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

• for their anion chelation capability achieved through the formation of hydrogen bonds with the pyrrolic units [19][20][21][22]. Subsequent studies have demonstrated that the introduction of additional chelation sites via extension of the phenolic groups of PCP can yield anionic receptors, ditopic

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

• . In aprotic media, these compounds, referred to as ‘tetraureacalix[4]arenes’, assemble into well-defined homo- or heterodimeric capsules, which are held together by cyclic belts of hydrogen bonds between interpenetrated urea groups from two molecules and are able to include a single neutral molecule

• pairs of distal triazole groups, and C4v-symmetric tetraureas 47 and 50. Due to the phenomenon of supramolecular chirality caused by the direction of hydrogen bonds in the capsules [100], tetraureacalixarenes of the first type should form two regioisomeric homodimers possessing C1-symmetry or a single

• present in a ratio of ≈1:1. The ratio of the isomers cannot be easily obtained from the spectrum except by analyzing the group of the most downfield-shifted signals corresponding to the half of the urea NHs involved in hydrogen bonds. According to the symmetry features discussed above, this group of

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

• regulation of the cell life cycle [8]. On the contrary, oxazolo[4,5-d]pyrimidines represent a poorly studied class of compounds because of limited access to this scaffold [9]. An in silico study showed that both isomeric forms of oxazolopyrimidines can form stable complexes due to hydrogen bonds between a

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

• (Figure 2). Both compounds crystallize as racemates, Figure 3 displaying their unit cell fragments. In 4b, the two enantiomers are connected through weak hydrogen bonds (N–H···O 2.612 Å) between the barbiturate rings. In contrast, compound 4c exhibits classical hydrogen bonding (N–H···O 1.878 Å) linking

• contacts: the barbiturate ring forms hydrogen bonds with water molecules through C=O···H–O and N–H···O–H interactions; the amide group of the barbiturate ring is engaged in a C=O···H–N hydrogen bond with the carbonyl oxygen of the maleimide fragment; additionally, a C=O···H–CH2 contact is observed between

• ), including O···H–N hydrogen bonds between barbiturate rings and O···H–Ph contacts involving maleimide carbonyl oxygens and phenyl ring hydrogens. The crystal structure of adduct 4c includes a molecule of dichloromethane. Due to the disorder of the dichloromethane molecule, the exact distances of the

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

• , the NH₂ group forms a hydrogen bond with ASP183, and the carboxylate interacts with ASN130 (Figure 3), with additional hydrogen bonds to water molecules. Consequently, intermolecular interactions dominate and override the intramolecular forces responsible for the gauche effect in the isolated molecule

• . This is consistent with the relative strength of hydrogen bonds (5–40 kcal mol−1) compared with typical hyperconjugative interactions [20]. Finally, because neutral amino acids dominate in the gas phase whereas zwitterions prevail in solution [21][22][23][24], the zwitterionic form of DFMO was examined

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• solid form Crystals of 1·HCl were grown from an ethanolic solution, and the crystal structure was determined by single-crystal X-ray diffraction (SCXRD, Figure 2). As seen in Figure 2a, 1·HCl adopts a twisted U shape and is involved in three hydrogen bonds. Therein, the ammonium N atom interacts with

• two different chloride ions, and the phenol OH moiety interacts with another chloride ion. The triclinic crystal packing (Figure 2b) reveals alternating layers, a polar layer with the observed hydrogen bonds, and a hydrophobic layer with van-der-Waals interactions and π–π-stacking (distance 4 Å

• , oxygen atoms red, and chloride ion green. b) The crystal packing reveals alternating layers, a polar layer with hydrogen bonds (black dashed lines), and a hydrophobic layer with π–π-stacking (grey dashed lines). SCXRD and XRPD spectra of different preparations of 1·HCl. Blue: SCXRD spectrum of 1·HCl. Red

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• led to the use of multifunctional catalysts of “homocooperativity,” where multiple units of the same catalyst perform different but complementary roles [17]. These catalysts employing noncovalent interactions via hydrogen bonds and also possess Lewis basic and π–π-interaction sites have been highly

• Mannich reaction between a 2-sulfonylpyridine protected imine and a malonate (Scheme 1). The pyridine-containing protecting group was chosen considering our catalyst design. We envisioned that halogen bond (XB) will complement hydrogen bonds to activate an imine towards the nucleophilic attack of the

• strengthened via hydrogen-bond-assisted halogen bonding [26][30]. Similarly, hydrogen bonds with the amidic proton are also possible. The direct effect of a specific interaction could not be determined based on the obtained data. The network of noncovalent interactions formed stabilizes the complex between the

