Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• dual-host systems for selective ion separation. Keywords: anion binding; cesium extraction; dual-host strategy; ion-pair interaction; solid–liquid extraction; Introduction Ion-pair interaction, defined as the electrostatic attraction between a positively charged cation and a negatively charged anion

• , is prevalent across various disciplines including biology, chemistry, materials science, and ion batteries [1][2][3]. Fundamental understanding of ion-pairing can help to regulate their roles and relevant applications in chemical catalysis, battery performance, and ion binding, transport and

• separation [4][5][6][7][8]. Building on the extensive research into anion and cation receptors within the realm of supramolecular chemistry [9][10][11][12], numerous heteroditopic ion-pair receptors have been elaborately developed [13][14][15]. These receptors, consisting of binding sites for both anions and

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• interactions also contribute to the stabilization of the ligand–iNOS complexes. In particular, 4-(1-methylamino)ethylidene-5-phenyl-1-(3-nitrophenyl)pyrrolidine-2,3-dione (5e) exhibited the strongest binding affinity (−9.51 kcal/mol) and demonstrated significant inhibitory activity against nitric oxide (NO

• ]ethylidene-1,5-disubstituted pyrrolidine-2,3-diones and methylamine. All studied compounds were successively investigated to what extent they inhibit nitric oxide (NO) production in LPS-stimulated RAW264.7 macrophages. In addition, a molecular docking simulation was performed to examine the binding

• ligands (Figure 4 and Figure 5). Additionally, dexamethasone (DEX) was employed as an experimental control for comparative purposes [34][35][36]. The docking scores (DS), reported in Table 5 as binding affinities, reveal that negative DS values correspond to stronger binding affinities between the ligand

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• competition between Ca-hydrazone and Ca–THF binding. Considering smoothness of catalytic hydrazone hydrocyanation, similar hydrofluorination or hydroiodination seemed feasible. However, replacement of TMSCN by TMSF or TMSI did not give any product. After establishing the activity of the model achiral catalyst

• set out to elucidate it by using DFT computations (Figure 2). As we have chosen as substrate in our experiments a self-prepared mixture of E- and Z-isomers (9:1) of N-acyl hydrazone 1, which allows for additional binding to oxophilic calcium via the carbonyl oxygen, we did not know a priori which of

• -tetrahedral coordination environment with cyanide, stemming from a common reagent (vide infra) and binding to the metal in a preferred side-on (π-complex) mode [54]. When the hydrazone substrate enters the catalytic cycle, it coordinates also as a bidentate ligand to calcium via oxygen and nitrogen atoms

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

• the structural determinants of the recognition process is a prerequisite for understanding and manipulating carbohydrate–protein interactions, such as in the inhibition of carbohydrate-specific bacterial adhesion. For receptor binding, glycoligands have to be properly oriented in three-dimensional

• - and heteromultivalency effects are crucial [8][9][10][11][12], but also many other aspects of glycoligand presentation govern carbohydrate recognition. Interestingly, even a subtle structural variation in heterobivalent glycoclusters can result in unexpected differences in lectin binding due to

• diverse interactions with primary and secondary carbohydrate binding sites of the protein [13]. For example, when an α-ᴅ-mannopyranosyl (Man) and a β-ᴅ-glucopyranosyl (Glc) unit were conjugated such that the relative orientation of the two sugar portions is varied – be it on enantiomeric or regioisomeric

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• are non-covalently bound to their fluorophore and despite high (usually nanomolar) binding affinities this can pose problems for RNA live-cell imaging. For instance, diffusion of the ligand and non-specific binding lead to unfavorable background and/or signal loss [10]. To address these problems, our

• fluorophore derivatives bind the Pepper aptamer with affinities in the low nanomolar range [12]. Crystal structure analyses revealed that in the ligand binding pocket, a characteristic hydrogen bond is formed between the hydroxy group of the N-hydroxyethyl substituent of HBC and the N7 of G41 [12][13]. We

• -dimensional structure of the Pepper binding site with a bound HBC derivative (pdb code 7EOM). The hydrogen bond between N7 of guanine in position 41 (G41) and the hydroxy group of HBC is highlighted as gray dashed line [12]; d) concept for covalent attachment of HBC fluorophores to the N7 atom of G41 of the

