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

• the LE state of the PTZ moiety. In contrast, Pe-Ph–PTZ(TPA)2, in which the donor–acceptor distance is increased by a phenyl spacer, does not show clear equilibrium behavior. These results underscore the crucial role of excited-state structural relaxation in tuning photoinduced charge separation, and

• series of novel Pe–PTZ derivatives by incorporating electron-donating triphenylamine (TPA) units and phenyl spacers to systematically modulate the donor strength and the spatial distance between the donor and acceptor. Four compounds – Pe–PTZ, Pe–PTZ(TPA), Pe–PTZ(TPA)2, and Pe–Ph–PTZ(TPA)2 – were

• coupling in the ground state, consistent with the π-orthogonal molecular design. The introduction of electron-donating TPA groups raises the HOMO energy levels, while the LUMO levels remain relatively unaffected, thereby reducing the HOMO–LUMO gaps. The presence of phenyl spacers in Pe–Ph–PTZ(TPA)2 lowers

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

• 060-0812, Japan 10.3762/bjoc.21.120 Abstract pH-Responsive molecular switches and motors are a class of organic molecules whose three-dimensional structure can be changed by acid–base stimuli. To date, pH-responsive molecular switches have been developed using various functional groups, but further

• advances require expanding the range of pH-responsive systems and discovering new molecular architectures. Here, we investigate the pH-responsive behavior of ortho-disubstituted benzamidine, which generates atropisomers and E/Z isomers. The amidine moiety allows modulation of the C–N and C–N/C–C rotational

• barriers by protonation, providing a novel approach to control the kinetics of isomerization via pH adjustment. The results showed that protonation of the amidine moiety significantly suppresses both C–N bond rotation and C–N/C–C concerted rotation, demonstrating the potential of ortho-disubstituted

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• . Keywords: azobenzene; protonation; sensing; spectral changes; temperature; Introduction Molecular switches are molecules that can reversibly shift between distinct (meta)stable states in response to external stimuli such as light, pH changes, or electric fields [1]. Over the past decades, they have

• emerged as staple building blocks in smart materials, from light-responsive norbornadienes in molecular solar thermal energy storage [2] to pH-sensitive spiropyrans in cell imaging [3], and redox-active viologens in memory junctions [4]. Among the different molecular switches azobenzenes stand out due to

• spectral changes caused by azobenzene protonation is a well-established concept, with methyl orange-based pH indicators dating back to the late 1800s [22]. Early studies primarily focused on characterizing these spectral changes, determining pKa values, and elucidating the protonation mechanism of

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• contained thioaminals 9, which underwent a slow isomerization in CDCl3 solution. Notably, in the case of products 9k and 10k, bearing a Ph group at N(1), after a successful chromatographic separation, the less stable 9k underwent isomerization in CDCl3 solution (at rt) and no registration of NMR spectra of

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

• 6 exhibiting enhanced chiroptical performance and protonation-induced CPL amplification [19]. Meanwhile, Audisio’s team developed heterohelicenes via regioselective [3 + 2]-cycloadditions, with compound 7 displaying pH-responsive CPL sign inversion (|glum| = +1.1 × 10−3 at 430 nm, −1.2 × 10−3 at 585

• reported azabora[6]helicenes 45a and 45b [60]. However, their enantiomers could not be isolated due to low racemization barriers. The F- and Ph-coordinated derivatives displayed moderate PLQYs in solution (0.26 and 0.18, respectively), which dropped markedly in the solid state (0.02 and 0.04) owing to

• thia-bridged triarylamine[4]helicene-functionalized polynorbornenes 63a–c via ring-opening metathesis polymerization (ROMP), introducing helicene chirality into polymer backbones with tunable electrochromic behavior [78]. These polymers exhibit reversible pH-responsive color changes. For instance, 63a

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• donors in the phenyl ring, while N–NH is a donor, favored by acceptors in Ph [3][7][89]. Following this model, a suitable substitution in the Ph ring of 1 can stabilize or destabilized KE and KK in respect to E and K. This opens an additional channel for fulfilling the requirements for a clean switching

• for clean switching. Obviously, a cooperative effect between substitution in the Ph ring and the 7-OH quinoline part is needed. In Scheme 3 and Table 3 the most suitable examples for cooperative substitution are shown. It seems that the substitution with strong donor substituents in the phenyl ring

• characteristics of the ground-state tautomers of the studied compounds as well as relative energies of the transition states between them in toluene and in acetonitrile (in parentheses). Relative stability of the tautomers of compound 1 in toluene as a function of the substituents in Ph ring. Relative stability

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• glycerol, 2.5 g of corn steep solids, 5 g of peptone, 10 g of soluble starch, 2 g of yeast extract, 3 g of CaCO3 and 1 g of NaCl) medium at pH 7.0 in 250 mL Erlenmeyer flasks and cultured on an open shaker (160 rpm) at room temperature for 10 days. The corresponding blank media were also maintained under

