Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• selective remediation strategies. Supramolecular materials, with their pre-organized structures, offer a promising route for uranium removal. Phenoxycalix[4]pyrroles (PCP) are well-known supramolecular scaffolds capable of selective metal binding, making them attractive candidates for designing uranium

• receptors bearing both anion- and cation-binding sites, as well as systems capable of promoting ion-pair formation [23][24]. As effective chelating agents for a broad range of transition metals, hydroxamic acids constitute an important class of organic compounds that have attracted considerable attention

• [4]resorcinarene hydroxamic acid has also shown a pronounced binding tendency and selectivity for uranyl and proved to be applicable for the determination of uranium in standard and environmental samples [34]. Importantly, more recent studies have demonstrated that pre-organized or cyclic hydroxamate

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• , like other benzamide HDAC inhibitors, exhibits slow on/off binding kinetics, hence once bound to the HDAC within the complex it should not readily dissociate [16]. A crystal structure of HDAC2 bound to an analogue of CI-994 (PDB: 4LY1) revealed that the acetamide moiety is oriented outside the HDAC

• active site [17]. Hence, we decided to functionalize this position with an alkyl linker consisting of 9 carbon atoms to mitigate any steric clashes between the HDAC inhibitor and the nanogold particle, which could be detrimental to the probe binding affinity (Figure 1). Further to this, we previously

• complex on the EM grid, glutaraldehyde cross-linking was performed, with successful cross-linking confirmed by SDS-PAGE. The cross-linked ternary complex was incubated with the Au–(CI-994) probe for 2 hours in 2:1 molar ratio to minimize non-specific binding. Screening and data collection were carried out

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• 27.92 ± 3 µM and 23.06 ± 3 μM, respectively. Molecular docking simulations revealed that NAP-SePh and NAP-Se(n-Oct) show binding affinities of −10.39 and −8.53 kcal/mol for the (1M17) active, and −10.66 and −10.59 kcal/mol for the (4HJO) inactive conformation of the tyrosine kinase domain of the

• binding components, including electron-deficient, electron-rich, and hydrophobic regions, which offer greater affinities towards biological targets. Structures of these compounds were confirmed through various spectroscopic analyses. The structure of compound 7 was confirmed using single-crystal XRD

• cancer cell line. Molecular docking simulation revealed strong binding interaction and affinities towards the tyrosine kinase domain of epidermal growth factor receptor (EGFR), and the protein–ligand interaction resembles the interaction found in the co-crystallised protein–erlotinib complex. Result and

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• ]. (Multi)calix[4]arenes having (dialkyl)amino groups at the wide rims are soluble in aqueous media at physiological pHs and may be used in protein sensing [18], DNA binding/recognition [19][20][21][22][23], and cell transfection [24][25][26]. Their water-soluble guanidinium derivatives are also

• affect the cycloaddition by, for instance, binding copper cations or counter anions, and thus their presence in the structures of calixarenes at the CuAAC step must be avoided. On the other hand, the unmodified amines may also contribute to undesired Cu(I) stabilization and complicate the CuAAC work up

• calixarene 37, there were no problems encountered with the copper complex destruction and the yield of the isomeric calixarene 40 having four 2-(4-phenyltriazol-1-yl)ethyl moieties at the narrow rim was much higher, indicating a weaker binding in the 40/Cu+ system than in the 37/Cu+ one, due to the outer

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• -mimicking scaffolds are a proven strategy in the design of anticancer drugs. Many cancer-related proteins (e.g., kinases, ATPases, DNA/RNA polymerases) have binding pockets designed for purine nucleotides (ATP, GTP). Oxazolopyrimidines can compete with purines or their analogues, inhibiting enzymatic

• interference with the assay itself, but to binding to possible targets. Conclusion The results of anticancer screening and virtual analysis suggest that among the synthesized derivatives, compounds 1, 7, and 9 showed activity and high relevant selectivity against the HeLa cell line. While compound 1 exhibited

