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

• the three bases. Given that the Db2 linker is the same as that for V, it is not surprising to observe that binding for C–G was slightly higher than that of U–A and we propose that the binding of the Db2 linker with C may mimic the binding of V [33] and other synthetic nucleobases with linkers derived

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

• reversible deformation upon irradiation with UV or visible light, which triggers the isomerization of the azobenzene moiety, leading to structural changes in the rotaxane linkers. Notably, the dry state of the material, when uniaxially stretched, shows an enhanced response compared to its hydrogel form

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

• functionalized MOFs to the Knoevenagel condensation reaction. A well-defined MOF material composed of both amine- and hydroxy-bearing linkers was reacted with a series of aliphatic isocyanates (isopropyl, tert-butyl, n-hexyl, and tetradecyl) and, incongruously, was found to preferentially react at the hydroxy

• -workers. In two separate reports, they synthesized well-defined MOFs composed of three different linkers: a proline-functionalized linker acted as the catalytic unit, while two auxiliary linkers were varied to alter catalyst activity and enantioselectivity [24], or product selectivity [25]. In those works

• , the researchers tailored their catalyst via de novo solvothermal synthesis of their MOFs using differently substituted auxiliary linkers; a non-trivial effort which involves the synthesis of several new organic linkers and their subsequent assembly into completely new frameworks (Figure 1A). In this

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

• macrocyclic crown ethers that are attached at the 3,3'-positions via additional phenylene spacers (see Figure 1e) [35][44][45]. Macrocycles M1b with a single BINOL unit were generated from the corresponding diol 2 by attachment of allylated linkers, followed by ring-closing metathesis [46][47][48][49][50

• syntheses were the best-yielding approach towards the desired macrocycles. This route was then applied for the synthesis of macrocycles featuring one or two BINOL units, featuring differently substituted phenylene linkers and featuring ethylene glycol linkers of different lengths. Results and Discussion

• , because in initial experiments, we obtained consistently higher yields and fewer side-products in comparison to other bases (such as NEt3 or K2CO3), as reported in the literature for related macrocyclizations [53][54][55]. We then investigated the impact of different substituents on the phenylene linkers

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• "formal" or "true" azulene subunits. However, one of the key objectives here is to highlight the differences between these structural types and provide a clear distinction between benzenoid structures with azulene-like linkers and molecules that can be considered “true” aromatic π-extended azulenes. This

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

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

• like glycoclusters 1 and 2 are capable of many conformational alternatives and therefore, the control of molecular shape by photoisomerization of azobenzene linkers has its limitations. In addition, water solubility requires improvement. Furthermore, our study, combining synthesis, analysis of

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

• ], therapeutic index, selectivity, and overall success of the ADC. The linker will ideally be stable in plasma for an extended period before the intended target can be reached, and after internalization, linkers play a key role in the drug-releasing event. Importantly, some exceptions exist. For example, in

• attractive for industrial applications, where both scalability and robustness are essential. Beyond its practical advantages, the method offers notable versatility, enabling the conjugation of a wide range of aryl linkers to Cys residues. This flexibility is crucial for the development of ADCs, where precise

• chemoselectivity should extend to any molecularly complex linkers and/or payloads being conjugated to the mAbs, allowing highly efficient entry to ADCs. DAR control A noteworthy characteristic of photochemical transformations is the ability to unambiguously start and stop reactions instantaneously using light on

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• accumulation in the environment after excretion [1][6][7]. These superior properties of diazocines have been exploited in several applications such as the control of protein folding by implementation as cross-linkers between protein side chains [8] or in peptide backbones [9], as photoswitchable

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

• formation possible in metal–ligand bonding provides chemists with a shortcut to access 3D scaffolds. When well-designed linkers and metals are combined, discrete cages emerge as the thermodynamic product (Figure 5A) [22][142][143][144]. Typically, rigid linkers are required to enforce geometry, although a

• can incorporate greater bond strain, and therefore the linkers themselves can contribute to cavity shape and symmetry outcomes. For instance, in our cages [38][39][40][41], due to the preference for N-phenylbenzamides to be planar, each amide group can be arranged in two metastable orientations: amide

• using the tools of self-assembly. Mathematical and computational models should accelerate the discovery of stable low-symmetry structures by identifying ligands or linkers featuring mutually reinforcing symmetry-breaking functionality [205]. Robust organic cages are also likely to offer advantages for

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• denotes the number of individual [1.1.1]bicyclopentane (BCP) linkers – are often observed and swiftly devalorized as side-products [1]. However, targeted synthesis of functionalized [n]staffanes as rigid "molecular spacers" as proposed by Kaszynski and Michl [2][3][4] could facilitate new developments in

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• quadricyclane signals, so that the quantitative analysis of the photostationary state was not possible with NMR spectroscopy. These observations are surprising, since the 3-acceptor-substituted derivatives and the ones without acetylene linkers have been reported to be converted quantitatively into their

