Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• solution was examined, for solubility reasons. a) CDs-mediated 1,2-difunctionalization of alkenes by alkyl halides R–Y and b) light-driven reduction of triarylsulfonium salts in the presence of CDs. Carbon dots tested in this project and their main (photo)physical characteristics. Emission parameters for

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• in chloroform or dichloromethane (DCM), converting entirely into the thermodynamically stable [1 + 1] isomer 39. This work demonstrates a solvent-driven approach for dynamically interconverting macrocycle sizes, governed by thermodynamic stability and solubility differences. In the same year, Chauhan

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

• extraction efficiency was seen for the dual-host strategy. Additionally, the use of 18-crown-6 alone displays better extraction efficiency than that of hexaurea receptor (Table 1), which is attributed to the relatively poor solubility of the hexaurea receptor in CHCl3. For cesium salts with various oxyanions

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

• classical azobenzenes. Heterocyclic rings offer, for example, enhanced polarity, electron pairs for metal coordination [27], better water-solubility, and variable pKa [28][29]. Special attention has been given to 5-membered N-heterocyclic azobenzenes, which not only maintain the azobenzenes properties but

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

• have shown that the choice of solvent significantly impacts the reaction. CH₃CN exhibits better than CH₃OH, with a wider electrochemical window and better reactant solubility. When the reaction was conducted in CH₃CN using n-Bu₄NPF₆ and n-Bu₄NBF₄ as electrolytes but without iodide salt and in the

• were obtained using platinum electrodes as the anode and cathode (Scheme 25). Studies showed that CH₃CN performed better than CH₃OH due to its wider electrochemical window and better solubility. The results indicated that the electronic properties of substituents had no significant effect on the yield

• ). Although using other solvents improved the solubility, it reduced the reaction yield. Ammonium thiocyanate is used as a sulfur source in the presence of DBU as a base and n-Bu4NBF4 as an electrolyte. When electron-donating groups were present at the C2-benzene ring, the reaction yield was higher than when

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

• α-ᴅ-mannoside (MeMan) measured on the same plate as reference. This leads to relative inhibitory potencies, so-called RIP values. Because of limited water solubility, the samples had to be dissolved in DMSO and therefore, the effect of pure DMSO was also tested in every individual assay (cf

• , Figures S13–S16), the analysis of the testing results shows that determination of the inhibitory potencies of the various isomers is indeed valid in spite of the limited water solubility of the samples. Looking over the measured inhibitory potentials, it can be concluded that (i) the isomeric state of the

• 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

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

• better solubility in the reaction buffer and did not require DMSO as co-solvent, making it a very promising candidate for in vivo applications. To complete the study, and given that the mesyloxy group has shown superior efficacy over all other functional groups tested for Pepper alkylation, we

• fluorophores also exhibited favorable solubility compared to the other functionalizations which is a critical aspect for applications in the cell. We also note that primary alkyl halides, and in particular, the mesyloxy alkyl handles presented here, are relatively underexplored for covalent labeling of nucleic

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

• spectroscopic characterization of C1 along with determination of its inherent aqueous solubility and self-association properties. Next, we present the X-ray crystal structure of C1 as its C1·Me6CHDA complex. Subsequently, we describe a qualitative investigation of C1·guest and M1·guest complexation by 1H NMR

• shows an ion at m/z = 751.13 which corresponds to [C1 − 2Na]2−. Inherent aqueous solubility of C1 After having firmly established the structure of C1 we decided to determine its inherent aqueous solubility. For this purpose, we added an excess of solid C1 to D2O and stirred the solution at room

• spectrum using a delay time between pulses of 20 seconds to ensure accurate integration. The inherent aqueous solubility of C1 was determined to be 3.97 mM by comparison of the integrals for Ha of C1 with that of the CH3-resonance for dimethyl malonic acid (Figure S5 in Supporting Information File 1

