Transient and intermediate carbocations in ruthenium tetroxide oxidation of saturated rings

• Manuel Pedrón,
• Laura Legnani,
• Maria-Assunta Chiacchio,
• Pierluigi Caramella,
• Tomás Tejero and
• Pedro Merino

Beilstein J. Org. Chem. 2019, 15, 1552–1562, doi:10.3762/bjoc.15.158

• –O distance increased to 3.00 Å in TS2 and to 3.15 Å in TS3 (similar data were found in acetonitrile, see Supporting Information File 1) clearly indicating a delay in the formation of the C–O bond. This situation is compatible with the stabilization of a developing positive charge at the carbon atom

• place in two separate events. The stabilization of the above-mentioned transient carbocation can be achieved by introducing heteroatoms. The ELF analysis corresponding to the oxidation of tetrahydrofuran (Figure 3A) again showed a typical one-step-two-stage situation. In this case, the gap between the H

• enhanced by the presence of heteroatoms that stabilize the developing positive charge by resonance, as in the case of tetrahydrofuran and tetrahydrothiophene. Moreover, the presence of a nitrogen atom provides enough stabilization to be located as an energy minimum and to be captured experimentally [26

A heteroditopic macrocycle as organocatalytic nanoreactor for pyrroloacridinone synthesis in water

• Piyali Sarkar,
• Sayan Sarkar and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2019, 15, 1505–1514, doi:10.3762/bjoc.15.152

• issue for the stabilization of the activated complex by a hydrophobic catalyst [31]. Again, the efficiency of an organocatalyst could be enhanced by downsizing the catalyst at nanorange distribution (i.e., nanoreactor) [13][14]. This is because a nanoreactor allows for precise interactions with the

• reactants. In fact, encapsulation can result in the stabilization of a specific transition state by stripping it out from solvent molecules [13][14]. Hence, in aqueous medium, the syntheses of nanoreactors with a covalent organic framework is important, which is indeed a difficult task due to their large

• stabilization. Consequently, the presented BATA-MC-catalyzed protocol demonstrates a general applicability furnishing a variety of multisubstituted acridines. Confirmation of structures All products (4,5-dihydropyrrolo[2,3,4-kl]acridinones 4a–p and pyrrolo[2,3,4-kl]acridinones 7a–c) were characterized by using

Selenophene-containing heterotriacenes by a C–Se coupling/cyclization reaction

• Pierre-Olivier Schwartz,
• Sebastian Förtsch,
• Astrid Vogt,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2019, 15, 1379–1393, doi:10.3762/bjoc.15.138

• DTT 1 to DSS 4, with stronger stabilization of the S2 transition which is coherent with the large atomic contribution from the heteroatoms to the involved molecular orbitals HOMO-1 and LUMO (vide supra). We can conclude that the theoretically calculated transitions S1 and S2 are reflected in the

• 3.91 eV for DTT 1 to 3.67 eV for DSS 4 due to a stabilization of the HOMO energy level with increasing number of selenium atoms in the heteroacene (vide infra). The extinction coefficients are as well sensitive to the heteroatom in the bridge for pair DTT 1/DTS 2 (26,800 to 22,100 L mol−1 cm−1) and DST

Bambusuril analogs based on alternating glycoluril and xylylene units

• Tomáš Lízal and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2019, 15, 1268–1274, doi:10.3762/bjoc.15.124

• reflecting the presence of conformers 1b-2 and 1b-1. However, the ratio of these conformers is 82:1 in favor of 1b-1 which translates to the energy difference of 2.04 kcal mol−1. Stabilization of the 1b-1 conformer can be attributed to the intramolecular hydrogen bonding interaction between the oxygen atom

Mechanochemical amorphization of chitin: impact of apparatus material on performance and contamination

