Search Results (132)

DFT study of graphene functionalized via carbene was performed to identify the preferred –OH adsorption sites and to assess how hydroxylation affects adsorption of NH₃ gas. The carbene attaches to the graphene basal plane through a [2+1] cycloaddition, producing a local cyclopropane-like motif with a C–C bond. This modification introduces localized mid-gap states and asymmetric charge redistribution that create chemically active anchoring sites for –OH groups. We systematically scanned possible –OH adsorption sites and identified site-dependent binding energies. NH₃ preferentially anchors at the carbene center and is further stabilized by multidentate hydrogen bonding with neighboring –OH groups. Calculated NH₃ adsorption energies range from moderate values (single –OH and some two –OH symmetric sites, E_ads ≈ −0.64 to −0.75 eV) to strong interaction for selected through-plane two –OH pairs (E_ads ≈ −1.78 to −1.83 eV), where synergistic hydrogen bonding amplifies the NH₃ interaction. Charge density difference and Bader analyses indicate polarization-dominated binding with minimal net charge transfer, consistent with hydrogen bonding rather than covalent bond formation. Desorption time estimation shows that moderate binding motifs provide rapid recovery at room temperature. We conclude that targeted placement of paired –OH groups on carbene-functionalized graphene offers a tunable route to balance sensitivity and reusability for NH₃ sensing. Full article

Human African Trypanosomiasis (HAT; sleeping sickness) and Malaria are life-threatening protozoan infections in tropical regions, with limited treatment options. As part of our ongoing efforts to discover new aminosteroid alkaloids from the Buxaceae family with antiprotozoal activity, which might serve as leads to new drugs against these infections, we investigated the dichloromethane extract from the leaves of Buxus obtusifolia (Mildbr.) Hutch. collected in Kenya, a species native to Kenya and Tanzania. To the best of our knowledge, and based on the most recent comprehensive literature review, this study represents the first phytochemical investigation of this plant. The alkaloid-enriched fraction yielded a total of 24 aminosteroid alkaloids, including 18 hitherto undescribed compounds (2, 3, 5–9, 11, 12, 15–19, and 21–24), along with six known compounds, two of which (1 and 4) are described as constituents of a natural source for the first time. Obtusiaminocyclin (24) represents the first Buxus alkaloid with a novel carbocyclic steroid skeleton with a cyclopropane ring comprising C-9, C-19 and C-11 accompanied by an unprecedented amino bridge between C-3 and C-10. The structures of the isolated compounds were determined using UHPLC/+ESI-QqTOF-MS/MS and NMR spectroscopy. The total crude extract, the alkaloid-enriched fraction, CPC subfractions and all isolated compounds were tested for in vitro antiprotozoal activity against Trypanosoma brucei rhodesiense (Tbr, responsible for East African HAT) and Plasmodium falciparum (Pf, responsible for tropical Malaria) as well as cytotoxicity against mammalian cells (L6 cell line). Deoxycyclovirobuxeine-B (12) (IC₅₀ = 0.8 µmol/L, SI = 108) and 29-trimethoxybenzoyloxy-obtusibuxoline (5) (IC₅₀ = 0.5 µmol/L, SI = 11) showed the highest activities with good selectivity indices against Tbr and Pf, respectively. Consequently, our findings provide valuable aminosteroid candidates that can serve as promising leads in our ongoing search for new drugs against HAT and Malaria. Full article

Pyridinium ylides, along with related azaheterocyclic ylides, are widely used in synthetic organic chemistry. However, reactions that yield stable zwitterionic adducts from these ylides remain underexplored. In this work, we demonstrate that the reaction of pyrrole-2,3-diones with in situ-generated pyridine-based azomethine ylides affords stable zwitterionic adducts, which are typically transient species in analogous processes. These betaines are used as key intermediates for the synthesis of cyclopropane-fused pyrroles or pyridine-2,3-diones via thermolysis in chlorobenzene. Full article

