Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

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

• analysis were carried out. These analyses were used to rapidly assess key features of the system, interrogate the dynamic structure of the ligand, and determine the role of glycosylation on the conformational equilibrium. The glycopeptide conformations in solution change relative to the peptide; thus a

• conformational preference at Asp3 and Thr4 which correlates with the preferred states seen for the glycosylated antigen in solution. There is some evidence of a pre-structuring or pre-organization effect, where O-glycosylation shifts the conformational equilibrium of the peptide towards conformations that are

• forward previously that glycosylation alters the conformational equilibrium of the antigen. Conclusion We have shown how an informatics approach can be used to rapidly obtain key indicators of structural features for understanding the molecular level behavior of a system. We illustrated this informatics

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

• conformational equilibrium of penoxsulam (I, Figure 1). This compound has a 1,2–disubstituted ethane motif that could adopt three main staggered conformations, namely Igg, Iag and Iga (g = gauche and a = anti; see Figure 1), thus we have explored the intramolecular interactions governing its conformational

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• ). Conformational equilibrium of the (1-6) arm in terms of phi/psi torsion angle values for the α(1-3)-fucosylated FA2G2 N-glycoform. The structure with the folded (1-6) arm where the terminal β(1-4)-Gal interacts with both fucose residues is shown on the left-hand side. The N-glycans structures are shown with the

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

• ), and δC= (142.5) showed a considerable line-broadening (coalescence), revealing a partially hindered rotation of the formylphenyl moiety, i.e., the occurrence of a conformational equilibrium has to be taken into account. Even the δHC−N 13C NMR signal remained under the noise level, indicating that the

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• intermolecular interactions (NCIs) between aromatic rings (π···π) [58][59] and alkyl and aromatic ring (Csp3–H)···π stackings [59][60][61][62] are widely recognized, from both the experimental and theoretical viewpoint, as a major factor governing the conformational equilibrium, supramolecular assembly and

α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• proved to be beneficial and an optimized yield of 89% was achieved after experimentation. The dehydro-SAHA derivative 11a was obtained as a colourless solid. It also displayed a characteristic signal broadening in 1H NMR when recorded as dilute solution in CDCl3 indicating a conformational equilibrium

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

• the hyperconjugative interactions that influenced the equilibrium. The σC–H → σ*C–X hyperconjugation and the interactions involving the LPX counterbalance each other, explaining the non-influence of the halogen on the conformational equilibrium. These interactions are responsible for the strong

• preference for the ea conformer in cis-2-halocyclohexylamines, being strong enough to restrain the shift in the equilibrium due to other factors such as steric repulsion or solvent effects. Keywords: conformational equilibrium; cyclohexane derivatives; dynamic NMR; hyperconjugation; principal component

• cause some effect on the conformational equilibrium. Freitas and co-workers have demonstred this effect on trans-1,2-dihalocyclohexanes [12], where the diequatorial repulsion between the bulky halogens make the diaxial conformer more stable. Similarly, in trans-2-halocyclohexanols the OH–X interaction

Conformational signature of Ishikawa´s reagent using NMR information from diastereotopic fluorines

• Laize A. F. Andrade,
• Lucas A. Zeoly,
• Rodrigo A. Cormanich and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2019, 15, 506–512, doi:10.3762/bjoc.15.44

• diastereotopic fluorines. Moreover, the possibility of experiencing both the generalized anomeric and gauche effects makes the Ishikawa´s reagent an ideal choice to study the governing stereoelectronic interactions of the conformational equilibrium of organofluorine compounds. The conformational equilibrium of

• dipole moments and, consequently, the conformer populations are expected to change with the solvent polarity [29]. Indeed, the 1H NMR outcomes in C6D12 (dielectric constant ε = 2.2), CDCl3 (ε = 4.8) and C5D5N (ε = 12.4) solutions are informative on the rotation of H–C2–C1–F and conformational equilibrium

• solvent dependence of 3JH,F(pro-S/R), indicating that the conformational equilibrium of 1 changes on going from cyclohexane (nonpolar) to pyridine (polar) solution. According to the calculated molecular dipole moments for the possible conformers of 1 (Table 2), a significant interplay of conformers 1B and

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• dielectric constant, as would be expected from an electrostatic interaction between the polar alkoxy group and the amide moiety (Figure 4). A somewhat similar situation has been recently reported by Siebler et al. for the C-terminal amide in dimethylamido N-acetylproline, where the conformational equilibrium