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• acyclic CB[n] are not macrocycles, they are preorganized into a C-shaped geometry by virtue of their polycyclic chemical structure and display binding affinities approaching those of macrocyclic CB[n]. M1 and analogues display outstanding biocompatibility and have been used for a number of in vivo

• ][66][67]. Previously, we have studied the influence of the length of the O(CH2)nSO3Na sidearm (n = 0, 2, 3, 4) and found that the M0 host – where the hydrophobic linker (CH2)n was completely removed – displayed higher binding affinity than M1 which we attributed to the location of the ionic group

• spectroscopy and quantitative investigation by isothermal titration calorimetry (ITC). Finally, we discuss the trends in binding affinity observed for C1·guest and M1·guest complexation. Design, synthesis and characterization of C1 In order to disentangle the effects of the ionic group (sulfonate versus

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

• composition such that the new molecule has a better-defined three-dimensional shape. Such “small molecule origami” can offer practical benefits. For example, if a drug molecule is pre-organised into the target-binding conformation, it should exhibit the desirable twin characteristics of high potency (since

• target binding will incur little entropic cost) and high selectivity (since off-target interactions will be minimised) [1]. There are several methods by which the conformations of small molecules can be controlled, but in this review we will focus upon one particular method, which is the installation of

• potent across a panel of HDAC isoforms than the erythro-isomer 17, and this was taken as evidence that an extended zigzag conformation of the alkyl chain is required for binding to HDAC. If two fluorines are introduced into the middle of an alkyl chain in a 1,3-pattern, a new conformational effect

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• unconjugated and “overloaded” antibodies. Unconjugated antibodies compete with antibodies containing payloads for binding, which can diminish the effectiveness of the antibody-payload materials. On the other hand, excessive loading of the antibody can lead to antibody aggregation, increased toxicity, decreased

• of the ArM significantly enhances the potential of the photocatalyst for antibody modification [43]. By inserting a [Ru(bpy)2dppz]2+ complex into the apo-form of riboflavin-binding protein (RFBP), a complete reversal of selectivity was achieved: the Ru complex alone enabled tyrosine modification via

• disulfide bridging sites in biomolecules to introduce specific functional groups (Figure 6) [44]. The bioconjugation reaction is based on thiol–yne coupling. Originally developed on peptides and proteins, this approach was applied to a fragment antigen-binding (Fab) antibody fragment (approximately 46 kDa

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• cytotoxic activity of natural products by increasing the hydrophobicity, enhancing cell membrane permeability and binding affinity with intracellular targets [26]. Structure–activity relationships analysis of both hemisynthetic products 2 and 3 revealed a shared conjugated methylene olefinic function that

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• binding of tryptophan is therefore important for diagnostic and medicinal applications. Recently, we reported a glucose naphtho crown ether which is a chemoselective receptor for the esters of aromatic amino acids, in particular tryptophan, in water. Herein, we demonstrate that the same compound also

• binds free tryptophan selectively in aqueous media. Furthermore, it is capable of binding to tryptophan within model tripeptides. The naphthalene functionality in the glucose-derived receptor enables the study of guest binding using fluorescence spectroscopy. Keywords: amino acids; macrocyclic

• binding of tryptophan in water [9]. However, the development of selective amino acid receptors in aqueous environments is challenging since it requires a combination of hydrophobic and polar interactions for binding [10][11][12]. As a result, the number of reported selective receptors for tryptophan in

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• ] and likely hints to favoured hydrophobic interactions around the binding pocket at unit B and D. In comparison, the cytotoxicity of Alloc-protected amine 26 decreased significantly (IC50 (KB-3-1) = 374 nM), which could be due to higher steric bulk as this is known to be less well tolerated; cf. unit B

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• . PreQ1 riboswitches sense the cellular concentration of preQ1 and regulate the expression of downstream located genes associated with the biosynthesis or transport of Q in a feedback-like manner. Binding of PreQ1 to the mRNA causes the riboswitch to commit an altered folding pathway, which affects the

• transcription or translation of the mRNA and results in altered transcript and/or protein levels [5]. In recent years, there has been a growing interest in the modification of preQ1. preQ1 derivatives, preQ1 analogs and mimics of preQ1 have greatly expanded our understanding of preQ1-binding biomolecules, such

