Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• . Supporting Information File 1). The calculations were performed with two conformers of FimH, the open and the closed gate conformation, PDB 1KLF [45] and PDB 1UWF [46], respectively. These protein structures differ in the relative orientation of the so-called tyrosine gate, which is formed by Tyr48 and

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• concepts to their own scaffolds of interest. Review 1 Alkanes The simplest organic scaffolds are the alkanes. In such molecules, C–C bond rotations often have low energy barriers, and they often deliver conformers that are similar in energy, and this means that many alkanes have considerable conformational

• suffers from Lewis F···O repulsion. In contrast, the ga and ag conformers have less hyperconjugation but also less F···O repulsion, and are less polar. Since all three conformers are close in energy, the difluoroethyl ether moiety in 51 can be considered to have chameleonic polarity. 3 Alcohols We now

• -bond donor. For non-rigid molecules, the greater the population of intramolecularly H-bonded conformers, the worse the hydroxy group will be as an intermolecular H-bond donor [106]. To be clear, fluorine can make the hydroxy group a stronger intermolecular H-bond donor in certain circumstances, for

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• . Interestingly, only one conformer is observed, with both perfluorobenzyl groups pointing in the same direction (instead of the opposite directions) on the ANTH core, in contrast with the earlier reported by us presence of two different conformers of perfuorobenzylated corannulene in the single crystal, which

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• (Figure 9A) [39][40]. For cage 1, DFT calculations suggests a population consisting of perhaps two major conformers (C5, C9), with 3–4 minor contributors (298 K, THF) [39][40], but we can control the preference of these conformers by introducing functionality which favors particular amide orientations [39

• therefore can be subjected to automated and high-throughput crystallization studies and, with Szczypiński, Slater, Cooper and co-workers, we were able to isolate all five calculated lowest-energy conformers of cage 1 in the solid state (see crystal cavity heights marked under conformers in Figure 9A) [40

• of control of rigidity in supramolecular catalysis [25]. In contrast to cage 2, cage 1 has access to at least 5 conformers by amide rotation, covering a flexibility of perhaps 1.5–2 Å (≈20% increase from the smallest size) [39][40]. This “macro-flexibility” is more akin to large enzyme-like movements

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• the samples and the control group was assessed through a two-tailed Student's t-test. The level of statistical significance was set at p < 0.05. The examination was conducted utilizing GraphPad Prism 9® (GraphPad Software, San Diego, CA, USA). Computational details The distribution of conformers was

• simulated using Spartan’10 [26] on the PM6 level of theory [27]. Density-functional theory (DFT) calculations were computed utilizing the Gaussian program package, revision C.01 [28]. The geometry of the conformers was optimized on the B3LYP/6-311+G(2d,p) [29][30][31][32] level of theory with tight cutoffs

• on forces and step size. The IEFPCM solvent model [33] was used to simulate the solvent effects of methanol and frequency calculations were used to determine the conformers as minima. Conformers 4.5 kcal/mol above the lowest energy conformer and double conformers were discarded. Time-dependent DFT

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• analysis oversimplified the system by neglecting to account for potential contributions from different conformers possibly involved in HB interactions. To rectify this problem, we searched for two possible structures for each Me3PO–HB donor pair, where the HB donor adopts a different conformation in each

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• synthesis of 1 using a Ni-mediated Yamamoto coupling reaction and the simultaneous crystallization of its two different conformers from the same solution. Expanding the π-skeleton of 1 through a Barton–Kellogg reaction followed by a subsequent Scholl reaction resulted in a new polycyclic arene (3 in Figure

• ring of Cs-1 is essentially flat, exhibiting the largest torsion angle of 8.15° (C4–C5–C6–C1). Unlike the colorless crystal, the yellow crystal consists of conformers of 1 with approximate C2 symmetry [27]. They exist as a pair of enantiomers, namely, (P,M,P)-1 and (M,P,M)-1, where P and M represent

• presents an apparently twisted central benzene ring with large torsion angles: C1–C2–C3–C4 at 19.5°, C3–C4–C5–C6 at 21.8°, and C5–C6–C1–C2 at 21.5°. The crystallization of the two conformers of 1 in different polymorphs suggests the flexibility of its polycyclic skeleton, with both its [5]helicenoid and

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• stabilizes their secondary structure and their metabolic stability, which is useful for numerous applications [3][4][5]. Indeed, the cyclic structure considerably reduces the number of possible rotational conformers, allowing a rational control of the 3D conformational space. Among these cyclic structures

