Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• . When correlating clogP and logk in Figure 5, the fitted line showed a moderate linear correlation (R2 = 0.673). According to the plot, the partition coefficients of the outliers (E)-7a, 3e, and 10b seemed to be overestimated by the Percepta software [36]. The lipophilicity of hydrazone (E)-7a was

• , it is likely the reason for the in silico overestimation. Removal of the outliers would have resulted in a substantially better correlation with R2 = 0.835 (see Supporting Information File 1). The positions of the colored datapoints clearly show that the least lipophilic compounds had the best

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

• conformers, obtained via DFT calculations, show a correlation with both the sign and intensity of the experimentally observed CD spectra. Keywords: absolute configuration; chiral amine; chiral quaternary ammonium salt; circular dichroism; DFT calculation; Introduction Determining the absolute

• , exciton-coupled CD has emerged as a powerful chiroptical method, providing a non-empirical correlation between the sign of the Cotton effect and the spatial arrangement of the electric transition dipole moments of interacting chromophores [7]. More recently, CD-based chiroptical probes have been developed

• , ([P] − [M])/([P] + [M]) × 100, was obtained with R2 = 0.963 (Figure 7). A similar linear correlation was observed when previously reported conjugates were applied (Figure S28 in Supporting Information File 1). By comparing the observed and calculated sign of the CD Cotton effect, the absolute

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• towards all tested cancer cell lines. However, no clear correlation between structure and activity was observed. For example, elongation of the alkyl substituents (N,N-diethylamino derivative 9b) led to a complete loss of antiproliferative activity, while its cyclic analog 9c showed the lowest IC50 value

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• diradical pathways resulting from thermal decomposition using UM06-2X/6-31G(d,p) with quasiclassical trajectories and machine-learning analysis [83]. The results suggested a correlation between the out-of-plane bending of the methylene bridge and the stereoselectivity of the formation of retained and

• present. To include partial dynamic correlation, we performed single-point energy calculations using extended multistate complete active space perturbation theory (XM2-CASPT2) [91] on the CASSCF-optimized geometries. Non-adiabatic molecular dynamics (NAMD) We performed NAMD using the fewest switches

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• into MOFs, we confined catalytically active amines within MOF pores of systematically increasing lipophilicity. Our results reveal a clear correlation between increased pore lipophilicity and enhanced catalytic activity. Additionally, increasing lipophilicity resulted in congruent changes in the

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• exclusively nitric acid under continuous-flow conditions, aiming to optimize process parameters. The distinctive feature of this kinetics modeling approach lies in its mechanistic foundation rather than statistical correlation. Mechanistic models are constructed based on scientific understanding of chemical

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

• show that, in the absence of barium, compound 18 exhibits almost coplanar components, so both systems form a combined fluorophore highlighted in green in Figure 5. The correlation between energy and this dihedral angle by means of a Karplus-like [31] equation up to the fourth degree in the form shows

• an excellent correlation (R2 = 0.9987). The situation is completely different in the presence of a naked barium cation (Figure 5B). Thus, the E(ω) – E(0) vs ω curve shows a wide minimum in the region of 90 deg. Also in this case, the correlation for a fourth-degree polynomial expansion in terms of

• cosnω in the form with a correlation factor of R2 = 0.9829. This minimum involves the simultaneous coordination of the cation to one nitrogen atom of the fluorophore 1, to the para-phenylene group and the crown ether, a result in line with our experimental results [8]. Next, we analyzed the geometry and

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

• isomerization of Z-2-H+ to E-2-H+ at different pH (pH 4.6, 5.5, and 6.5). In the bottom graph, each circle represents the experimental ratio of the Z isomer at each time point, and each curve shows the theoretical value obtained from the curve-fitting analysis of the experimental data. Correlation between E/Z

• isomerization rate constant and pH. The result indicates that C–N rotation from the molecular form of amidine was dominant in the observed isomerization. a) Correlation between isomerization rate constant and electronic effects of the substituents. b) Possible protonated states of compound 7. Analysis of the

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• , which provided the best yields in the scope. Moreover, the strong correlation of the yield with the electronic effects in aryl rings was clearly shown in the experiment with iodonium salt 1q (Scheme 3). We believe that the reason for the predominant transfer of the electron-poor ligands under the given

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

• -15. Strong HMBC correlations observed from H-18 to C-16, C-20 (δH 116.5) and from H-20 to C-18 (δH 133.8) and H-15 to C-16 (see Figure 2) confirmed the presence of a monosubstituted imidazole subunit of histamine linked to the methylene groups at C-16 as evidenced by a two-bond correlation from H-15

• H-11 to C-10 (δC 173.5), H3-12 to C-9 (δC 128.1) and C-11 (δC 133.9). The relative stereochemistry of the double bond of the dehydrobutyrine moiety was established as Z based on a medium NOE correlation observed between the amide proton, H-8 (δH 9.82) and the methyl protons, H3-12 (see Figure 2 and

• (H3-13) with an integral of three was observed in 4 confirming a methoxy group replacement. This was evidenced in an upfield resonance signal in C-10 (δC 164.7) and a strong HMBC cross peak correlation from H3-13 to C-10 in relation to 3. The dehydrobutyrine moiety of 4 displayed the same relative

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• using density functional theory (DFT) with the Becke three-parameter exchange and Lee–Yang–Parr correlation (B3LYP) functional [49], along with the 6–311++G(d,p) basis set for gas-phase calculations of all compounds. After completing the molecular geometry optimizations, vibrational frequency

