NMR Analysis Research Articles

Polyphenolic Antioxidants in Bilberry Stems and Leaves: A Non-Targeted Analysis by Two-Dimensional NMR Spectroscopy and Liquid Chromatography-High-Resolution Mass Spectrometry.

Compared with those of berries, the stems and leaves of the genus Vaccinium are important and underestimated sources of polyphenols with high antioxidant activity. In the course of this work, aqueous methanol extracts of the aerial parts of common bilberry (Vaccinium myrtillus L.) and bog bilberry (Vaccinium uliginosum L.) were studied to analyze the component compositions of their biologically active polyphenolic compounds. The aqueous methanol fractions of the stems and leaves of the studied samples contained 8.7 and 4.6% extractives, respectively, and were comparable in total polyphenol content, but presented significant differences in antioxidant activity. The identification of polyphenolic compounds was carried out via the following two-stage analytical procedure: (1) non-targeted screening of dominant structures via the 2D NMR method and (2) analysis of HPLC-HRMS data via the scanning of precursor ions for a specific ion. A total of 56 phenolic compounds were identified, including the glycosides quercetin, proanthocyanidins, and catechins, as well as various conjugates of caffeic and p-coumaric acids, including iridoids. Some of the latter, such as caffeoyl and p-coumaroyl hydroxydihydromonotropein, as well as a number of lignan glycosides, were described for the first time in V. uliginósum and V. myrtillus.

Enhanced Rheological and Structural Properties of the Exopolysaccharide from Rhizobium leguminosarum VF39 Through NTG Mutagenesis.

Microbial exopolysaccharides (EPSs) are biopolymer materials with advantages such as biodegradability, biocompatibility, ease of mass production, and reproducibility. The EPS that was isolated from Rhizobium leguminosarum bv. viciae VF39 is an anionic polysaccharide with a backbone structure consisting of one galactose, five glucose molecules, and two glucuronic acids, along with 3-hydroxybutanoyl, acetyl, and pyruvyl functional groups. Through N-methyl-N'-nitro-N-nitrosoguanidine (NTG) mutagenesis, we isolated and purified a mutant EPS from VF39, VF39 #54, which demonstrated enhanced physicochemical and rheological properties compared to the wild-type VF39. The EPS structure of the VF39 #54 mutant strain showed a loss of glucuronic acid and 3-hydroxybutanoyl groups compared to the wild-type, as confirmed by FT-IR, NMR analysis, and uronic acid assays. The molecular weight of the VF39 #54 EPS was 250% higher than that of the wild-type. It also exhibited improved viscoelasticity and thermal stability. In the DSC and TGA analyses, VF39 #54 had a higher endothermic peak (172 °C) compared to the wild-type (142 °C), and its thermal decomposition point was 260 °C, surpassing the wild-type's value of 222 °C. Additionally, the VF39 #54 EPS maintained a similar viscosity to the wild-type in various pH, temperature, and metal salt conditions, while also exhibiting a higher overall viscosity. The cytotoxicity test using HEK-293 cells confirmed that the VF39 #54 EPS was non-toxic. Due to its high viscoelastic properties, the VF39 #54 EPS shows potential for use in products such as thickeners, texture enhancers, and stabilizers. Furthermore, its thermal stability and biocompatibility make it a promising candidate for applications in food, pharmaceuticals, and cosmetic formulations. Additionally, its ability to maintain viscosity under varying environmental conditions highlights its suitability for industrial processes that require consistent performance.

9,10-Bis(5H-dibenzo[b,f]azepino)anthracene

The title compound with a donor–π–donor (D–π–D) type triad structure was synthesized by Buchwald–Hartwig amination using 9,10-dibromoanthracene and 5H-dibenzo[b,f]azepine, and characterized by 1H, 13C{1H} NMR, HRMS, and X-ray diffraction analysis. The azepine–anthracene–azepine units are nearly orthogonal to each other, with a torsion angle of 88°. A broad and weak absorption band around 410–480 nm and the low emission character (ΦF = 0.01) suggest the weak intramolecular charge transfer from the azepine to the anthracene unit due to the twisted structure.

