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Biomaterials Nov 2020Driven by the clinical need for a strong tissue adhesive with elastomeric material properties, a departure from legacy crosslinking chemistries was sought as a...
Driven by the clinical need for a strong tissue adhesive with elastomeric material properties, a departure from legacy crosslinking chemistries was sought as a multipurpose platform for tissue mending. A fresh approach to bonding wet substrates has yielded a synthetic biomaterial that overcomes the drawbacks of free-radical and nature-inspired bioadhesives. A food-grade liquid polycaprolactone grafted with carbene precursors yields CaproGlu. The first-of-its-kind low-viscosity prepolymer is VOC-free and requires no photoinitiators. Grafted diazirine end-groups form carbene diradicals upon low energy UVA (365 nm) activation that immediately crosslink tissue surfaces; no pre-heating or animal-derived components are required. The hydrophobic polymeric environment enables metastable functional groups not possible in formulations requiring solvents or water. Activated diazirine within CaproGlu is uniquely capable of crosslinking all amino acids, even on wet tissue substrates. CaproGlu undergoes rapid liquid-to-biorubber transition within seconds of UVA exposure-features not found in any other bioadhesive. The exceptional shelf stability of CaproGlu allows gamma sterilization with no change in material properties. CaproGlu wet adhesiveness is challenged against current unmet clinical needs: anastomosis of spliced blood vessels, anesthetic muscle patches, and human platelet-mediating coatings. The versatility of CaproGlu enables both organic and inorganic composites for future bioadhesive platforms.
Topics: Adhesiveness; Animals; Biocompatible Materials; Diazomethane; Humans; Tissue Adhesives; Viscosity
PubMed: 32891870
DOI: 10.1016/j.biomaterials.2020.120215 -
Current Protocols Jul 2021This protocol enables identification of the interaction partners of O-GlcNAcylated proteins. The method involves the introduction of the diazirine photocrosslinker onto...
This protocol enables identification of the interaction partners of O-GlcNAcylated proteins. The method involves the introduction of the diazirine photocrosslinker onto the O-GlcNAc modification within living cells. The photocrosslinker is activated by UV light to yield covalent crosslinking between O-GlcNAcylated proteins and neighboring molecules. The binding partners can be further characterized by immunoblot or proteomics mass spectrometry methods. The benefits of using the photocrosslinker include the capacity to trap low-affinity binding interactions and the ability to selectively target the interaction partners of the O-GlcNAcylated form of the protein of interest. © 2021 Wiley Periodicals LLC. Basic Protocol 1: In-cell production and crosslinking of O-GlcNDAzylated proteins Basic Protocol 2: Immunoblot analysis to assess O-GlcNDAz crosslinking Support Protocol: Detection of UDP-GlcNDAz from cell lysates.
Topics: Acetylglucosamine; Diazomethane; Mass Spectrometry; Protein Processing, Post-Translational; Proteins
PubMed: 34288588
DOI: 10.1002/cpz1.201 -
Topics in Current Chemistry (Cham) Sep 2023Herein, recent developments for Selectfluor-mediated C-H functionalization of N-heteroarenes are described. This type of C-H bond activation is an attractive and... (Review)
Review
Herein, recent developments for Selectfluor-mediated C-H functionalization of N-heteroarenes are described. This type of C-H bond activation is an attractive and competitive alternative to traditional methodologies, allowing the functionalization of a variety of chemical functions. In addition, Selectfluor is a more sustainable and economically accessible oxidant compared with expensive/toxic metals or hazardous peroxides. For a practical understanding, the current review classified systematically the reported strategies in four subsections as follows: (1) carbon-carbon formation, (2) carbon-nitrogen bond formation, (3) carbon-chalcogen bond, and (4) carbon-halogen bond formation. Mechanistic aspects and reaction conditions are fully discussed to provide an understanding of the aspects that govern C-H functionalization in N-heteroarenes mediated by Selectfluor.
Topics: Carbon; Diazonium Compounds; Nitrogen; Peroxides
PubMed: 37736818
DOI: 10.1007/s41061-023-00437-6 -
The Journal of Organic Chemistry Aug 2022To find their potential use in protein research, direct addition of a disulfide compound to alkyne (namely disulfide-yne reaction) and S-arylation with arenediazonium...