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• .21.96 Abstract Aerobic copper(II)-mediated phosphorylation of enol acetates with H-phosphonates leading to the formation of β-ketophosphonates was discovered. The proposed method is applicable to a wide range of H-phosphonates or phosphine oxides as PH-reagents and enol acetates. Unlike previous reports

• produced by the oxidation of PH-reagents by copper(II)-containing species. Employing anhydrous CuSO4 instead of the pentahydrate led to a dramatic phosphorylation yield drop from 70 to <5%. It seems that the ligand environment of copper is very important for the effective reaction: other Cu(II) and Cu(I

• oxides as PH-reagents. The developed protocol utilizes a simple copper catalyst under mild reaction conditions and synthetically available enol acetates (compared to traditionally employed alkenes, alkynes, cinnamic, and α,β-alkynyl carboxylic acids). The present approach showed good functional group

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• Novozyme 435 in a pH 7 buffer to hydrolyze the acetate group. The resulting alcohol, (R)-118, was isolated in 73% yield with 96% ee. This alcohol was then reacted with o-diphenylphosphanylbenzoate (o-DPPB) in the presence of DCC, affording (R)-120 in 83% yield (>99% ee, E/Z >99:1) after recrystallization

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• networks to optimize the chemical parameters of the extraction. An optimal value of gold removal, lying between 98 and 98.9%, was found to occur with a contact time of 40 minutes, a concentration of α-CD of 11.61 g/L and KOH was added in enough quantity to raise the solution pH to 5 [47][48]. Complexes of

• leachates (pH < 2) [52]. To better understand the chemistry behind this precipitation method, it is worth mentioning that the AuCl4− anion is a complex ion, formed by gold(III) and chloride ions, and that the presence of the extra choride ion to render it an anionic complex instead of a salt is a factor

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• . The formyl group can be cleaved under acidic conditions to yield the esters (2R,6S)-11. Treatment of the solution with LiOH at pH 9–10 and at 40 °C leads to saponification of the methyl ester (Scheme 5c and Scheme 6). Conclusion In conclusion, we present a straightforward and efficient method for the

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• was refluxed over sodium with benzophenone as an indicator and freshly distilled prior to use. Column chromatography was performed on silica gel (normal phase, 200–300 mesh) from Anhui Liangchen Silicon Material Co., Ltd. or basic aluminum oxide (pH 9–10) from Shanghai Titan Technology Co., Ltd

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• further conversion of (S)-13a into the malononitrile derivative (S)-16 without loss of optical purity. Compound 1 and 2. Chiral ligands 3–7. Preparation and optical resolution of 7. Pd-catalyzed asymmetric allylic amination of acetate 12 (Ar = Ph) or 15 (Ar = p-ClC6H4) with isatin derivatives 11 using (aR

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

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

• that a tripodal hexaurea receptor L (Figure 1b) could selectively and reversibly extract sulfate and phosphate anions from water into organic phase (under pH control) [30][31][32][33]. Single crystal structures of the receptor–K2SO4 complex in the presence of 18-crown-6 clearly displayed ion-dipole

Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• further issue, we observed some instability at acidic pH during analysis. Thus, we tested the stability of NAc-PAP-H (1 mM, MeOH, ambient conditions, 2 h) at pH 2, 12, and in the presence of DBU (10−2 M) and found that the acetyl group was lost (cf. Supporting Information File 1, section 2.4). UV–vis

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

• using the pkCSM web server [28]. Docking molecular simulation: The structure of nitric oxide synthase (iNOS) protein (PDB ID: 3E7G) [45] was obtained from the Protein Data Bank. Protonation of the protein was carried out using the Protonate 3D tool in MOE to assign correct protonation states at pH 7.4

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• according to the following mechanism via an anodic trimethylsilyl cyanide radical formation (Scheme 24). The formation of the Ph₃P=O as the side product was assumed to be due to the presence of water or oxygen in the reaction mixture, which competes with the aminating reagent. Electrochemical O–P bond

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

• containing potassium and magnesium ions at a physiological pH of 7.0 for 5 hours. Analysis of the reaction mixture by anion-exchange HPLC revealed that the bromopropyl handle (C3 homolog 8) gave the highest yield of covalently tethered HBC-RNA complex (50%). Significantly less RNA alkylation yield was

• in 40 µL of water, followed by the addition of 12 µL of buffer (250 mM HEPES, 500 mM KCl, pH 7.0) and 6.0 µL of MgCl2 solution (20 mM). The aptamer was annealed by heat shock at 90 °C for 2 minutes and cooled on ice. Then, 2.0 µL of a ligand stock solution (3.0 mM, in DMSO) was added. The final