The Stability Challenge of Furanic Platform Chemicals in Acidic and Basic Conditions.

The transition toward renewable resources is pivotal for the sustainability of the chemical industry, making the exploration of biobased furanic platform chemicals derived from plant biomass of paramount importance. These compounds, promising alternatives to petroleum-derived aromatics, face challenges in terms of stability under synthetic conditions, limiting their practical application in the fuel, chemical, and pharmaceutical sectors. Our study presents a comprehensive evaluation of the stability of furan derivatives in various solvents and under different conditions, addressing the significant challenge of their instability. Through systematic experiments involving GC-MS, NMR, FT-IR and SEM analyses, we identified key degradation pathways and conditions that either promote stability or lead to undesirable degradation products. These findings demonstrate the strong stabilizing effect of polar aprotic solvents, especially DMF, and reveal the dependence of furan stability on solvent and additive type. This research opens new avenues in the utilization of renewable furans by providing critical insights into their behavior under synthetic conditions, significantly impacting the development of sustainable materials and processes. The broad appeal of this study lies in its potential to guide the selection of conditions for the efficient and sustainable synthesis of furan-based chemicals, marking a significant advance in green chemistry and materials science.

Synthesis and Mechanistic Study of Naphthalimide Derivative Formation via Cu-Mediated Ullmann-Type Reactions.

Cu-mediated Ullmann-type coupling reactions are fundamental to organic synthesis, garnering significant academic and industrial interest since their inception. Optimizing reaction parameters, particularly temperature control, is crucial for maximizing efficiency while maintaining high yields. Bidentate ligands, such as amino acids, have demonstrated potential in facilitating these reactions at lower temperatures (<100 °C). This study explores the Cu-catalyzed Ullmann-type coupling of naphthalimide derivatives with amino acid substitutions. Naphthalimide dyes, known for their diverse applications in bioimaging, solar cells, medicine, and sensors, were selected for their potent anticancer properties. The synthesized compounds were characterized by using 1H NMR, ESI-MS, and melting point analyses. Compounds with significant steric hindrance exhibited lower yields, leading to the development of a novel catalytic system employing l-carnosine as a bidentate ligand, which significantly improved yields. Mechanistic insights, derived from density functional theory calculations, identified "L-complex 3" as the most stable and reactive intermediate during oxidative addition to aryl halides. The oxidative addition transition state "OX1-TS" was found to be the most favorable, with a relatively low energy barrier of 6.13 kcal/mol, suggesting that this step, despite being the rate-limiting stage, is energetically accessible. In contrast, reductive elimination was facilitated by a Cu(III) penta-coordinated intermediate, with a barrier of just 8.34 kcal/mol, making it a more straightforward process. Theoretical findings aligned closely with experimental data, reinforcing the oxidative addition/reductive elimination pathway as the operative mechanism for this reaction.

Towards Precision Biocatalysis ‐ Leveraging Inline NMR for Autonomous Experimentation in Flow Reactors

AbstractReactor automation is a transformative force for chemical processes, but the potential of reaction monitoring for machine‐assisted autonomous biocatalytic reaction optimization is still largely unexplored. To address this gap, we report on automated reactor optimization for biocatalytic flow‐through microreactors. For this purpose, the inline NMR analysis of an enzymatically catalyzed stereoselective reduction of a prochiral diketone was combined with a self‐developed open‐source analysis and control software. The algorithm is continuously fed with spectra from a benchtop NMR instrument acquired from a reaction solution from a microreactor filled with biocatalytically active materials and adjusts the flow rate of the pumps to achieve predetermined target concentrations of the product. We show that through this automated coupling of data analysis and process parameterization, for example, maximum conversion efficiency can be achieved for a given bioreactor. This work illustrates the potential of inline NMR reaction monitoring for biocatalytic processes and provides a starting point for innovation to develop automated processes for precision biocatalysis through integrated data analysis.

Visualizing supramolecular assembly behavior, stimulus response, and solid state emission of higher-order Pt2+ aggregates.

