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

• Raphael Bereiter Ronald Micura Institute of Organic Chemistry, Center for Molecular Biosciences, Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria 10.3762/bjoc.21.56 Abstract The fluorescent light-up aptamer (FLAP) Pepper can utilize fluorophores that are equipped

• and the new ones) for covalent attachment to the Pepper aptamer in vitro. Results and Discussion Background The fluorescent light-up aptamer Pepper binds a series of structurally related synthetic dyes that contain a stilbene core. The lead compound is (4-((2-hydroxyethyl)(methyl)amino)benzylidene

• usefulness of this type of bifunctional fluorescent ligands in RNA affinity purification has recently been demonstrated by our group [11]. Conclusion Covalent fluorescent light-up aptamers (coFLAPs) are opening new avenues for RNA imaging [11]. In this work, we describe robust synthetic routes for twelve HBC

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

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• ][11][12], luminophores in light-emitting devices [13][14][15], organic semiconductors [16][17][18], and even as aromatic superconductors [19]. Later, parent and chemically modified phenacenes were applied to active layers in high-performance organic field-effect transistors. Thus, the phenacene

• 18-crown-6 produced fluorine-containing diarylethene 8 as a mixture of E- and Z-isomers. Subsequently, the E/Z mixture of 8 was subjected to the Mallory photoreaction without separation. Thus, compound 8 was irradiated with fluorescent black-light lamps (300 nm, 6 × 16 W) in the presence of a

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• ) was carried out on aluminum plates coated with silica gel 60 F254 (Merck, Darmstadt, Germany). The TLC plates were analyzed using UV light at 254 nm. Flash chromatography was performed on silica gel 60 M from Macherey-Nagel (grain size of 40−63 μm). The conditions are given in the form “(A/B = a:b

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

• proteins. By harnessing light to drive chemical transformations, photoredox techniques can facilitate the synthesis of antibody bioconjugates. This perspective will discuss the drive to develop and empower photoredox methods applied to antibody functionalization. Keywords: antibodies; bioconjugation

• selective chemical reactions, often for bioconjugation, by utilizing photoaffinity reagents. These reagents are typically photoreactive molecules that can be activated by light to form covalent bonds with nearby molecules [31][32][33]. PAL involves using a light-activated group (often a photo-crosslinker

• ) that can form covalent bonds when exposed to UV or visible light. These photoaffinity tags or crosslinkers are designed to bind to specific biomolecules, such as proteins, nucleic acids, or lipids, in a highly selective manner. The light irradiation triggers a chemical reaction, such as a bond

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• emitters for organic light emitting diodes (OLEDs) [4][5][6][7][8]. More recently, an increased interest in the studies of triplet–triplet annihilation mechanisms in anthracene emitter materials [9] and the design of efficient OLED emitters based on hyperfluorescence [10][11], which could exhibit high

• efficiencies in OLED performance, since lower applied voltages will be required. It has been shown that a desired applied voltage should be below 10 V to obtain significant light intensity from ANTH-based OLEDs [8]. Such low operating voltage may reduce power consumption and increase the lifetime of a blue

• achieved due to chemical modification of ANTH [25][32]. Changes in the UV–vis spectra were typically used as an indication of the compounds’ decomposition. It is well established that ANTH is rapidly oxidized to form anthraquinone upon exposure to light in the presence of oxygen. Furthermore, endoperoxides

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

• E. M. Kosower in 1978. In this study, we report the topochemical cycloaddition of diethyl 2,6-dichloro-1,7-dioxo-1H,7H-pyrazolo[1,2-a]pyrazole-3,5-dicarboxylate (Cl2B), initiated by visible light. Crystal structure analysis confirmed that the reactive double bonds are parallel and coplanar, in line

• with the Schmidt criteria for topochemical cycloaddition. Additionally, two other bimane derivatives with different substitution patterns were synthesized and investigated. Our findings suggest that functionalizing bimanes to redshift their absorption maxima into the visible-light spectrum provides a

• crystal lattice and are often reversible, requiring either high-energy light or heat for initiation [6][7][8]. Notably, topochemical polymerizations align with the principles of green chemistry, as they are solvent-free and do not involve toxic reagents [9]. The highly ordered and uniform nature of

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

• subsequently activated with light at the site of illness with high spatiotemporal resolution. Thus, collateral damage in the surrounding healthy tissue can be avoided. In addition, the quantitative thermal back-isomerization from the active E to the inactive Z configuration prevents contamination and

• designing a photoswitchable drug is to place the switch at a position in the pharmacophore that allows switching of the biological effect by irradiation with light without greatly reducing the overall activity by unselective interference with the inhibitor–receptor interaction. This is a difficult task

