Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• , the peptide portion has hydrogen bonds between Arg5–Pro8 (26.69% and 26.58%), Arg5–Asp3 (12.45%), an Arg5–Pro2 interaction is observed with an occupancy of 7.13%, and an intramolecular hydrogen bond between the C3 alcohol and the carbonyl of the N-acetyl moiety of the GalNAc has an occupancy of 6.92

• %), Tyr37–Pro2 (46.73%), Arg55–Asp3 (37.77%), and Tyr54–Asp3 (31.44%). A hydrogen bond (0.15%) was observed between the hydroxy group of Tyr100 of chain B of the antibody and the 6-hydroxy group of the GalNAc. While seemingly short-lived, it occurs with some frequency throughout the simulation (see Figure

• dispersion interactions would be insufficient to explain a 20-fold increase in affinity. It is unlikely that this hydrogen bond explains a 20-fold increase in affinity yet note that the mobility of the glycan moiety allows the hydrogen-bond interaction to occur. The hydrogen-bonding preferences and

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• Juaristi and Notario [9], and O’Hagan and co-workers [10]. Besides, there is also an interaction between the fluorine electron lone pair nF and the σ*NH orbital of the amine group (of 3.2 kcal mol−1, see Table 1). Iga also experiences this stabilizing hydrogen bond-like intramolecular interaction (nF → σNH

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• hydrogen-bond accepting capacity with proteins or enzymes would be restored [14]. The synthesis of fluoroalkene precursors of modified acyclonucleosides (VIII) has been explored by Choi, and more recently by us [15][16][17]. Nevertheless, it was reported that no antiviral activity for compounds of series

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• stability, non-flammability, and low volatility. These are mixtures usually obtained from the combination of 2 or 3 safe, inexpensive and nature-inspired components able to engage in reciprocal hydrogen-bond interactions, and that form fluids at a specified mixing ratio at the desired temperature. Owing to

• by dehydration. The two tautomers 3/3' would most probably originate by two competitive pathways (a and b; Scheme 4) via a [1,5]-hydrogen shift [28][29]. Hydrogen-bond catalysis promoted by DES components may be playing an important role in favoring the loss of nitrogen under mild conditions from a

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• moiety fulfils several key design requirements. At least four hydrogen bonding sites (N–H groups) are available and positioned in a favourable geometry for carboxylates. Additional hydrogen-bond-donor (HBD) groups can be added with substituents. The solubility of such receptors can be tuned using

• out of the macrocycle plane. It was expected that these macrocycles will have lower affinity constants. MC002 was of sufficient size to accommodate smaller carboxylate ions. However, in the most stable computed structures the hydrogen-bond donor NH fragments directed towards the outside of the ring

• , starting with formate. MC008 was able to fit acetate and lactate. Thus, an additional binding site was available for lactate. In the complexes of lactate with MC006–MC009, a hydrogen bond was present between the oxygen of the hydroxy group of lactate and the NH group of the macrocyclic amide. See Figure 5

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• C5 hydroxy group very often interacts with the catalytic base aspartate D372 side chain. Moreover, in the poses where this interaction has been found, the C5 hydroxy group creates a hydrogen bond with the ammonium group of the lysine K369 residue. In many docking poses the interaction of the C3

• share the common binding interactions described above. However, the 1bα binding mode slightly differed from the modes of the other compounds. In this case the PO4 and hydroxy group on C5 interacted with a metal ion and the hydroxy groups on C2 and C3 created the hydrogen bond with the tyrosine Y236

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• polarity drops down. The second scenario would occur if there was an N–H…O=C hydrogen bond in the structure. Thus, the presence of proline would leave an unsolvated carbonyl group, and its appearance leads to a polarity rise. Finally, a proline residue usually prefers extended secondary fold and may

One-pot synthesis of isosorbide from cellulose or lignocellulosic biomass: a challenge?