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• terpenoid modification in nature are depicted. Terpene synthase enzymes are centrally important for determining the carbon skeleton and thus family the terpenoid belongs to. These cyclisation enzymes are divided into Class I (active site cleft contains multiple Mg2+-binding motifs which are responsible for

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• absorption (HIA), in vitro permeability to Caco-2 cells (Caco2), in vitro binding to plasma proteins (PPB), solubility, and inhibition of CYP2D6. The following were selected as descriptors of toxicity: carcinogenicity for rats and mice, mutagenicity according to the Ames test, and cardiotoxicity by

• inhibition of hERG in vitro. The results are shown in Supporting Information File 1, Table S5. As can be seen from the table, the obtained results suggest that the compounds have a good intestinal absorption and medium permeability. However they are expected to have low plasma protein binding and permeation

• . Taking into account that the conformation of the actin monomer in the described structures is basically the same, the structure of non-muscle β-actin (8DNH, 2.99 Å) obtained by cryo-electron microscopy was used for this study. Docking was performed to both known clefts (hydrophobic or target-binding one

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• configuration promotes strong binding to π-acidic ligands, effectively compensating for the loss of aromaticity upon η2-coordination to arenes, while disfavoring oxidative addition due to geometric constraints of the octahedral complex. The resulting η2-arene complexes, encompassing both arenes and heteroarenes

• (Figure 6C), so suitable aromatic ligands are limited to those lacking strongly π-acidic functional groups, e.g., alkenes, alkynes, aldehydes, certain ketones, and nitriles. Lewis-basic heteroarenes, such as pyridines or imidazoles, tend to coordinate via nitrogen instead, disfavoring η2-binding (Figure

• aromatic complexes is their fluxionality [47]. Despite clear thermodynamic preferences for specific binding sites, the metal can migrate across the π-system without detaching from the aromatic ring (Figure 7A). This flexibility allows for the generation of multiple organic functionalities from a single

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• activity [33]. Halogen substituents in this position have been shown to modulate antibacterial, antiviral, and antiproliferative activities, likely through electronic effects and improved target binding. The C3 position was functionalized with a propanoic acid moiety, explored in both its open-chain (acid

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• decarboxylase from Leishmania infantum complexed with PLP and DFMO, the bound ligand corresponds instead to human arginase I (PDB code 3GN0). While binding to arginase I is not related to DFMO’s pharmacological activity, both enzymes recognize ornithine-related substrates, allowing DFMO to occupy the arginase

• amino acid residues and water molecules, while the ligand is delineated by a contour line to distinguish it from the binding cavity. Lowest-energy type-I, type-II, and type-III conformers of the zwitterionic form of (S)-DFMO. Color labels: H = blue, C = pink, N = orange, O = red, F = yellow. DFT

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• competing dicyanoargentate(I) anions. We also examine the recyclability of the material and assess its stability in organic solvents, comparing its performance with that of a previously developed material containing noncovalently bound bambusuril. Keywords: anion binding; anion extraction; anion receptor

• -sized” molecular box has been used to extract various anions from water [12]. Another family of macrocyclic compounds suitable for anion recognition and binding are bambusurils (BUs). BUs act as very potent anion receptors in both organic solvents and water. Furthermore, their portals can be variously

• , exhibiting near-quantitative binding at millimolar concentrations [17]. The lower binding efficiency of BUs attached to the material compared to the free macrocycle in solution can likely be attributed to the heterogeneous nature of the solid-phase system. Moreover, the anion binding ability of BU1 may be

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• core, successfully completing the first asymmetric total synthesis of ryanodol (4) in 41 steps. To elucidate the role of the C15 hemiacetal hydroxy group in ryanodine (1)-type diterpenoid natural products in binding to ryanodine receptors, the authors initially proposed reducing the lactone moiety in