Tungstophosphoric acid (TPA) has been supported on mesoporous silicas prepared using urea as the pore forming agent. The amount of urea (20, 30, or 40% w/w) influences the silica specific surface area (S_BET), total pore volume (Vp), and average pore diameter (Dp). The materials synthetized using 20% w/w (SiU20) display mainly mesoporous structures, with the highest Vp and Dp values being chosen to be used as TPA support. The SiU20-TPA solids with different TPA loadings (10, 20, or 30% w/w) have been used as supports for chiral copper catalysts with bis(oxazoline) or azabis(oxazoline) ligands. The catalytic efficiency of enantioselective cyclopropanation strongly depends on support morphology and TPA loading. SiU-TPA20 has been shown to be the optimal one. The stability of the complex is also a very important parameter, and the best results are obtained with an excess of chiral ligand to ensure the correct formation of the complex on the solid. In this way, with azabox-Cu/SiU20-TPA20 it is possible to obtain a highly selective (90% ee for the trans-cyclopropanes) and recoverable catalyst. Full article

Bacterial outer-membrane vesicles (OMVs) mediate stress tolerance, biofilm formation, and interkingdom communication, but their role in beneficial endophytes remains underexplored. We isolated 11 non-redundant isolates associated with Bacillus, Enterococcus, Kosakonia and Kocuria from Agave tequilana seeds, identified by MALDI-TOF MS and 16S rRNA gene sequencing. We focused on the catalase-negative Enterobacter cloacae SEA01, which exhibits plant-promoting traits and support agave growth under nutrient-poor microcosms. In addition, this endophyte produces OMVs. Time-resolved SEM documented OMV release and cell aggregation within 9 h, followed by mature biofilms at 24 h with continued vesiculation. Purified OMVs (≈80–300 nm) contained extracellular DNA and were characterized by dynamic light scattering and UHPLC–ESI–QTOF-MS lipidomics. The OMV lipidome was dominated by phosphatidylethanolamine (~80%) and was enriched in monounsaturated fatty acids (16:1, 18:1), while the stress-associated cyclopropane fatty acids (17:1, 19:1) were comparatively retained in the whole-cell membranes; OMVs also exhibited reduced ubiquinone-8. SEA01 is catalase-negative, uncommon among plant-associated Enterobacter, suggesting a testable model in which oxidative factors modulate OMV output and biofilm assembly. These may have implications for recognition and redox signaling at the root interface. Future works should combine targeted proteomics/genomics with genetic or chemical disruption of catalase/OMV pathways. Full article

Cyclopropanes are important in drug discovery because their unique structure, including inherent three-dimensionality, can enhance a drug’s properties, such as metabolic stability, target binding, and membrane permeability. In this communication, (5R*,6R*) 11-benzoyl-4,10-dimethyl-2,8-diphenyl-2,3,8,9-tetraazadispiro[4.0.4⁶.1⁵]undeca-3,9-diene-1,7-dione was prepared via a stereoselective one-pot reaction of phenylglyoxal hydrate with two equivalents of 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one in EtOH in the presence of sodium acetate and N-bromosuccinimide. The structure of the newly synthesized compound was established by ¹H and ¹³C NMR, IR spectroscopy, high-resolution mass spectrometry, and elemental analysis. Full article

Terpenes, representing one of the most extensive classes of natural products, hold significant value in the fields of pharmaceuticals, fragrances, and biofuels. Extracting these compounds from natural sources is often environmentally unsustainable, and the structural diversity found in nature is inherently limited. Metabolic engineering using microbial hosts offers a scalable and sustainable alternative, utilizing optimized biosynthetic pathways—such as the mevalonate (MVA) and the methylerythritol phosphate (MEP) pathways—to achieve high-yield production of natural terpene scaffolds. This review focuses on the various strategies in developing microbial cell factories, ranging from enhancing precursor supply to optimizing terpene synthase systems. A new and promising frontier is the increase in structural diversity of terpenes by integration of non-biological chemical transformations into engineered biosynthetic pathways. We discuss the use of artificial metalloenzymes such as engineered cytochrome P450 variants that catalyze non-natural carbene transfer reactions (cyclopropanation). The merging of synthetic biology and synthetic chemistry goes beyond the normal synthesizing capabilities found in nature, which may pave the way for the design of “non-natural” terpenoids that contain new additions and better capabilities. Full article

(+)-Isocampholenic acid, prepared in two steps from (1S)-(+)-10-camphorsulfonic acid in 60% yield (on a scale of 172 mmol), served as the starting compound for the synthesis of small libraries of isocampholenic acid derivatives, comprising a total of 60 compounds, which are of interest due to their olfactory properties. Although isocampholenic acid derivatives are thermodynamically up to 5.9 kcal/mol less stable than endocyclic alkene isomers according to DFT calculation, only minor (up to 2%) isomerization to α-campholenic acid isomers was observed in most cases. The products were fully characterized, and their odor properties were preliminarily assessed by untrained laypersons. This study represents the first systematic exploration of the chemical space of isocampholenic acid. Novel derivatives with distinct odor profiles were discovered, and promising directions for future functionalization for fragrance development were identified. Full article