• Isaline Bonnin,
• Raphaël Mereau,
• Thierry Tassaing and
• Karine De Oliveira Vigier

Beilstein J. Org. Chem. 2020, 16, 1713–1721, doi:10.3762/bjoc.16.143

• ; isosorbide; lignocellulosic biomass; Introduction Cellulose, a homopolymer of ᴅ-glucose, is the most abundant component of lignocellulosic biomass. Cellulose is a crystalline polymer due to its intra- and intermolecular hydrogen bond network. The conversion of cellulose to added value chemicals has received

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• , preferred conformation or hydrogen bond forming ability, among others, may result in a dramatic effect in the therapeutic potential of a drug candidate [5][6]. All these properties may be fine-tuned by the selective incorporation of fluorine into the structure of the molecule [7]. In addition to therapeutic

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• parsimonious as possible but at the same time generally applicable [99]. The alternative patchwork of competing bonding models based on non-separable and non-unique interactions cannot provide a stable framework for AI and ML. In this respect, the IUPAC definition of the hydrogen bond [104] serves as an

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• ). According to the single-crystal X-ray experiments of compounds 3b, 8b, and 23a, the solid-phase structures are stabilized by a hydrogen bond between the amide NH and the carbonyl oxygen atom of the other amide group. The H–C–C–H dihedral angles between the two asymmetric centers are not far from 90° as

• in 23b indicates a weaker hydrogen bond, compared to the value of 9.39 ppm obtained for 23a [27]. The detected 3J(H,H) coupling constant for the hydrogens attached to the two asymmetric centers is 10 Hz in this case, indicating a dihedral angle of ca. 180° in 23b. Moreover, an unexpected extremely

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• inversion of the local electronic environment, or the precise deletion of hydrogen-bond donors, respectively, with minimal steric variation [7]. The latter aspect is a crucial determinant in enabling fluorinated materials to adopt intriguing conformations which are a manifest representation of stabilising

Five-component, one-pot synthesis of an electroactive rotaxane comprising a bisferrocene macrocycle

• Natalie Lagesse,
• Luca Pisciottani,
• Maxime Douarre,
• Pascale Godard,
• Brice Kauffmann,
• Vicente Martí-Centelles and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2020, 16, 1564–1571, doi:10.3762/bjoc.16.128

• macrocycle-thread hydrogen bonds, thereby reducing self-aggregation. To this end, a five-component clipping strategy was adopted using different tetrabutylsuccinamide threads (Figure 2) with varying hydrogen-bond basicity (amides > esters) [4][15]. Threads containing an ester group were selected as esters

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• and the exocyclic C–C double bond. The geometry of the nitrogen atom is also planar most likely because of conjugation with the exocyclic C–C double bond and the C=O groups. The nitrogen planarity is probably also caused by a hydrogen bond between the NH group and the neighboring carbonyl oxygen atom

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

• small molecular volume increases the pharmacokinetic abilities of the compounds. In addition, 3 and 4 have a greater dipole moment compared to 5 and 6. The hydrogen-bond formation and the noncovalent interactions are influenced by the dipole moment. This means that an increased dipole moment can improve

• distance from the oxygen atom to the amide hydrogen atom (or a 3.09 Å O–N distance, Figure 4a). Compound 4 only displayed one hydrogen bond of the double bonded carbonyl oxygen atom to an amide hydrogen atom located between Asn218 and Tyr219. This interaction was regarded as weak, with an energy of −0.47

• kcal/mol and a 3.51 Å O–N distance (Figure 4b). Also, for compound 5, only one hydrogen bond interaction was seen. Indeed, the oxygen atom double bonded to the phosphorus atom of the phosphonate group was strongly bonded to an amide hydrogen atom localized between Ile159 and Leu160, with a 3.08 Å O–N

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• , proved to be completely inactive as the photosensitizer. Also, no reaction was observed when salicylaldehyde (68) was employed as a photosensitizer, despite of a triplet state energy of ≈70 kcal/mol, most probably due to an internal hydrogen bond (Scheme 16). As mentioned before, in the section on the

• photosensitizers. Salicylaldehyde (68) forms an internal hydrogen bond. Olefin isomerization via energy transfer from a carbonyl compound. Mechanistic pathways for the Paterno–Büchi reaction. Isomeric oxetanes formed after photochemical addition of aryl aldehydes to 2-butenes. Rotation of the C3–C4 bond of the