To find their potential use in protein research, direct addition of a disulfide compound to alkyne (namely disulfide-yne reaction) and S-arylation with arenediazonium salt (namely disulfide-diazonium reaction) were investigated in aqueous or protic solutions. The reaction of dimethyl disulfide with 5-hexynol performed best under 300 nm irradiation in the presence of sodium acetate to afford 5,6-bis(methylthio)-5-hexenol in 60% yield. Without the prior reduction of a disulfide bond to thiols, the disulfide-yne reactions have the advantage of 100% atom economy. Disulfide-diazonium reaction was triggered by sodium formate and accelerated by photoirradiation with a 450 nm LED lamp (5 W). The reaction of 3,4-dihydroxy-1,2-dithiane with 2-(prop-2-yn-1-yloxy)benzene-1-diazonium tetrafluoroborate () afforded 2-(benzofuran-3-yl)-1,3-dithiepane-5,6-diol (), confirming that both S substituents originate from the same disulfide molecule. The trastuzumab antibody was incubated with diazonium , followed by α-lytic protease digestion, LC-ESI-MS/MS analysis, and Mascot search, to verify that the proximal C229 and C232 residues on the same heavy chain were reconnected with a (benzofuranyl)methine moiety that originated from , unlike the expected disulfide rebridging across two heavy chains. Nonetheless, disulfide-diazonium reactions still have potential for rebridging disulfide bonds if appropriate proteins and diazonium agents are chosen.
Topics: Chromatography, Liquid; Disulfides; Proteins; Sulfhydryl Compounds; Tandem Mass Spectrometry
PubMed: 35815579
DOI: 10.1021/acs.joc.2c00903 -
Molecules (Basel, Switzerland) Jul 2016The synthesis of diazonium salts is historically an important transformation extensively utilized in dye manufacture. However the highly reactive nature of the diazonium...
The synthesis of diazonium salts is historically an important transformation extensively utilized in dye manufacture. However the highly reactive nature of the diazonium functionality has additionally led to the development of many new reactions including several carbon-carbon bond forming processes. It is therefore highly desirable to determine optimum conditions for the formation of diazonium compounds utilizing the latest processing tools such as flow chemistry to take advantage of the increased safety and continuous manufacturing capabilities. Herein we report a series of flow-based procedures to prepare diazonium salts for subsequent in-situ consumption.
Topics: Chemistry Techniques, Synthetic; Diazonium Compounds; Solid-Phase Synthesis Techniques; Temperature
PubMed: 27428944
DOI: 10.3390/molecules21070918 -
Molecules (Basel, Switzerland) May 2020The use of light-activated chemical probes to study biological interactions was first discovered in the 1960s, and has since found many applications in studying diseases... (Review)
Review
The use of light-activated chemical probes to study biological interactions was first discovered in the 1960s, and has since found many applications in studying diseases and gaining deeper insight into various cellular mechanisms involving protein-protein, protein-nucleic acid, protein-ligand (drug, probe), and protein-co-factor interactions, among others. This technique, often referred to as photoaffinity labelling, uses radical precursors that react almost instantaneously to yield spatial and temporal information about the nature of the interaction and the interacting partner(s). This review focuses on the recent advances in chemical biology in the use of benzophenones and diazirines, two of the most commonly known light-activatable radical precursors, with a focus on the last three years, and is intended to provide a solid understanding of their chemical and biological principles and their applications.
Topics: Benzophenones; Diazomethane; Photoaffinity Labels; Photochemistry
PubMed: 32414020
DOI: 10.3390/molecules25102285 -
Advanced Healthcare Materials Jun 2024Carbene-based bioadhesives have favourable attributes for tissue adhesion, including non-specific bonding to wet and dry tissues, but suffer from relatively weak...
Carbene-based bioadhesives have favourable attributes for tissue adhesion, including non-specific bonding to wet and dry tissues, but suffer from relatively weak fracture strength after photocuring. Light irradiation of carbene-precursor (diazirine) also creates inert side products that are absent under thermal activation. Herein, a dual activation method combines light irradiation at elevated temperatures for the evaluation of diazirine depletion and effects on cohesive properties. A customized photo/thermal-rheometer evaluates viscoelastic properties, correlated to the kinetics of carbene:diazoalkane ratios via F NMR). The latter exploits the sensitive -CF functional group to determine joule-based light/temperature kinetics on trifluoroaryl diazirine consumption. The combination of heat and photoactivation produced bioadhesives that are 3× tougher compared to control. Dual thermal/light irradiation may be a strategy to improve viscoelastic dissipation and toughness of photo-activated adhesive resins.