Here, we present the first instance of a highly efficient red tetramer aggregate with tunable emission based on a cationic platinum(II) complex in conjunction with a silver cluster anion counterpart. This system exhibits multicolor emission response behaviors, which can be conveniently and directly detected through spectroscopic analysis, showcasing intriguing luminescence changes. The self-assembly of Pt⋯, π-π, and hydrogen bonding interactions not only enables an intriguing color adjustment from green to yellow emission, and eventually to red emission, but also demonstrates the co-existence of the monomer, excimer, and aggregation. These phenomena are further accompanied by well-defined nanostructures. The self-assembly process of these structures exhibits an isodesmic growth mechanism, which is dependent on temperature. In this regard, it exhibits potential applicability in multi-mode logic gates that rely on external stimuli such as concentration, solvent, and temperature. The sensitivity of the aggregates towards chemical stimuli combined with their exceptionally bright emission characteristics renders them suitable for diverse applications including solid-state lighting sensing mechanisms and anticounterfeiting measures. The multi-stimuli responsive phosphorescence and self-assembly behaviors of the cationic platinum(II) complex were substantiated by X-ray crystal structure determination, 1H NMR analysis spectroscopic investigations, computational calculations and scanning electron microscopy (SEM) studies.

A Discrete Four‐Stranded β‐Sheet through Catenation of M2L2 Metal–Peptide Rings

AbstractMethods for precisely constructing a β‐sheet assembly with number‐defined strands in solution remains quite limited due to its intense aggregation property. Here, we report the precise construction of a four‐stranded anti‐parallel β‐sheet by utilizing a non‐covalent approach. This was achieved by folding and assembly of Ag+ and a pentapeptide (1) with the Ala‐D3pa‐Gly‐3pa‐Val (3pa: β‐(3‐pyridyl)‐alanine) sequence, which was designed to form an interlocking Ag2(1)2 ring through metal cross‐linking of the side chains. NMR analyses and X‐ray crystallographic studies characterized the structure of the discrete β‐sheet assembly as well as the remarkable structural selectivity in terms of strands’ number, orientation and the sheet type.

Synthesis and Antifungal Activity Evaluation of Novel L-Carvone-Based 1,3,4-Thiadiazole-amide Derivatives as a Potential Succinate Dehydrogenase Inhibitor.

In an effort to explore new-type high-efficiency antifungal agents, 25 novel L-carvone-based 1,3,4-thiadiazole-amide derivatives were designed, synthesized, and structurally characterized by IR, 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS) analyses. The antifungal activity of the target compounds was preliminarily assayed at a concentration of 50 μg/mL, and boscalid, a commercialized fungicide identified as a succinate dehydrogenase inhibitor (SDHI), was employed as the positive control. It was found that all of the target compounds showed moderate to potent antifungal activity against the tested fungi compared to boscalid. Surprisingly, compound 4b exhibited broad-spectrum and significant inhibition activity against the growth of eight phytopathogenic strains with inhibitory rates of 67-89%. Further, the results of the EC50 value test suggested that the EC50 values of compound 4b against Physalospora piricola and Colletotrichum orbiculare were 16.33 and 18.06 μg/mL, respectively, and both of them were better than those of boscalid (16.64 and >50). Therefore, compound 4b deserves further study as a lead compound for novel fungicides. In addition, the inhibitory activity of compound 4b against succinate dehydrogenase (SDH) was evaluated as well to prove that compound 4b (IC50 = 3.38 μM) displayed higher SDH-inhibition activity than boscalid (IC50 = 7.02 μM). The binding mode of compound 4b and SDH was simulated by molecular docking and found to be similar to that of boscalid. The structure-activity relationships (SARs) of the target compounds were analyzed by establishing a 3D-QSAR model. Besides, a 4b-loaded complex 4b/CSTA on a reported L-carvone-based nanochitosan carrier CSTA containing the 1,3,4-thiadiazole-amide group was constructed, and its sustained release performance was investigated in the EtOH-H2O system (1:9, v/v). The complex 4b/CSTA exhibited preferred sustained release performance, indicating its potential for developing environmentally friendly nanofungicides.

