Article
Chemistry and Materials Science
Organic Chemistry
Aminoalkyl-Substituted 2-Hetarylimidazophenazines: Synthesis, DNA Binding and Cytotoxicity
Maksim S. Abramovich
,Elena S. Barskaya
,Mariia I. Vitiazeva
,Purbo S. Bymbygydenov
,Dmitry N. Kaluzhny
,Ekaterina S. Ivanova
,Alexander A. Shtil
,Leonid D. Popov
,Elena K. Beloglazkina
Abstract:
A series of ethylamino- and propylamino-substituted 2-(pyridin-2-yl)imidazophenazines bearing various tertiary amine moieties, as well as a series of 2-hetarylimidazophenazines with N,N-diethylethan-1-amine moiety, were synthesized via the reaction of phenazine-2,3-diamine with heterocyclic aldehydes followed by alkylation with chloro-substituted alkylamines. In a study on HCT116, K562 and Kelly cells compounds containing N-methylindole, 2-chloroquinoline, and N-phenylpyrrole moieties exhibited the highest cytotoxicity. The values of binding constants with G-quadruplexes tel22, c-Myc for the leader compounds, determined by the method of fluorescence spectroscopy, were within the order of 105-106 M-1.
Abstract:
A series of ethylamino- and propylamino-substituted 2-(pyridin-2-yl)imidazophenazines bearing various tertiary amine moieties, as well as a series of 2-hetarylimidazophenazines with N,N-diethylethan-1-amine moiety, were synthesized via the reaction of phenazine-2,3-diamine with heterocyclic aldehydes followed by alkylation with chloro-substituted alkylamines. In a study on HCT116, K562 and Kelly cells compounds containing N-methylindole, 2-chloroquinoline, and N-phenylpyrrole moieties exhibited the highest cytotoxicity. The values of binding constants with G-quadruplexes tel22, c-Myc for the leader compounds, determined by the method of fluorescence spectroscopy, were within the order of 105-106 M-1.
Posted: 27 October 2026
Article
Chemistry and Materials Science
Organic Chemistry
Study of Bioinsecticidal Activity of Water-Soluble Linalool Derivative
Gulnara Shakirzyanova
,Omon Kholbekov
,Ulugbek Togaev
,Olimjon Matchanov
Abstract: Plant-derived compounds are increasingly being investigated as potential alternatives or supplements to conventional insecticides. This study evaluated the insecticidal activity of linalool and its ester derivative against adults of Eurygaster integriceps and Eurygaster maura, two important pests of cereal crops. Llinalool monomethyl succinate derivative were synthesized, and their formation was assessed using thin-layer chromatography and Fourier-transform infrared spectroscopy. Linalool, formulated as an aqueous emulsion, and linalyl monomethyl succinate, formulated as an aqueous alcoholic solution, were selected for laboratory bioassays. Their insecticidal activity was evaluated at concentrations of 1%, 5%, 10%, and 20%, with a 0% vehicle control, following topical application. Both formulations caused concentration-dependent mortality and reduced locomotor activity in the tested insects. At a concentration of 20%, the linalool emulsion caused 100% mortality in both species within 24 h, while linalyl monomethyl succinate produced 90% mortality within 72 h under the reported experimental conditions. These findings indicate that linalool and linalyl monomethyl succinate are promising candidates for further investigation as insecticidal agents against E. integriceps and E. maura. Additional field studies and assessments of their environmental fate and non-target effects are required before their potential application in integrated pest management can be established.
Abstract: Plant-derived compounds are increasingly being investigated as potential alternatives or supplements to conventional insecticides. This study evaluated the insecticidal activity of linalool and its ester derivative against adults of Eurygaster integriceps and Eurygaster maura, two important pests of cereal crops. Llinalool monomethyl succinate derivative were synthesized, and their formation was assessed using thin-layer chromatography and Fourier-transform infrared spectroscopy. Linalool, formulated as an aqueous emulsion, and linalyl monomethyl succinate, formulated as an aqueous alcoholic solution, were selected for laboratory bioassays. Their insecticidal activity was evaluated at concentrations of 1%, 5%, 10%, and 20%, with a 0% vehicle control, following topical application. Both formulations caused concentration-dependent mortality and reduced locomotor activity in the tested insects. At a concentration of 20%, the linalool emulsion caused 100% mortality in both species within 24 h, while linalyl monomethyl succinate produced 90% mortality within 72 h under the reported experimental conditions. These findings indicate that linalool and linalyl monomethyl succinate are promising candidates for further investigation as insecticidal agents against E. integriceps and E. maura. Additional field studies and assessments of their environmental fate and non-target effects are required before their potential application in integrated pest management can be established.
Posted: 23 October 2026
Article
Chemistry and Materials Science
Organic Chemistry
Synthesis and Antiproliferative Activity of New Carnosic Acid Derivatives: 14-Acetyl and 14-Formyl from Methyl Carnosate
Nerea Lluch-Cerezo
,William E. Mendoza-Hernández
,Aday González-Bakker
,José M. Padrón
,Miguel A. González-Cardenete
Abstract: Four new derivatives of bioactive natural carnosic acid were obtained during a planned project of target synthesis starting from readily available natural products. In this work, we describe the synthesis of methyl 11,12-di-O-methyl-14-acetylcarnosate and methyl 11,12-di-O-methyl-14-formylcarnosate from methyl 11,12-di-O-methylcarnosate, which was obtained from commercial carnosic acid, by Friedel-Crafts acylation and formylation, respectively. Despite the low yield of the acylation reaction, 17% (56% brsm) yield, alternative formylation worked well which followed by Grignard addition and oxidation increased to 53% the overall yield of the 14-acetyl derivative. Subsequent selective 11-O-demethylation at low temperature afforded in high yield the corresponding hydroxy derivatives. The structure assignment of the newly synthesized compounds was established by 1H and 13C NMR, 2D-NMR and mass spectrometry. The proximity of the acetyl group at C14 to the characteristic isopropyl group of abietane-type diterpenes at C13 resulted in unusual signals in the 1H and 13C NMR spectra. These four novel compounds were screened in a panel of tumor cell lines and basic structure-activity relationships were deduced. They showed improved antiproliferative activity in comparison with natural carnosic acid, even in the low micromolar range for certain cells.