• orientation, respectively [79][80]. This conformational equilibrium manifests in the χ angles, which is reflected by the J-coupling observed between the α-CH and β-CH2 groups in the 1H NMR spectra (Jαβ) [81][82]. A recent analysis of the Jαβ values by Braga et al. was used to quantify the pucker equilibrium

• . Four-state conformational equilibrium model used by Siebler et al. [72] for explanations of the elevated trans/cis ratio in nonpolar solvents, which occurs for X = N(CH3)2 and does not occur for X = OCH3. B. The two-state lowest energy model. C. The simplistic explanation of the C-terminal polarity

Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• conformational equilibrium among three staggered conformers, namely gt(+), gg(−) and tg around the 1,2-diacyl moiety. 1H NMR spectra of 1,2-dipalmitin (3) in CDCl3 after partial isomerization into the 1,3-isomer. (a) The expanded spectrum of 3 in CDCl3, (b) 3 in a mixed solvent with ca. 10% methanol-d4 in CDCl3

Conformational impact of structural modifications in 2-fluorocyclohexanone

• Francisco A. Martins,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2017, 13, 1781–1787, doi:10.3762/bjoc.13.172

• physicochemical/biological property of interest. In this work, structural changes in 2-fluorocyclohexanone were theoretically studied with the aim at finding intramolecular interactions that induce the conformational equilibrium towards the axial or equatorial conformer. The interactions evaluated were hydrogen

• bonding, hyperconjugation, electrostatic and steric effects. While the gauche effect, originated from hyperconjugative interactions, does not appear to cause some preferences for the axial conformation of organofluorine heterocycles, more classical effects indeed rule the conformational equilibrium of the

• transition state) or in the ligand assessment to an enzyme binding site. Thus, the replacement of the endocyclic oxygen in 3-fluorodihydro-2H-pyran-4(3H)-one, as well as of the carbonyl oxygen, with other groups, can shift the conformational equilibrium of the resulting molecule towards the equatorial or the

Conformational study of L-methionine and L-cysteine derivatives through quantum chemical calculations and ³J_HH coupling constant analyses

• Weslley G. D. P. Silva,
• Carolyne B. Braga and
• Roberto Rittner

Beilstein J. Org. Chem. 2017, 13, 925–937, doi:10.3762/bjoc.13.94

• solvents. The results showed that the conformational stability of the esterified derivatives is not very sensitive to solvent effects, whereas the conformational equilibrium of the N-acetylated derivatives changes in the presence of solvent. According to the natural bond orbital (NBO), quantum theory of

• ), derived from ΔE energies for 1 and ΔG for 2, show that the most stable conformers of 1 and 2 are in the form b in both isolated phase and solution. Furthermore, the conformers b of the compound 1 are favored in the conformational equilibrium, since their populations together are larger than 50% of the

• conformers of 1 are not very sensitive to the solvent effect. The same conformers were found in isolated phase and in solution for compound 2. Moreover, its four more stable geometries (2-Ib, 2-IIa, 2-IIIa and 2-IVa) represent approximately 80% of the conformational equilibrium (Table 2) in all different

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

• affected by the electron density of the aromatic counterpart. Keywords: acrylic esters; asymmetric synthesis; biomass; conformational equilibrium; π-stacking interaction; Introduction Noncovalent interactions have demonstrated to have relevant importance in chemistry and biology [1][2][3][4]. Considering

• approximately a 9:1 ratio, according to the relative area of the signals. Some authors have claimed that this effect could be due to a conformational equilibrium of s-cis and s-trans species that is shifted toward the s-trans conformer at lower temperatures [18][19][20][21]. Similar studies were carried out for

• crystal structure due to crystal lattice stabilization. These experimental and theoretical results led us to postulate that acrylates 6a–c are present in a conformational equilibrium between at least 4 different species: π-stacked and face-to-edge, and each of them in an s-cis/s-trans conformation. This

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

• interactions govern the conformational equilibrium in a biological-free environment. Indeed, Lesarri et al. [15] pointed out that anomeric effects owing to donor–acceptor (LP → σ*) interactions are responsible for the conformational preference of isoflurane. Despite the contribution from specific

• bonding is not a decisive interaction for the conformational equilibrium of isoflurane. Using a solvation model with explicit water, where specific solute–solvent interactions take place, conformer 1 is again the most stable form, suggesting that implicit solvation describes satisfactorily the actual