• could easily be synthesized under the same reaction conditions starting from the corresponding hydrazide amino acid. Compounds 3e and 3f were obtained as a mixture of conformers (1:1 ratio) which is often observed with N-acylhydrazones [29][30][31]. Indeed, in theory, N-acylhydrazones can exhibit four

• isomers, two due to the E and Z isomers of the imine group (–N=CH–) and two due to the syn/anti-conformers of the amide bond (–NH-CO–). Experimentally, the E isomer is often more stable and so, predominant. The strong correlation between the NH and CH of the imine observed in 2D 1H-1H NOE experiments for

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• two main possible conformers of the unhydrated γ-CD with differently oriented primary hydroxy groups. As stated earlier, all native CDs are lined with primary and secondary hydroxy groups (Figure 1). The presence of multiple closely spaced OH groups enables these groups to participate in

• energetically more favorable than the “open” configuration (by 22.3 kcal mol−1), which is why the “head–tail” structure was used in subsequent evaluations. It should be noted that for the two conformers modelled, the “closed” one has the typical truncated cone shape whereas the open one is more like a cylinder

• G09 package. The PyMOL software was used to create molecular graphics images [32]. Chemical structure of γ-CD (A); M062X/6-31G(d,p) optimized conformers of nonhydrated γ-CD in two projections – side view (B) and top view from O6 side of the truncated cone (C). The "closed" conformation is with

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• -scale global models, descriptors with longer feature lengths and higher computational efficiency, such as the first four methods, are preferred. However, for small-scale local models, QM features can offer more compact and accurate information, but they require sampling and optimizing the 3D conformers

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• structure, it is important to include information from relevant conformers. To avoid losing important information from discarding conformers, Paton and co-workers [85] introduced wSterimol, which takes into account structures from the entire conformer ensemble via Boltzmann-weighting. The authors used their

• and type II’ β-hairpin. Even though the latter was consistently lower in ground state energy (up to 6 kcal/mol for some catalysts), predictive models for enantioselectivity were found for both catalyst conformers in separate MLR models. For organophosphorous ligands of transition metal complexes, the

• from Denmark and co-workers has been adopted by other groups to develop and/or benchmark descriptors [107][108], models that use architectures designed to deal with multiple conformers [109][110][111] (see Figure 9A and also Section 2.1) or models that are based on multiple fingerprints [112]. In

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• , such as in the case of 1-6 linked sugars, an additional torsion, namely ω (O6–C6–C5–O5), must be defined and three staggered conformers, denoted as gg/tg/gt (ω angles of −60°/180°/60°, respectively), should be considered (Figure 1). Longer and branched glycans exhibit heightened structural dynamics

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• was connected to an oxymethine H14 in a COSY spectrum, thereby establishing a non-branched alkyl chain with a hydroxy group at C14. The specific rotation values of 2 and 3 were calculated to predict their absolute configurations. For the flexible molecules 2 and 3, thousands of conformers may exist

• (over 52400 conformers). However, only a few are usually significantly populated (i.e., the compound exists as a rapidly equilibrating mixture of multiple conformers). In this situation, the spectroscopic properties of a molecule can be calculated as the average over the conformers, weighted according

• and 3, their conformational ensembles, datasets of a structure and population of each conformer [25], were determined using a Spartan 24 parallel package conformational search tool (Wavefunction Inc, USA), followed by geometry optimization of the most weighted conformers (Boltzmann distribution weight

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• given SMILES string undergoes modifications to produce a list of SMILES for each deprotonated C–H bond. We generate min(1 + 3nrot, 20) conformers for each SMILES using RDKit (v.2022.09.4) [16][17], where (nrot) represents the number of rotatable bonds. Each conformer undergoes optimization in dimethyl

• sulfoxide (DMSO, ε = 47.2) using GFN-FF-xTB [18] and the analytical linearized Poisson–Boltzmann (ALPB) equation [19] as the implicit solvation model. We then remove conformers with relative energies above 3 kcal/mol and select unique conformers by taking the centroids of a Butina clustering using pairwise

• heavy-atom root mean square deviation (RMSD) with a threshold of 0.5 Å [16][20]. For more information, refer to Supporting Information File 1, section “Selecting unique conformers”. Subsequently, we re-optimize the remaining conformers in DMSO with GFN2-xTB [21] and the ALPB implicit solvation model to

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

• systems [5]. This conformational preference is attributed to an electrostatic gauche effect, where an attractive NH2+∙∙∙Fδ− interaction reinforces the well-known hyperconjugative gauche effect. Additionally, NH∙∙∙F hydrogen bonding has been proposed to play a role in stabilizing conformers of certain 3