Abstract: Four new derivatives of bioactive natural carnosic acid were obtained during a planned project of target synthesis starting from readily available natural products. In this work, we describe the synthesis of methyl 11,12-di-O-methyl-14-acetylcarnosate and methyl 11,12-di-O-methyl-14-formylcarnosate from methyl 11,12-di-O-methylcarnosate, which was obtained from commercial carnosic acid, by Friedel-Crafts acylation and formylation, respectively. Despite the low yield of the acylation reaction, 17% (56% brsm) yield, alternative formylation worked well which followed by Grignard addition and oxidation increased to 53% the overall yield of the 14-acetyl derivative. Subsequent selective 11-O-demethylation at low temperature afforded in high yield the corresponding hydroxy derivatives. The structure assignment of the newly synthesized compounds was established by 1H and 13C NMR, 2D-NMR and mass spectrometry. The proximity of the acetyl group at C14 to the characteristic isopropyl group of abietane-type diterpenes at C13 resulted in unusual signals in the 1H and 13C NMR spectra. These four novel compounds were screened in a panel of tumor cell lines and basic structure-activity relationships were deduced. They showed improved antiproliferative activity in comparison with natural carnosic acid, even in the low micromolar range for certain cells.
Posted: 14 October 2026
Communication
Chemistry and Materials Science
Organic Chemistry
Synthesis of Chiral 1,2-Diamines from (R)-2-Phenyl-2-(Piperidin-1-yl)Ethan-1-ol
Ailed Arenas-González
,Saul Torres Reyes
,Cuauhtémoc Alvarado Sánchez
,Omar Santiago Sosa
,Jorge R. Juarez-Posadas
,Manuel Velasco-Ximello
Abstract: Three chiral 1,2-diamines were successfully synthesized from readily available (R)-2-phenyl-2-(piperidin-1-yl)ethan-1-ol. The reaction proceeded through the regioselective ring opening of a common N,N-dialkylaziridinium ion by weakly nucleophilic anilines. The structures of newly synthesized diamines were confirmed by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, and high-resolution mass spectrometry (HRMS). Anticancer activity assays of the synthesized compounds are currently underway.
Abstract: Three chiral 1,2-diamines were successfully synthesized from readily available (R)-2-phenyl-2-(piperidin-1-yl)ethan-1-ol. The reaction proceeded through the regioselective ring opening of a common N,N-dialkylaziridinium ion by weakly nucleophilic anilines. The structures of newly synthesized diamines were confirmed by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, and high-resolution mass spectrometry (HRMS). Anticancer activity assays of the synthesized compounds are currently underway.
Posted: 12 October 2026
Article
Chemistry and Materials Science
Organic Chemistry
HFIP-Promoted Cascade Cyclization for Catalyst-Free Synthesis of Quinazolinones
Xiaxia Zhu
,Junmei Xia
,Meng Jin
Abstract: A Quinazolinones are privileged N‑heterocycles with broad pharmaceutical relevance, yet catalyst‑free synthesis from readily available 1,3‑diketones remains challenging. We report an 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP)‑mediated cascade strategy that integrates Schiff base formation with retro‑Mannich reaction between 2‑aminobenzamides and 1,3‑diketones, enabling a rare example of HFIP‑promoted C–C bond cleavage and delivering a wide range of quinazolinones in high yields. The protocol features broad substrate scope, excellent functional group tolerance, and readily enables late‑stage diversification of complex molecules. DFT calculations uncover a dual role of HFIP in substrate activation and transition‑state stabilization, with particular emphasis on its ability to facilitate the challenging C–C scission. This catalyst‑free approach offers a practical and environmentally benign entry to pharmaceutically relevant quinazolinones.
Abstract: A Quinazolinones are privileged N‑heterocycles with broad pharmaceutical relevance, yet catalyst‑free synthesis from readily available 1,3‑diketones remains challenging. We report an 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP)‑mediated cascade strategy that integrates Schiff base formation with retro‑Mannich reaction between 2‑aminobenzamides and 1,3‑diketones, enabling a rare example of HFIP‑promoted C–C bond cleavage and delivering a wide range of quinazolinones in high yields. The protocol features broad substrate scope, excellent functional group tolerance, and readily enables late‑stage diversification of complex molecules. DFT calculations uncover a dual role of HFIP in substrate activation and transition‑state stabilization, with particular emphasis on its ability to facilitate the challenging C–C scission. This catalyst‑free approach offers a practical and environmentally benign entry to pharmaceutically relevant quinazolinones.
Posted: 06 October 2026
Article
Chemistry and Materials Science
Organic Chemistry
Unsaturated Gemini Surfactants with a Semi-Rigid Spacer: Micellization and Antimicrobial Activity
Iwona Kowalczyk
,Adrianna Szulc
,Justyna Brycka
,Anna Komasa
,Anna Koziróg
,Bartosz Grabowski
,Bogumił Brycki
Abstract: A homologous series of but-2-ene-1,4-bis(N-alkyl-N,N-dimethylammonium bromides) containing C12, C14, C16, and C18 alkyl chains was investigated to determine the influence of hydrophobic-chain length and a semi-rigid unsaturated spacer on aggregation and antimicrobial properties. The critical micelle concentration decreased from the C12 to the C16 derivative, whereas further chain elongation to C18 resulted in an increase in CMC, indicating that micellization is governed not only by hydrophobicity but also by molecular packing effects. Negative standard Gibbs energies confirmed spontaneous micellization. Antimicrobial activity showed the opposite trend: the C12 derivative was the most active compound against all tested microorganisms, with MIC (minimum inhibitory concentration) values as low as 0.006 mM. Increasing alkyl-chain length markedly reduced activity, particularly against Escherichia coli, for which the MIC increased from 0.012 mM for C12 to >125 mM for C18, demonstrating a pronounced cut-off effect. Staphylococcus aureus remained more susceptible to longer-chain homologues than E. coli, while notable activity was also observed against yeast and filamentous fungi. DFT calculations further indicated that spacer unsaturation affects the electronic properties of the molecules. Overall, the results demonstrate a strong relationship between alkyl-chain length, micelliza-tion, spacer rigidity, and antimicrobial performance.