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• independent molecules. Note that crystals 2, 3, 9a and 9b have a relatively high density (dcalc/g cm−3 1.739, 1.748, 1.595 and 1.567) for crystals that do not contain heavy atoms. In the absence of hydrogen bonds in the crystals of 2, 3, 9a and 9b, multiple specific interactions of the types such as lone

• (electron) pair – the π-system of the nitro group, and bonds of the Cl···O, Cl···N, C–H···X (X = Cl, O, N) are realized, which are shown in Figures S47–S57 in Supporting Information File 1. The energy of such interactions can be comparable with the energy of “classical” hydrogen bonds [47]. Conclusion In

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• the OH group. The crystal packing of single crystals 4att, 4atc, 4acc, 4act, 4dct is ordered by intermolecular hydrogen bonds linking O–H groups and heteroatoms O/N of neighboring molecules (see Table S8 in Supporting Information File 1); N–H groups of the hexahydropyrimidine ring and a carbonyl

• hexahydrooxazolopyridone 5ctt is ordered by intermolecular hydrogen bonds of the NH2 group with the hydroxy and carbonyl functions of two other molecules (Figure 3b). The OH substituent of the piperidone ring is in the trans-configuration relative to O(4) atom. In the oxazolidine ring, the CH2NH2 group occupies a pseudo

• -equatorial position and is in the trans-position toward the Bu group. The single crystal structure of the bicycle 5ctc is ordered by intermolecular hydrogen bonds between the hydroxy group and the amino group as well as between the amino group and fluorine of the CF3 substituent of the neighboring molecule

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• interactions are observed in both compounds forming dimer-like structures. The compounds show hydrogen bonds between N1–H1···O1’ with a distance of 2.06 Å in 3n (Figure 4b) and 1.98 Å in 4n (Figure S250b in Supporting Information File 1). The anomaly observed in the NMR spectra may be attributed to

• : a) 1H NMR spectra (600 MHz, DMSO-d6) with expansions, and b) 13C NMR spectra (151 MHz, DMSO-d6) with expansions. a) Molecular structure of 3n with crystallographic labeling (50% probability displacement). b) Perspective views of intermolecular hydrogen bonds (dotted lines) of 3n. (‘) symmetry

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• stability of intramolecular hydrogen bonds in the peptide backbone, thereby promoting the formation of stable secondary structures (such as α-helices or β-sheets) in cyclic peptides. Spectra acquired in H2O, 0.01×PBS, and 30% TFE (Table S1, Supporting Information File 1) demonstrate: (i) definitive β-sheet

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

• and ultimately forming Hoogsteen hydrogen bonds with adenosine. Three new monomers were prepared and incorporated into PNAs that were screened against matched RNA hairpins using UV thermal melting and isothermal titration calorimetry experiments. Two of the three PNA oligonucleotides that contained

• 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

• PNA oligomer with the N-(2-aminoethyl)glycine backbone (in red); (b) Representative monocyclic synthetic nucleobase triples through Hoogsteen hydrogen bonding (blue dashed lines). Watson–Crick hydrogen bonds are in red (dashed lines). Representative extended nucleobase triples through Hoogsteen

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

• form selective hydrogen bonds between the carbonyl oxygen of the fumaramide unit and the N–H groups of benzylic amide rings. Upon isomerization to the cis isomer, the hydrogen-bonding interactions are weakened, enabling the macrocycle to migrate to a second recognition station [61]. Despite their

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

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• [46] (“High-energy, stable and recycled molecular solar thermal storage materials using AZO/graphene hybrids by optimizing hydrogen bonds” by W. Luo et al., Nanoscale, vol. 7, © 2015); permission conveyed through Copyright Clearance Center, Inc. This content is not subject to CC BY 4.0. Conjugated

• azobenzene polymer solar thermal fuels: (a) Photoisomerization and thermally induced reverse isomerization of diacetylene monomers. The inset depicts the crystal structure of diacetylene monomer (n = 6, X = N–H) with dashed lines indicating intermolecular hydrogen bonds. Figure 4a was used with permission of

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 time within 50% of the metastable isomer is thermally converted to the stable one [3]. It depends on the photoswitch class, solvent, substitution pattern, and temperature. For some photoswitch classes, proton exchange and intramolecular hydrogen bonds are known to accelerate the thermal relaxation

• weaken the hydrogen bonds between N–H and the ester moieties of the rotor and the stator. The Cigáň group focused on the synthesis of benzoylpyridine hydrazones with different substitutions in the rotor benzene [97]. The p-NMe2 group causes red-shift of both absorption maxima of the E- and Z-isomer

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• electrostatically complementary negative and positive faces. These interactions are mediated through electrostatic hydrogen bonds. This "Janus-like" polarity also facilitates interactions with ions, particularly sodium and chloride. These findings contribute valuable insights for the rational design of drugs and