• Thomas Di Nardo and
• Audrey Moores

Beilstein J. Org. Chem. 2019, 15, 1217–1225, doi:10.3762/bjoc.15.119

• systematic study of the effects of a number of medium parameters onto a model reaction, namely the amorphization of chitin where interchain stabilization is greater than 250 kJ/mol based on density functional theory (DFT) calculation [58]. We explored the role of the material of the jar and the ball, ball

Molecular recognition using tetralactam macrocycles with parallel aromatic sidewalls

• Dong-Hao Li and
• Bradley D. Smith

Beilstein J. Org. Chem. 2019, 15, 1086–1095, doi:10.3762/bjoc.15.105

• macrocycle. Supramolecular picture of the amide-bond-formation step that clips tetralactam A around a biscarbonyl template to form a [2]rotaxane. Complex stabilization due to guest back folding and aromatic stacking with the surrounding tetralactam macrocycle. Acknowledgements We are grateful for funding by

Coordination chemistry and photoswitching of dinuclear macrocyclic cadmium-, nickel-, and zinc complexes containing azobenzene carboxylato co-ligands

• Jennifer Klose,
• Tobias Severin,
• Peter Hahn,
• Alexander Jeremies,
• Jens Bergmann,
• Daniel Fuhrmann,
• Jan Griebel,
• Bernd Abel and
• Berthold Kersting

Beilstein J. Org. Chem. 2019, 15, 840–851, doi:10.3762/bjoc.15.81

• drastically alter its structural properties and reactivities. Prominent examples are the cis-bromination of α,β-unsaturated carboxylato ligands [2], regioselective Diels–Alder reactions of encapsulated dienoate ligands [3], and the stabilization of unusual co-ligand conformations, respectively [4]. The

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

• Camila B. Francisco,
• Cleverton S. Fernandes,
• Ulisses Z. de Melo,
• Roberto Rittner,
• Gisele F. Gauze and
• Ernani A. Basso

Beilstein J. Org. Chem. 2019, 15, 818–829, doi:10.3762/bjoc.15.79

• halogens, as mentioned before, the pronounced ea preference observed in our case led us to investigate the specific effects that may be responsible for this behavior. Delocalization, electrostatic and steric interactions In order to determine which effects are responsible for the stabilization of each

• , the sum was made of all hyperconjugative stabilization energies (Eij) involving both bonding and antibonding orbitals, as well as the energies of nitrogen and halogen lone-pair interactions (LPN and LPX, respectively), resulting in 22 variables corresponding to all the bonds of the structure of the

• respective orbitals (C–X bonds and antibonds) increases in the same way; however, the LPX follows the reverse order, with a decrease in the donor ability as LPF > LPCl > LPBr > LPI. These observations allow us to analyze which specific orbitals are responsible for the great stabilization of the ea conformer

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• -deazapurine class, which could be explained by a better stabilization of the ICT excited state by the solvatic shell. A decrease of QY accompanied by a high red shift of the emission maxima with increasing polarity of the surrounding media is a typical characteristic for the enhanced ICT of the excited states

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• -position of the aromatic ring could contribute to the stabilization of TS1, in which the Ar–C3–C2–P dihedral angle is close to 0°, by considering the mesomeric form TS2. The observed dependence of the diastereoselectivity on the σ+ Hammett constant of the para substituents further supported the proposed

• nature of the rearrangement (Scheme 10) [33][34]. The acidic promotor may be simply assisting the dissociation of the C4–O bond in the transition state TS3 whilst an aromatic group (R1 = Ar) would contribute to the stabilization of a developing positive charge at C4. The [3,3]-sigmatropic rearrangement

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• kcal mol−1, Table 3, entries 1–3, Figures 6–8). Responsible for the lower Ea is an additional stabilization by an interaction of the remaining chloro atom to the attacking water (dotted line to the Cl(ax) Figure 6 and Cl(eq) Figure 7). The small energy difference for the TSfront1 7 and TSfront2 7 is to

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• inhibitor). Overall, the calculations reveal that the relative stabilities of the cofactor states are greatly affected by the presence and identity of the bound ligands. A surprising finding is that benzoylformate binding, while favoring ylide formation, provided even greater stabilization to a