Abstract: A homologous series of but-2-ene-1,4-bis(N-alkyl-N,N-dimethylammonium bromides) containing C12, C14, C16, and C18 alkyl chains was investigated to determine the influence of hydrophobic-chain length and a semi-rigid unsaturated spacer on aggregation and antimicrobial properties. The critical micelle concentration decreased from the C12 to the C16 derivative, whereas further chain elongation to C18 resulted in an increase in CMC, indicating that micellization is governed not only by hydrophobicity but also by molecular packing effects. Negative standard Gibbs energies confirmed spontaneous micellization. Antimicrobial activity showed the opposite trend: the C12 derivative was the most active compound against all tested microorganisms, with MIC (minimum inhibitory concentration) values as low as 0.006 mM. Increasing alkyl-chain length markedly reduced activity, particularly against Escherichia coli, for which the MIC increased from 0.012 mM for C12 to >125 mM for C18, demonstrating a pronounced cut-off effect. Staphylococcus aureus remained more susceptible to longer-chain homologues than E. coli, while notable activity was also observed against yeast and filamentous fungi. DFT calculations further indicated that spacer unsaturation affects the electronic properties of the molecules. Overall, the results demonstrate a strong relationship between alkyl-chain length, micelliza-tion, spacer rigidity, and antimicrobial performance.
Posted: 01 October 2026
Article
Chemistry and Materials Science
Organic Chemistry
Synthesis of 3,6-Dihydro-2H-thiopyrans via Diffusion-Controlled Generation of Thioaldehydes as Dienophiles for [4+2] Cycloaddition
Dmitry E. Shybanov
,Ivan A. Leonov
,Yuri K. Grishin
,Nikolai V. Zyk
,Elena K. Beloglazkina
Abstract: In this work we propose a mild, diffusion-controlled method for generating unstable thioaldehydes from stable precursors (Bunte salts or thiocycnates) using tertiary amine vapors (NEt3 or DIPEA). The reactions were conducted in a closed system consisting of two nested vials, allowing slow amine evaporation to maintain a low steady-state concentration of thiocarbonyl intermediates in the reaction mixture. This technique effectively suppressed side oligomerization and enabled efficient trapping by cyclopentadiene, 2,3-dimethylbutadiene, and isoprene at room temperature. While thiocyanates served as alternatives for low-polarity solvents, Bunte salts proved superior, providing a wider substrate range and higher cycloadduct yields (up to 81%). Additionally, a rapid transesterification of the thiocarbonyl intermediate was observed when using methanol as a solvent. Overall, the diffusion-mixing technique avoids thermal activation, offering a mild and efficient synthetic route to 3,6-dihydro-2H-thiopyrans, particularly when employing less reactive dienes.
Abstract: In this work we propose a mild, diffusion-controlled method for generating unstable thioaldehydes from stable precursors (Bunte salts or thiocycnates) using tertiary amine vapors (NEt3 or DIPEA). The reactions were conducted in a closed system consisting of two nested vials, allowing slow amine evaporation to maintain a low steady-state concentration of thiocarbonyl intermediates in the reaction mixture. This technique effectively suppressed side oligomerization and enabled efficient trapping by cyclopentadiene, 2,3-dimethylbutadiene, and isoprene at room temperature. While thiocyanates served as alternatives for low-polarity solvents, Bunte salts proved superior, providing a wider substrate range and higher cycloadduct yields (up to 81%). Additionally, a rapid transesterification of the thiocarbonyl intermediate was observed when using methanol as a solvent. Overall, the diffusion-mixing technique avoids thermal activation, offering a mild and efficient synthetic route to 3,6-dihydro-2H-thiopyrans, particularly when employing less reactive dienes.
Posted: 30 September 2026
Article
Chemistry and Materials Science
Organic Chemistry
A New Look at the Isomeric Purity and Its Impact on the Thermotropic Properties of Alkylbenzene Sulfonate-Derived Catanionic Surfactants
Robin Jose
,Aileen M. Sanchez Medina
,Reema Rawal
,Seonghyeok Lee Cox
,Haesook Han
,Pradip Kumar Bhowmik
,Chris Schmiedl
,Michael Fisch
Abstract: Thermotropic polymorphism of catanionic surfactants and its dependance on molecular structure was studied in seven catanionic surfactants with varying cationic and anionic chain lengths that were synthesized using isomerically pure para-alkylbenzene sulfonates as the anionic moiety and quaternary ammonium as its cationic counterpart. Thermal and structural properties of these materials were studied using TGA, DSC, POM, and VTXRD. A comparison of the thermotropic properties of these compounds with that of ortho/para mixture compounds derived from commercial alkylbenzene sulfonates is presented. Catanionic surfactants of corresponding alkylbenzene sulfonates exhibited similar thermal stabilities that did not show a dependance on the chain-length or the structural isomerism of the anionic moiety. All the isomerically pure compounds, except one, formed hexagonal crystalline phases at high temperatures. Their polymorphism depended on the number of alkyl chains, while the crystal formation was controlled by headgroup interactions. This behavior is different than that of surfactants synthesized from ortho/para mixtures. The temperature range over which polymorphs were formed in these materials showed a complex dependance on the isomeric purity, chain length, and number of alkyl chains.