Design, synthesis and biological studies of new isoxazole compounds as potent Hsp90 inhibitors

Heat shock protein 90 (Hsp90), a molecular chaperone, contributes to the preservation of folding, structure, stability, and function proteins. In this study, novel compounds comprising isoxazole structure were designed, synthesized and their potential ability as Hsp90 inhibitors was validated through docking studies. The active site-based compounds were prepared through a multi-step synthesis process and their chemical structures were characterized employing FT-IR, NMR, and mass spectrometry analysis. Cytotoxic and Hsp90 inhibition activities of synthesized compounds were assessed by MTT assay and ELISA kit, respectively. Based on the obtained results, compound 5 exhibited the highest cytotoxicity (IC50; 14 µM) against cancer cells and reduced Hsp90 expression from 5.54 ng/mL in untreated (normal cells) to 1.56 ng/mL in cancer cells. Moreover, molecular dynamics (MD) simulation results indicated its high affinity to target protein and approved its excellent stability which is essential for exerting an inhibitory effect on cancer cell proliferation.

Roseomonas aestuarii, as a Potential In Situ Surfactin Producer During Hydrocarbon Biodegradation.

In situ biosurfactant production by hydrocarbon degrader microorganisms is an attractive approach in the bioremediation of oil contamination because of their compatibility, biodegradability, environmental safety, and stability under extreme environmental conditions. Given the high efficiency of bacteria in degrading petroleum hydrocarbons, the present work studied the detection and characterization of a biosurfactant-producing hydrocarbon degrader, Roseomonas aestuarii NB833. This strain was able to synthesize a biosurfactant during the biodegradation of crude oil, which reduced the surface tension of the aqueous system from 70 to 34 mN m-1, with a critical micelle concentration of 200 mg L-1. The emulsification ability of the biosurfactant was sustained at various temperatures, pH values, and salinities. The biosurfactant chemical structure was identified via FT-IR, LC-MS, and NMR analyses. These analyses confirmed the production of surfactin-C14 with a molecular mass of 1007 g mol-1. These results revealed the high potential of R. aestuarii NB833 as an in situ surfactin-producing bacteria for bioremediation applications under extreme environmental conditions.

Synthesis and Fungicidal Activity Evaluation of Novel Triazole Thione/Thioether Derivatives Containing a Pyridylpyrazole Moiety.

Compounds containing N-pyridylpyrazole motif have aroused interest and brought about research hotspots due to their highly-efficient insecticidal activity. The fungicidal potential of N-pyridylpyrazole derivatives has gradually been disclosedin recent years. To discover new agrochemicals with poly-heterocyclic features, a series of novel triazole thione/thioether derivatives containing pyridylpyrazole motif (8-11) wassynthesized.The new compounds were identified by melting point, 1H NMR, 13C NMR, 19F NMR, HRMS,and elemental analysis. The bioassaysshowed that most of the pyridylpyrazole-containing triazole thione Mannich bases possessed favorable in vitrofungicidal activitytoward pathogenic fungi, such as Magnaporthe oryzae, Sclerotinia sclerotiorum, Botrytis cinerea andFusarium verticillioides, and were comparable with those of the contrast compounds Aand triadimefon. Some of them exhibited moderate to good in vivofungicidal activityagainst S. sclerotiorumat 0.2 mg/mL(e.g. 8fcontrol efficacy: 60.9±3.2%).The SEM observation displayed that 8f might cause disruptionof cell membrane and wall of S. sclerotiorum.Compounds 8a, 8c, 8f-8h, 8pand 9bcan serve as promising new fungicidal agents to make further structural optimization.The findings in this article provide useful clue and guidance for the design and development of new poly-heterocyclic agrochemicals.

1H and 13C NMR and FTIR Spectroscopic Analysis of Formic Acid Dissociation Dynamics in Water.