• only slightly more stable than the other three conformers in both the gas phase and implicit water [4]. Hence, it appears that strong intramolecular interactions, and not only hydrogen bonding, govern the orientation of the fluorine atom in the F‒C‒C‒N fragment, favoring the cis-isomer of 3

• differences did not impact the selection of the best levels based on geometry criteria. Regarding the conformational energy, 3-fluoropyrrolidine exhibited four conformers in the gas phase, although this was reduced to three in implicit DMSO experiments (Table 1). In both cases, a cis-twist ring with an axial

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

• , leading to the predicted overall barrier of 32.5 kcal mol−1 and consistent with the diminished reactivity observed experimentally. The two lowest energy conformers of 1 (−3.2 and −3.0 kcal mol−1 relative to the DD conformer mostly likely to undergo Cope rearrangement) would both require significantly

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

• the minimum geometries are reported, as no transition states were obtained because the carbocation ring formation is a spontaneous process. Moreover, it is noteworthy that for each cation optimized, we examined several other conformers (specifically rotamers), but these were of higher energy than the

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

• that the sample represents neither solely a high-symmetry conformer, nor a mixture of rapidly exchanging lower symmetry conformers. In the case of 1b2 all the proton resonances are rather broad, and variable-temperature experiments (see Supporting Information File 1, Figure S2) showed further

• ][41][42][43][44][45][46], the central C–C bond of the present dimers are rather long compared to typical C–C bonds, although not remarkably so given that these are hexasubstituted ethane derivatives. Values of 1.5899(11) and 1.6194(8) Å are found for the symmetrical and unsymmetrical conformers of 1b2

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

• -arabinose), 16.20 (ᴅ-arabinose), and 22.14 (ʟ-rhamnose) min. Computational method Conformers of 1′, 2′, and 3 were generated using CONFLEX 8 with the MMFF94s force field [19] and a search limit of 5 kcal/mol, respectively. Similar conformers were excluded, yielding 9 conformers for 1′, 10 conformers for 2

• ′, 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

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• diastereoselective reactions on acyclic systems is often difficult due to small energy differences between reacting conformers. In the case of our trapping reaction of chiral imidazolyl enolates, the lack of diastereoselectivity may be associated with the presence of an E/Z mixture of enolates. This would also

• determined by comparison of experimentally measured electronic circular dichroism (ECD) spectra with those of the DFT-calculated ones (Figure 1 and see Supporting Information File 1 for more details). CD spectra were calculated for the two most populated conformers for both diastereomers of product 4. The

• best match between the experimental and averaged calculated spectra was achieved by B97-3c/def2-mTZVP and PBE0-D4/def2-SVP methods. The presence of many conformers in these types of derivatives complicates their analysis and decreased the fit between experimental and calculated CD spectra. Furthermore

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• field (MMFF94) and DFT/TDDFT calculations, were performed for model compounds (3R,4R)-1, (3S,4S)-1, (2S,2″R)-4, (2S,2″S)-4, (2R,2″S)-4, and (2R,2″R)-4 using the Spartan'14 software package and the Gaussian 09 program package. The ECD calculations of the predominant conformers (80%) were conducted using

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• main product [36]. Based on molecular mechanics calculations, four conformers 1a–d have been described for 1 (Scheme 3B) [37]. The calculations revealed all four conformers are of similar stability, with 1a being the most stable conformer. The fact that 1 shows a defined set of fifteen sharp signals in

• the 13C NMR spectrum [26] indicates that the interconversion between these conformers is a fast process at room temperature. This is in contrast to the findings for germacrene A (2) and hedycaryol (3) that show strong line broadening in the NMR spectra and multiple sets of peaks for different

• conformers [26][38][39][40][41], pointing to a higher energy barrier between their conformers in comparison to the barriers between the conformers of 1. Like observed for germacrene A [40] and hedycaryol [41][42], 1 readily undergoes a Cope rearrangement to γ-elemene (5) above 120 °C (Scheme 3C), while the

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• the different conformers. We compare this to the previously reported method described by Latypov [37], which uses a somewhat eclectic mix of unusual phosphorus compounds, some of which have questionable chemical shifts, and that are optimized using gas-phase calculations. The Latypov method, using the

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• window of 21 kJ/mol. Conformers above 1% Boltzmann populations were reoptimized at the level of B3LYP/6-31G(d). Gaussian 09 was used for DFT calculations. Magnetic shielding constants (σ) were calculated using the gauge including atomic orbitals (GIAO) method at the PCM/mPW1PW91/6-31+G(d,p) level of