Abstract: Thermotropic polymorphism of catanionic surfactants and its dependance on molecular structure was studied in seven catanionic surfactants with varying cationic and anionic chain lengths that were synthesized using isomerically pure para-alkylbenzene sulfonates as the anionic moiety and quaternary ammonium as its cationic counterpart. Thermal and structural properties of these materials were studied using TGA, DSC, POM, and VTXRD. A comparison of the thermotropic properties of these compounds with that of ortho/para mixture compounds derived from commercial alkylbenzene sulfonates is presented. Catanionic surfactants of corresponding alkylbenzene sulfonates exhibited similar thermal stabilities that did not show a dependance on the chain-length or the structural isomerism of the anionic moiety. All the isomerically pure compounds, except one, formed hexagonal crystalline phases at high temperatures. Their polymorphism depended on the number of alkyl chains, while the crystal formation was controlled by headgroup interactions. This behavior is different than that of surfactants synthesized from ortho/para mixtures. The temperature range over which polymorphs were formed in these materials showed a complex dependance on the isomeric purity, chain length, and number of alkyl chains.
Posted: 29 September 2026
Article
Chemistry and Materials Science
Organic Chemistry
Paired Experimental 1H/13C NMR Fingerprint Prediction Under Molecule- and Scaffold-Disjoint Evaluation
Carlos Alberto López-Rosas
,Nadia Caram-Salas
,José Luis Olivares-Romero
Abstract: Machine-learning approaches for small-molecule nuclear magnetic resonance (NMR) often rely on predicted spectra or evaluation schemes that insufficiently control structural overlap. Here, we curated 555 paired experimental 1H/13C NMR observations representing 514 canonical structures from nmrshiftdb2 to establish an auditable benchmark for NMR-to-molecular-fingerprint prediction. Spectra were encoded as fixed-length peak-count vectors and molecular structures as 2,048-bit radius-2 Morgan fingerprints. Ridge models were evaluated across ten molecule-disjoint and ten Bemis–Murcko scaffold-disjoint partitions, with replicate spectra grouped by structure and model selection restricted to validation data. For molecule-disjoint evaluation, fused 1H+13C data achieved a mean Tanimoto similarity of 0.327 ± 0.019 and Top-10 retrieval of 39.0%, outperforming 13C (0.316 ± 0.021; 33.5%) and 1H (0.268 ± 0.013; 20.5%) alone. Under scaffold-disjoint evaluation, fused performance decreased to 0.265 ± 0.036 and 23.7% Top-10. Moreover, adding 410 provenance-confirmed simulated structures did not improve experimental-test performance. These results establish a rigorously curated experimental benchmark, demonstrate reproducible complementarity between 1H and 13C peak information, and identify scaffold novelty and spectral provenance as key challenges for robust NMR-based molecular fingerprint prediction.
Abstract: Machine-learning approaches for small-molecule nuclear magnetic resonance (NMR) often rely on predicted spectra or evaluation schemes that insufficiently control structural overlap. Here, we curated 555 paired experimental 1H/13C NMR observations representing 514 canonical structures from nmrshiftdb2 to establish an auditable benchmark for NMR-to-molecular-fingerprint prediction. Spectra were encoded as fixed-length peak-count vectors and molecular structures as 2,048-bit radius-2 Morgan fingerprints. Ridge models were evaluated across ten molecule-disjoint and ten Bemis–Murcko scaffold-disjoint partitions, with replicate spectra grouped by structure and model selection restricted to validation data. For molecule-disjoint evaluation, fused 1H+13C data achieved a mean Tanimoto similarity of 0.327 ± 0.019 and Top-10 retrieval of 39.0%, outperforming 13C (0.316 ± 0.021; 33.5%) and 1H (0.268 ± 0.013; 20.5%) alone. Under scaffold-disjoint evaluation, fused performance decreased to 0.265 ± 0.036 and 23.7% Top-10. Moreover, adding 410 provenance-confirmed simulated structures did not improve experimental-test performance. These results establish a rigorously curated experimental benchmark, demonstrate reproducible complementarity between 1H and 13C peak information, and identify scaffold novelty and spectral provenance as key challenges for robust NMR-based molecular fingerprint prediction.
Posted: 22 September 2026
Article
Chemistry and Materials Science
Organic Chemistry
Screening of Commercial Hydrolases in Aqueous and Hydrated Deep Eutectic Solvent Media: Hydrolysis of p-Nitrophenyl Substrates as a Probe of Enzyme Promiscuity
D. Alonzo Durante-Salmerón
,Isabel Rodríguez-Veiga
,Niuris Acosta
,Inmaculada Aranaz
,Andrés R. Alcántara
Abstract: Several commercial hydrolases were screened to assess substrate-dependent activity and the influence of hydrated deep eutectic solvents on canonical and non-canonical hydrolysis. Liquid formulations from Novozymes, comprising proteases from Bacillus species and lipases from Candida antarctica, Rhizomucor miehei, and Thermomyces lanuginosus, and solid lipases from Meito Sangyo derived from Stutzerimonas stutzeri and Limtongozyma cylindracea, were evaluated in aqueous buffer and 20 wt% hydrated reline, composed of choline chloride and urea at a 1:2 molar ratio. Hydrolysis of p-nitrophenyl acetate, p-nitrophenyl butyrate, and p-nitrophenyl N-acetyl-β-D-glucosaminide was monitored spectrophotometrically, and activities were normalized to protein content determined by the bicinchoninic acid assay. SDS-PAGE supported the presence of the principal lipase components in selected liquid formulations. In aqueous buffer, activity profiles depended strongly on substrate structure. Hydrated reline selectively enhanced or suppressed activity, depending on the enzyme–substrate pair, and in some cases abolished measurable activity. Selected liquid lipases and purified CALB hydrolyzed p-nitrophenyl N-acetyl-β-D-glucosaminide under acidic conditions, whereas the solid lipases showed no detectable activity under the tested conditions. These results indicate that this substrate may serve as a preliminary screen for selecting preparations for subsequent chitosan-hydrolysis studies, although its predictive value requires validation by direct analysis of chitosan depolymerization.
