Molecular tweezer–peptide conjugates disrupt the protein–protein interaction between survivin and histone H3 essential in mitosis

• Catherine Gsell,
• Philipp Rebmann,
• Karina Opara,
• Christine Beuck,
• Peter Bayer,
• David Bier,
• Ingrid R. Vetter and
• Thomas Schrader

Beilstein J. Org. Chem. 2026, 22, 557–567, doi:10.3762/bjoc.22.41

• by computational modeling (MD and QM/MM simulations) as well as structural biology (NMR/X-ray). Following our powerful concept of reinforcing natural peptide–protein interactions by tweezer conjugation [9][10], we envisaged to attach molecular tweezers to the histone H3 terminus at a distance which

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

• stoichiometric conjugation with suitable substrates. The small size of Au–NH2 minimizes steric hindrance and allows for enhanced spatial resolution, relative to colloidal nanogold particles, thereby facilitating high precision labeling of the HDAC active site. CI-994 was synthesized using previously established

• , and was stable for days stored at −20 °C (stability determined by 1H NMR, Figures S1–S4 in Supporting Information File 1). For the conjugation of 9 to Au–NH2, an excess of 9 was used to drive the conjugation reaction to completion. Unreacted 9 was then removed by repeated washing with water and buffer

• confirm that the conjugation of CI-994 to the nanogold particle did not significantly affect HDAC inhibition. The HDAC1-LSD1-CoREST complex, incorporating a FLAG tag in CoREST, was expressed and purified from HEK293F cells as previously reported [10]. Fluorescent deacetylase assays were carried out using

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• still observed in the measurement at 5 °C, albeit only slightly. The phenyl-substituent effect on the stereochemical stability can be understood as a destabilization of the ground state due to the transannular repulsion, and a stabilization of the transition state for racemization by a conjugation

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• , security inks, and information-storage materials, where both helicity and emission characteristics must be precisely controlled [23][24][25][26]. A central design element in helicene chemistry is helical extension. Increasing the number of ortho-fused rings amplifies π-conjugation, structural rigidity, and

• ]helicenes 5a and 5b in chloroform (1 × 10−5 M) were recorded and compared with those of the corresponding oxaza[7]helicenes 6a and 6b (Figure 4A and 4B). As expected, extension of the helical π-systems in 5 leads to enhanced conjugation relative to 6, manifested in red-shifted absorption and emission bands

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• substituents on the nitrogen (e.g., tosyl, carbamate, or acyl groups) distorts the planarity of the amide and diminishes amidic conjugation (Scheme 1b). These “twisted” amides exhibit a dramatically enhanced electrophilicity at the carbonyl carbon and a significantly weaker C–N bond strength [28][29][30][31

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

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

• emphasized heteroatom-driven reactions in which metal coordination enhances the natural polarization of the molecule, primarily by disrupting its aromaticity. For example, a π-base preferentially binds to the C(2) and C(3) positions of monosubstituted arenes, maintaining linear conjugation between the

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• the utility of the parent helicene in diverse areas, thereby offering a more versatile alternative to classical helicene extension strategies. Discussion Only a handful attempts have been made for the asymmetric synthesis of helical molecules using π conjugation extension [28][29][30]. This prevalent

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• ). The vinyl bridges were added to the design, which have the potential to open nucleophilic addition reactions (Michael type) due to their electron deficiencies, in addition to acting as π-bridges for the D–A conjugation. Furthermore, a symmetric design with increased π-conjugation was planned to shift

• cyanide to dyes, the absorption bands at longer wavelength, 550–700 nm, disappeared while shorter wavelength absorption maxima, 350-450 nm, showed a slight increment in absorbance. The disappearance of the ICT band indicates that the conjugation through the structure of dyes between the donor and acceptor

• and phenyl rings (C13–C21–C23–C24 and C11–C19–C33–C34) are (157.30, −157.30); (159.29, −159.29); 154.46, −156.48) for 2a–c, respectively, which is an indicator of large degrees of conjugation and good ICT. When CN− interacts with the 2a–c via the proposed addition mechanism (Scheme 2), the planarity

