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Nature Communications Jun 2024The generation of alkyl radical from C(sp)-H substrates via hydrogen atom abstraction represents a desirable yet underexplored strategy in alkylation reaction since...
The generation of alkyl radical from C(sp)-H substrates via hydrogen atom abstraction represents a desirable yet underexplored strategy in alkylation reaction since involving common concerns remain adequately unaddressed, such as the harsh reaction conditions, limited substrate scope, and the employment of noble metal- or photo-catalysts and stoichiometric oxidants. Here, we utilize the synergistic strategy of photoredox and hydrogen atom transfer (HAT) catalysis to accomplish a general and practical functionalization of unactived C(sp)-H centers with broad reaction scope, high functional group compatibility, and operational simplicity. A combination of validation experiments and density functional theory reveals that the N-centered radicals, generated from free N - H bond in a stepwise electron/proton transfer event, are the key intermediates that enable an intramolecular 1,5-HAT or intermolecular HAT process for nucleophilic carbon-centered radicals formation to achieve heteroarylation, alkylation, amination, cyanation, azidation, trifluoromethylthiolation, halogenation and deuteration. The practical value of this protocol is further demonstrated by the gram-scale synthesis and the late-stage functionalization of natural products and drug derivatives.
PubMed: 38876986
DOI: 10.1038/s41467-024-49337-3 -
Nature Communications Jun 2024Chiral 1,2,3-triazoles are highly attractive motifs in various fields. However, achieving catalytic asymmetric click reactions of azides and alkynes for chiral triazole...
Chiral 1,2,3-triazoles are highly attractive motifs in various fields. However, achieving catalytic asymmetric click reactions of azides and alkynes for chiral triazole synthesis remains a significant challenge, mainly due to the limited catalytic systems and substrate scope. Herein, we report an enantioselective azidation/click cascade reaction of N-propargyl-β-ketoamides with a readily available and potent azido transfer reagent via copper catalysis, which affords a variety of chiral 1,2,3-triazoles with up to 99% yield and 95% ee under mild conditions. Notably, chiral 1,5-disubstituted triazoles that have not been accessed by previous asymmetric click reactions are also prepared with good functional group tolerance.
PubMed: 38858346
DOI: 10.1038/s41467-024-49313-x -
Chemical Science Jun 2024Despite significant research, the mechanistic nuances of unusual reactivity at the air-water interface, especially in microdroplets, remain elusive. The likely...
Despite significant research, the mechanistic nuances of unusual reactivity at the air-water interface, especially in microdroplets, remain elusive. The likely contributors include electric fields and partial solvation at the interface. To reveal these intricacies, we measure the frequency shift of a well-defined azide vibrational probe at the air-water interface, while independently controlling the surface charge density by introducing surfactants. First, we establish the response of the probe in the bulk and demonstrate that it is sensitive to both electrostatics and hydrogen bonding. From interfacial spectroscopy we infer that the azide is neither fully hydrated nor in a completely aprotic dielectric environment; instead, it experiences an intermediate environment. In the presence of hydrogen bond-accepting sulphate surfactants, competition arises for interfacial water with the azide. However, the dominant influence stems from the electrostatic effect of their negative heads, resulting in a significant blue-shift. Conversely, for the positive ammonium surfactants, our data indicate a balanced interplay between electrostatics and hydrogen bonding, leading to a minimal shift in the probe. Our results demonstrate partial solvation at the interface and highlights that both hydrogen bonding and electrostatics may assist or oppose each other in polarizing a reactant, intermediate, or product at the interface, which is important for understanding and tuning interfacial reactivity.
PubMed: 38846382
DOI: 10.1039/d4sc01311e -
Heliyon Jun 2024Linseed is a valuable oilseed crop with huge therapeutic importance due to its high content of omega-3 fatty acids in the form of Alpha-linolenic acid (ALA). It is a...