Abstract: Several commercial hydrolases were screened to assess substrate-dependent activity and the influence of hydrated deep eutectic solvents on canonical and non-canonical hydrolysis. Liquid formulations from Novozymes, comprising proteases from Bacillus species and lipases from Candida antarctica, Rhizomucor miehei, and Thermomyces lanuginosus, and solid lipases from Meito Sangyo derived from Stutzerimonas stutzeri and Limtongozyma cylindracea, were evaluated in aqueous buffer and 20 wt% hydrated reline, composed of choline chloride and urea at a 1:2 molar ratio. Hydrolysis of p-nitrophenyl acetate, p-nitrophenyl butyrate, and p-nitrophenyl N-acetyl-β-D-glucosaminide was monitored spectrophotometrically, and activities were normalized to protein content determined by the bicinchoninic acid assay. SDS-PAGE supported the presence of the principal lipase components in selected liquid formulations. In aqueous buffer, activity profiles depended strongly on substrate structure. Hydrated reline selectively enhanced or suppressed activity, depending on the enzyme–substrate pair, and in some cases abolished measurable activity. Selected liquid lipases and purified CALB hydrolyzed p-nitrophenyl N-acetyl-β-D-glucosaminide under acidic conditions, whereas the solid lipases showed no detectable activity under the tested conditions. These results indicate that this substrate may serve as a preliminary screen for selecting preparations for subsequent chitosan-hydrolysis studies, although its predictive value requires validation by direct analysis of chitosan depolymerization.
Posted: 20 September 2026
Review
Chemistry and Materials Science
Organic Chemistry
Stereoselective Photochemistry: The Role of Hydrogen Bond in Heterocylic Systems
Rocco Racioppi
,Maurizio D’Auria
Abstract: The development of photochemical techniques represents one of the possible ways to achieve green chemistry. The control of stereochemical behavior of photochemical reactions is a crucial problem to be solved. Two possible solutions of this problem, where the formation of hydrogen bonds in supramolecular structures on heterocyclic compounds is considered, has been discussed.
Abstract: The development of photochemical techniques represents one of the possible ways to achieve green chemistry. The control of stereochemical behavior of photochemical reactions is a crucial problem to be solved. Two possible solutions of this problem, where the formation of hydrogen bonds in supramolecular structures on heterocyclic compounds is considered, has been discussed.
Posted: 17 September 2026
Review
Chemistry and Materials Science
Organic Chemistry
Pyrazine Based Chemosensors for Cations Detection
Tatyana N. Moshkina
,Emiliya V. Nosova
,Galina N. Lipunova
Abstract: Pyrazine (1,4-diazine) and its annelated derivatives have emerged as promising platforms for developing selective and sensitive colorimetric and/or fluorescent chemosensors for biologically and environmentally relevant metal cations, including Hg²⁺, Cu²⁺, Zn²⁺, Pb²⁺, Fe³⁺, Al³⁺, etc. Their sensing potential arises from the strongly electron-deficient character of the pyrazine ring, low-lying unoccupied molecular orbitals, and considerable synthetic versatility. Reported sensor architectures include pyrazinamide, pyrazinehydrazide, 2-acetylpyrazine, aminopyrazine, hydrazinopyrazine, and aryl(hetaryl) substituted pyrazine derivatives, as well as pyrazines fused with five-membered carbocyclic or heterocyclic rings, quinoxaline systems, and pyrido[2,3-b]pyrazines. Rational molecular design enables the incorporation of multiple coordination sites with suitable properties and geometries for the specific recognition of metal cations. Sensors operate through CHEF/CHEQ, PET, ICT, ESIPT, FRET mechanisms, or combinations thereof, producing responses that can be observed visually or recorded instrumentally as changes in the intensity and/or position of absorption and emission bands. This review summarizes the structural diversity, metal-ion recognition strategies, photophysical response mechanisms, and practical applications of pyrazine-derived chemosensors for metal-cation detection, with particular emphasis on studies published between 2015 and 2026. It also highlights current limitations, remaining gaps in the literature, and promising directions for the development of more selective, biologically compatible, portable, sensing platforms.
Abstract: Pyrazine (1,4-diazine) and its annelated derivatives have emerged as promising platforms for developing selective and sensitive colorimetric and/or fluorescent chemosensors for biologically and environmentally relevant metal cations, including Hg²⁺, Cu²⁺, Zn²⁺, Pb²⁺, Fe³⁺, Al³⁺, etc. Their sensing potential arises from the strongly electron-deficient character of the pyrazine ring, low-lying unoccupied molecular orbitals, and considerable synthetic versatility. Reported sensor architectures include pyrazinamide, pyrazinehydrazide, 2-acetylpyrazine, aminopyrazine, hydrazinopyrazine, and aryl(hetaryl) substituted pyrazine derivatives, as well as pyrazines fused with five-membered carbocyclic or heterocyclic rings, quinoxaline systems, and pyrido[2,3-b]pyrazines. Rational molecular design enables the incorporation of multiple coordination sites with suitable properties and geometries for the specific recognition of metal cations. Sensors operate through CHEF/CHEQ, PET, ICT, ESIPT, FRET mechanisms, or combinations thereof, producing responses that can be observed visually or recorded instrumentally as changes in the intensity and/or position of absorption and emission bands. This review summarizes the structural diversity, metal-ion recognition strategies, photophysical response mechanisms, and practical applications of pyrazine-derived chemosensors for metal-cation detection, with particular emphasis on studies published between 2015 and 2026. It also highlights current limitations, remaining gaps in the literature, and promising directions for the development of more selective, biologically compatible, portable, sensing platforms.