Topics: Methane; Diazomethane; Viscosity; Tissue Adhesives; Light; Materials Testing
PubMed: 38431774
DOI: 10.1002/adhm.202303666 -
Organic Letters Apr 2022Herein, we described an efficient method for the construction of highly functionalized diazirines from the carbohydrazide and diazo-substituted hypervalent iodine...
Herein, we described an efficient method for the construction of highly functionalized diazirines from the carbohydrazide and diazo-substituted hypervalent iodine reagents. Unambiguous transformation has been designed with user applicable and easy practicable conditions. Remarkably, d-glucose, menthol, aspirin, proline, and lithocholic acid were efficiently diazirinated. Furthermore, the method is mild, robust, and highly selective, which successfully converted a variety of aryl, alkyl, benzyl, and heterocyclic hydrazides into the corresponding diazirine derivatives.
Topics: Diazomethane; Indicators and Reagents; Iodides; Iodine
PubMed: 35412324
DOI: 10.1021/acs.orglett.2c00717 -
Current Computer-aided Drug Design Jul 2023Due to the biological importance of the benzoxazole derivatives, some 1-(benzo[d]oxazol-2-yl)-3,5-diphenyl-formazans (4a-f) were synthesized and screened for in-silico...
BACKGROUND
Due to the biological importance of the benzoxazole derivatives, some 1-(benzo[d]oxazol-2-yl)-3,5-diphenyl-formazans (4a-f) were synthesized and screened for in-silico studies and in-vitro antibacterial activity.
METHODS
The benzo[d]oxazole-2-thiol (1) was prepared by reacting with 2-aminophenol and carbon disulfide in the presence of alcoholic potassium hydroxide. Then 2-hydrazinylbenzo[d]oxazole (2) was synthesized from the reaction of compound 1 with hydrazine hydrate in the presence of alcohol. Compound 2 was reacted with aromatic aldehydes to give Schiff base, 2-(2-benzylidene-hydrazinyl)benzo[d]oxazole derivatives (3a-f). The title compounds, formazan derivatives (4a-f), were prepared by a reaction of benzene diazonium chloride. All compounds were confirmed by their physical data, FTIR, 1H-NMR, and 13CNMR spectral data. All the prepared title compounds were screened for in-silico studies and in-vitro antibacterial activity on various microbial strains.
RESULTS
Molecular docking against the 4URO receptor demonstrated that molecule 4c showed a maximum dock score of (-) 8.0 kcal/mol. MD simulation data reflected the stable ligand-receptor interaction. As per MM/PBSA analysis, the maximum free binding energy of (-) 58.831 kJ/mol was exhibited by 4c. DFT calculation data confirmed that most of the molecules were soft molecules with electrophilic nature.
CONCLUSION
The synthesized molecules were validated using molecular docking, MD simulation, MMPBSA analysis, and DFT calculation. Among all the molecules, 4c showed maximum activity. The activity profile of the synthesized molecules against tested micro-organisms was found to be 4c>4b>4a>4e>4f>4d.
PubMed: 37403393
DOI: 10.2174/1573409919666230703103135 -
Angewandte Chemie (International Ed. in... Mar 2021Aromatic compounds containing triazenyl groups (N RR') have a profound impact on synthetic organic and medicinal chemistry. In contrast, the chemistry of vinyl and... (Review)
Review
Aromatic compounds containing triazenyl groups (N RR') have a profound impact on synthetic organic and medicinal chemistry. In contrast, the chemistry of vinyl and alkynyl triazenes was a largely uncharted territory until recently. The situation has changed over the last five years, and it has become apparent that vinyl and alkynyl triazenes are highly interesting compounds with a unique reactivity. The electron-donating properties of the triazenyl group provide alkynyl triazenes with an ynamide-like reactivity, which can be exploited in reactions of the triple bond. Vinyl triazenes, on the other hand, can be used for electrophilic vinylation reactions. The foundation for this new triazene chemistry are synthetic pathways which allow preparing vinyl and alkynyl triazenes in few steps from readily available starting materials. In this Minireview, we summarize recent developments in this area.
PubMed: 33142011
DOI: 10.1002/anie.202011031