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

The phenyl vinyl ether–methanol complex: a model system for quantum chemistry benchmarking

• Dominic Bernhard,
• Fabian Dietrich,
• Mariyam Fatima,
• Cristóbal Pérez,
• Hannes C. Gottschalk,
• Axel Wuttke,
• Ricardo A. Mata,
• Martin A. Suhm,
• Melanie Schnell and
• Markus Gerhards

Beilstein J. Org. Chem. 2018, 14, 1642–1654, doi:10.3762/bjoc.14.140

• significantly. The moiety with the largest potential as dispersion energy donor (DED) is the phenyl ring. This results in the strongest stabilization for the two conformers whereby the methanol is closest to the ring (OH–P and OH–P’). The other conformers have much more spread out contributions. What is

• contact is reminiscent of stabilization effects observed in coupled diamondoids [69] or supramolecular complexes [70], where such interactions can be found in large numbers. Electronic ground state spectra FTIR spectroscopy The results of an FTIR exploration of the conformational diversity of this system

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

• -phenylpyridine furthermore highlight that London dispersion is an important factor that enables this challenging C–H transformation. Nonbonding interactions between the Cp* ligand and aromatic and C–H-rich fragments of other ligands at the cobalt center significantly contribute to a stabilization of cobalt

• the desired transformation. As the calculated rate-limiting transition state TS3 benefits from a stabilization of the developing negative charge on the sulfonamide, the relative rates of Scheme 3 provide further support for the migratory insertion representing the rate determining step [44]. As

• affected by London dispersion, which also results in a significant stabilization of the rate-limiting transition state. Computational Details For all structures, geometry optimizations were performed with three different functionals using the def2-TZVP (def2-TZVPP for M06-L) basis set [52] and the m4

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

• stabilizing contribution from dispersion forces that in many systems turns the ‘steric repulsion’ into a ‘steric attraction’. In addition to London dispersion, such systems benefit from electrostatic stabilization, which arises from a short-range effect of charge penetration and gets bigger with increasing

• -tert-butyl substituents (termed ‘dispersion donors’) can be synthesized and characterized thanks to sufficient stabilization by dispersion (Figure 1B). This realization sparked a race towards the longest covalent C–C bonds [5][6]: already impressive 1.67 Å in hexakis(3,5-di-tert-butylphenyl)ethane is

• 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

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• fully cationic α-oligonucleotides bound to single-stranded DNA and RNA targets with high affinity, with duplex stabilization being proportional to the number of cationic modifications. It was also reported that these oligonucleotides showed retained base pairing fidelity, i.e., the Tm value was

London dispersion as important factor for the stabilization of (Z)-azobenzenes in the presence of hydrogen bonding

• Andreas H. Heindl,
• Raffael C. Wende and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 1238–1243, doi:10.3762/bjoc.14.106

• important classes of molecular switches is crucial for the design of light-responsive materials using this entity. Herein, we present the stabilization of metastable (Z)-azobenzenes by London dispersion interactions, even in the presence of comparably stronger hydrogen bonds in various solvents. The Z→E

• isomerization rates of several N-substituted 4,4′-bis(4-aminobenzyl)azobenzenes were measured. An intramolecular stabilization was observed and explained by the interplay of intramolecular amide and carbamate hydrogen bonds as well as London dispersion interactions. Whereas in toluene, 1,4-dioxane and tert

• -butyl methyl ether the hydrogen bonds dominate, the variation in stabilization of the different substituted azobenzenes in dimethyl sulfoxide can be rationalized by London dispersion interactions. These findings were supported by conformational analysis and DFT computations and reveal low-energy London

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• diarylmethanes. Most probably, electron-donating groups on aryls facilitate both Zn complexation and stabilization of the intermediate carbocationic species formed. Conclusion In summary, a new example of the selective functional group transformation of diarylmethanols (Ar1Ar2CH(OH)) to diarylmethanes (Ar1Ar2CH2

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• could not bind into the minor groove due to change in their conformation, thereby showing negligible DNA binding. Thus, their antibacterial activity is not attributed to DNA binding affinity due to lack of DNA stabilization by these conjugates. 2.3. Bisamidines One of the oldest known clinically

2-Iodo-N-isopropyl-5-methoxybenzamide as a highly reactive and environmentally benign catalyst for alcohol oxidation

• Takayuki Yakura,
• Tomoya Fujiwara,
• Akihiro Yamada and
• Hisanori Nambu

Beilstein J. Org. Chem. 2018, 14, 971–978, doi:10.3762/bjoc.14.82

• in common organic solvents. To overcome these drawbacks, IBX analogs [12][13][14][15][16][17][18][19][20][21][22] and several iodoxyarene derivatives [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] have been developed, and the stabilization of IBX by combining it with benzoic and

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• transfer and metal ion binding, for stabilization of transition states may be elucidated and systematic variation of the basicity of the entering or departing nucleophile enables determination of the position of the transition state on the reaction coordinate. Such data is important on analyzing enzyme

• , for stabilization of transition states may be elucidated and systematic variation of the basicity of the entering and departing nucleophile enables determination of the position of the transition state on the reaction coordinate. Such data is important on analyzing enzyme mechanisms based on