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

• valuable property in the context of drug design, because chameleonic fluorinated molecules such as compounds 2 and 3 might be expected to pass more easily through cell membranes, a manoeuvre which requires some level of solubility in both aqueous and organic environments. Another consequence of introducing

• be altered, too [44]. For example, consider compounds 26 and 27 (Figure 4), which are fluorinated analogues of the multiple sclerosis drug gilenya (25) [45]. The syn,anti-fluorinated stereoisomer 26 has a much higher water solubility than gilenya (25), attributable to the presence of new polar bonds

• in 26 (although the different alkyl chain lengths in 25 and 26 should also be acknowledged). Notably, the all-syn fluorinated stereoisomer 27 displays a further increase in water solubility, even compared to the syn,anti-stereoisomer 26, highlighting the dramatic impact that a seemingly minor

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

• was obtained by a Migita–Kosugi–Stille coupling between bromophenanthrene 15 and (E)-1,2-bis(tributylstannyl)ethene to afford diarylethene 18 followed by Mallory photoreaction. The obtained intermediate 18 contained residual palladium and isolation was not successful due to its poor solubility in

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• amount of water was reduced from 33% to 17% (Table 1, entry 8 vs entry 7), an observation that might be useful for substrates of low aqueous solubility. However, further reduction of water amount to 5 equivalents completely inhibited the anodic oxidation of 9a, and only traces of the desired 6a were

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

• facilitated a site-specific covalent linkage to the antibody, resulting in the formation of a DAR 2 ADC precursor. For their ADC design strategy, the group selected a polyethylene glycol (PEG) linker, as it enhances the water solubility of the ADC, while the payload consists of the cytotoxic agent DM1, which

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• carbon atom, due to the readiness for losing a water molecule. Formaldehyde is commonly used in its polymeric form (paraformaldehyde) or in a 37% aqueous solution (formalin). The exceptional solubility of formaldehyde in water or biobased solvents, such as ethanol and glycerol, enhances the feasibility

• ]. They argued that organic bases such as DBU are superior than inorganic bases in improving the yields, probably because of the low solubility of the last ones in the reaction system. In the same way, other bases such as DABCO [64], DBU [66], and TMG (1,1,3,3-tetramethylguanidine) [65][67] were shown to

• well for a wide variety of solvents and under mild basic conditions, since the solubility of the reagents and ease of product isolation are the factors that govern the choice. Sisko et al. used DMF/K2CO3 as the best conditions to carry out the cycloaddition of a wide variety of amines, aldehydes, and

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• conditions and the obtained results are summarized in Table 1. It should be mentioned that all experiments were carried out at reflux due to low solubility of the starting compound 1a in all used solvents. At first, we carried out the process under conditions developed above for the synthesis of enamines 4

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

• azobenzene is that the switching efficiency decreases sharply with increasing water content in the solvent. In a recently published paper, we reported that replacing one CH2 group in the bridge with NCOCH3 not only confers intrinsic water solubility, but also largely eliminates the problem of reduced

• ]. Moreover, the parent diazocine is insoluble in water (precipitation in water/DMSO > 9:1). Substitution with polar substituents such as CH2NH2 provides water solubility, however, it does not restore the high Z → E conversion rates of the parent system in organic solvents, which is a disadvantage, since

• biochemical reactions usually take place in aqueous environments [13]. The substitution of one CH2 group in the CH2CH2 bridge by N–C(=O)–CH3 leads to an intrinsic water solubility of the N-acetyl diazocine 1 (Figure 1) [3]. Furthermore the photoconversion of 1 shows no significant drop in pure water in

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• derivatives have been reported [22][23][24][25][26]. Among these reports, various silylation and protection strategies have been employed to address the poor solubility of preQ1 (and analogs) in organic solvents [9][22][23][25][26][27][28][29]. Herein, we report an optimized three-step protocol, free of

• -step synthesis of O6-methyl preQ1 (16, m6preQ1) [28]. The direct reduction of the precursor O6-methyl preQ0 (15, m6preQ0) was possible, eliminating the need for the previously introduced protection/solubility concept, which shortened the synthetic route to only four steps (Supporting Information File 1