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• salt was used to break two intramolecular hydrogen bonds at a time while with the use of substituted benzoates the systematic approach to study association was achieved. Both, titrations and variable temperature measurements shed the light on the importance of conformational equilibrium and its

• intramolecular HB and formation of a complex in alternative rotameric state. This observation gives the opportunity to control such processes [2] making conformational equilibrium [4][31][32][33][34][35] one of the factors, or a tool, that should be taken into account in molecular design. To the best of our

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• assessed the possibility of conformational equilibrium for the six-membered arylpalladium species bearing L1 (Scheme 4). The non-planar six-membered palladacycle [66][67][68][69] can potentially adopt one of two conformations: I1, in which the syn-tert-butyl substituent at phosphorus assumes a pseudo

• ]. Intermolecular asymmetric Heck reaction by Hayashi [16]. Mechanistic rationale of asymmetric Heck reaction. Synthetic scheme for preparation of PHOX ligands with chiral cyclopropyl backbone. Conformational equilibrium in cationic arylpalladium(II) complexes with chiral ligand L1. For discussion on asymmetric

• induction imparted by chiral ligands L1 and L2 (originally published in [64]). For discussion on asymmetric induction imparted by chiral ligands L3 (originally published in [64]). Conformational equilibrium in cationic arylpalladium(II) complexes with chiral ligand L4. For discussion on asymmetric induction

Conformational analysis and intramolecular interactions in monosubstituted phenylboranes and phenylboronic acids

• Josué M. Silla,
• Rodrigo A. Cormanich,
• Roberto Rittner and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2013, 9, 1127–1134, doi:10.3762/bjoc.9.125

• equilibrium in 1 due to a predominant OH∙∙∙F hydrogen bond or to other effects. A series of 2-X-phenylboranes (X = Cl, Br, NH2, PH2, OH and SH) were further computationally analyzed to search for electron donors to boron, capable of influencing the conformational equilibrium. Overall, the intramolecular OH

• OH∙∙∙F hydrogen bonds as the governing interaction of the conformational equilibrium and, consequently, of the observed 1hJF,H(O) coupling constant [9]. However, it has been recently found that such coupling in this compound and in 2-fluorophenol itself is better described as 1TSJF,H(O), because of a

• coupling pathway based on the overlap of proximate electronic clouds rather than hydrogen bonding [10]. Indeed, dipolar effects have been invoked as the determining role of the conformational equilibrium in 2-fluorophenols instead of intramolecular hydrogen bonding [11], contrary to that found elsewhere

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• -dependent CD experiments reveal an isodichroic point at λ ≈ 209 nm indicating a conformational equilibrium (Figure 3a). The difference spectrum reveals a typical β-sheet- or β-strand-like structure (Figure 3b). The propensity to adopt a PPII helical structure is reduced in the aglycon 6 compared to the

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• regiospecifically manipulated through diazotransfer to form diazoimide 11 [27]. Rhodium(II)-catalyzed cyclization of 11 between modules 1 and 2 could generate a carbonium ylide intermediate 12. In this system, there is a dynamic conformational equilibrium of the tertiary amide, which is expected to allow divergent

Computational evidence for intramolecular hydrogen bonding and nonbonding X···O interactions in 2'-haloflavonols

• Tânia A. O. Fonseca,
• Matheus P. Freitas,
• Rodrigo A. Cormanich,
• Teodorico C. Ramalho,
• Cláudio F. Tormena and
• Roberto Rittner

Beilstein J. Org. Chem. 2012, 8, 112–117, doi:10.3762/bjoc.8.12

• , the intramolecular HB C=O···H–O is the dictating force of the conformational equilibrium of 2'-haloflavonols, but a nonbonding C–X···O–C interaction is also operating. Other intramolecular HBs are experienced by 2'-fluoroflavonol, including in particular an unusual C–F···H–O interaction. In fact, the

Intraannular photoreactions in pseudo-geminally substituted [2.2]paracyclophanes

• Henning Hopf,
• Vitaly Raev and
• Peter G. Jones

Beilstein J. Org. Chem. 2011, 7, 658–667, doi:10.3762/bjoc.7.78

• -conformation, which has been shown to be present as a conformer in the solid state by X-ray structural analysis does not photocyclize to 8. Moreover, syn,syn-7 is evidently too sterically hindered (by repulsion of the relevant hydrogen atoms as shown in Scheme 3) to be part of the conformational equilibrium