• , epoxidation of the C1–C2 double bond, and Li/NH3-promoted reductive cyclization to construct the core E ring, completing the asymmetric total synthesis of (+)-ryanodol (4). The 800-fold greater binding affinity of (+)-ryanodine (1) for cardiac ryanodine receptors (RyRs) compared to its hydrolysis product

• , (+)-ryanodol (4), indicates that the pyrrole-2-carboxylate unit at the C3 position is critical for receptor binding, as established by structure–activity relationship (SAR) studies [28]. However, the direct and selective modification of the highly sterically hindered C3 hydroxy group within this

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• . Multiple ligand–receptor interactions can significantly enhance receptor binding affinity and cellular uptake, as well as more effectively modulate signal transduction pathways, for instance when receptor clustering is necessary on the cell membrane [3]. Designing multivalent bioactive compounds thus

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• regions of RNA. We herein report the synthesis and binding studies of new isoorotamide-based PNA monomers that target uridine–adenosine base pairs via a distal base recognition strategy. Monomers were designed with an arylisoorotamide core attached to a linker aimed at bypassing the uridine in a U–A pair

• distal binding monomers (Db) demonstrated slightly higher affinity for A–U base pairs while one demonstrated slightly higher affinity for the G–C base pair. These results provide insight into the nature of PNA monomer design particularly around linker design and rigidity. Keywords: Hoogsteen hydrogen

• possible base pairs (G–C, A–U, C–G, and U–A). Notably, each synthetic nucleobase takes advantage of favorable hydrogen bonding interactions to the proximal nucleobase in the Watson–Crick base pair. Strong binding has been reported for purine recognition given the propensity for two Hoogsteen hydrogen bonds

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• work represents one of the earliest comparative studies on the anion-binding behaviors of carbazole-based structural analogs, demonstrating that a flexible macrocycle markedly improves iodide binding affinity via an induced-fit mechanism. The flexible analog PBG exhibits a 22.78-fold higher

• fluorescence quenching efficiency upon iodide binding compared to the rigid WDG (KPBG/KWDG = 22.78), demonstrating its potential as a highly sensitive optical probe and offering a novel strategy for engineering dynamic supramolecular receptors. Two carbazole-based macrocyclic probes, PBG (flexible benzene ring

• demonstrated that flexible PBG achieves superior I− binding (KPBG = 1.387 × 105 M−1) through induced-fit conformational adjustments, whereas rigid WDG (KWDG = 6.089 × 103 M−1) is constrained by preorganized cavity geometry, adhering to a conformational selection mechanism. This work elucidates the synergistic

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• reported in 2014 the first examples of rotaxanes with a dithienylethene switch on the axle [57]. They synthesized [3]- and [5]rotaxanes with a symmetric axle containing a dithienylethene in the center and alkylammonium binding sites on each side, which interact with N-hetero crown ether macrocycles

• fluorescence quenching phenomena with aggregate-induced emission (AIE) in aqueous media. They synthesized a [2]rotaxane with one dithienylethene unit as a stopper, and one BAA and one urea binding site, as well as one DB24C8 macrocycle with a tetraphenylethene (TPE) fluorophore [16] (Figure 7). Addition of

• incorporation of functional hydrazone photoswitches into rotaxanes began more recently with Leigh. Thus, these photoswitches are underexplored in MIMs. Specifically, Leigh and co-workers synthesized [2]rotaxanes in which a pyridyl-acyl hydrazone moiety functioned as both photo- and thermal-switchable binding

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• cucurbit[n]uril (CB[n]) molecular containers [21][22]. Macrocyclic CB[n] display ultratight binding toward hydrophobic cations in water which renders them an attractive new class of sequestrants [23][24][25][26]. For example, Buschmann and Jekel demonstrated the use of CB[6] (Figure 1) for the removal of

