Search Results (284)

Sulfur(VI) fluoride exchange (SuFEx) chemistry is a powerful click reaction for modular synthesis, distinguished by high chemoselectivity, broad functional-group tolerance and the formation of robust sulfur(VI)-based linkages. These attributes are particularly valuable for polymer functionalization, as S(VI)–F handles on either the polymer or the modifier enable covalent coupling under controlled conditions. This review spans SuFEx-mediated post-polymerization modification and architectural control of synthetic polymers, surface, interfacial and porous-material functionalization, and SuFEx-based conjugation and covalent capture in natural and sequence-defined biopolymers. Across these contexts, we compare the advantages, supporting mechanistic and analytical evidence, current limitations and future opportunities of SuFEx-enabled polymer functionalization. Full article

The emergence of antifungal resistance highlights the need for new chemotypes with improved biological activity. In this study, a series of new 3-CF₃-1,2,4-triazin-6(1H)-ones was synthesized via a (3+3)-cycloaddition of in situ-generated CF₃-nitrile imines with amino acid esters, followed by DDQ-mediated chemoselective oxidation of the corresponding 4,5-dihydro intermediates. The compounds were evaluated for antifungal, antibacterial, and cytotoxic activities. The synthesized derivatives displayed selective antifungal activity, whereas only weak antibacterial and cytotoxic effects were observed. The highest potency was observed for C(5)-unsubstituted derivatives, which exhibited the broadest antimicrobial spectrum and inhibited the growth of Candida albicans, Trichophyton rubrum, and Epidermophyton floccosum with MIC₅₀ values below 4 mg/L. In addition, the dermatophytes showed a biphasic dose-dependent response, characterized by growth stimulation at low concentrations and inhibition at higher concentrations, consistent with hormesis. These findings identify trifluoromethylated 1,2,4-triazin-6(1H)-ones, particularly C(5)-unsubstituted derivatives, as promising scaffolds for the development of new antifungal agents. Full article

A sustainable and scalable one-pot impregnation protocol, avoiding high-temperature calcination/activation, was employed to prepare Pd/Al₂O₃ (0.24 wt%), Pd/TiO₂ (0.18 wt%), Pd/ZrO₂ (0.21 wt%), Pd/SiO₂ (0.37 wt%), Rh/Al₂O₃ (0.18 wt%), and Rh/TiO₂ (0.15 wt%). Support effects on activity, selectivity, and recyclability of these low-metal content heterogeneous catalysts were investigated, using (E)-cinnamaldehyde and levulinic acid as probe molecules. In cinnamaldehyde hydrogenation, Pd catalysts were highly effective for chemoselective C=C reduction to 3-phenylpropanal under mild conditions, with Pd/TiO₂ displaying the highest activity and robust performance over several recycles. However, the Lewis acidity of TiO₂ promoted a solvent-involving side reaction in 2-propanol, with hemiacetal and ether formation, highlighting that apparent selectivity is strongly shaped by support acidity and product residence time. Rh/Al₂O₃ exhibited lower activity than Pd analogues but near-quantitative selectivity to the saturated aldehyde, whereas Rh/TiO₂ again favored hemiacetal formation. In levulinic acid hydrogenation, Pd catalysts were essentially inactive toward ketone hydrogenation even at elevated temperature and H₂ pressure, while Rh catalysts achieved high productivity with exclusive formation of γ-valerolactone, Rh/Al₂O₃ being the most active at comparatively mild pressures. Full article

Protein-based biosensors require controlled and site-selective functionalization strategies to enable stable and oriented immobilization without compromising protein structure and signal transduction efficiency. We evaluated a chemoselective linchpin-directed modification (LDM) approach targeting Lys–His pairs as a tool for site-specific labeling of the model fluorescent biosensor green fluorescent protein (GFP). LDM molecules with variable spacer lengths were prepared, and a structure-guided computational workflow was implemented to map Lys–His distances on the protein and identify candidate modification sites. Experimental validation by UV-Vis spectroscopy and mass spectrometry demonstrated efficient conjugation and a final degree of labeling close to unity, consistent with single-site modification, with all LDM molecules selectively targeting the same histidine residue (His181), independently of spacer length. Structural analysis revealed that this residue is located within an accessible internal cavity that favors productive interactions with the reactive group. Importantly, the modification preserves GFP fluorescence and pH response, confirming retention of sensing functionality. These results demonstrate that LDM enables selective modification not only of surface residues, but also of structurally guided, non-surface residues. This approach provides the proof of concept of a new, promising strategy for the controlled functionalization and immobilization of protein-based biosensors. Full article

