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

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

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

• 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

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

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, 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

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• represent promising candidates for drug discovery, because of their improved water solubility, membrane permeability, and improved recognition by the respective receptors [16]. The present article aims to provide an updated review of the chemistry and biological applications of N-glycosides of indigo

• -rhamnosides α-17a and α-17c, respectively (Scheme 14) [23]. Water solubility plays an important role with regard to the pharmacological activity. It was previously shown that the water solubility and anticancer activity of non-glycosylated indirubins can be improved by conversion of the keto to an oxime group

• -glycosylated indirubins act as a ligand for the aryl hydrocarbon receptor (AhR) and also directly inhibit several cyclin-dependent kinases (CDK). A problem is generally the low water solubility of these compounds. The commercially available indirubin-3’-monoxime (34) shows a better solubility, due to the

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• , such as nontoxicity, inexpensiveness, nonflammability, low volatility and good water solubility, which are consistent with the concept of green chemistry [74][75]. Therefore, we tested the reaction in the presence of PEG-400 (Table 1, entries 7–9). It was found that the reaction uniquely produced 3a in

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• , was found to be 67–129 Å2 for all compounds except products 4 and 2e. None of the compounds penetrate the BBB (blood–brain barrier) except for seleno-2p and desulfurized product 7. Regarding water solubility, we can conclude that all compounds are either soluble or moderately soluble. For more details

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• is introduced on the azobenzene to increase the water solubility. The influence of ortho, meta, and para-substitution patterns of the azobenzene on the lectin binding has also been studied. Synthesis The β-O-galactosyl p,p'-bis-substituted azobenzene derivative 1 was prepared from galactose and

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• reactions in water due to the remarkable lack of water solubility of the highly hydrophobic aminofurans selected in this study. Therefore, the decision was made to perform these reactions using vegetable oil as an alternative green solvent system. For this purpose, SSO, OO, OA and LM, which can act as

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• -oxabicyclo[2.1.1]hexanes To further increase the water solubility of 1,5-BCHs, Mykhailiuk and co-workers proposed 1,5-disubsituted-3-oxabicyclo[2.1.1]hexanes (3-oxa-1,5-BCHs) as isosteres for ortho-benzenes, introducing an oxygen atom into the hydrocarbon scaffold (Figure 10) [45]. Exit vector analysis

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• biomaterials since related in vitro bioassay systems require water solubility of the chemicals for testing. To overcome this important obstacle, over the past decades, a variety of water-soluble fullerenes have been reported [10]. General approaches towards enhancing the water solubility of fullerenes involve

• -soluble C60 and C70 derivatives by covalently attaching biocompatible water-soluble polymers, such as polyethylene glycol (PEG) [37][38] and PVP [39]. Although these C60– and C70–polymer conjugates revealed high water-solubility, it was found that they, especially the PEG conjugates, formed micelle-like

• C60–peptide conjugates in this study. In addition to the water solubility introduced by the peptides, these conjugates have a superior biocompatibility compared to those with synthetic polymers, such as PEG and PVP. We utilized the previously reported biscarboxylic acid derivative 3, which was

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• thiazole moiety into a thiazoline unit had a measurable impact on several physicochemical parameters, such as LogP and water solubility. Whilst thiazolo[4,5-b]pyridine 5 afforded a moderate water solubility of 49 mg/L, paired with a LogP of 2.28 (pH 2.3), the corresponding 2,3-dihydro[1,3]thiazolo[4,5-b

• ]pyridine 7b had a higher water solubility of 173 mg/L and a lower LogP of 1.59 (pH 2.3). However, the lipophilicity of the new 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines was highly dependent on the substituents. For example, the brominated analogs 13b and 13c showed considerably higher LogP values of 2.88

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• because of their low water solubility. The styrylpyridine derivatives 2a–g were irradiated in oxygen-saturated solutions in MeCN, H2O, MeOH, or MeCN/H2O with a high-pressure Hg lamp (λ > 220 nm), and the course of the photocyclization reaction was monitored by absorption spectroscopy (Figure 2). In

• S6A). Because of the low water solubility of the styrylpyridine derivatives 2a–g, solvent mixtures of MeCN/H2O or pure MeCN were used for the preparative photocyclization reactions (Scheme 3, cf. Supporting Information File 1, Figure S2C,D) to provide sufficient solubility of the substrates, as well

• , both as photo-controllable DNA binder and as DNA-damaging photosensitizer. Still, some key parameters have to be optimized by variation of the substitution pattern. For example, the water solubility of the styrylpyridine substrates has to be increased, and the excitation wavelength for the

Facile access to pyridinium-based bent aromatic amphiphiles: nonionic surface modification of nanocarbons in water

• Lorenzo Catti,
• Shinji Aoyama and
• Michito Yoshizawa

Beilstein J. Org. Chem. 2024, 20, 32–40, doi:10.3762/bjoc.20.5

• -solubilities. It is noteworthy that an AA derivative featuring three nonionic –O(CH2CH2O)2CH3 side-chains on the phenylene spacer is insoluble in water (see Figure S45 in Supporting Information File 1), emphasizing the importance of the hydrophilic pyridinium core for the observed water-solubility. Formation

