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Organic & Biomolecular Chemistry Jun 2024Herein, the synthesis of branched α,β-unsaturated amides by a hydroaminocarbonylation reaction of alkynes with various amine substrates such as aromatic amines,...
Herein, the synthesis of branched α,β-unsaturated amides by a hydroaminocarbonylation reaction of alkynes with various amine substrates such as aromatic amines, aliphatic amines, solid amine sources like NHHCO, and even strongly basic piperidines is reported, using a Pd(OAc)/hybrid N-heterocyclic carbene-phosphine-phosphine (CPP) catalytic system. The reactions feature no additives, wide substrate scope, high selectivity (b/l > 99 : 1) and excellent yields. Mechanistic studies have disclosed that the reaction takes place a palladium hydride pathway. CPP adopts a hybrid bidentate ligand conformation with a carbene-phosphine coordination mode, wherein one phosphorus atom remains externally accessible, potentially serving as a stabilizing auxiliary during catalytic cycles.
PubMed: 38915273
DOI: 10.1039/d4ob00644e -
ACS Chemical Biology Jun 2024Quenched activity-based probes (qABP) are invaluable tools to visualize aberrant protease activity. Unfortunately, most studies so far have only focused on cysteine...
Quenched activity-based probes (qABP) are invaluable tools to visualize aberrant protease activity. Unfortunately, most studies so far have only focused on cysteine proteases, and only a few studies describe the synthesis and use of serine protease qABPs. We recently used phosphinate ester electrophiles as a novel type of reactive group to construct ABPs for serine proteases. Here, we report on the construction of qABPs based on the phosphinate warhead, exemplified by probes for the neutrophil serine proteases. The most successful probes show sub-stoichiometric reaction with human neutrophil elastase, efficient fluorescence quenching, and rapid unquenching of fluorescence upon reaction with target proteases.
PubMed: 38913607
DOI: 10.1021/acschembio.3c00203 -
ACS Catalysis May 2024This report describes a detailed study of Ni phosphine catalysts for the Suzuki-Miyaura coupling of dichloropyridines with halogen-containing (hetero)aryl boronic acids....
This report describes a detailed study of Ni phosphine catalysts for the Suzuki-Miyaura coupling of dichloropyridines with halogen-containing (hetero)aryl boronic acids. With most phosphine ligands these transformations afford mixtures of mono- and diarylated cross-coupling products as well as competing oligomerization of the boronic acid. However, a ligand screen revealed that PPhMe and PPh afford high yield and selectivity for monoarylation over diarylation as well as minimal competing oligomerization of the boronic acid. Several key observations were made regarding the selectivity of these reactions, including: (1) phosphine ligands that afford high selectivity for monoarylation fall within a narrow range of Tolman cone angles (between 136° and 157°); (2) more electron-rich trialkylphosphines afford predominantly diarylated products, while less-electron rich di- and triarylphosphines favor monoarylation; (3) diarylation proceeds via intramolecular oxidative addition; and (4) the solvent (MeCN) plays a crucial role in achieving high monoarylation selectivity. Experimental and DFT studies suggest that all these data can be explained based on the reactivity of a key intermediate: a Ni-π complex of the monoarylated product. With larger, more electron-rich trialkylphosphine ligands, this π complex undergoes intramolecular oxidative addition faster than ligand substitution by the MeCN solvent, leading to selective diarylation. In contrast, with relatively small di- and triarylphosphine ligands, associative ligand substitution by MeCN is competitive with oxidative addition, resulting in selective formation of monoarylated products. The generality of this method is demonstrated with a variety of dichloropyridines and chloro-substituted aryl boronic acids. Furthermore, the optimal ligand (PPhMe) and solvent (MeCN) are leveraged to achieve the Ni-catalyzed monoarylation of a broader set of dichloroarene substrates.
PubMed: 38911467
DOI: 10.1021/acscatal.4c00648 -
Spectrochimica Acta. Part A, Molecular... Jun 2024Nitroxyl (HNO), a reactive nitrogen species (RNS), is essential for plant growth. However, the action of HNO in plants has been difficult to understand due to the lack...