We report a highly chemoselective N-sulfonylation of 3-(methylthio)-1H-1,2,4-triazol-5-amine with 4-nitrobenzenesulfonyl chloride promoted by N,N-diisopropylethylamine in acetonitrile under mild conditions. This transformation selectively affords N-(4-nitrophenyl)sulfonylation at the N1 position of the 1,2,4-triazole ring over the exocyclic amine functionality. The product was fully characterized by IR, 1D and 2D NMR spectroscopy, as well as high-resolution mass spectrometry, unequivocally confirming its molecular structure. Full article

The synthesis of hydroxamic acids from sterically hindered substrates, such as abietane-type resin acids, remains a synthetic challenge due to the congestion of the tricyclic skeleton. This study reports an efficient one-pot protocol for the direct conversion of abietic and dehydroabietic acids into their corresponding hydroxamic derivatives, achieving 65% and 74% isolated yields, respectively. Systematic screening of activating agents identified diethyl chlorophosphate (DCP) as the reagent for the hydroxyamidation. A critical finding of this work is that the optimization of the isolation process specifically minimizing the water amount during aqueous work-up was key to recovering these polar products and preventing important yield loss. The reaction proceeds through diethyl phosphate mixed anhydride intermediate, which was successfully isolated, providing direct experimental evidence of the activation pathway. The reaction mechanism was further elucidated using Density Functional Theory (DFT) calculations at the M062X/6-31G** level, identifying a concerted transition state for the simultaneous addition of hydroxylamine and expulsion of the phosphate group. Furthermore, the study rationalizes the observed chemoselectivity; although the ester is the more stable thermodynamic product, the formation of the N-hydroxy amide is kinetically favored through a substantially lower activation barrier. This combined experimental and theoretical approach establishes a practical and scalable methodology for the functionalization of abundant similar natural terpenoids. Full article

Molecular on-surface photochemistry has emerged as a promising alternative to thermal activation for fabricating low-dimensional carbon-based nanomaterials, offering unique advantages such as non-thermal initiation and high chemoselectivity. Controlling the selectivity and efficiency of on-surface photoreactions remains challenging due to the complex interplay among molecular excitation pathways, substrate properties, and reaction conditions. This review briefly summarizes recent advances in light-driven on-surface synthesis under ultra-high-vacuum conditions. We focus on molecular photoexcitation pathways that can be probed by scanning tunneling microscopy and spectroscopy (STM and STS). Studies of light-driven reactions in three categories are overviewed, i.e., dehalogenative C-C coupling, [2+2] and [4+4] cycloadditions, and photoisomerization. Typical strategies for tuning reactivity are exemplified, including molecular pre-organization via self-assembly, surface passivation, and wavelength/polarization control. The summary of successful case studies may not only facilitate the fundamental understanding of on-surface photochemistry but also inspire the design of functional low-dimensional architectures and light-responsive molecular devices. Full article

Silk fibroin (SF) is an ideal biomaterial for next-generation clinical wound dressings due to its biocompatibility and tunable mechanical properties. Cell therapies for wound healing have explored using SF as the base for delivering beneficial cargo; however, retention is poor due to exudate “wash out.” To address concerns with the premature release of cargo from SF-fabricated wound dressings, we utilized amine-reactive chemistry to conjugate SF mats with azido-reactive dibenzocyclooctyne (DBCO) that can then attach complementary azido-tagged cargo through chemoselective immobilization. SF mats were made using electrospinning of a 1:1 SF/PCL solution and were then conjugated with N-Hydroxysuccinimide-dibenzocyclooctyne ester (DBCO). PBS soaking was used for control SF mats. SF mats were then imaged and characterized using the following metrics: pore size, fiber alignment, fiber distribution, fiber diameter, ultimate tensile strength, tangent modulus, proteolytic degradation, absorption, and retention. Successful DBCO conjugation of SF mats was confirmed through the presence of the Az-Cy5 dye while exhibiting no significant changes to the DBCO SF mats in any of the tested metrics compared to controls. Our results provide evidence that the amine chemistry responsible for the DBCO conjugation does not alter important SF mat properties. This confirms that DBCO augmentation paired with Az-Cy5 tags may be a viable approach for immobilizing different therapeutic cargoes to aid wound healing efforts. Full article