Linseed is a valuable oilseed crop with huge therapeutic importance due to its high content of omega-3 fatty acids in the form of Alpha-linolenic acid (ALA). It is a self-pollinated crop with a low-yielding potential that restricts its improvement endeavors. To overcome low-yielding potential, individual and combination treatments of gamma rays and sodium azide were employed in widely grown linseed varieties. The results revealed a dose-dependent decline in seed germination, seedling height, pollen fertility, chlorophyll, and carotenoid contents and a dose-independent decline in carbonic anhydrase activity. Bio-physiological parameters decreased substantially in combination treatments compared to individual treatments of gamma rays and sodium azide. In contrast, lower doses of gamma rays, sodium azide, and their combinations effectively increased mean values of yield and yield-attributing traits in a few putative mutants. Such putative mutants represent a valuable genetic resource that could be used in future breeding programs for the genetic improvement of linseed and related medicinal plants.
PubMed: 38845881
DOI: 10.1016/j.heliyon.2024.e31329 -
Acta Crystallographica. Section E,... May 2024The title compound, tetra-ethyl-ammonium...
The title compound, tetra-ethyl-ammonium tri-azido-tri-μ-sulfido-[μ-(tri-methyl-sil-yl)aza-nediido][tris-(3,5-di-methyl-pyrazol-1-yl)hydro-borato]triiron(+2.33)molybdenum(IV), (CHN)[FeMoS(CHBN)(CHNSi)(N)] or (EtN)[(Tp*)MoFeS(μ-NSiMe)(N)] [Tp* = tris-(3,5-di-methyl-pyrazol-1-yl)hydro-bor-ate(1-)], crystallizes as needle-like black crystals in space group . In this cluster, the Mo site is in a distorted octa-hedral coordination model, coordinating three N atoms on the Tp* ligand and three μ-bridging S atoms in the core. The Fe sites are in a distorted tetra-hedral coordination model, coordinating two μ-bridging S atoms, one μ-bridging N atom from MeSiN, and another N atom on the terminal azide ligand. This type of heterometallic and heteroleptic single cubane cluster represents a typical example within the Mo-Fe-S cluster family, which may be a good reference for understanding the structure and function of the nitro-genase FeMo cofactor. The residual electron density of disordered solvent mol-ecules in the void space could not be reasonably modeled, thus the SQUEEZE [Spek (2015). . C, 9-18] function was applied. The solvent contribution is not included in the reported mol-ecular weight and density.
PubMed: 38845704
DOI: 10.1107/S2056989024004833 -
Bio-design and Manufacturing 2024Melt extrusion-based additive manufacturing (ME-AM) is a promising technique to fabricate porous scaffolds for tissue engineering applications. However, most synthetic...
UNLABELLED
Melt extrusion-based additive manufacturing (ME-AM) is a promising technique to fabricate porous scaffolds for tissue engineering applications. However, most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate. Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct; however, there are limited strategies available to control the surface density. Here, we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone) (PCL) containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL at different ratios. Stable porous three-dimensional (3D) scaffolds were then fabricated using a high weight percentage (75 wt.%) of the low molecular weight PCL. As a proof-of-concept test, we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface, yielding a density of 201-561 pmol/cm. Subsequently, a bone morphogenetic protein 2 (BMP-2)-derived peptide was grafted onto the films comprising different blend compositions, and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) was assessed. After two weeks of culturing in a basic medium, cells expressed higher levels of BMP receptor II (BMPRII) on films with the conjugated peptide. In addition, we found that alkaline phosphatase activity was only significantly enhanced on films containing the highest peptide density (i.e., 561 pmol/cm), indicating the importance of the surface density. Taken together, these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface. Moreover, we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of (modified) polymers. Furthermore, the use of alkyne-azide "click" chemistry enables spatial control over bioconjugation of many tissue-specific moieties, making this approach a versatile strategy for tissue engineering applications.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s42242-024-00286-2.
PubMed: 38818303
DOI: 10.1007/s42242-024-00286-2 -
Chemical Science May 2024Most reported porous materials are either extended networks or monomeric discrete cavities; indeed, porous structures of intermediate size have scarcely been explored....
Most reported porous materials are either extended networks or monomeric discrete cavities; indeed, porous structures of intermediate size have scarcely been explored. Herein, we present the stepwise linkage of discrete porous metal-organic cages or polyhedra (MOPs) into oligomeric structures with a finite number of MOP units. The synthesis of these new oligomeric porous molecules entails the preparation of 1-connected (1-c) MOPs with only one available azide reactive site on their surface. The azide-terminated 1-c MOP is linked through copper(i)-catalysed azide-alkyne cycloaddition click chemistry with additional alkyne-terminated 1-c MOPs, 4-c clusters, or 24-c MOPs to yield three classes of giant oligomeric molecules: dimeric, tetrameric, or satellite-like, respectively. Importantly, all the giant molecules that we synthesised are soluble in water and permanently porous in the solid state.