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

• simplifies experimental procedures. Moreover, it often leads to shorter reaction times [43][44] and can overcome solubility limitations [45]. Similar to the effect of photons in light-mediated synthesis, mechanical forces generated during ball milling can induce unconventional reaction pathways [46] enabling

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

• self-directing and self-correcting, and the term “self-assembly” [290][291][292] often used [286][293][294][295][296]. Products can be thermodynamic or kinetic, but are often isolated by precipitation due to low solubility [297], though many have useful solubility [288][298]. Since POCs typically have

• the past few years [20][70][235][315], and true organocatalysis is exceedingly rare [316]. Instead, catalytic systems tend to be composed of cavities that increase substrate solubility [317], or host nanoparticles [318][319][320][321][322][323][324][325][326], metals [44][327][328], photoactive groups

• , which can act as an oxidation catalyst (Figure 7C) [44]. The long-standing challenges of synthesis, stability, solubility and internal functionalization are beginning to be tackled, and the remainder of this Perspective will discuss specifics of these hard-earned advances and the opportunities they

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• represent molecular switches of optical and fluorescent properties under sequential addition of CN− and Hg2+ ions and the transformation cycle presented in Scheme 3 can be repeated at least 5–6 times. The resulting compounds 7b and 8a,b have extremely low water solubility, which makes it impossible to

• prepare concentrations sufficient for studying cellular cytotoxicity. In this regard, 1,3-tropolone 7a, which has an acceptable level of solubility in water, was used for biological testing. The in vitro cytotoxic activity was investigated with A431 skin cancer and H1299 lung cancer cell lines. A standard

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• been further decreased, in the end, 0.5 mL of DMF was used because of the solubility of the reagents. Increasing the amount of catalyst to 20 mol % resulted in a significant increase in the yield, but further increases did not significantly change the yield (Table 1, entries 14 and 15). A decrease in

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• bond donors. Our experiment with neutral HB donors reproduced literature results (Table 1, compounds 10, 11, and 12) [20][22][47] and revealed an expected trend in HB donation ability; for example, compound 1a is a weaker HB donor than 3a. However, due to limited solubility, the 1H NMR spectroscopic

• 1H NMR chemical shift change, thereby allowing the interactions of individual HB donating moieties with n-Bu3PO to be probed (Figure 4B and C). Moreover, we used anhydrous deuterated acetonitrile (CD3CN) as the solvent, in which both neutral and ionic compounds exhibited appreciable solubility. In

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• optimized the coupling reaction using potassium phosphate as a base and increasing the nickel catalyst loading to 20 mol %, achieving a yield of 78% for the desired product 3bg. When 2-naphthylboronic acid (2i) was employed, its solubility was enhanced using a mixed solvent system of toluene, methanol, and

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• -consuming. Additionally, the effect of the addition order of the reagents was evaluated, and the results are also provided in Supporting Information File 1. Furthermore, methanol, 2-propanol, and water were independently tested as reaction solvents. Solubility issues, which lead to the formation of dense

• suspensions and precipitation of the starting materials, make these solvents unsuitable for this reaction and the isolation of the products troublesome. The use of 2-propanol/water (2:1), together with the application of heat, ensures optimal solubility of the species involved. Moreover, the workup procedure

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

• reaction (Table 1, entry 1) [4]. In the presence of potassium carbonate, only starting material 4a was detected. A stronger base to generate the nucleophilic intermediate was tested, and sulfonamide 5aa was detected in trace amounts (Table 1, entry 2). Considering the low solubility of the hypervalent

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• activity towards AβpE3-42 but accomplishing increased solubility. Due to the multifactorial pathogenesis of AD, one of the current drug discovery approaches is the so-called multitarget-directed ligands (MTDLs). In 2015, Benchekroun et al. [38] reported the design, synthesis, and biological evaluation of a