The formation and transport of ionic charges in formic acid-water (HCOOH-H2O) mixtures with initial water mole fractions ranging from XH2Oi = 0 to 1 were investigated using 13C and 1H NMR, FTIR spectroscopy, viscosity, conductivity, and pH measurements. The maximum molar concentration of ions (H3O+ and HCOO-), along with the relative differences between theoretical and experimental densities, spin-lattice relaxation times (T1), activation energies (Ea), viscosity (η), and conductivity (σ), were identified within the range of XH2Oi ≈ 0.5-0.7. These results indicate that pure formic acid (FA) solutions predominantly consist of cyclic dimers at room temperature. As the water mole fraction increases up to 0.6, a structural shift occurs from cyclic dimers to a mixture of linear and cyclic dimers, driven by the formation of strong hydrogen bonds. Beyond a water mole fraction of 0.6, the structure transitions to linear dimers, with FA molecules behaving as free entities in the water. Furthermore, the acidity was found to increase approximately 2-fold with every 0.1 increment in water mole fraction. These findings are critical for understanding the kinetics of formic acid anions in body fluids, the structure of the hydrogen bonding network, and ionization energies.

Synthesis and Anti-Inflammatory and Analgesic Potentials of Ethyl 2-(2,5-Dioxo-1-Phenylpyrrolidin-3-yl)-2-Methylpropanoate.

Background/Objectives: Inflammation and analgesia are two prominent symptoms and often lead to chronic medical conditions. To control inflammation and analgesia, many marketed drugs are in practice but the majority of them have severe side effects. Methods: This study involved the synthesis of a pivalate-based Michael product and evaluated it for in vitro COX-1, COX-2, and 5-LOX inhibitory potentials using specific assays. Molecular docking studies were also assessed. Based on the in vitro results, the compound was also subjected to in vivo anti-inflammatory and antinociceptive studies. Results: The pivalate-based Michael product (MAK01) was synthesized by an organocatalytic asymmetric Michael addition of ethyl isobutyrate to N-phenylmaleimide with an isolated yield of 96%. The structure of the compound was confirmed through 1H and 13C NMR analyses. The observed IC50 values for COX-1, COX-2, and 5-LOX were 314, 130, and 105 μg/mL, respectively. The molecular docking studies on the synthesized compound showed binding interactions with the minimized pockets of the respective enzymes. In a carrageenan model, a percent reduction in edema when administered at 10 mg/kg (a reduction of 33.3 ± 0.77% at the second hour), 20 mg/kg (a reduction of 34.7 ± 0.74% at the second hour), and 30 mg/kg (a reduction of 40.58% ± 0.84% after the fifth hour) was observed. The compound showed a significant response at concentrations of 50, 100, and 150 mg/kg with latency times of 10.32 ± 0.82, 12.16 ± 0.51, and 12.93 ± 0.45 s, respectively. Conclusion: In this study, we synthesized a pivalate-based Michael product for the first time. Moreover, based on its rationality and potency, it was found to be an effective future medicine for the management of analgesia and inflammation.

Engaging Two Anions with Single Cation in Energetic Salts: Approach for Optimization of Oxygen Balance in Energetic Materials.

The field of high energy density materials faces a long-standing challenge to achieve an optimum balance between energy and stability. While energetic salt formation via a combination of oxygen- and nitrogen-rich anions (providing energy) with nitrogen-containing cations (providing stability) has been a proven approach for improving physical stability, constraints such as lowering density and energetic performance remain unresolved. This can be addressed by utilizing oxygen-containing cations for salt formation. However, this approach is rarely explored because its synthesis is challenging. In this work, we have designed an oxygen-rich cationic precursor 2 by incorporating 4-amino-3,5-dinitropyrazole with 3,4-diaminotriazole via an N-methylene-C bridge. Further combination with energetic acids resulted in the formation of high-performing, physically stable energetic salts 3-10. The salts were found to be generally more energetic than the salts of respective energetic acids with previously reported cations and showed prominent improvement in physical stability with respect to their anionic precursors. All the compounds were thoroughly characterized through IR, NMR spectroscopy, HRMS, and elemental analysis. Salt 9 was confirmed through 15N NMR analysis, and salts 2 and 8 were confirmed through single-crystal X-ray diffraction. Additional analyses such as Hirshfeld surface analysis, noncovalent interaction (NCI) analysis, and electrostatic potential studies were also carried out to correlate the structure-property relationship.