• the employed PA-R side-chain, likely due to the difference in water-solubility of the corresponding amphiphiles. The efficiency was found to be in the order of PA-Im > PA-OH > PA-OCH3 >> PA-CH3, as judged by the guest absorbance at 525 nm (Figure 4c). Importantly, PA-OCH3, PA-OH, and PA-Im displayed

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

• Ghenwa Nasr,
• Hélène Greige-Gerges,
• Sophie Fourmentin,
• Abdelhamid Elaissari and
• Nathalie Khreich

Beilstein J. Org. Chem. 2023, 19, 1570–1579, doi:10.3762/bjoc.19.115

• internal cavity and a hydrophilic outer surface [1]. The common CDs are the native α-CD, β-CD, and γ-CD consisting of 6, 7, and 8 ᴅ-glucopyranose units, respectively. Due to their limited water solubility (especially β-CD), native CDs can be chemically or enzymatically modified (by e.g., alkylation

• , arylation, hydroxypropylation, amination, etherification, etc.) giving rise to synthetic CD derivatives with greater water solubility [2]. Thanks to their unique structure, CDs can offer exclusive advantages by allowing the entrapment of lipophilic molecules inside their inner cavities. This inclusion

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• materials [1][2][3][4][5][6][7][8][9][10]. Due to its different characteristics such as basicity, stability, water solubility, small molecular size, and ability to form hydrogen bonds, pyridine continues to be a suitable moiety in organic synthesis. In addition, it has been observed that pyridine rings

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene

• Nan Yang,
• Yi-Yan Zhu,
• Wei-Xiu Lin,
• Yi-Long Lu and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2023, 19, 635–645, doi:10.3762/bjoc.19.45

• improved water solubility of the supra-amphiphile due to the highly water-soluble behavior of TBTQ-C6 under alkaline conditions in its carboxyl anion form. As a result, the polymer chains were extended, releasing the entanglement and wrapping of the TPE fluorogens, thereby reducing the emission of the

• could be repeated several times. The TEM results showed that the spherical nanoparticles were disrupted when the pH increased from 5.3 to 10.4 without forming significant aggregations (Figure 6b) as in the case of CS-TPS-10% alone (Figure 3e), and this difference may be attributed to the enhanced water

• solubility of CS-TPS-10% after combining with TBTQ-C6. Furthermore, the complex reassembled into spherical nanoparticles when the pH of the solution was restored to 5.3 (Figure 6c). These results are consistent with the transmittance measurements, and similar phenomena were observed for the TBTQ-C6/CS-TPE-2

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• bond of 28 leads to compounds of increasing activity, being the more polar hydroxy-substituted derivatives the most active (Table 2) [73]. One of the major obstacles in the development of highly potent drugs is the water solubility. Pettit and co-workers [55] conducted an extensive study in an attempt

• to improve the water solubility of combretastatin D-2 (2) by converting it into a series of phosphate salts and other prodrugs. Thus, phosphorylation of combretastatin D-2 (2) using dibenzyl phosphite gave derivative 183. Further cleavage of the benzyl groups using TMSBr followed by the reaction of

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• , leading to high water solubility. On the other hand, the tetrahydropyran moieties of the Glcp units provide the hydrophobic property of the CD cavity [4]. As a consequence of their unique structure, CDs can encapsulate hydrophobic molecules or hydrophobic moieties of geometrically compatible bioactive

• compounds [5]. The resulting supramolecular inclusion complexes provide enhanced water solubility and bioavailability/bioaccessibility of the nanoencapsulated bioactive compounds, higher oxidative and thermal stability or photostability of labile compounds, and their controlled release [6][7]. Vegetable oil

• apparent water solubility and bioaccessibility of the oil and fat components. The oxidative stability of the polyunsaturated FA glycerides or free FAs is significantly increased by CD nanoencapsulation. Thus, a high thermal stability was obtained for linoleic acid encapsulated into α-CD by co

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• porphyrin 174 and stirred at room temperature for 24 h, solubilization occurred, resulting in a homogeneous solution. This is due to the formation of a supramolecular assembly in which the hydrophobic adamantane arms of 176b are sequestered by the β-CD arms of porphyrin 174, resulting in water solubility

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• substituted rims are partially methylated CDs. Methylation reduces the formation of intramolecular hydrogen bonds, enhancing CDs water solubility, and also extends the hydrophobic cavity, thus improving its binding potential. A substantial increase of binding constant (K) for per-6-methylated CD compared to

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• , plausibly because of a degree of water solubility of the ammonium salts of compound 3{1,1} and 4{1,1}. The effect of using triethylamine instead of sodium hydroxide as a base was remarkable. At room temperature, after an 18 hours-long reaction, hydroxypyrazine 4{1,1} was the sole isomer detected and, out of