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

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• groups play a role by increasing the number of hydrogen bonds (C–H···O, 3.18(5)–3.62(6) Å) The intermolecular distances between the C–H groups and the chlorine atoms in Cl2B (A) are C13A–H13···Cl1A, 3.69(5), and C18A–H18C···Cl2A, 3.69(3) Å, indicating further molecular attraction [22]. A previously

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• coordinative bonds on one side and hydrogen bonds on the other. Surprisingly, when the crystals were manually ground for 5 min before irradiation, the conversion to dimer 1.2 remarkably increased to 88% in only 4 h of UV irradiation time. Overall, the role of manual grinding was not only to increase the

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

• ]. Chemists thus turned toward scaffolds that were easier to access [36][111]. Self-assembled containers, capsules, nanoreactors In the 1990s, Rebek popularized “softball”/”tennis ball” reactors [112][113][114]. These “capsules” [115][116][117] are two or more molecules that self-assemble via hydrogen bonds

• the cage framework to polarize adjacent aryl–hydrogen bonds in the ligands by enough to coordinate and activate substrates (Figure 5E) [190]. Here, the use of bulky counteranions reinforces the cationic cage interior, which is enhanced further by use of lower polarity solvents, and the pKa of confined

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• region of the DNA double helix, leading to the formation of a reversible covalent bond [9][10][11][12]. In this process, the oxygen functional groups at the C8 and C18 positions of the core scaffold interact with the DNA bases through multipoint hydrogen bonds (HBs), allowing recognition of approximately

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

• aromatic amide macrocycles [36][37][38][39][40][41][42], a class of cyclic compounds comprising a number of aromatic residues with consecutive intramolecular hydrogen bonds and amide linkages, stand out as versatile host molecules as their cavity size, peripheral side chains, and recognition sites are

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• the azodicarboxylate as crucial to forming hydrogen bonds with the organocatalyst. Benzylation of this nitrogen or substitution of just one of the carboxylate groups led to no product being observed. A series of naphthylindoles 71 was tested for potential biological activity and showed promising

• with key hydrogen bonds between substrates, organocatalyst, and HFIP. Sheng et al. utilized the BINOL-derived organocatalyst C34 in the reaction of benzylindoles 148 and 2-indolylmethanols 149 leading to the bisindoles 150 (Scheme 44) [72]. Very good yields and good to high enantioselectivities were

• racemization process of 161 was observed at 70 °C, and the experimentally determined rotational barrier of 30.5 kcal/mol was observed at 100 °C in toluene. Control experiments gave insights into the potential importance of hydrogen bonds on the nitrogen atoms of the isoindolinone ring in 160 and one indole

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• , commonly referred to as sulfa drugs. These include top seller drugs, e.g., antimicrobials, anti-inflammatories, antihypertensives, and antitumor agents [24][25][26]. Particularly, the sulfonamide motif can act as a bioisostere of carboxylic acids, establishing a set of hydrogen bonds similar to those

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

• phenylalanine) indicate that they are not involved in hydrogen bonds. Furthermore, the 2D 1H-1H NOE NMR spectra and the chemical shifts of the NH protons of compounds 8f’, 8e, and 8e’ did not show any significant differences compared to 8f. Overall, the ability of the new fluorinated β-analogs of

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

• adopts a 1,3-alternate conformation and binds simultaneously to the epoxide O-atom and iodide anion via (NH···O and NH···I) hydrogen-bonding interactions. The TBA countercation is bound to the O-atom of the epoxide ring with hydrogen bonds and is situated away from the I− anion. This crucial transition

• ) via NH+···O2 hydrogen bonds initiated the ORR, whereas an increase in the HTB concentration inhibited the ORR by blocking NH+ binding sites for O2. Further, the role of the proton source on ORR was confirmed by testing a stronger acid, TFA: in this case, the O2 reduction rate is decreased to almost