• vitro and in living cells using rationally designed electrophile-tethered derivatives of preQ1 (1) and its Watson–Crick diamino-faced counterpart DPQ1 (2, Scheme 1A). These ligands (compound classes 3 and 4, Scheme 1A) were tailored to target a conserved guanine nucleobase within a natural preQ1-binding

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

• catalysis has fared best using approaches such as destabilizing ground states by constrictive binding, guiding molecular collisions to reduce large entropic costs (e.g., pericyclic reactions), and broad, undirected coulombic stabilization of charged transition states [36], for example of cations by

• water (Figure 2A) [71][72][73], or by binding a hydrophobic substrate and holding it close to a functional(ized) rim (e.g., as in cyclodextrins) that performs a reaction (Figure 2B) [74][75][76][77][78][79]. These effects are driven mostly by effective concentration/molarity (i.e., proximity of reacting

• groups) with little [73], if any, transition-state binding [36][80][81]. Thus, these macrocycles depend on the catalytic concept of organization; polarization is a minor contributor. Size-exclusion and regioselective outcomes are possible [56][82][83][84][85], and symmetric arrays of chiral units (like

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• h. *Significant difference compared to control samples, p < 0.05. Synthesis of 2-hetaryl-substituted 1,3-tropolones 1. Synthesis of 1,3-tropolones 7a,b and 8a,b. Reagents and conditions: method A: dioxane, reflux; method B: AcOH, 40–50 °C. Possible binding mode of 7 and 8 with CN− and F−. Total

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

• surfaces and the subsequent accumulation to form multilayered cell clusters [17]. To investigate the action of farinosones D (1) and A (2) on planktonic cells and their adherence to the substrate, growth curve and fibrinogen binding assay were conducted. The findings obtained from these assays demonstrated

• Information File 1). Additionally, in fibrinogen binding assay, both compounds reduced the initial attachment of planktonic cells by approximately 30% at a concentration of 62.5 µg/mL (Figure S1C, Supporting Information File 1). Based on the results of fibrinogen binding assay (Figure S1C, Supporting

• Information File 1), it is likely that the activity of farinosones D (1) and A (2) does not interfere with the factors essential for fibronectin binding, particularly the fibronectin-binding proteins such as fibronectin binding protein (FnBPA and B) [18]. FnBPs are adhesions and are known to play a key role

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

• . We expect this information to be useful for the rational application of the CF2H group in drug development and molecular design. Previous quantum mechanical calculations revealed that the CF2H···O binding energy (ΔE) ranges from 1.0 kcal/mol to 5.5 kcal/mol [14][15][18][21]. In addition, as measured

• inconsistent with the corresponding A values (Table 1), which typically provide reliable measurements of the HB donation ability of neutral compounds. We attribute the inconsistency to several factors. First, because the binding affinity is determined solely by the absorbance change of Reichardt's dye, the

• constructs. Although many of the CF2H HB donors studied here can promote relatively strong hydrogen bonding interactions with n-Bu3PO, even the strongest CF2H HB donor (3b) is still 30 times weaker than phenol (10), corresponding to about a 2 kcal/mol reduction in binding energy at 25 °C. These results

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• effectively applied to form orthogonal supramolecular polymers. The macrocycle-mediated connectivity was confirmed by single-crystal X-ray diffraction, which revealed a unique 2:2 binding motif between host and guest, bridged by two cationic pyridinium end groups through π-stacking interactions and other

• capable of dimerization by binding to a macrocycle in a 2:2 stoichiometry [22][23]. Such binding motifs are intriguing for macrocycle-mediated supramolecular dimerization since they may enable multiple modes of noncovalent connectivity through combination with other noninterfering interactions (e.g

• amide macrocycle with six aromatic residues (hereafter called cyclo[6]aramide for brevity, Scheme 1a) could mediate dimerization as a host. That is because such a 2D macrocycle has six carbonyl oxygen atoms pointing inwards as binding sites, demonstrating excellent affinity for cationic organic guests

Chemical glycobiology

• Elisa Fadda,
• Rachel Hevey,
• Benjamin Schumann and
• Ulrika Westerlind

Beilstein J. Org. Chem. 2025, 21, 8–9, doi:10.3762/bjoc.21.2

• . [12] in the context of photoswitchable ligands to the lectin LecA. Staying in the theme of lectin characterization, Lundstrøm et al. study the glycan binding profile of CMA1 originating from melon [13]. A time that sees great opportunities in computational biology also breeds innovative applications