PubMed: 38817590
DOI: 10.1039/d4sc01974a -
Science and Technology of Advanced... 2024Targeted nanoparticles offer potential to selectively deliver therapeutics to cells; however, their subcellular fate following endocytosis must be understood to properly...
Targeted nanoparticles offer potential to selectively deliver therapeutics to cells; however, their subcellular fate following endocytosis must be understood to properly design mechanisms of drug release. Here we describe a nanoparticle platform and associated cell-based assay to observe lysosome trafficking of targeted nanoparticles in live cells. The nanoparticle platform utilizes two fluorescent dyes loaded onto PEG-poly(glutamic acid) and PEG-poly(Lysine) block co-polymers that also comprise azide reactive handles on PEG termini to attach antibody-based targeting ligands. Fluorophores were selected to be pH-sensitive (pHrodo Red) or pH-insensitive (Alexafluor 488) to report when nanoparticles enter low pH lysosomes. Dye-labelled block co-polymers were further assembled into polyion complex micelle nanoparticles and crosslinked through amide bond formation to form stable nano-scaffolds for ligand attachment. Cell binding and lysosome trafficking was determined in live cells by fluorescence imaging in 96-well plates and quantification of red- and green-fluorescence signals over time. The platform and assay was validated for selection of optimal antibody-derived targeting ligands directed towards CD22 for nanoparticle delivery. Kinetic analysis of uptake and lysosome trafficking indicated differences between ligand types and the ligand with the highest lysosome trafficking efficiency translated into effective DNA delivery with nanoparticles bearing the optimal ligand.
PubMed: 38817250
DOI: 10.1080/14686996.2024.2351791 -
RSC Advances May 2024Two novel bicyclo[6.1.0]nonyne (BCN) linker derivatives, which can be directly incorporated into oligonucleotide sequences during standard automated solid-phase...
Two novel bicyclo[6.1.0]nonyne (BCN) linker derivatives, which can be directly incorporated into oligonucleotide sequences during standard automated solid-phase synthesis, are reported. Stabilities of BCN-carbinol and two BCN-oligonucleotides are evaluated under acidic conditions. In addition, derivatized BCN linkers (non-acidic and acid treated) are evaluated for strain-promoted alkyne-azide cycloaddition (SPAAC).
PubMed: 38813131
DOI: 10.1039/d3ra08732h -
Nature Communications May 2024Phosphanorcaradienes are an appealing class of phosphorus compounds that can serve as synthons of transient phosphinidenes. However, the synthesis of such species is a...
Phosphanorcaradienes are an appealing class of phosphorus compounds that can serve as synthons of transient phosphinidenes. However, the synthesis of such species is a formidable task owing to their intrinsic high reactivity. Herein we report straightforward synthesis, characterization and reactivity studies of a phosphanorcaradiene, in which one of the benzene rings in the flanking fluorenyl substituents is intramolecularly dearomatized through attachment to the phosphorus atom. It is facilely obtained by the reduction of phosphorus(III) dichloride precursor with potassium graphite. Despite being thermally robust, it acts as a synthetic equivalent of a transient phosphinidene. It reacts with trimethylphosphine and isonitrile to yield phosphanylidene-phosphorane and 1-phospha-3-azaallene, respectively. When it is treated with one and two molar equivalents of azide, iminophosphane and bis(imino)phosphane are isolated, respectively. Moreover, it is capable of activating ethylene and alkyne to afford [1 + 2] cycloaddition products, as well as oxidative cleavage of Si-H and N-H bonds to yield secondary phosphines. All the reactions proceed smoothly at room temperature without the presence of transition metals. The driving force for these reactions is most likely the high ring-constraint of the three-membered PC ring and recovery of the aromaticity of the benzene ring.
PubMed: 38811584
DOI: 10.1038/s41467-024-49042-1