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• makes a hydrogen bond interaction with the NH of the 5-methoxyindole (1a) and form the adduct B. This interaction assists 1a reacting with an electrophilic ketone (2a) to form the intermediate D via C–C bond formation (C). Re-aromatization of D generates E, which then protonates to form the desired

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• modifications to the pteridine core which disrupt the hydrogen-bond assembly, such as benzylation of the lactam oxygen or conversion of the exocyclic amine to the pivalic amide [12][13]. The installation and subsequent removal of these groups naturally affects the overall yield and time necessary to generate

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• suggested to explain the reaction pathway: After irradiation, the copper catalyst, in an excited state, is quenched by the HEH, as demonstrated by a quenching experiment. Then, the reduced catalyst is involved in a hydrogen bond interaction with the carbonyl derivative, attributed to the acidic proton

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

• compounds 25–27 were calculated using DFT computational methods with discrete solute–solvent hydrogen bond interactions [66] (see optimized structures in Supporting Information File 1). Geometry optimizations were calculated at the DFT (B3PW91) level, using the 6-31G(d) basis set. The predicted 1H chemical

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• , molecules 4g formed centrosymmetric dimers due to the N1–H···N4 intermolecular hydrogen bonds (1 x, 1 y, 2 z; H···N 2.22 Å, N–H···N 164°). The dimers were bound by a N6–H···O1 intermolecular hydrogen bond (x 1, y, z; H···O 2.16 Å, N–H···O 162°), forming chains along the [100] crystallographic direction

Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin: experimental and computational evidence for intramolecular and intermolecular C–F···H–C bonds

• Vuyisa Mzozoyana,
• Fanie R. van Heerden and
• Craig Grimmer

Beilstein J. Org. Chem. 2020, 16, 190–199, doi:10.3762/bjoc.16.22

• : DFT; F···H hydrogen bond; fluorinated phenylcoumarin; Pechmann reaction; through-space coupling; Introduction Coumarins constitute one of the big classes of naturally occurring compounds. The first coumarin was isolated from the tonka bean (Dipteryx odorata) in 1820 and, to date, more than 1300

• activity of a molecule. Oxygen and nitrogen have been proven to be good hydrogen-bond acceptors which form strong intermolecular and intramolecular hydrogen bonds, however, fluorine is still denied hydrogen-bond acceptor status by some scientists. There is evidence of the existence of C–F···H interaction

• interaction was observed, although the conclusions of the two groups were different – O’Hagan et al. concluded that fluorine is not a good hydrogen-bond acceptor, whereas Desiraju et al. concluded that the interaction has genuine hydrogen-bond character [24][33][34][35][36]. The C–F···H–C interaction is

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds

• Itamar L. Gonçalves,
• Rafaela R. da Rosa,
• Vera L. Eifler-Lima and
• Aloir A. Merlo

Beilstein J. Org. Chem. 2020, 16, 175–184, doi:10.3762/bjoc.16.20

• ability to establish intra- and intermolecular hydrogen bonds [11]. In addition to π–π, dipole–dipole and van der Waals interactions, hydrogen bond interactions are involved in gel formation through self-aggregation of the small gelator molecules. In recent years, there has been increased interest in the

The interaction between cucurbit[8]uril and baicalein and the effect on baicalein properties

• Xiaodong Zhang,
• Jun Xie,
• Zhiling Xu,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 71–77, doi:10.3762/bjoc.16.9

• ] easily. Because the hydroxy group on the carboxylic acid of the baicalin formed a hydrogen bond with the oxygen atoms of Q[8] at the portal, cycle C of baicalin was pushed into the cavity of Q[8]. Therefore, the inclusion model of cucurbit[8] with flavonoid compounds was determined by the structure of

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• compound 12. Due to the absence of a hydrogen bond, azido-protected glycal 13 could be used as acceptor for reactions at its OH-4 and OH-8 group [36][37]. Moreover, it was used as sialyl donor in α-selective glycosylation reactions [35]. Next, acetolysis of 2,7-anhydro derivative 6 was examined with SnCl4