• efficiency. In any case the light-induced geometry change via isomerization should selectively control the interaction between the inhibitor and the receptor [21]. Currently there is only one example reported in the literature for the incorporation of N-acetyl diazocines into biologically active molecules

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

• Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy 10.3762/bjoc.21.33 Abstract Photomechanochemistry, i.e., the merger of light energy and mechanical forces, is emerging as a new trend in organic synthesis, enabling unique reactivities of fleeting excited states under solvent

• -minimized conditions. Despite its transformative potential, the field faces significant technological challenges that must be addressed to unlock its full capabilities. In this Perspective, we analyze selected examples to showcase the available technologies to combine light and mechanical forces, including

• research. Keywords: light-mediated synthesis; mechanochemistry; photomechanochemistry; Introduction Light-mediated synthetic methodologies have significantly transformed contemporary organic chemistry by enabling a broad array of previously unattainable transformations [1]. In fact, the absorption of a

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

• chemistry [200]. “Switchable” metal-organic cages [212] use a stimulus like light to change ligand geometries. This often triggers disassembly since new geometries can lead to new thermodynamic minima, though where geometric changes are tolerated within the original structure the stimuli can trigger guest

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• have low to negligible inhibition potential but dialkylated ones have no inhibition potential at all for directed CAs (I, II, IX, and XII). From the low inhibiting compounds, 7b showed the highest inhibition potential with a minimum Ki value of 72.9 μM. In light of the above findings, these newly

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• data, they luminesce in DMSO solution when irradiated with light at wavelengths of 352 and 283 nm. Compounds 7a–f are capable of existing as lactim–lactam tautomers due to the presence of an amide fragment in their structure (Scheme 7). At the same time, the 1H and 13C NMR spectra of compounds 7a–f

• phase and visualized under UV light (λ 254 nm). X-ray structure determination X-ray diffraction studies of single crystals of compounds 5a, 5b, 6b, 6c, and 7a were carried out on a Bruker D8 QUEST diffractometer. The cell parameters and experimental data were obtained at 100 K (graphite monochromator

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

• Picardie Jules Verne UR 7378, 10 rue Baudelocque, 80000 Amiens, France Institute of Physics and Chemistry of Materials of Strasbourg (IPCMS), University of Strasbourg UMR 7504, 23 rue du Loess, BP 43, 67034 Strasbourg CEDEX 2, France 10.3762/bjoc.21.22 Abstract Red-light-activated photocatalysis has

• become a powerful approach for achieving sustainable chemical transformations, combining high efficiency with energy-saving, mild conditions. By harnessing the deeper penetration and selectivity of red and near-infrared light, this method minimizes the side reactions typical of higher-energy sources

• , making it particularly suited for large-scale applications. Recent advances highlight the unique advantages of both metal-based and metal-free catalysts under red-light irradiation, broadening the range of possible reactions, from selective oxidations to complex polymerizations. In biological contexts

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• Molecular photoswitches have been studied for a long time because their physicochemical properties such as refractive index [1][2], dipole moment [3][4], conductivity [5][6], magnetism [7][8], and fluorescence [9][10][11] can be spatiotemporally modulated by light without physical contact. Therefore

• -withdrawing substituents on the N-aryl moieties enhanced the thermal stability of the Z-isomers while maintaining the advantageous photoswitching properties upon irradiation with red light [52]. The effect of substituents on the thermal cis–trans isomerization of azobenzenes has also been widely studied, and

• Information File 1. The photochromic properties of N3, N4, and I1–I4 were investigated in n-hexane. Figure 1a,b and Figure S1 in Supporting Information File 1 show the absorption spectral changes of N3, N4, and I1–I4 in n-hexane upon UV light irradiation. Compounds N3(o), N4(o), and I1(o)–I4(o) have

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• , Palestine 10.3762/bjoc.21.15 Abstract An efficient and eco-friendly approach for synthesizing difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles was established via a visible-light-promoted radical cyclization reaction. This method employed the readily accessible and inexpensive

• target products in good to excellent yields. Mechanistic studies revealed that the reaction proceeds via a radical pathway. Keywords: cyclization; difluoromethylation; hypervalent iodine; polycyclic imidazole; visible light; Introduction Organofluorine compounds continue to play important roles in

• reaction of unactivated alkenes within benzimidazole molecules using CF2HSO2Na [18]. Subsequently, in 2024, Jin [19] and Yang [20] developed visible light-induced difluoromethylation strategies for unactivated alkenes within benzimidazoles using different CF2H sources (CF2HSO2Na and ([Ph3PCF2H]+Br