Posted: 16 September 2026
Communication
Chemistry and Materials Science
Organic Chemistry
Synthesis of 2-((2-(4-(Benzyloxy)-4-Oxobutanamido)ethyl)dimethylammonio)propane-1-Sulfonate and 2-((2-(5-(Benzyloxy)-5-Oxopentanamido)ethyl)dimethylammonio)propane-1-Sulfonate
Marta Fiéis
,João Sarrato
,Ricardo Chagas
,Luísa Maria Ferreira
Abstract: Two previously undescribed sulfobetaine zwitterions bearing benzyl ester and amide functionalities were synthesised through a concise three-step sequence starting from benzyl alcohol and either succinic or glutaric anhydride. The route comprised esterification, amidation with N,N-dimethylpropane-1,3-diamine and ring-opening of 1,3-propanesultone by the resulting tertiary amine. Differing only in the length of the diacid-derived spacer, the two compounds constitute a matched pair well suited to probing structure–property relationships in sulfobetaine surfactants and thermoresponsive materials.
Abstract: Two previously undescribed sulfobetaine zwitterions bearing benzyl ester and amide functionalities were synthesised through a concise three-step sequence starting from benzyl alcohol and either succinic or glutaric anhydride. The route comprised esterification, amidation with N,N-dimethylpropane-1,3-diamine and ring-opening of 1,3-propanesultone by the resulting tertiary amine. Differing only in the length of the diacid-derived spacer, the two compounds constitute a matched pair well suited to probing structure–property relationships in sulfobetaine surfactants and thermoresponsive materials.
Posted: 08 September 2026
Article
Chemistry and Materials Science
Organic Chemistry
Fluorescent Chiral Multilayer Polymer for Hexavalent Chromium Sensing
Dianyuan Hu
,Xien Tang
,Cheng Han
,Yiming Zhu
,Hua Bian
,Sisi Long
,Sai Zhang
Abstract: Hexavalent chromium (Cr⁶⁺) pollution critically threatens ecological and human health, driving demand for efficient fluorescent sensors. This work fabricated a chiral multilayer three-dimensional aggregation-induced emission (AIE) conjugated polymer via palladium-catalyzed asymmetric Suzuki-Miyaura cross-coupling, using thiophene diboronic ester, 1,8-dibromonaphthalene, and dibromodibenzofuran as aromatic monomers with chiral Pd[S-BINAP]Cl₂ as the catalyst. The stereoregular layered network was confirmed by ¹H NMR and GPC. Photophysical tests revealed excitation-wavelength-tunable luminescence, typical AIE effects, and solvatochromic behavior in THF/water, THF/simulated body fluid, and THF/simulated urine systems. Ion sensing experiments showed the polymer exhibits excellent selective recognition for Cr⁶⁺, with fluorescence intensity linearly correlated to Cr⁶⁺ concentration and a detection limit of 316.5 μM. Mechanistic studies via dynamic light scattering and electrochemistry indicated that sensing proceeds through coordination-induced aggregate enlargement and intermolecular charge transfer. This work offers a reliable platform for Cr⁶⁺ detection in complex aqueous and biomimetic environments, significantly expanding the application of ternary monomer-assembled chiral AIE polymers in environmental and biological sensing.
Abstract: Hexavalent chromium (Cr⁶⁺) pollution critically threatens ecological and human health, driving demand for efficient fluorescent sensors. This work fabricated a chiral multilayer three-dimensional aggregation-induced emission (AIE) conjugated polymer via palladium-catalyzed asymmetric Suzuki-Miyaura cross-coupling, using thiophene diboronic ester, 1,8-dibromonaphthalene, and dibromodibenzofuran as aromatic monomers with chiral Pd[S-BINAP]Cl₂ as the catalyst. The stereoregular layered network was confirmed by ¹H NMR and GPC. Photophysical tests revealed excitation-wavelength-tunable luminescence, typical AIE effects, and solvatochromic behavior in THF/water, THF/simulated body fluid, and THF/simulated urine systems. Ion sensing experiments showed the polymer exhibits excellent selective recognition for Cr⁶⁺, with fluorescence intensity linearly correlated to Cr⁶⁺ concentration and a detection limit of 316.5 μM. Mechanistic studies via dynamic light scattering and electrochemistry indicated that sensing proceeds through coordination-induced aggregate enlargement and intermolecular charge transfer. This work offers a reliable platform for Cr⁶⁺ detection in complex aqueous and biomimetic environments, significantly expanding the application of ternary monomer-assembled chiral AIE polymers in environmental and biological sensing.
Posted: 04 September 2026
Article
Chemistry and Materials Science
Organic Chemistry
Divergent Chiral-Pool Synthesis of the C1–C8 and C9–C13 Fragments of Pladienolide B from L-Malic Acid
Sai Krishna Chilaka
,Nerella Ashok
,Marumamula Hanumaiah
,Ramachandra Reddy Putta
Abstract: Pladienolide-B, a macrocyclic polyketide isolated from Streptomyces platensis Mer-11107, displays potent antiproliferative and antitumor activities by targeting the SF3b subunit of the spliceosome. Herein, we report a divergent, stereoselective synthetic route to access both the C1–C8 and C9–C13 fragments of the core moiety of Pladienolide-B starting from a common, inexpensive chiral pool precursor, L-malic acid. Key stereocenters and structural motifs were established using Sharpless asymmetric epoxidation, regioselective nucleophilic epoxide opening, Mannich reaction for exo-methylene introduction, and a tandem iodination–zinc elimination cascade. This unified precursor approach offers a streamlined tactical route toward the core macrolide framework.