Donor–acceptor (D–A) cyclopropanes are important precursors in the synthesis of complex molecules due to their bidentate character and high reactivity. Among them, cyclopropane-1,1-dicarbonitriles are less commonly reported in modern literature, primarily because of the high reactivity of the nitrile groups and their limited compatibility with metal-catalyzed processes, which is caused by the geometrical constraints imposed by the linear cyano substituents. While the cyano groups can be seen as a limitation, they also offer synthetic versatility by serving as handles for further functionalization. In this work, we performed a cycloaddition reaction with mercaptoacetaldehyde, leading to a new class of DA cyclopropanes bearing a thiazole moiety. This one-pot, two-step transformation requires only a single purification step. The resulting thiazolyl-substituted cyclopropanes were subjected to ring strain-release reactions, showing reactivity comparable to the parent cyclopropane-1,1-dicarbonitriles. Full article

The Red Sea is rich in symbiotic microorganisms that have been identified as sources of bioactive compounds with antimicrobial, antifungal, and antioxidant properties. In this study, we aimed to explore the potential of marine sponge-associated bacteria as sources of antibacterial compounds, emphasizing their significance in combating antibiotic resistance (AMR). The crude extracts of Micrococcus, Bacillus, and Staphylococcus saprophyticus exhibited significant antibacterial activity, with inhibition zones measuring 12 mm and 14 mm against Escherichia coli, Staphylococcus aureus, Candida albicans, and other infectious strains. The DPPH assay showed that the bacterial isolates AN3 and AN6 exhibited notable antioxidant activity at a concentration of 100 mg/mL. To characterize the chemical constituents responsible for the observed bioactivity, a GC–MS analysis was performed on ethyl acetate extracts of the potent strains. The analysis identified a range of antimicrobial compounds, including straight-chain alkanes (e.g., Tetradecane), cyclic structures (e.g., Cyclopropane derivatives), and phenolic compounds, all of which are known to disrupt microbial membranes or interfere with metabolic pathways. The bioprospecting and large-scale production of these compounds are challenging. In conclusion, this study underscores the potential for marine bacteria associated with sponges from the Red Sea to be a source of bioactive compounds with therapeutic relevance. Full article

Untapped bioactive compounds from microbial endophytes offer a promising solution to counter antimicrobial and chemotherapeutic drug resistance when complexed as silver nanoparticles (AgNPs). AgNPs were biosynthesized using cell-free supernatants from endophytic Streptomyces sp. KE4D and Bacillus safensis KE4K isolated from the Kenyan medicinal plant Teclea nobilis, following fermentation in three different media. Bacterial extracts were analyzed using gas chromatography–mass spectrometry. AgNPs were characterized using Fourier-transform infrared spectroscopy and high-resolution transmission electron microscopy. Antimicrobial activity was assessed using agar well diffusion assays, and quorum sensing inhibition (QSI) was investigated using Chromobacterium violaceum. Anti-cancer potential was evaluated against breast (MCF-7) and prostate cancer (DU-145) cell lines using MTT assays. AgNPs were 5–55 nm in size, with KE4D AgNPs being spherical and KE4K AgNPs exhibiting various shapes. Cyclopropane acetic acids and fatty acids were identified as possible capping agents. Medium-dependent antimicrobial activity was observed, with medium Mannitol and medium 5294 AgNPs displaying stronger activity, particularly against Gram-negative indicators. KE4D medium 5294 AgNPs demonstrated 85.12% violacein inhibition at 140 µg/mL and better QSI activity, whilst KE4K AgNPs were better antimicrobials. The AgNPs IC₅₀ values were <3.5 µg/mL for MCF-7 and <2.5 µg/mL for DU-145 cells. The bioactivity of biosynthesized AgNPs is influenced by the bacterial isolate and fermentation medium, suggesting that AgNP synthesis can be tailored for specific bioactivity. Full article

