Chemistry at HARvard Macromolecular Mechanics) and

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• geometry distortion of nitrile oxide 6a has a major contribution to the activation energy barrier, whereas the geometry distortion energy of the enamine is minor. Also, the analysis shows close values of the orbital interaction energy for all the found transition states (Table 1). It should be noted the

• close orbital interaction energy values are obtained at longer distances between the reactants in case of transition states 1a_3a and 1a_9, as compared to transition states 1a_8 and 1a_10, respectively. This indicates a longer-range orbital interaction between the reactants in the case of formers

• 8. Calculated data of the electronic activation energy (∆E), orbital interaction energy (∆Ei), and geometry distortion energies (∆Ed).a Supporting Information Supporting information features copies of 1H and 13C NMR spectra for all compounds synthesized and full experimental and analytical data for

Experimental and theoretical insights in the alkene–arene intramolecular π-stacking interaction

• Valeria Corne,
• Ariel M. Sarotti,
• Carmen Ramirez de Arellano,
• Rolando A. Spanevello and
• Alejandra G. Suárez

Beilstein J. Org. Chem. 2016, 12, 1616–1623, doi:10.3762/bjoc.12.158

• complexes in s-cis conformation, the π–π interaction energy computed at the M06-2X/6-31+G(d) level is −7.2 kcal/mol for 7 + 8, −6.9 kcal/mol for 7 + 9 and −6.5 kcal/mol for 7 + 10 (similar values were computed for 7 in its s-trans conformation, see Supporting Information File 1). Similar trends were found

• using ADF. In this approach, the interaction energy (ΔEi) is decomposed as the sum of four terms [28]: ΔEi = ΔVelstat + ΔEPauli + ΔEoi + ΔEdisp, where ΔVelstat accounts for the usually attractive classical electrostatic interaction between the deformed fragments, ΔEPauli, the Pauli repulsion term

• . As shown in Table 1 a slightly higher interaction energy was found for 7 + 8 (−7.7 kcal/mol). It is important to point out the great significance of the dispersion forces in these π-stacked complexes, representing ≈60% of the total attractive forces. Noteworthy, the distances from the centroid of the

Molecular weight control in organochromium olefin polymerization catalysis by hemilabile ligand–metal interactions

• Stefan Mark,
• Hubert Wadepohl and
• Markus Enders

Beilstein J. Org. Chem. 2016, 12, 1372–1379, doi:10.3762/bjoc.12.131

• is different: the interaction energy of the nitrile group with the chromium center leads to an energy gain which is 15.2 kcal mol−1 higher compared to the energy of the corresponding ethylene complex. Consequently, the ethylene can hardly displace the nitrile. However, addition of Al–alkyls leads to

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

• option would be to obtain the ligand geometries inside an enzyme active site. Since conformational search inside a receptor normally gives the mode of interaction between substrate and enzyme, as well as the intermolecular interaction energy (related to the ligand–receptor affinity and, consequently, to

Direct estimate of the internal π-donation to the carbene centre within N-heterocyclic carbenes and related molecules

• Diego M. Andrada,
• Nicole Holzmann,
• Thomas Hamadi and
• Gernot Frenking

Beilstein J. Org. Chem. 2015, 11, 2727–2736, doi:10.3762/bjoc.11.294

• –acceptor bonds was investigated by an energy decomposition analysis (EDA) which was developed by Morokuma [88] and by Ziegler and Rauk [89][90]. The bonding analysis focuses on the instantaneous interaction energy ∆Eint of a bond A–B between two fragments A and B in the particular electronic reference

• calculations. The total interaction energy ΔEint between the carbon atom and the remaining fragment in the frozen geometry [118] is composed from the stabilizing orbital (covalent) interactions ΔEorb and the Coulombic term ΔEelstat and the destabilizing Pauli repulsion ΔEPauli. The strongest attraction comes

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

• during the MD runs after equilibration to determine the interaction energy and the system geometry, either in the most stable final state or in some largely populated geometry met within the dynamic run in order to characterize the main features of the (pseudo) equilibrium nucleation states. In the

• the largest interaction energy, in absolute value, and the smallest radius of gyration but the largest surface accessible to the solvent (see Figure S1 of the Supporting Information File 1) as shown in Table 1. Here and in the following, the interaction energy is defined as Eint = Eaggr – nEisol

• intermolecular hydrogen bonds. In particular, the initial H–H arrangement yielded the final geometry of Figure 6a, with an interaction energy (see Table 1) intermediate between the most (Figure 6c) and the least stable one having the H–P arrangement (Figure 6b) due to somewhat weaker dipolar interactions of the

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

• implicit solvent models such as Generalized Born (GB) [37][38], Poisson–Boltzmann (PB) [39][40] and Reference Interaction Site Model (RISM) [41]. Meanwhile, the other methods such as linear interaction energy (LIE) [42][43][44] and linear response approximation (LRA) [45][46][47] calculate the ΔGsolv based

• 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

• % v/v), the stability of the hydrophobic aromatic ring of the α-MGS outside the inclusion cavity was promoted resulting in a reduced binding interaction but enhanced solubility of the α-MGS/β-CD inclusion complex. As a compromise between those two factors, interaction energy and solvation free energy