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

• degassed solvent and light-shielding flask, the oxidative conversion of 12 to the imidate 18 proceeded smoothly. Notably, the transient intermediate 18, exhibiting a sky-blue fluorescence, further underwent a ring opening to afford the tetracyclic 14 with the simultaneous regeneration of both a nitrile and

• , excited at 375 nm): 0.07 (c = 10 μM). Emission image was captured under UV light (365 nm, c = 100 μM in CHCl3). Strategies for the construction of the pentacyclic core scaffold of saframycin A (1). (a) Biosynthetic machinery catalyzed by an NRPS module SfmC. (b) Total syntheses utilizing the Pictet

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

• , when G2 and zinc salt were mixed together in a 1:1 molar ratio, results from dynamic light scattering experiments showed that the average hydrodynamic diameter (Dh) was 524 nm, and no particles of discernible size were observed for a mixture of the macrocycle H1 and G2, or H1 and the salt, whereas with

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• products and drugs has proven to be useful in these reactions. As shown in Figure 7, the photocatalyst sodium anthraquinone-2,7-disulfonate (AQDS) is excited by 395 nm light to form AQDS* and undergoes electron transfer with arylalkanes 20 to generate an ion-radical pair (AQDS•−, 20•+). This ion radical

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• and sulfur dioxide afforded vinyl sulfones with excellent regio- and stereoselectivity (Scheme 9) [22]. The authors used DABCO(SO2)2 to generate sulfur dioxide, and visible light irradiation and the mandatory presence of a photocatalyst for this transformation suggested a radical mechanism. The

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

• astounding enantioselectivities. Both, light and organocatalyst proved crucial for the reaction. The photochemical aspect isomerizes the double bond to (Z)-configuration, and CPA stabilizes the structure whilst mediating the cyclization. The wavelength of 405 nm was chosen so that only the starting material

• , not the organocatalyst nor the product being formed, effectively absorb the light. An atroposelective C–H amination was done with the help of SPINOL-derived chiral phosphoric acids C51, C40, and C42 (Scheme 66) [96]. It was a reaction of naphthalenyldiazene carboxylates 222 with derivatives of

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• broadening their potential applications in drug delivery and nanotechnology. Our findings shed light on the unique capabilities of polysarcosine-based polymers, paving the way for further exploration and harnessing of their distinctive properties in biomedical research. Keywords: biodegradable; poly(benzyl

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• with feedback DOE facilitated the rapid identification of appropriate solvents. Notably, the use of DMSO, DMF, and pyridine led to an enhanced yield of the monoalkylated product. An experimental setup was developed for single-droplet studies of visible-light photoredox catalysis using an oscillatory

• light [40]. The design allows the screening to be more material- and time-efficient in the optimization of both continuous variables (e.g., temperature and residence time) and discrete variables (e.g., catalyst, base). Pieber et al. [46] reported the application of a segmental flow reactor for

• . Photochemical reactions require uniform light penetration of the reaction mixture, and flow setups with uniform path lengths would be ideal for such reactions. A self-optimizing continuous-flow reactor was designed by Poscharny et al. [59] for [2 + 2]-cycloaddition reactions promoted by light. The optimization

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• the colorless crystal, two of these [5]helicenoid moieties display P and M helix structures respectively, whereas the third moiety (colored in light blue) adopts a structure with approximate plane symmetry, recognized as a transition state for the enantiomerization of helicenes. The central benzene

• to Cs-1 (4.37 eV) as calculated at the B3LYP/6-311++G(d,p) level of DFT. The reduced HOMO–LUMO gap of C2-1 can be attributed to the greater conjugation in the essentially flat dibenzotropone moiety. This finding aligns with the fact that the yellow crystal of C2-1 absorbs light of a longer wavelength

• represent the helicity of the three [5]helicenoid moieties. The geometry of 3 deviates from ideal C2 symmetry, as the light blue moiety of 3 (top view in Figure 3) is shaped like a saddle. However, the 1H NMR spectrum of 3 shows only 12 different signals in the aromatic region, indicating a two-fold

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• phosphine oxide (PO) groups have recently received considerable attention for their high thermal stability and unique optoelectronic features, and thus being widely applied in organic light-emitting diodes (OLEDs) [1][2]. To date, tremendous efforts have been devoted to the development of a variety of high

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• fluorescent chemosensors and probes [4][5][6], as well as materials for applications in organic light-emitting diodes (OLEDs) [7][8][9], organic field-effect transistors (OFETs) [10], and perovskite solar cells [11]. In this respect, replacing either one or more of the carbons or rings of a fluoranthene with