• analyzed by AE chromatography (Dionex DNAPac PA-100 column; 4 mm × 250 mm) at 80 °C with a flow rate of 1.0 mL/min. A gradient of 25–37.5% B in A in 25.0 minutes was used; Eluent A: 25 mM Tris∙HCl, 10 mM NaClO4, 20% acetonitrile, pH 8.0; eluent B: 25 mM Tris∙HCl, 600 mM NaClO4, 20% acetonitrile, pH 8.0

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• JEOL AccuTOF electrospray instrument. ITC data was collected on a Malvern Microcal PEAQ-ITC instrument with a cell volume of 200 µL and an injection syringe with a capacity of 40 μL. For ITC experiments, the host and guest solutions were prepared in a 20 mM phosphate-buffered water (pH 7.4). The sample

• %; c) dry pyridine, pyridine sulfur trioxide complex (20 equiv), 90 °C, 18 h, 68%. Thermodynamic parameters (Ka (M−1), ∆H° (kcal/mol) determined for the C1·guest, M1·guest and M0·guest complexes by ITC. Conditions: 298.0 K, phosphate-buffered saline, pH 7.4. Supporting Information The X-ray crystal

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

• pendant aryl moiety, is better for target-binding and hence 41 is a ≈10-fold more potent inhibitor of BACE-1 than 40. Several further examples of cyclic ethers will be examined in section 5 (sugars). The anomeric effect applies in acyclic ethers, too. Consider the non-fluorinated scaffold, Ph–O–CH3 (42

• neutral pH, and the partially negative fluorine atom (I, Figure 11) [96]. This attraction has the outcome of favouring a gauche F–C–C–N+ alignment. This gauche alignment can be further stabilised by two additional interactions: hyperconjugation (II, Figure 11) [148], and intramolecular hydrogen bonding

• ][179][180][181]. For example, consider the analgesic drug fentanyl (104, Figure 11). This drug contains a piperidine moiety, which is protonated at physiological pH and forms a salt bridge with an aspartate residue in the binding site of the μ-opioid receptor. One of the drawbacks of fentanyl (104) is

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

• filtrate, MeCN (18.5 mL) and EDTA-Na2 (3.45 g, 9.26 mmol, 1.0 equiv) were added and the reaction mixture was stirred at room temperature for 2 h. Subsequently, the solution was treated with aq NaOH (18 M) to pH 7 and Na2CO3 (1.96 g, 18.5 mmol, 2.0 equiv) was added. FmocOSu (3.12 g, 9.26 mmol, 1.0 equiv

• ) was dissolved in acetone (37.0 mL) and added dropwise to the reaction mixture. After 17 h of stirring at room temperature, MeCN and acetone were removed under reduced pressure, H2O (40 mL) was added, and the mixture was treated with aq HCl (6 M) to pH 2. The resulting solution was extracted with EtOAc

• treated with aq NaOH (18 M) to pH 7 and Na2CO3 (2.71 g, 25.6 mmol, 2.0 equiv) was added. FmocOSu (4.32 g, 12.8 mmol, 1.0 equiv) was dissolved in acetone (51.2 mL) and added dropwise to the reaction mixture. After 17 h of stirring at room temperature, MeCN and acetone were removed under reduced pressure

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• dependent on both the leaving group of the allylic electrophile and the choice of the supporting ligand. When (+)-1,2-bis{(2S,5S)-2,5-diphenylphospholano}ethane {(S,S)-Ph-BPE} (L1) was employed as the supporting chiral ligand, initially allylic chloride was found to provide the desired product 32 with

• excellent enantioselectivity, although in moderate yield. Notably, the presence of a chloride anion in the reaction mixture proved crucial for high enantioselectivity, leading to the discovery that a 1:1 complex of copper(I) chloride and (S,S)-Ph-BPE (L1) could serve as an optimal catalyst system. Further

• phosphate. The absolute stereochemistry of the products was found to be consistent with that of previously reported CuH-catalyzed transformations using (S,S)-Ph-BPE (L1) as the supporting ligand, suggesting a common mode of stereoinduction. In parallel, Hoveyda and co-workers demonstrated the first copper

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

• to modify them. Reactions must be carried out at or near ambient temperatures and near-neutral pH. Aqueous media is often required to solubilize the substrates and/or to prevent denaturation, and reactions are normally carried out under very dilute (micromolar) conditions. As importantly, the highly

• for the types of reactions that can be used for the elaboration of ADCs. Among the signature features of photochemical, single-electron transformations is their ability to be conducted in dilute aqueous media at room temperature and at neutral pH [47]. Additionally, the distinctive mechanistic

• conditions can lead to denaturation, aggregation, or loss of functionality. Buffers, which are commonly used to stabilize antibodies by maintaining their pH and ionic strength, must also be compatible with the photoredox process to prevent unwanted side reactions or instability. Thus, although photoredox

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• extract, pH 6.3) by the endophytic fungus Dendrothyrium variisporum. This fungus, isolated from the roots of the Algerian plant Globularia alypum, was explored for the first time for its potential to produce secondary metabolites [16]. Despite the abundant production of massarilactone D, it did not