• (Table 1). Although these results clearly suggest that substrate binding results in catalytically productive states of the cofactor, this is not the whole story. Model D also indicates that substrate binding produces a major stabilization of the two non-productive tricyclic species. In fact, the most

• the binding of the (R)-mandelate causes a stabilization of the AP/APH+ states relative to the others. As seen from Table 1, despite having the same overall charge and similar bulkiness of the substituents, the binding of the benzoylformate (model D) and (R)-mandelate (model E) result in quite

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

• interactions were nearly exclusively attributed to electrostatic interactions. We discuss the importance of dispersion interactions for the stabilization in systems that are traditionally explained in terms of the “special interactions” mentioned above. System stabilization can be explained by using

• obvious advantage of using the scalar quantity, energy, instead of the vector quantity, force, is that it is simpler to describe and categorize system stabilization by using properly defined stabilization energies calculated as differences in the values of the energy functions. In chemistry, stabilizing

• interactions are roughly classified as strong or weak according to the magnitude of stabilization energies [1]. Strong interactions are 1) Coulomb interactions in ionic solids ranging between 600 kJ/mol (CsI) and 3900 kJ/mol (MgO), 2) covalent interactions in molecules ranging between about 150 kJ/mol (I2) and

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• . The reason for the stabilization is an increased strength of the Watson–Crick base pairing and base stacking interactions due to the electronic effects of the axially oriented 2’-fluorine atom [11][12]. Additionally, FC–H···O hydrogen bonds between the 2’-fluorine and the 4’-oxygen or 5’-oxygen of the

• denaturation experiments with complementary RNA displayed a duplex stabilization for FHNA and a duplex destabilization for Ara-FHNA. The reason for the stabilization of the former was accounted to a combination of the increased rigidity of the six-membered ring and the positioning of the axial oriented

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• ]. The comparison of the modified with the natural duplexes disclosed an entropic stabilization (ΔΔS = +28.9 and +38.0 cal·mol−1·K−1) and an enthalpic destabilization (ΔΔH = +13.8 and +17.0 kcal·mol−1) for both the DNA and RNA complement. This pattern was observed along the whole bc-DNA series and was

• entropical stabilization of the duplex structure. The cyclohexene ring of the modified unit adopted either a twist-boat or a boat alignment in the fully modified strand of both duplex types. Consequently, the fluorine atom was arranged in a way that the repulsive electrostatic interactions with the C(5

Dispersion interactions

• Peter R. Schreiner

Beilstein J. Org. Chem. 2018, 14, 3076–3077, doi:10.3762/bjoc.14.286

• but it is certainly attenuated [8]. We are still in the process of understanding just by how much. LD is a driving force for molecular aggregation that plays a key role in the thermodynamic stability, molecular recognition, chemical selectivity through transition-state stabilization, protein folding

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• identification requires detailed structure elucidation, which in the end makes the design of an effective PPI modulator both difficult and challenging [19][20][21][22]. PPI modulation can be achieved through two opposite but complementary approaches: stabilization or inhibition (Figure 1). Although so far the

• vast majority of protein–protein interaction modulators execute their activity through inhibition, stabilization of specific protein complexes could also be therapeutically beneficial [23][24]. Even though historically PPIs have been considered to be “undruggable”, recent remarkable medicinal chemistry

• –protein interactions and have validated PPI stabilization as a biological target. One of the most prominent examples of PPI-stabilizing natural products that are currently used in the treatments of human diseases is rapamycin (7, Figure 2), an immunosuppressant that inhibits the protein kinase TOR (target

Oxidative and reductive cyclization in stiff dithienylethenes

• Michael Kleinwächter,
• Ellen Teichmann,
• Lutz Grubert,
• Martin Herder and
• Stefan Hecht