The [3+2] cycloaddition chemistry of (2S)-5-methylene-2-t-butyl-1,3-dioxolan-4-one, derived from lactic acid, has been examined, and spiro adducts have been obtained with benzonitrile oxide, acetonitrile oxide, diazomethane and diphenyldiazomethane. The structure and absolute stereochemistry of the benzonitrile oxide adduct has been confirmed by X-ray diffraction, and all the adducts have been fully characterised by ¹H and ¹³C NMR. Attempted cycloaddition with a nitrile sulfide, a nitrile imine and azides failed. Pyrolysis results in a range of novel gas-phase reactions, with the nitrile oxide adducts giving pivalaldehyde, CO₂, the nitrile and ketene, the diazomethane adduct losing only N₂ to give a cyclopropane-fused dioxolanone, and the diphenylcyclopropane derived from diphenyldiazomethane giving mainly benzophenone in a sequence involving the loss of pivalaldehyde and methyleneketene. Full article

In hay milk production, fermented feed, like silage, is forbidden. This study aims to reveal the presence of silages made from maize or grass in the diet of dairy cows through the detection of cyclopropane fatty acids (CPFAs) in their milk. It also investigates how CPFAs in their milk declines when the diets of the cows are transitioned from one containing silage to one that does not include silage. CPFAs were quantified in silages collected on the farm, and the relationship between the dietary intake of CPFAs from silages and the marker concentration in milk was investigated. Except for one sample (below LOQ), CPFAs were never detected in hay milk, while they were found in 98% and 85% of milk samples obtained from cows whose diet included maize or grass silage as the only fermented component, respectively. CPFAs were found to still be detectable in milk 56 days after the removal of maize silage from the diet, while they were no longer detectable about three weeks after removing grass silage from the ration. A quantitative positive relationship was detected between CPFAs content in the milk and the dietary intake of CPFAs from silages. CPFAs can be regarded as reliable markers to detect the occurrence of silages in the ration, but it is more effective for maize than for grass silage. Full article

This review probes the recent developments in stereoselective reactions within the area of sulfoxonium ylide chemistry since the early 2000s. An abundance of research has been applied to sulfoxonium ylide chemistry since its emergence in the early 1960s. There has been a continued effort since then with work in traditional areas, such as epoxidation, aziridination and cyclopropanation. Efforts have also been applied in novel areas, such as olefination and insertion reactions, to develop stereoselective methodologies using organocatalysis and transition metal catalysis. The growing research area of interrupted Johnson–Corey–Chaykovsky reactions is also described, whereby unexpected stereoselective cyclopropanation and epoxidation methodologies have been developed. In general, the most observed mechanistic pathway of sulfoxonium ylides is the formal cycloaddition: (2 + 1) (e.g., epoxides, cyclopropanes, aziridines), (3 + 1) (e.g., oxetanes, azetidines), (4 + 1) (e.g., indanones, indolines). This pathway involves the formation of a zwitterionic intermediate through nucleophilic addition of the carbanion to an electrophilic site. An intramolecular cyclization occurs, constructing the cyclic product. Insertion reactions of sulfoxonium ylides to X–H bonds (e.g., X = S, N or P) are also observed, whereby protonation of the carbanion is followed by a nucleophilic addition of X, to form the inserted product. Full article

The formation of the four 3-ring systems c-(CH₂)_3−k(SiH₂)_k ($k=0$: cyclopropane, $k=1$: silirane, $k=2$: disilirane, $k=3$: cyclotrisilane) by addition of methylene and silylene to the double bond in ethene, disilene, and silaethene, as well as the elimination of the carbene analogs from the 3-rings, was studied with CAS(4,4) wave functions in both $C_{2v}$ and $C_s$ symmetry. To reveal the charge and spin redistribution during these reactions the CAS(4,4) wave functions were analyzed using the orthogonal valence bond method (OVB). The potential energy curves, different internal coordinates, and the results of the OVB analysis show that, frequently, the addition and elimination reactions follow different minimum energy paths, because they are indeed diabatic reactions. In these cases, there are no energy barriers corresponding to saddle points on the potential energy surfaces but the energy increases during one diabatic reaction until, at a certain point, the system jumps to the other diabatic state and, in the following, the energy decreases. This happens for reactions in $C_{2v}$ symmetry; as soon as the system can change to the lower symmetry, the diabatic states combine to an adiabatic one and the reaction follows a single minimum energy path. Full article