Abstract: Pladienolide-B, a macrocyclic polyketide isolated from Streptomyces platensis Mer-11107, displays potent antiproliferative and antitumor activities by targeting the SF3b subunit of the spliceosome. Herein, we report a divergent, stereoselective synthetic route to access both the C1–C8 and C9–C13 fragments of the core moiety of Pladienolide-B starting from a common, inexpensive chiral pool precursor, L-malic acid. Key stereocenters and structural motifs were established using Sharpless asymmetric epoxidation, regioselective nucleophilic epoxide opening, Mannich reaction for exo-methylene introduction, and a tandem iodination–zinc elimination cascade. This unified precursor approach offers a streamlined tactical route toward the core macrolide framework.
Posted: 03 September 2026
Article
Chemistry and Materials Science
Organic Chemistry
Stereochemical 2D NMR Assignment of Thietane, Synthesis and Antiplatelet Activity of Novel Thietane-Containing 1-Isobutylpurine-2,6-dione Derivatives as Potential GPIIb/IIIa Inhibitors
Ferkat A. Khaliullin
,Zhekshen K. Mamatov
,Iuliia V. Shabalina
,Wang Yi
,Aleksandr N. Lobov
,Elena E. Klen
,Kudaiberdi G. Kozhobekov
,Dmitry A. Kudlay
,Aleksandr V. Samorodov
Abstract: 1-Isobutylpurine-2,6-diones possess a broad spectrum of pharmacological activities, highlighting their relevance in the search for new biologically active agents. In this study, we report the synthesis of a series of novel thietane-containing 1-isobutylpurine-2,6-dione derivatives. A crucial aspect of this work is the detailed stereochemical and conformational analysis of the thietanyl substituent. For the first time, the unambiguous assignment of axial and equatorial protons within the thietane ring was achieved using 2D NMR spectroscopy, exemplified by a comprehensive study of the starting substance. Furthermore, the newly synthesized compounds were evalu-ated for their antiplatelet activity, revealing inhibition of platelet aggregation exceed-ing that of acetylsalicylic acid. Based on structural analogy to established antiplatelet agent, we hypothesize that the observed biological effect is mediated via the inhibition of the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor complex. These findings demonstrate that the incorporation of a thietane fragment into the 1-isobutylxanthine scaffold yields promising candidates for the development of novel GPIIb/IIIa-targeted an-tiplatelet therapeutics.
Abstract: 1-Isobutylpurine-2,6-diones possess a broad spectrum of pharmacological activities, highlighting their relevance in the search for new biologically active agents. In this study, we report the synthesis of a series of novel thietane-containing 1-isobutylpurine-2,6-dione derivatives. A crucial aspect of this work is the detailed stereochemical and conformational analysis of the thietanyl substituent. For the first time, the unambiguous assignment of axial and equatorial protons within the thietane ring was achieved using 2D NMR spectroscopy, exemplified by a comprehensive study of the starting substance. Furthermore, the newly synthesized compounds were evalu-ated for their antiplatelet activity, revealing inhibition of platelet aggregation exceed-ing that of acetylsalicylic acid. Based on structural analogy to established antiplatelet agent, we hypothesize that the observed biological effect is mediated via the inhibition of the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor complex. These findings demonstrate that the incorporation of a thietane fragment into the 1-isobutylxanthine scaffold yields promising candidates for the development of novel GPIIb/IIIa-targeted an-tiplatelet therapeutics.
Posted: 31 August 2026
Review
Chemistry and Materials Science
Organic Chemistry
Aziridines as Versatile Scaffold: Synthesis of Aza-Heterocycles of Pharmaceutical Importance via Ring Expansions
Anindita Chandra Mukherjee
,Sougata Chandra Santra
,Nibin Joy Muthipeedika
,Grigory V. Zyryanov
,Adinath Majee
,Brindaban C. Chandra Ranu
Abstract: Aziridine, a three-membered nitrogen-containing heterocyclic ring, is a versatile building block in organic synthesis. Due to the high ring strain it tends to undergo ring opening reactions under the influence of nucleophilic reagents. Facile construction of four to seven-membered aza-heterocyclic ring systems is a challenging task for the synthetic organic chemists. Fortunately, this small scaffold (aziridine) is an ideal starting material for conversion into larger nitrogenated heterocycles. This review presents some of the illustrative and contemporary examples to demonstrate the synthetic utility and efficiency of the ring-expansion strategies of the aziridines towards a wide range of small to medium-sized aza-heterocyclic moieties of pharmaceutical importance.
Abstract: Aziridine, a three-membered nitrogen-containing heterocyclic ring, is a versatile building block in organic synthesis. Due to the high ring strain it tends to undergo ring opening reactions under the influence of nucleophilic reagents. Facile construction of four to seven-membered aza-heterocyclic ring systems is a challenging task for the synthetic organic chemists. Fortunately, this small scaffold (aziridine) is an ideal starting material for conversion into larger nitrogenated heterocycles. This review presents some of the illustrative and contemporary examples to demonstrate the synthetic utility and efficiency of the ring-expansion strategies of the aziridines towards a wide range of small to medium-sized aza-heterocyclic moieties of pharmaceutical importance.