Nitroxyl (HNO), a reactive nitrogen species (RNS), is essential for plant growth. However, the action of HNO in plants has been difficult to understand due to the lack of highly sensitive and real-time in-situ monitoring tools. Herein, we presented a near-infrared fluorescent probe, DCI-HNO, based on dicyanoisophorone fluorophore, for real-time mapping HNO in plants. The introduction of a phosphine moiety as a specific HNO recognition unit can inhibit the intramolecular charge transfer (ICT) of probe DCI-HNO. However, in the presence of HNO, the ICT process occurred, leading to the emission at 665 nm. Probe DCI-HNO exhibited high sensitivity (97 nM), rapid response time (8 min), large Stokes shift (135 nm) for detection of HNO in plants. The novel developed probe has successfully imaged endogenous HNO produced during NO/HS cross-talk in plant tissues. Additionally, the up-regulated in HNO levels during tobacco aging and in response to stress has been confirmed. Therefore, probe DCI-HNO has provided a reliable method for monitoring the NO/HS cross-talk and revealing the role of HNO in plants.
PubMed: 38905899
DOI: 10.1016/j.saa.2024.124672 -
Food Chemistry Jun 2024A validated silver nanoparticle assay (SNaP-C) for quantitation of Vitamin C, as ascorbic acid (AA) and total AA (TAA), was applied to 31 beverages. SNaP-C assay results...
A validated silver nanoparticle assay (SNaP-C) for quantitation of Vitamin C, as ascorbic acid (AA) and total AA (TAA), was applied to 31 beverages. SNaP-C assay results (LOD of 2.2 mg/L AA) were compared to AA and TAA determined by high-performance liquid chromatography with UV/Vis (LOD = 0.4 mg/L AA), and two well-known assays. All approaches were calibrated using meta-phosphoric acid stabilized AA, where the reducing agent tris(2-carboxyethyl) phosphine hydrochloride was added to convert dehydroascorbic acid to AA for determination of TAA. Statistical comparisons of these four resulting datasets were completed. SNaP-C and HPLC were not statistically significantly different (P > 0.05) for comparison of AA and TAA (mg/L) in these samples, whereas the CUPRAC and Folin-Ciocalteu assays statistically significantly overestimated values of AA and TAA content, respectively. The SNaP-C method is a novel assay that has high specificity for AA capable of quantifying TAA with addition of TCEP.
PubMed: 38905840
DOI: 10.1016/j.foodchem.2024.140112 -
Chemical Communications (Cambridge,... Jun 2024A silver-catalyzed chemoselective cascade nucleophilic addition of a P-centered anion to isocyanides and cyclization reaction was developed for the efficient and...
A silver-catalyzed chemoselective cascade nucleophilic addition of a P-centered anion to isocyanides and cyclization reaction was developed for the efficient and practical synthesis of a wide range of 2-phosphinoyl indole and indol-3-ol derivatives. Unlike the well-documented synthesis of phosphorus-functionalized heterocycles a P-centered radical, an anionic reactivity profile of phosphine oxides is most likely involved in this domino transformation.
PubMed: 38904457
DOI: 10.1039/d4cc01984a -
Chemical Science Jun 2024Palladium-catalyzed selective cleavage of the distal C-C bond and proximal C-C bond of keto-vinylidenecyclopropanes by altering the sterically bulky phosphine ligands...
Palladium-catalyzed selective cleavage of the distal C-C bond and proximal C-C bond of keto-vinylidenecyclopropanes by altering the sterically bulky phosphine ligands has been realized. The proximal C-C bond cleavage can be achieved by using dtbpf as a phosphine ligand, affording bicyclic products containing dihydrofuran skeletons in good yields along with broad substrate scope. In proximal C-C bond cleavage reactions, the eight-membered cyclic palladium intermediate plays a key role in the reaction. The [3 + 2] cycloaddition of keto-vinylidenecyclopropanes through the distal C-C bond cleavage can be effectively accomplished with BuXPhos as a phosphine ligand and ZnCl as an additive, delivering bicyclic products containing tetrahydrofuran skeletons in good yields. The further transformation of these bicyclic products has been demonstrated, and the reaction mechanisms of two different C-C bond cleavage reactions have been investigated by control experiments and DFT calculations.
PubMed: 38903235
DOI: 10.1039/d4sc02536a -
Angewandte Chemie (International Ed. in... Jun 2024Palladium-catalyzed coupling reactions of small nucleophiles are of great interest, but challenging due to difficulties in selectivity control. Herein, we report the...