Beilstein J. Org. Chem. 2018, 14, 2812–2821, doi:10.3762/bjoc.14.259

• low scan rates (for a comparison of full redox cycles of C-sDTE66-Me and C-sDTE66-PhOMe see Figure S30, Supporting Information File 1). This observation confirms the enhanced stabilization of the C2+ cation by electron-donating groups [8]. 3) Upon reduction of FP2+, both FP as well as C are formed

• , similarly to what is known for normal DAEs [40][41]. The differences between the first and second oxidation wave seem to depend on the nature of the substituents with donors reducing the gap, presumably by more efficient stabilization of the dication, and on conformational rigidity dictating the extent of π

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

• significant stabilization, especially for larger adsorbates and/or polarizable substrates. At shorter distances, covalent bond formation leads to a steeper attractive potential well. The resulting covalently bonded state is usually called chemisorbed [10]. Bonding of intermediate states can be dominated by

• (stabilization by less than 5 kJ·mol−1) are found by including dispersion in the computation. If one molecule of 1 is already present at the surface, parts of the surface are inaccessible due to strong Pauli repulsion and overlapping molecules. This is indicated by the white areas around the first adsorbate in

• molecules. The picture changes completely when dispersion attraction is considered. The PBE-D3 computations show a pronounced feature in the PES scan on the precovered surface with a strong energetic preference for adsorption on the surface dimer next to the first adsorbate. The stabilization can be seen in

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• reactants, leading to nearly quantitative yields of 2b with complete chemoselectivity (Table 1, entry 10). The different reactivity of o- and p-nitrofluorobenzenes in SNAr displacements had previously been reported, and is attributed to a differential stabilization of the reaction intermediate in the former

Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes

• Carmine Gaeta,
• Carmen Talotta and
• Placido Neri

Beilstein J. Org. Chem. 2018, 14, 2112–2124, doi:10.3762/bjoc.14.186

• , the VT 1H NMR studies indicate that the 1,2,3-alternate is the most stable conformation for hexahexyloxycalix[6]arene 1 in solution. This conclusion is in perfect accord with the results previously reported by Reinhoudt [41], which evidenced an increased stabilization of the 1,2,3-alternate

• ). Differently, in the DFT-optimized structure of 2+11,2,3-alt atropoisomer (Figure 7, right), the stabilization of the 2+11,2,3-alt atropoisomer was brought, principally by two H-bonding interactions between the ammonium group of 2+ and the oxygen atoms of anti-oriented phenol rings of 1 with an average N···O

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• amino groups in the ethylenediamine fragment (pK2 = 9.08 and pK3 = 9.97 for the diethylenetriamine conjugated acid [48]). Thus, stabilization of the monocationic form prevents the formation of a dicationic species. The premicellar aggregates of the lipophilic dicationic macrocycle 10b demonstrate a

Rational design of boron-dipyrromethene (BODIPY) reporter dyes for cucurbit[7]uril

• Mohammad A. Alnajjar,
• Jürgen Bartelmeß,
• Robert Hein,
• Pichandi Ashokkumar,
• Mohamed Nilam,
• Werner M. Nau,
• Knut Rurack and
• Andreas Hennig

Beilstein J. Org. Chem. 2018, 14, 1961–1971, doi:10.3762/bjoc.14.171

• combination of properties has enabled numerous applications in the life sciences, for example, for protein binding [5][6], stabilization [7], immobilisation [8], isolation [9], self-assembly [10][11], and regulation [12], or for drug solubilisation and delivery [13][14][15]. The combination of CBs with

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• depend significantly on the solvent properties, which indicate the absence of specific stabilization or destabilization of the excited molecule, even after solvent relaxation. In contrast, the phenanthryl-substituted derivative 2d shows fluorosolvatochromism, specifically indicated by the strong blue

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• stabilization via Leu-side chain interactions [25][27] (Figure 1 – [Leu]8-Dec-NH2 and [Leu]10-Dec-NH2). The remaining Dec-NH2 derivatives were engineered by rationally introducing single and double substitution mutations (Figure 1). To introduce a net positive charge into the peptide sequences [28], we used Lys