Posted: 28 August 2026
Article
Chemistry and Materials Science
Organic Chemistry
Relative Interacting Atomic Energy Analysis of the Anomeric Effect in Cyclic and Acyclic O–C–X Systems
Luis R. Domingo
,Mar Ríos-Gutiérrez
,Patricia Pérez
Abstract: The conformational preferences of 2-substituted cyclic and acyclic ethers, caused by the anomeric effect, have been analyzed using the Relative Interacting Atomic Energy (RIAE) analysis within Molecular Electron Density Theory. Comparison of substituted tetrahydropyrans and cyclohexanes enables the proposal of the anomeric index, which isolates the electronic contributions of the O–C–X motif to axial stabilization in 2-substituted tetrahydropyrans. The RIAE analysis reveals two distinct patterns in the distribution of the atomic-energy contributions associated with anomeric stabilization, dominated by either intra-atomic or interatomic terms, which correlate with the period of the X atom. Accordingly, the studied compounds can be classified into two groups: Group I, comprising compounds with second-period X elements (X = N, O, and F), in which axial stabilization is dominated by favorable intra-atomic energy contributions within the basin of the anomeric C carbon; and Group II, comprising compounds with third- and fourth-period X elements (X = S, Cl, and Br), in which stabilization is primarily associated with favorable interatomic energy contributions between the ether O oxygen and the anomeric C carbon atoms. This atomic-energy based analysis accounts for the X-dependent conformational trends and provides a transferable description of the O–C–X motif across cyclic and acyclic molecular frameworks.
Abstract: The conformational preferences of 2-substituted cyclic and acyclic ethers, caused by the anomeric effect, have been analyzed using the Relative Interacting Atomic Energy (RIAE) analysis within Molecular Electron Density Theory. Comparison of substituted tetrahydropyrans and cyclohexanes enables the proposal of the anomeric index, which isolates the electronic contributions of the O–C–X motif to axial stabilization in 2-substituted tetrahydropyrans. The RIAE analysis reveals two distinct patterns in the distribution of the atomic-energy contributions associated with anomeric stabilization, dominated by either intra-atomic or interatomic terms, which correlate with the period of the X atom. Accordingly, the studied compounds can be classified into two groups: Group I, comprising compounds with second-period X elements (X = N, O, and F), in which axial stabilization is dominated by favorable intra-atomic energy contributions within the basin of the anomeric C carbon; and Group II, comprising compounds with third- and fourth-period X elements (X = S, Cl, and Br), in which stabilization is primarily associated with favorable interatomic energy contributions between the ether O oxygen and the anomeric C carbon atoms. This atomic-energy based analysis accounts for the X-dependent conformational trends and provides a transferable description of the O–C–X motif across cyclic and acyclic molecular frameworks.
Posted: 26 August 2026
Article
Chemistry and Materials Science
Organic Chemistry
1,4-Benzo[b]dithiine Derivatives Accessed via Ring Expansion of 1,3-Dithioles
Dawid Leja
,Wojciech Depa
,Maja Morawiak
,Agata Bajek-Bil
,Jaromir Lechowicz
,Grażyna Groszek
Abstract: Herein, we disclose an efficient route to the synthesis of brominated 1,4-benzo[b]dithiine derivatives via ring expansion of aromatic 1,3-dithiole promoted by bromine (51% - 94%). The use of a methyl-substituent on aromatic ring lead to formation of an inseparable, equimolar mixture of regioisomers. Additionally, 4-methoxyacetophenone derivative yielded unprecedented dimeric products, which structure was confirmed by single crystal X-ray crystallography. We propose a reaction mechanism, rationalizing the formation of regioisomers originating.
Abstract: Herein, we disclose an efficient route to the synthesis of brominated 1,4-benzo[b]dithiine derivatives via ring expansion of aromatic 1,3-dithiole promoted by bromine (51% - 94%). The use of a methyl-substituent on aromatic ring lead to formation of an inseparable, equimolar mixture of regioisomers. Additionally, 4-methoxyacetophenone derivative yielded unprecedented dimeric products, which structure was confirmed by single crystal X-ray crystallography. We propose a reaction mechanism, rationalizing the formation of regioisomers originating.
Posted: 21 August 2026
Short Note
Chemistry and Materials Science
Organic Chemistry
1,2-Dimethoxy-12-methyl-13H-[1,3]benzodioxolo [5,6-c]phenanthridine
Peter Mbugua Njogu
,Benson Joseph Atako
,Kennedy Omondi Abuga
,John Norman Lisgarten
,Jeremy Karl Cockcroft
,Grace Njeri Thoithi
Abstract: The crystal structure of benzophenanthridine alkaloid dihydrochelerythrine (1,2-dimethoxy-12-methyl-13H-[1,3]benzodioxolo[5,6-c]phenanthridine), C21H19NO4, was determined by single-crystal X-ray diffraction analysis. The alkaloid was isolated from the stem bark of Zanthoxylum usambarense (Engl.) Kokwaro (Rutaceae) collected from Nairobi, Kenya. In contrast to the earlier reported semisynthetic form which crystallized in the monoclinic space group P21/c, the present natural isolate adopts the orthorhombic Pbca space group. The molecule displays an approximately planar benzophenanthridine framework, but with the dihydro group resulting in a distinctly puckered ring and an out-of-plane methyl group on the tertiary amine. Non-covalent interactions are responsible for the characteristic herringbone packing motif.
Abstract: The crystal structure of benzophenanthridine alkaloid dihydrochelerythrine (1,2-dimethoxy-12-methyl-13H-[1,3]benzodioxolo[5,6-c]phenanthridine), C21H19NO4, was determined by single-crystal X-ray diffraction analysis. The alkaloid was isolated from the stem bark of Zanthoxylum usambarense (Engl.) Kokwaro (Rutaceae) collected from Nairobi, Kenya. In contrast to the earlier reported semisynthetic form which crystallized in the monoclinic space group P21/c, the present natural isolate adopts the orthorhombic Pbca space group. The molecule displays an approximately planar benzophenanthridine framework, but with the dihydro group resulting in a distinctly puckered ring and an out-of-plane methyl group on the tertiary amine. Non-covalent interactions are responsible for the characteristic herringbone packing motif.
Posted: 20 August 2026
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