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

• behavior is not expected from hydrogen-bonded carbon atoms in aromatic rings. Since peak intensities depend on spin-lattice relaxation times, the absence of peaks implies some degree of molecular rigidity, which could be related to two factors: the viscosity of DMSO and the conjugation between the six

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• compounds. The utility of click chemistry [11][12] for achieving chemoselective conjugation in a diversity of chemical environments has established the 1,2,3-triazole ring as a ubiquitous heterocycle in many research areas such as therapeutics [13][14][15][16], chemosensors [17][18][19], bioconjugation [20

• shape differences by allowing such subunits to rotate out of coplanarity due to steric strain, diminishing conjugation between subunits. Formation of pentacyclic ring systems via annulation led to several expected spectroscopic signatures indicating the formation of an expanded aromatic π-system. 1H NMR

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• bond. Therefore, the π-electron conjugation is widespread almost over the chromophores. However, the UV spectrum of 1–ʟ-alaninol conjugate (S)-2a shows an intense absorption, maintaining the nature of methoxybiphenyl chromophore. The absorption band at 259 nm is attributed to the π–π* transition

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• 69 and lactone 70 at 456 nm with fac-Ir(ppy)3 as the photocatalyst furnished a mixture of isomeric olefins. Finally, DBU-promoted the isomeric olefins conjugation and removal of the two silyl ether completed the first total synthesis of (+)-randainin D (13). Total synthesis of (−)-hunterine A and

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• absorption maximum of MC1 is more redshifted by 42 nm compared to MC2, which is attributed to the extended conjugation after the fusion of one pyrene unit. Similarly, both MC1 and MC2 have higher ΦF values of 0.45 and 0.69 than compound MC3 (ΦF = 0.13). The optical energy bandgaps were determined to be 2.48

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

• to the strong electron conjugation, these compounds usually show much shorter thermal lifetime, alongside with strong bathochromic shifts [17][18][19][20][21][22][23][24][25][26]. They are useful when fast responsive T-type photoswitches are needed. Moreover, some compounds show interesting non

• ” conjugation (Figure 4B). The “complete” conjugation implies shorter lifetimes, due to the ability to rearrange the electrons more efficiently, thus showing a stronger push character. A follow-up study showed that di-ortho-fluorination (9c and 9d) and di-ortho-methoxylation (9e) of the phenyl moiety of 4

• lifetimes with great accuracy [7]. In summary, the more extended the conjugation of the heterocycle with the N=N bond, the more feasible the inversion mechanism (which does not involve the rupture of the double N=N bond). The less conjugated switches, however, would undergo rotation around the (instant

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

• cyclodextrins in terms of controllable functionalization [61]. In clinical applications, particularly for anticancer drug conjugation, CAs demonstrate remarkable cancer cell selectivity, minimized off-target effects, enhanced delivery efficiency, and reduced systemic toxicity. Additionally, their synthetic

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• imidazo[1,2-a]pyridine components. In reaction A, an hyperhomodesmotic equation [19] 2 + 3 → 4 + 1 was defined, in which the conjugation of the bicyclic imidazo[1,2-a]pyridine unit was removed, while preserving the ortho-disubstituted phenyl ring, highlighted in yellow in Scheme 1A. This reaction yielded

• considered: a total delocalized geometry denoted as 1a in Figure 3A, a peripheric conjugation 1b that excludes the participation of the lone pair of the central N atom and, finally, a two-component delocalization scheme denoted as 1c. The chief features of fully optimized structures of 1 at the ground state

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• photoluminescence (PL) spectra of (Sp)-6 and (Sp)-7 in diluted CHCl3 solutions (1.0 × 10−5 M) are depicted in Figure 1. The absorption bands are derived from the π–π* transitions of a phenylene–ethynylene conjugation system. The spectra of (Sp)-6 and (Sp)-7 are similar, and the absorption peak top of (Sp)-7 is red