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• fluorine atoms, inserted in the aromatic rings, which considerably modifies the dipole moment of the corresponding fluorinated aromatic rings with respect to their hydrogenated homologs, thus influencing their behavior, binding affinities, and optoelectronic properties. These interactions already represent

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• (IC50 = 1.28 μM), and non-toxicity in liver HepG2 cells. Hantzsch-based strategies: As mentioned before, in response to the challenges posed by the multifactorial nature of AD, the MTDL approach has emerged as a promising strategy. This approach involves designing drugs capable of binding simultaneously

• heterocyclic core. The novel compounds were first evaluated using β-arrestin recruitment assays in CHO (chinese hamster ovary) cells overexpressing human GPR55. These new compounds have been evaluated in competitive binding assays for cannabinoid receptors, but all of them showed to be selective for GPR55 (>4

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• other binding sites required for substrate binding and/or promotion of the catalytic activity. Past studies have shown that modifying the porphyrin core with urea functionalities and amino acid substituents leads to the formation of ureaporphyrins, which significantly enhance sugar binding in non-polar

• solutions [18]. Similarly, Burns and co-workers reported di- and tetra-urea picket porphyrins highlighting, the impact of buried solvent molecules, such as DMSO, on the selectivity, affinity, and stoichiometry of anion binding [19]. Iron complexes of tetra-urea picket porphyrins further demonstrate how

• , and calixarenes has been extensively studied using both enzyme mimics and non-biomimetic systems, due to the presence of an internal cavity (binding sites) and nearby functional groups (catalytic sites) [27][28][29]. Tetrapyrrolic macrocycles contain an internal cavity with multiple inner –N/NH groups

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• ][53][54][55][56][57]. The exception is the 10 residues that constitute the A domain active site, whose high variability creates binding pockets of varying shapes and sizes. These residues therefore dictate substrate BB specificity of an A domain and are referred to as the nonribosomal code (in analogy

• the glycopeptide antibiotic family [62][63]. Their aromatic rings undergo oxidative coupling to form biaryl moieties that restrict atropisomerism; the resulting rigid structure is key to their high affinity binding to peptidoglycan intermediates [64][65]. Glycopeptide antibiotics include vancomycin

• , the A domain (gray rectangles in a) is responsible for activating the substrate BB to be incorporated, and the substrate BB specificity is dictated by the nonribosomal code (the 10 residues that defines its binding pocket, small red circles). Algorithms for A domain substrate prediction were trained

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• can easily replace ligand strands leading to a partial or full receptor decomposition. Herein, we present a charge-neutral zinc(II)-based metallocontainer which was tuned to contest oxalate as most competitive dicarboxylate. The dianion is bound in a 1:1 fashion with a binding constant of log K = 4.39

• ][43][44]. Additionally, organic receptors featuring metal centers which are strongly bound in a multidentate fashion with the sole purpose of acting as binding sites are utilized beside the pure organic systems [26][45][46][47][48][49][50][51][52][53][54][55]. In the last decade, metallocages and

• inevitable presence of counteranions necessary to balance the positive charge increases the complexity of the underlying equilibria. Competition between the desired guest and the counteranions can lead to significantly weakened binding strength of the target analyte in the worst case. One option to mitigate

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• upon binding of the enolate molecule to iodine either through a carbon–iodine or an oxygen–iodine bond. Both intermediates, I and II, are in rapid equilibrium with each other and further undergo two different types of reactions: [1,2]-ligand coupling and [2,3]-rearrangement (Scheme 2). Either of these

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• this work was a preliminary evaluation of the potential bioactivity of the obtained compounds. In particular, a molecular docking experiment to investigate the binding mechanisms to the CYP51 enzyme and an evaluation of the antifungal activity of imidazo[1,2-a]pyrimidines against Candida albicans were

• desired pharmacological properties. Therefore, the design and synthesis of new compounds of this class with improved ADMET (absorption, distribution, metabolism, excretion, toxicity) pharmacological properties is an urgent task. Molecular docking was carried out to identify potential binding positions of