• and side views of two 1.2.3-c.c. molecules interacting, with an H···F distance of 2.70 Å. (c) QTAIM plot illustrating bond paths between hydrogen and fluorine atoms, indicative of electrostatic hydrogen bonds. Calculated complexes of 1.2.3-c.c. with Na+ (top) and Cl− (bottom). Standard Gibbs free

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• -phenylene and aza[5]helicene segments, and between the o-phenylene and thiophene segments, were 37.52° and 44.28°, respectively. Four NH sites of the aza[5]helicene moiety formed hydrogen bonds with DMSO molecules in the crystal lattice, as observed in aza[n]helicenes recently reported [28], while the other

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• by the same research group [65][66], the Ir catalyst initially interacts through hydrogen bonds with the quinolone substrate 84, and then upon irradiation, energy transfer occurs to the unbound ketone which enantioselectively reacts with the bound quinolone. Unfortunately, investigations of the

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• dicarboxylate C72− is included within the cavity of B4aH. The two subcavities interact synergistically with the included dicarboxylate; the two terminal carboxylate groups are respectively positioned within electron-deficient cavities of the submacrocycles, forming hydrogen bonds (2.49–2.59 Å) with the two

• ) Crystal structure of B4aH (hydrogen atoms are omitted for clarity), and (c) the stacking structure of the crystal of B4aH (the blue dotted lines represent hydrogen bonds). (a) The structures of host and guests, (b) 1H NMR spectra (298 K, 400 MHz, CD3CN) of B4aH upon titration with C62− (c(B4aH) = 1 mM

• ), (c) chemical shift changes of Ha versus titration equivalents c(dicarboxylate)/c(B4aH), and (d) association constants of host and guests. (a–c) DFT-optimized structure of the B4aH-C72− complex. The blue dotted lines represent hydrogen bonds and the black dotted lines represent anion–π interactions

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

• highly efficient Cs3PO4 extraction. Results and Discussion The tripodal hexaurea receptor L is comprised of a central tren (tris(2-aminoethyl)amine) core and three arms of ortho-phenylene bis(urea) units, which can fold inward to encapsulate an anion inside the cavity through up to 12 hydrogen bonds [30

• %). The cooperative interaction of complexed Cs+ with complexed phosphate is illustrated in single crystal structure (Figure 5). Like other anions, phosphate is also complexed inside the cavity of hexaurea receptor through twelve hydrogen bonds. The average N···O distance is 2.79 ± 0.03 Å, corresponding

• ion-dipole and ion-pairing are shown. Single crystal structure of complexed Cs2SO4 with 18-crown-6 and tripodal receptor L (CCDC: 2411573). One sulfate anion is encapsulated inside the hexaurea cavity through 12 × N–H···O hydrogen bonds. One Cs+ cation is co-stabilized by electrostatic interactions

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

• well as ADMET properties. All compounds satisfied these criteria, indicating favorable oral bioavailability. Molecular docking analysis showed that compounds 5a–e act as ligands for inducible nitric oxide synthase (iNOS), especially with Cys200 and Ser242 via hydrogen bonds. In addition, van der Waals

• π–π stacking is observed in the crystal packing of the complexes, but only C–H···π interactions are present. Two C–H···O hydrogen bonds complete the interactions stabilizing the crystal packing (Figure S1 and Table S2 in Supporting Information File 1). Inhibitory activity of NO production It is

• affinity, with a docking score of −9.51 kcal/mol, outperforming the reference compound dexamethasone (iNOS–DEX, −8.55 kcal/mol). Key hydrogen bonds with residues Cys200 and Ser242, together with extensive van der Waals interactions involving Thr190, Trp194, Gly202, Pro350, Phe369, and Tyr489, further

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

• of hydrogen bonds (cf. Supporting Information File 1, Figures S20 and S21 for 1 and Figures S23 and S24 for 2). Apparently, secondary interactions at the periphery of the FimH CRD, which can be exerted by the scaffold mannoside and the second antenna in 1 or 2, respectively, can be quite different

• with FimH (Supporting Information File 1, Figures S19–S21). In addition to the π–π interaction of the CRD-bound mannose-projecting antenna of the EE isomer with Tyr48, the complex is stabilized by hydrogen bonds of the scaffold mannoside to Tyr48 and in case of the glucose moiety to Thr51, Ile52, and

• Thr53. The high binding energy of the ZZ isomer, on the other hand, can be explained by additional hydrogen bonds of the scaffold mannoside to Asn138 and Ser139 (but not to Tyr48) and furthermore, the glucose moiety interacts with Arg92, Asn135, Asn138, and Asp140. The binding energies predicted for the

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• the double bond to the carbonyl in a relative re-si approach, generating intermediate I, which undergoes a tautomerization to recover the aromatic pyrazole ring. The increased yield observed in some cases with SQ-1 may be attributed to the formation of additional hydrogen bonds that enhance