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• /mol (Figure 2a) [28][29][30]. Almost 5 kcal/mol difference between two species could spontaneously undergo a HAT process. That also justifies the selectivity and efficiency of amidyl radical serving as HAT reagent. 2) Recent research indicated a critical correlation between electronic effects and

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• meaningful correlation between thermodynamic stability and kinetic accessibility, as expressed by the BEP principle. Although this principle has been successfully applied in many cases, the correlation between reaction energies and activation barriers is often imperfect. For instance, studies on hydrogen

• atom transfer and cycloaddition reactions have reported correlation coefficients (R2) of around 0.7 at best, indicating significant deviations from ideal behaviour [12][13]. This means that even when intermediate energies are accurately computed, the predicted regioselectivity may still carry a degree

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• ). This significant energy difference supports the observed stronger binding of Li+ in these systems. The higher binding constant for the Li+ cation is consistent with the correlation between binding constants and binding energies for a 2:1 model [25]. Conclusion In conclusion, we have explored the

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

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

• found. We thus suspect that the substituents play a crucial role in in the population of the respective exited state and we can at this state not rule out a contribution also from the triplet state. Moreover, we could not find a quantitative correlation between the R-substituents and ΦE→Z, however, some

• →E ). Strong EWGs or EDGs enhanced the quantum yields for the π→π* transitions, whereas the n→π* transitions exhibited no clear correlation with substitution patterns. Notably, the acetylation of nitrogen significantly increased the ΦE→Z for π→π* transitions in almost all compounds studied (excluding

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

• ). Furthermore, the 2D 1H–13C HMBC NMR spectrum of 5a also exhibited the correlation between protons of two methyl groups and the same carbon atom resonance at 165.52 ppm, respectively (see Supporting Information File 1). Consequently, the signal at 165.52 ppm in the 13C NMR spectrum corresponds to the sp2

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• unknown photoisomer (N-UnS1). Structural investigations using exhaustive 2D-correlation NMR spectroscopy were also inconclusive. Next, the push–pull functionalized derivatives O-NBD2 and N-NBD2 were investigated. Notably, N-NBD2 exhibited the most pronounced red shift (Table 1) and was the only nitrogen

• potential further rearrangements or photodecomposition. To gain a better understanding of the ongoing conversion processes, we conducted NMR spectroscopy. The assignment of individual proton signals was supported by 2D correlation NMR spectroscopy (Supporting Information File 1). First, O-NBD2 is

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• the computational investigation, could not be isolated either – probably due to its high sensitivity to hydrolysis. However, a 2D 1H-15N NMR correlation spectrum showed no interactions of hydrogen nuclei in silicon-bound methyl groups and any of the nitrogens in the product. This led us to conclude

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

• boronate complexes and correlation with reactivity. Copper-catalyzed stereospecific allylic alkylation of secondary alkylboronic esters via tert-butyllithium activation. Copper-catalyzed stereospecific allylic alkylation of chiral tertiary alkylboronic esters via adamantyllithium activation. DFT-calculated

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

• confirmed the presence of these groups. The HMBC correlation from H-4 (δH 5.65, dd, J = 4.4, 1.0 Hz) to C-1'' (δC 165.7) and the upfield shift of H-3 (δH 3.98, dd, J = 5.1, 4.4 Hz) compared to the same proton in compounds 2–5 evidenced that the crotonyl moieties were linked at C-4 and C-7. Compound 8 was

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• cryptophycins 1 and 2 showed high cytotoxicity with 313 pM (1) and 6.36 nM (2) and outstandingly low resistance factors. Furthermore, the new cryptophycin 1 confirms the correlation between degree of alkylation and cytotoxicity of m-chloro-p-amino unit B derivatives. Since MDR is responsible for over 90% of

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• that the enantiomeric ratio values in Table 5 correspond to the major anti-diastereomer. The absolute configuration of the significant diastereoisomer obtained in the kinetic resolution of compound 3 was established by chemical correlation with (2R,3S)-1,2,3-triphenylpentan-1-one (19), previously

• acetate mixtures as eluent. Experimental procedure for the chemical correlation of 3 with 19. In a Wheaton flask, 3 (53 mg, 0.16 mmol), 1,3-propane dithiol (21 mg, 0.19 mmol, 1.2 equiv), and scandium triflate (3 mg, 0.0064 mmol, 0.04 equiv) in CH2Cl2 were mixed, and the resulting mixture was stirred for

• : hexane/ethyl acetate 2:1), obtaining 19 (19 mg, 0.06 mmol, 50%). Previous work. Hypothesis, retro-Michael reaction, and its application in kinetic resolution. Model reaction. Kinetic resolution of the Michael adduct 1. Chemical correlation of 3 with 19. Epimerization of the anti-1 adduct promoted by A

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

• transformation from a conceptual standpoint. Another fundamental law in photochemistry is the Beer–Lambert law, which describes a negative exponential correlation between the transmittance of a solution containing chromophores (i.e., a light-absorbing species) and the optical path length (Figure 1). In essence

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• correlation between Ep of the redox event and the square root of the scan rate (Scheme 3B) suggested that compound 4a is not significantly adsorbed on the electrode surface [23]. Comparison of the jp vs v0.5 slope with our previously obtained results for the anodic oxidation of aryl bromides 6a (two-electron