Whole-cell biocatalysis presents a sustainable and efficient approach for the selective reduction in α,β-unsaturated bonds in flavonoid derivatives. This study investigates the capability of yeast strains from the Yarrowia clade to catalyze the chemoselective reduction of 4′-methoxychalcone (1a) to its dihydro derivative. All tested strains exhibited similarly high hydrogenation activity, indicating a broadly conserved enoate reductase function within the clade. Among them, Yarrowia lipolytica KCh 71, previously reported and well characterized in the literature, was selected for preparative-scale transformation of a diverse series of synthetic methoxychalcones bearing additional methoxy groups in positions C-2, C-3, C-4, C-5, and C-6 of ring B. All derivatives were effectively converted into the corresponding dihydrochalcones, with yields ranging from 62% to 92%. Among the tested derivatives, the 2′,4′,6′-trimethoxy chalcone (7a) did not undergo biotransformation under our conditions, whereas mono- and di-methoxy derivatives (2a–6a) were efficiently reduced. These results confirm the broad substrate tolerance, high efficiency, and potential scalability of Y. lipolytica KCh 71, supporting its potential as a whole-cell biocatalyst for the sustainable synthesis of bioactive dihydrochalcones. The consistently high hydrogenation activity observed across 21 tested strains suggests the involvement of evolutionarily conserved enoate reductases. Bioinformatic analysis supports that the Yarrowia clade possesses a robust complement of Old Yellow Enzymes (OYE), providing a reliable enzymatic basis for the observed chemoselective reductions. All Yarrowia tested strains showed the same general transformation type, although the extent and rate of conversion differed among strains, and Y. lipolytica KCh 71 was one of the most tolerant. The broad reduction in α,β-unsaturated chalcones is consistent with the action of flavoenzymatic ene-reductases, particularly Old Yellow Enzyme (OYE)–like reductases. Bioinformatic analysis of Yarrowia genomes reveals putative OYE homologs, supporting this mechanistic interpretation, although the specific enzymes were not identified in this study. Full article

A systematic study of the chemoselectivity of the reduction of 3-methylcyclohex-2-enone (seudenone) to 3-methylcyclohex-2-enol (seudenol) was performed. Two approaches were investigated, namely the reduction of this ketone using NaBH₄ with modifiers and Catalytic Transfer Hydrogenation (CTH). The former resulted in higher conversions (95–99%) and high selectivity (up to 95%), whereas with CTH, a selectivity of 100% was achieved, albeit with a low conversion. The study therefore demonstrated that it is possible to chemoselectively reduce an α,β-unsaturated ketone in the liquid phase CTH using MgO as the catalyst and 2-pentanol as the hydrogen donor. The application of modifiers such as CeCl₃ · 7H₂O and MCl₂, where M = Be, Mg, Ca, Sr, and Ba, resulted in a significant improvement of the chemoselectivity (up to 95%) of the reduction with NaBH₄. The effect of parameters such as the solvent mixture composition, reaction temperature and modifier:NaBH₄ molar ratio was also investigated. In CTH, although high conversions of the ketone were observed for Al₂O₃, ZrO₂ and MgO in the vapor phase, the first two did not yield 3-methylcyclohex-2-enol among the obtained products. It was shown that 3-methylcyclohex-3-enol was the main product of the transformations of 3-methylcyclohex-2-enone in the presence of MgO, with yields of 25–33%. In a series of experiments, it was shown that 3-methylcyclohex-3-enol is formed as a result of the transformation of 3-methylcyclohex-2-enol in the presence of MgO as a catalyst. Full article

1,3-Dipolar cycloaddition reactions of nitrile imines are a powerful tool for the construction of spirocyclic frameworks, yet controlling chemoselectivity remains challenging when dipolarophiles contain multiple reactive sites. In this study, we investigated the cycloaddition of nitrile imines with 5-arylmethylene-2-methylthiohydantoins, which possess both exocyclic C=C and endocyclic C=N bonds. Nitrile imines were generated from hydrazonoyl chlorides under basic conditions and reacted with the thiohydantoin substrates under optimized reaction conditions. The cycloaddition proceeded smoothly, affording spiro-fused thiohydantoin–pyrazoline derivatives. In all cases, the reaction occurred selectively at the exocyclic C=C bond, while the C=N bond remained unreactive even in the presence of excess dipole. This chemoselectivity is attributed to the greater steric accessibility of the exocyclic double bond. These results clarify key factors governing nitrile imine chemoselectivity and provide a reliable approach to structurally complex spirocyclic thiohydantoin derivatives. Full article