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• discuss the properties and applications of different chemical proteomics linkers with special focus on their fragmentation releasing diagnostic ions and how these may improve the confidence in identified active compound–peptide conjugates. The application of advanced search options improves the

• comprehensively in several reviews [45][46][47][48]. Applications of cleavable linkers, which might be considered as pioneers of MS fragmentation-based platforms to search peptide-linker remainders, were reviewed thoroughly as well [49][50][51]. Recent advances in mass spectrometers technology and analysis

• pipelines enable to obtain more information from already established workflows, because they are becoming practically feasible only now. These will be discussed further in this review. We primarily focus on the linkers utilized for enrichment and identification of the probe–protein conjugates resembling

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• influence of various linkers of cinchona squaramide organocatalysts immobilised on a poly(glycidyl methacrylate) (PGMA) solid support [127]. The support consisted of well-defined monodispersed PGMA microspheres, which were prepared through thorough parameter optimisation. Three amine-functionalised cinchona

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• molecular cages [46][47] and at porous materials, as linkers in metal-organic frameworks (MOFs) [48], used in the evaluation of the cycloaddition of CO2 to epoxides [49] and CO2 uptake [50]. Taking in consideration the strategy of the incorporation of dopants to promote the proton conduction in Nafion

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• , extended Bemis–Murcko scaffolds were generated by cutting off the side chains of the molecules and retaining ring systems and linkers between them. After removal of duplicates, Tanimoto similarity coefficients were calculated for each pair of the molecules in the compared databases (T = 1 and 0 for similar

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• reversibility of the other compounds, DAn with shorter alkyl linkers were also examined in THF solvent by UV–vis absorption spectroscopy, where they showed photochemical properties similar to those of DA11 (Figure 1a and Figure 1b). THF solutions of DA7 and DA6 showed a strong absorption band at 470–685 nm

• cellular compatibility was good. These DAn biocompatibility results are the first example showing the intrinsic cytocompatibility of macroscopic soft DA scaffolds. Conclusion Amphiphilic DASAs with alkyl linkers of different length connecting to a carboxylic acid were prepared. Photochemical properties of

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• systematically. Results and Discussion Triazenes have previously been established as versatile intermediates and linkers for conventional and solid-phase synthesis [22][23][24][25] that can be considered as protected diazonium salts [3]. According to the previous work [3], triazenylpyrazoles could serve as azide

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• π-stacking may also enable exploration of molecular assemblies. The experimental lone-pair electron densities were directed outward in 3a and could be used as linkers for metal atoms to assemble trigonal pyramidal macrocycles, for instance, in networks of metal organic frameworks [23][24

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• -dioxaoctane (21) and 1,13-diamino-4,7,10-trioxatridecane (22) in DMSO at 70 °C for 30 min to form amino-conjugates 23 and 24 in 71 and 84% yield, respectively, containing ethylene glycol linkers with terminal primary amino groups (Scheme 6). The presence of ethylene glycol residues in bioactive molecules is

• linkers capable to connect these porphyrins with biomolecules, thus improving their biomedical characteristics and theraputic efficacy for PDT and BNCT due to the combination of different substituents within porphyrin framework. Amide coupling of A3B-type carboranylporphyrin containing an amino

Possible bi-stable structures of pyrenebutanoic acid-linked protein molecules adsorbed on graphene: theoretical study

• Yasuhiro Oishi,
• Motoharu Kitatani and
• Koichi Kusakabe

Beilstein J. Org. Chem. 2024, 20, 570–577, doi:10.3762/bjoc.20.49

• ) linkers on graphene. The activation barrier between two bi-stable conformations exhibited by PASE is confirmed to be based on the steric hindrance effect between a hydrogen on the pyrene group and a hydrogen on the alkyl group of this molecule. Even after the protein is supplemented, this steric hindrance

• the steric hindrance effect between two hydrogen atoms in the molecule. A discussion on how the activation barrier between possible conformations of a protein immobilized on graphene by linkers appears is also provided. We consider the adsorption of the linker molecule forming a bond with a protein

• , the magnitude of the activation barrier is expected to be close to that in PASE. This is expected to be the case since a protein weakly bound to the carbon graphitic network can be supplemented onto graphene only by linkers as PASE, which has often been observed experimentally [1]. This type of

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• a variety of linkers with which these molecules are immobilized. In general, we observed two binding preferences that were strongly enriched among bound sequences, namely glycans containing Fucα1-2Gal epitopes and glycans containing terminal GalNAc residues (Figure 2c). Amongst the bound sequences

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• pyrrole unit to one of the dithiole rings of an IF-TTF, allowing for dimerization of extended TTFs via the nitrogen atom by different linkers [14]. Donor–acceptor chromophores can be obtained by replacing one of the dithiafulvene (DTF) rings of the IF-TTF by an electron acceptor. Cyclic and acyclic

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• ). Thanks to the symmetry of the axle and non-symmetry of the macrocycle the signals of the components could be easily distinguished by integrals. The aliphatic region is crowded with triplets corresponding to the ethyleneglycole and pentyl linkers. However, the difference in symmetry allowed the