• have studied water-soluble acyclic CB[n] based on methylene-bridged glycoluril monomer–tetramer and found that glycoluril tetramer-derived hosts displayed the highest binding affinity toward hydrophobic alicyclic dications due to enhanced ion–dipole interactions [40][41]. Separately, we studied

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• , examination of the structure of CLK3 shows that this key lysine 241 is very close to the entry of the ATP binding site (Figure 1B). Lysine 241 could be considered as an opportunity to design new molecules with an improved affinity to CLK3, by adding specific interactions with this amino acid bearing a primary

• linker between the core of the inhibitor and the acidic function. The acid could be placed in meta or para positions taking into account the flexible backbone of lysine 241 (Figure 3). Further, in case the binding of these new targets would require a little more flexibility around the basic skeleton, we

• ). Second, molecular docking using DYRK1A crystal structure was used to understand the unexpected binding on the DYRK kinases (Figure 6). Surprisingly, another lysine (K175) is also located near the acidic group of VS-77 (at 3.2 Å between the carbonyl carbon atom and nitrogen from amine). This residue is

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• . Such compounds can intercalate into nucleic acids, primarily through π–π stacking interactions with nitrogenous bases. The introduction of side chains with terminal amino groups enhances binding to oligonucleotides via additional ionic interactions and hydrogen bonds. The indolo[1,2-c]quinazolin-6(5H

• (Figure S1 in Supporting Information File 1). The interaction of compounds 7a–c with duplex DNA was then investigated by fluorescence titration, measuring the quenching of ligand fluorescence upon binding to the nucleic acid. Fluorimetric titration studies confirmed the interaction of 7a–c with double

• ionic strength of the solution to 20 mM Tris buffer significantly enhanced DNA binding (Figure S2 in Supporting Information File 1). Notably, the spectral characteristics of the compounds remained virtually unchanged upon DNA binding. Scatchard plot analysis of the binding isotherms revealed a binding

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• , the significant suppression or disappearance of the HSA oxidation peak upon addition of glycidyl esters 1–3 can be interpreted as evidence of covalent modification (alkylating) of nucleophilic sites on HSA, rather than non-specific binding or merely non-reactive association [27][28][29]. The observed

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• by increasing the binding affinity for the lipophilic reactants and by decreasing the energy required to desolvate acid/base amino acid catalysts [34][35]. Lipophilicity has also been found to be beneficial in condensation reactions as the removed water molecules are repelled by the hydrophobic

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• the protein-binding site than the bent Z-isomer. However, it would be more desirable to have an inactive molecule in its most stable state which can be activated by irradiation [51][59]. Hernando and co-workers were able to design photoswitchable neurotransmitters of ionotropic kainate receptors by

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• , stimulus responsiveness, specific recognition and binding, and multi-target synergistic action [14][15][16]. These characteristics enable precise control of drug release and targeted drug delivery, thereby improving drug stability and bioavailability, and reducing drug toxicity and side effects

• in pH, light, and enzyme activity, the binding affinity between the guest and host molecules can be altered, thereby achieving controlled drug release and targeted delivery. (2) Drugs are loaded into self-assembled host–guest systems [29][30][31][32]. The chemical structure or properties of the host

• of supramolecular interactions [33][34]. Different external stimuli, including pH changes, enzymes, light irradiation, hypoxia, and multi-stimuli responses, can alter the supramolecular structure or binding affinity to activate the opening and closing of the nano-valves. In addition to the three

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• ) [41][42][43] have been used for attaching the crown ether macrocycle, although this strategy has the advantage that the 2,2'-hydroxy groups remain intact and can be used for further binding or functionalization. Our group recently became interested in synthesizing BINOL derivatives featuring

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• exhibits activity against multidrug-resistant Streptococci and Staphylococci including S. aureus via a unique mechanism involving binding to an exclusive site on the bacterial ribosome [10][59]. Accordingly, the β-anomeric configuration in the 3-O-p-methoxybenzyl-protected mannose lactol 31 was fixed by