Alkyl-substituted pyridines are ubiquitous structural motifs found in natural products, pharmaceuticals, agrochemicals, and functional organic materials. However, their direct synthesis remains challenging because of the electron-deficient nature of the pyridine ring and the harsh conditions typically required for conventional carbonyl-to-alkane reduction. Herein, we report a mild and environmentally benign Pd/C–H₂ catalytic system that enables one-pot oxidative aromatization–deoxygenation of dihydropyridinedione derivatives to afford alkyl-substituted pyridines. The transformation proceeds efficiently at room temperature under atmospheric hydrogen pressure using ethanol as a green solvent, delivering the desired products in up to 91% isolated yield. The protocol exhibits broad substrate scope, high chemoselectivity, operational simplicity, and excellent catalyst recyclability. Mechanistic studies, including hydrogen-free control experiments and intermediate isolation, support a sequential Pd-mediated pathway involving oxidative aromatization, stepwise hydrogen-transfer reduction, and final deoxygenation, with water as the sole stoichiometric by-product. This method provides a sustainable and scalable alternative to classical harsh or reagent-intensive deoxygenation strategies for the synthesis of alkyl-substituted pyridines. Full article

Lanthanide coordination polymers have been developed at a fast rate during the past two decades due to their appealing applications in the modern field of materials science and emerging technologies like luminescence, magnetism, sensing, gas adsorption, and catalysis. The role of lanthanides in imparting specific properties to the coordination polymers has been fully documented in extensive studies carried out by numerous research groups. It has been shown that because lanthanide(III) ions possess a variable coordination number, they readily build two-dimensional and three-dimensional architectures with definite channels, permanent pores, and distinct surface areas. Due to their strong oxophilic propensity and hard Lewis acid character, lanthanides favor the construction of stable coordination polymers and MOF configurations by strongly binding the coordinating groups of the organic linkers. Associated with palladium complexes, the lanthanide ions provide synergistic effects with Lewis acid sites, beneficial to the catalytic activity. These attractive characteristics of lanthanides enabled them to be fruitfully applied in Pd-Ln coordination polymers with catalytic properties. This review covers an array of Pd-Ln coordination polymers applied as heterogeneous catalysts in Suzuki–Miyaura C(sp²)-C(sp²) cross-coupling reactions. The activity and chemoselectivity of Pd(II) ions and Pd nanoparticles associated in coordination polymers with different lanthanides from a selected array of rare earth elements (Eu, Sm, Eu, Gd, Pr, Nd, Ce, La, or Tb) is discussed. High yields (>99%) are attained under optimized reaction conditions. The specific role of lanthanides and organic ligands in creating sustainable and recyclable heterogeneous Pd catalysts is evidenced. Mechanistic aspects of the C(sp²)-C(sp²) cross-coupling reactions are considered. The synergistic interaction between lanthanides and palladium as well as with the organic ligands is highlighted. Full article

Expanding the chemical diversity of DNA–encoded libraries (DELs) is crucial for identifying binders to emerging drug targets using DEL technology. In the present study, as part of our ongoing efforts to develop on–DNA diazide platforms (D–DAPs)—platform molecules possessing both aromatic and aliphatic azide groups on a single core reactive scaffold—we designed and synthesized a new compact diazide platform, designated as a compact D–DAP (C–D–DAP). This molecule is based on a low–molecular–weight reactive scaffold, 3–azido–5–(azidomethyl)benzoic acid, to facilitate small–molecule drug discovery targeting enzymes and G protein–coupled receptors (GPCRs). Furthermore, we established two distinct stepwise warhead construction strategies that exploit the chemoselective transformations of the azide groups in the C–D–DAP, which exhibit different reactivities. In addition, four virtual DELs were generated based on stepwise warhead elaboration from the C–D–DAP scaffold. Comparative chemical diversity analysis against bioactive compounds from ChEMBL revealed that these virtual libraries populate structural regions that are sparsely represented among known molecules. Each virtual library also occupies a distinct region of structural space relative to the others and displays intermediate quantitative estimate of drug–likeness (QED) values. Full article

Haloketoesters are synthetic intermediates in various cyclization reactions that facilitate the production of biologically active compounds. Nonetheless, the selective synthesis of dihaloketoesters and trihaloketoesters, which are expected to be highly versatile, presents significant challenges. In this study, we designed a new synthetic approach that selectively and efficiently produces haloketoesters through the halogenative C–C bond cleavage and ring-opening reactions of cyclic 1,3-diketones. This convenient method enables the direct synthesis of di- and trichloro-functionalized ketoesters from 1,3-cyclohexadiones under mild conditions. Na₂HPO₄, employed as a buffer salt, proved to be effective in facilitating the alcoholytic ring-opening reaction of 2,2-dichloro-1,3-cyclohexadiones, which were generated as synthetic intermediates. Full article