Unraveling the Facet-Dependent Surface Chemistry at Molecular Scale: Photoassisted Oxidation of InP Nanocrystals.

The facet-dependent surface chemistry of nanocrystals (NCs) provides fundamental insights into chemical reactivities, which are critical for obtaining precise control over the NC surface. In this study, by obtaining InP NCs with well-defined {111} and {110}/{-1-1-1} facets (tetrahedrons and tetrapods, respectively) capped with chloride-oleylamine ligands, the previously underinvestigated facet-dependent surface chemistry of III-V materials is explored. Solid-state and solution NMR analyses show that InP tetrahedrons, with their smaller surface heterogeneity (single facet composition and lesser edge/vertex contribution) and stronger Lewis acidity, exhibit narrow 31P and 115In resonances as well as deshielded 13C signals of α-carbon adjacent to the NH2 group of oleylamine. As a result, InP tetrahedra exhibit strong ligand binding and a notable presence of less-mobile oleylamine ligands on the surface, leading to the blocking of access to external species. This is also consistent with the minimal blue shift of the first excitonic peak in absorption spectra and the strong resistance to photoassisted surface oxidation of InP tetrahedrons. Our findings, supported by solid-state/solution NMR, FT-IR, and XPS analyses, highlight the significance of facet-dependent reactivities to surface ligands and, thus, atmospheric moieties, enhancing the potential of III-V NCs in various optoelectronic applications.

Solvent‐free synthesis of medium chain triacylglycerols by esterification of capric, caprylic acids with 1, 3‐specific and non‐specific lipases

AbstractMedium chain triacylglycerols (MCTs) are used as a functional oil in various food and pharmaceutical formulations because of their numerous health benefits and physical properties. Enzymatic esterification of glycerol with caprylic (C8:0) and capric acids (C10:0) in a molar ratio of 1:3.5 [50% (C8:0) and 50% (C10:0)] was carried out for the solvent free synthesis of MCTs using 5% (w/w) 1,3 specific lipase, Lipozyme RM IM and non‐specific lipase, Novozym 435 in the presence of molecular sieves (10%) and low pressure conditions (50 and 150 mbar) at 50°C. Novozym 435 was more effective in the esterification reaction under 50 mbar reduced pressure, achieving ~54.74% triacylglycerol formation in 6 h, compared to Lipozyme RMIM, which achieved ~31.25% under the same conditions. Further reactions with Novozym 435 for 24 h showed that the maximum formation of MCTs occurred at 20 h (86.46 ± 3%), after which the reaction reached equilibrium. When 50 mbar was used, the formation of triacylglycerols enhanced 13 times compared with the results obtained at atmospheric pressure condition. Chemical characterization of the final MCTs confirmed the formation of four triacylglycerol species (TAG (8:0/8:0/8:0), TAG (8:0/8:0/10:0), TAG (8:0/10:0/10:0), and TAG (10:0/10:0/10:0) with LC–MS and NMR analysis. The melting and crystallization points of the synthesized oil was found to be −3.47°C and −23.48°C, respectively. Our findings contribute to developing a green process for synthesizing MCTs using two different fatty acids. The final product can be used as a nutraceutical oil or as an ingredient to enhance the food's physical properties.

Solid-State NMR Analysis of the Dynamics of Cofactors: Comparison of Heliobacterial and Purple Bacterial Reaction Centers.