• -shifted compared with that of (Sp)-6 because of the bent structure of the p-phenylene–ethynylene moieties in (Sp)-6 and extended π-conjugation of (Sp)-7. Such a red-shift of a UV–vis absorption spectrum has been observed in previously reported [2.2]paracyclophane-based cyclic oligomers [39]. CHCl3

• ). Molecular orbitals of (Sp)-6 and (Sp)-7 in their ground and excited states were calculated using DFT and TD-DFT calculations (Figures S20–S23, Supporting Information File 1). In both molecules, the orbitals were localized to part of the π-conjugation systems rather than the whole system in the ground and

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• driven by the enhanced electron-donating ability of the TPA units, but rather by the stabilization of the PTZ 1LE state, which is facilitated by planarization of the PTZ moiety in the excited state and the resulting increase in π-conjugation. This behavior led to the persistent presence of 1LE-state

• simple molecular framework, subtle intramolecular interactions – such as increased conjugation induced by planarization – can have a significant impact on the nature of photoinduced charge separation. Such molecules with finely tunable excited-state dynamics are expected to play an important role in the

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• 0.6 Å and 0.3–0.4 Å, respectively. This result indicates that protonation has a greater impact on the local minimum structures, as the p orbital of the nitrogen atom in the NMe₂ moiety and the C=N π orbital are located in the same plane, allowing for effective conjugation between them. The DFT study

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• greater involvement of the N1 electron pair in conjugation with the imide fragment of the dipolarophile and its deactivation in the reaction with nitrile oxide. This pattern is consistent with the one previously observed when studying the reactions of these dipolarophiles with nitrile imines [22]. It is

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• ]. Various figure-eight π-systems including aromatic hydrocarbons, belt-type extended π-systems, and porphyrinoids have been reported. The structural twisting in figure-eight macrocycles leads to cross-linked conjugation at the molecular center and a highly symmetric chiral structure with D2-symmetry

• optical HOMO–LUMO gap of 5 despite the presence of 26 sp2 carbons is due to the cross-conjugation at the exocyclic olefins. Mono-olefin 3 is virtually non-emissive, similarly to CBBC 1, which could originate from the non-radiative decay via intersystem crossing due to the carbonyl group. In sharp contrast

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• azahelicenes represent a particularly significant subclass due to their extended π-conjugation and potential for enhanced chiroptical properties. Over the past few years, multiple research groups have investigated their synthesis, structural characteristics, and optoelectronic behavior. Notably, in 2021, Jux

• and 17b, among which compound 17b exhibited red-shifted emission (538–632 nm in CHCl3) and the largest Stokes shift (192 nm), attributed to extended conjugation and sulfur incorporation [30] (Table 4). These findings collectively underscore how structural modulation and heteroatom doping can tailor

• = 2.1 × 10−2, and BCPL values up to 76 M−1 cm−1. Collectively, these investigations underscore the efficacy of heteroatom doping, extended π-conjugation, and radical design in advancing azahelicene-based systems. These approaches significantly enhance optical and chiroptical performance, paving the way

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

• –base reaction. Cyclization of alkynes: The extension of π-conjugation in polycyclic aromatic hydrocarbons (PAHs) through alkyne-benzannulation reactions has become an increasingly popular method in recent years [91]. Such benzannulations can be mediated by Brønsted acids, Lewis acids or transition

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

• electronic effects will cause the Cz-unit to twist out of conjugation almost completely with the TTM radical core plane, leading to marginal orbital overlap between the D0 and D1 states. The reason for this increase in fluorescence lifetime τ is not completely understood; however, if the emission involves a

• radicals are connected through the meta-positions of the central phenyl ring, Schlenk-Brauns (m-PTH) diradicals are obtained where no Kekulé-conjugation between the radical centers is possible (see Figure 13) [89]. While the para-coupled Thiele, Chichibabin, and Müller radicals can acquire a closed-shell

• quinodal electronic structure, diradicals with broken Kekulé-conjugation exhibit much stronger diradical character. In accordance with the above-described nomenclature, these diradicals are termed non-Kekulé diradicals. This tendency of diradicals to form a closed-shell electronic configuration can be