Palladium-catalyzed coupling reactions of small nucleophiles are of great interest, but challenging due to difficulties in selectivity control. Herein, we report the development of a new platform of P,N-ligands consisting of ylide-functionalized phosphines with aminophosphonium groups (NYPhos) to address this challenge. These phosphine ligands are easily accessible in a wide structural diversity with highly modular electronic and steric properties. Based on a family of 14 ligands the selective monoarylation of acetone as well as other challenging ketones and amides was accomplished with record-setting activities even for aryl chlorides at room temperature including late-stage functionalizations of drug molecules. Moreover, ammonia and other small primary amines could be coupled at mild conditions. Isolation and structure analyses of palladium complexes within the catalytic cycle confirmed the P,N-coordination mode necessary to reach the observed selectivities and proved the facile adjustability of the N-donor strength, which is beneficial for the targeted design of tailored P,N-ligands for future applications.
PubMed: 38899792
DOI: 10.1002/anie.202408947 -
RSC Pharmaceutics Jun 2024A mucus gel layer lines the luminal surface of tissues throughout the body to protect them from infectious agents and particulates. As a result, nanoparticle drug...
A mucus gel layer lines the luminal surface of tissues throughout the body to protect them from infectious agents and particulates. As a result, nanoparticle drug delivery systems delivered to these sites may become trapped in mucus and subsequently cleared before they can reach target cells. As such, optimizing the properties of nanoparticle delivery vehicles, such as their surface chemistry and size, is essential to improving their penetration through the mucus barrier. In previous work, we developed a mucin-based hydrogel that has viscoelastic properties like that of native mucus which can be further tailored to mimic specific mucosal tissues and disease states. Using this biomimetic hydrogel system, a 3D-printed array containing synthetic mucus barriers was created that is compatible with a 96-well plate enabling its use as a high-throughput screening platform for nanoparticle drug delivery applications. To validate this system, we evaluated several established design parameters to determine their impact on nanoparticle penetration through synthetic mucus barriers. Consistent with the literature, we found nanoparticles of smaller size and coated with a protective PEG layer more efficiently penetrated through synthetic mucus barriers. In addition, we evaluated a mucolytic (tris(2-carboxyethyl) phosphine, TCEP) for use as a permeation enhancer for mucosal drug delivery. In comparison to -acetyl cysteine (NAC), we found TCEP significantly improved nanoparticle penetration through a disease-like synthetic mucus barrier. Overall, our results establish a new high-throughput screening approach using synthetic mucus barrier arrays to identify promising nanoparticle formulation strategies for drug delivery to mucosal tissues.
PubMed: 38899149
DOI: 10.1039/d3pm00057e -
Inorganic Chemistry Jul 2024Bioinspired tungsten acetylene complexes containing pyridine-2-selenolato (PySe) or 6-methyl-pyridine-2-selenolato (6-MePySe) ligands were synthesized. Se NMR...
Bioinspired tungsten acetylene complexes containing pyridine-2-selenolato (PySe) or 6-methyl-pyridine-2-selenolato (6-MePySe) ligands were synthesized. Se NMR spectroscopy allowed for an assessment of the resonance structures in the pyridine-2-selenolato ligands and the rationalization of chemoselectivity observed in regard to 1,2 migratory insertion of HC≡CH. [W(CO)(CH)(CHCH-PySe)(PySe)] is formed exclusively via insertion of HC≡CH into the W-N bond, while the use of bulkier 6-MePySe allows for the isolation of [W(CO)(CH)(6-MePySe)], which only partially reacts with excess HC≡CH to give [W(CO)(CH)(CHCH-6-MePySe)(6-MePySe)]. Oxidation of [W(CO)(CH)(6-MePySe)] with pyridine--oxide gave the tungsten(IV) complex [WO(CH)(6-MePySe)]. Complexes [W(CO)(CH)(6-MePySe)] and [WO(CH)(6-MePySe)] react with trimethyl phosphine to carbyne complex [W(CO)(CCHPMe)(PMe)(6-MePySe)]Cl and alkylidene complex [WO(CHCHPMe)(PMe)(6-MePySe)]Cl, respectively. The addition of substituted alkynes to [W(CO)(PySe)] via thermal decarbonylation gave complexes [W(CO)(MeC≡CMe)(PySe)] and [W(CO)(HC≡C-Bu)(PySe)], respectively. The here presented complexes are relevant for the modeling of the active site of acetylene hydratase from , in which a tungsten atom is enclosed in a sulfur-rich coordination sphere. A recently published theoretical study concluded that the exchange of sulfur for selenium would increase the activity of the enzyme. Our findings contrast this claim as comparative analysis concludes negligible structural and electronic differences between the selenium-based and previously published sulfur-based complexes.
PubMed: 38898818
DOI: 10.1021/acs.inorgchem.4c01636