Photosynthetic reaction centers (RCs) serve as natural engines converting solar energy to chemical energy. Understanding the principles of efficient charge separation and light-induced electron transfer (ET) between the chlorophyll-type pigments might guide the synthesis for artificial photosynthetic systems. We present detailed insight into the dynamics at the atomic level using solid-state NMR techniques applied to the RCs of Heliobacillus (Hb.) mobilis (HbRCs) and the purple bacterium Rhodobacter (R.) sphaeroides (PbRCs). It is assumed that heliobacteria were among the first phototrophic organisms; therefore, their RC can be regarded as ancient. They are constructed homodimerically with perfect C2 symmetry, enabling ET over both branches of cofactors. Modern RCs of R. sphaeroides wild-type (WT) have higher redox power and are functionally highly asymmetric. The dynamics of the cofactors in both RCs has been explored using nuclear hyperpolarization, induced by the solid-state photochemically induced dynamic nuclear polarization (photo-CIDNP) effect. Based on the individual incorporation of 13C positions of the cofactors (through supplementation by 13C-δ-aminolevulinic acid), photo-CIDNP magic-angle spinning (MAS) NMR experiments provide access to the local dynamics of the cofactors along the ET path over a broad range of time scales. Theoretical analysis of the dynamic deformation of these macrocycles is also discussed in terms of function. The dynamics observed in HbRCs appears to be correlated to ET. The cofactors in PbRC are significantly less dynamic than those in the HbRC. Relevance for efficiency and redox properties are discussed.

Studies on the synthesis, crystal structures, biological activities and molecular docking of novel natural methylxanthine derivatives containing piperazine moiety.

A series of novel methylxanthine Mannich base derivatives containing substituted piperazine groups were synthesized through Mannich reaction. The structures of these new compounds were confirmed by NMR, HRMS or elemental analyses, and X-ray single crystal diffraction. Bioassay results showed that some of the compounds exhibit favorable fungicidal and insecticidal potentials. Particularly, compounds IIk, IIq, IIs and compounds If, IIk against Physalospora piricola and Rhizoctonia cerealis, respectively, were comparable with Azoxystrobin and Chlorothalonil; compound Ik exhibited higher potency than Triflumuron against Plutella xylostella L., suggesting its potential as a lead compound for further development in insecticidal applications. Despite possessing weak herbicidal activities, the target compounds, especially the methylxanthine S-Mannich base derivatives I displayed remarkable inhibitory activities toward ketol-acid reductoisomerase (KARI); compounds Ib, If, and Ik which had Ki values of 2.41-8.08 µmol/L can be novel potent KARI inhibitors for deeper exploration. The SARs were analyzed in detail. The molecular docking studies on the highly active inhibitors with KARI provided possible binding modes between inhibitor and the target enzyme. The physicochemical parameter predictions indicated that compounds Ik, IIk, IIq and IIs have "druglike structure" features. The research results in this article may bring a new inspiration to the extensive explorations on new methylxanthine derivatives in pesticide area.

Chalcogen Bond-Driven Alkylations: Selenoxide-Pillar[5]arene as a Recyclable Catalyst for Displacement Reactions in Water.

A novel strategy to catalyze alkylation reactions through chalcogen bond interaction using a supramolecular structure is presented herein. Utilizing just 1.0 mol % of selenoxide-pillar[5]arene (P[5]SeO) as the catalyst we achieved efficient catalysis in the cyanation of benzyl bromide in water. Our approach demonstrated high efficiency and effectiveness, with the results supported by designed control experiments and theoretical models, highlighting the catalytic effect of the pillar[5]arene through noncovalent interactions. Quantum-chemical calculations (ωB97X-D/def2-TZVP@SMD) pointed out that the catalyzed cyanation reaction followed an SN2-like mechanism, with energy barriers (ΔH≠) ranging from 16.7 to 18.2 kcal mol-1, exhibiting dissociative character depending on the para-substituent. 1H NMR analysis revealed that P[5]SeO acted as a catalyst through inclusion complex formation, facilitating the transfer of the electrophilic substrate to the aqueous solution for nucleophilic displacement. Our reaction protocol proved applicable to various substrates, including aromatic and alpha-carbonyl derivatives. The use of sodium azide as the nucleophile was also feasible. Importantly, our method allowed scalability, and the catalyst P[5]SeO could be recovered and reused effectively for multiple reaction cycles, showcasing sustainability.