623-11-0Relevant articles and documents
Effect of Malt-PEG-Abz@RSL3 micelles on HepG2 cells based on NADPH depletion and GPX4 inhibition in ferroptosis
Cheng, Xu,Gao, Chuya,Gong, Chen,Li, Wenhua,Liu, Xiaoying,Peng, Haisheng,Tang, Shukun,Tao, Haiquan,Yang, Bo,Zhang, Wenyuan
, (2021)
Ferroptosis is a regulated cell death pathway which depends on iron. Ferroptosis can be induced by limiting intracellular glutathione (GSH) synthesis, or inhibiting the activity of GPX4, or increasing intracellular accumulation of PE-AA-OOH, all of which involve NADPH. Therefore, NADPH depletion, excessive PE-AA-OOH, and GPX4 deficiency are generally considered to be the main characteristics of ferroptosis. In this research, the novel self-assembly nanomicelles modified by maltose ligand (Malt-PEG-Abz@RSL3) with superior nano characteristics were designed and fabricated. Malt-PEG-Abz@RSL3 micelles achieved active targeted drug delivery due to the high expression of glucose transporter (GLUT) and high uptake by HepG2 cells. Maltose-polyethylene glycol broke to release RSL3 for inhibiting GPX4 activity when Malt-PEG-Abz@RSL3 micelles entered the cells. Meanwhile, key coenzyme NADPH that participated in synthesis of GSH and Trx(SH)2 was depleted by azobenzene moiety, resulting in decreasing GSH and Trx(SH)2, which dually induced ferroptosis in tumour cells and promoted cell apoptosis.
Rhodium(III)-catalyzed regioselective C–H nitrosation/annulation of unsymmetrical azobenzenes to synthesize benzotriazole N-oxides via a RhIII/RhIII redox-neutral pathway
Zhang, Yuanfei,Chen, Zhe-Ning,Su, Weiping
supporting information, (2021/05/19)
A Rh(III)-catalyzed regioselective C–H nitrosation/annulation reaction of unsymmetrical azobenzenes with [NO][BF4] has been developed to achieve high-yielding syntheses of benzotriazole N-oxides with excellent functional group tolerance. Computational studies have revealed that this oxidative C–H functionalization reaction involves an interesting redox-neutral Rh(III)/Rh(III) pathway without the change of Rh oxidation state.
Understanding Mechanistic Differences between 3-Diazoindolin-2-Imines and N-Sulfonyl-1,2,3-Triazoles in the Rh2(II)-Catalyzed Reactions with Nitrosoarenes
Bao, Xiaoguang,Fu, Rui,Gao, Ke,Kou, Luyao,Zhou, Shaofang
supporting information, p. 1565 - 1572 (2021/05/28)
The employment of α-iminometallocarbenes to construct valuable N-containing compounds has attracted significant research interest. Herein, the nucleophilic addition of nitrosoarenes with the α-imino rhodium carbene species (I), which is derived from Rh2(II)-catalyzed denitrogenation of 3-diazoindolin-2-imines, to produce synthetically useful 2-iminoindolin-nitrones is described. Mechanistically, the N-attack of nitrosoarenes with the carbene site of I is proposed. For the analogous Rh2(II)-catalyzed reaction of nitrosoarenes with N-sulfonyl-1,2,3-triazoles reported by Li and co-workers (Org. Lett. 2014, 16, 6394), however, the O-attack of nitrosoarenes with the carbene site of α-imino rhodium carbene species (II) is more favorable to occur than the N-attack. The subsequent transformation to yield the product of N-acylamidines is rationalized based on computational studies. The mechanistic differences for the reactions of nitrosoarenes with α-imino rhodium carbene species I and II are discussed.
Reversible Photoswitchable Inhibitors Generate Ultrasensitivity in Out-of-Equilibrium Enzymatic Reactions
Teders, Michael,Pogodaev, Aleksandr A.,Bojanov, Glenn,Huck, Wilhelm T. S.
supporting information, p. 5709 - 5716 (2021/05/07)
Ultrasensitivity is a ubiquitous emergent property of biochemical reaction networks. The design and construction of synthetic reaction networks exhibiting ultrasensitivity has been challenging, but would greatly expand the potential properties of life-like materials. Herein, we exploit a general and modular strategy to reversibly regulate the activity of enzymes using light and show how ultrasensitivity arises in simple out-of-equilibrium enzymatic systems upon incorporation of reversible photoswitchable inhibitors (PIs). Utilizing a chromophore/warhead strategy, PIs of the protease α-chymotrypsin were synthesized, which led to the discovery of inhibitors with large differences in inhibition constants (Ki) for the different photoisomers. A microfluidic flow setup was used to study enzymatic reactions under out-of-equilibrium conditions by continuous addition and removal of reagents. Upon irradiation of the continuously stirred tank reactor with different light pulse sequences, i.e., varying the pulse duration or frequency of UV and blue light irradiation, reversible switching between photoisomers resulted in ultrasensitive responses in enzymatic activity as well as frequency filtering of input signals. This general and modular strategy enables reversible and tunable control over the kinetic rates of individual enzyme-catalyzed reactions and makes a programmable linkage of enzymes to a wide range of network topologies feasible.
Photochromic controlled permeable small molecule cross-linked vesicle as well as preparation method and application thereof
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Paragraph 0033-0036, (2021/09/01)
The invention discloses a photochromic controlled-permeation small-molecule crosslinked vesicle CSMVs as well as a preparation method and application thereof. Belong to micromolecule self-assembly technical field. The invention firstly synthesizes an azobenzene amphiphilic compound, and then further cross-linking to prepare the photochromic controllable permeable small-molecule cross-linked vesicle. The controlled release system is simple to prepare, high in stability, intelligent in control, and capable of exhibiting real-time controllable permeability in time and space, CSMVs at the molecular level due to the molecular structure of the vesicle wall, and instantaneous controlled release is exhibited. In cancer. The method has wide application prospects in the accurate treatment of diseases such as diabetes and bacterial infection.
Azobenzene-Based Cross-Linked Small-Molecule Vesicles for Precise Oxidative Damage Treatments Featuring Controlled and Prompt Molecular Release
Yao, Yongchao,Yu, Yunlong,Wan, Xiaohui,Yan, Daoping,Chen, Ying,Luo, Jianbin,Vancso, G. Julius,Zhang, Shiyong
, p. 7357 - 7366 (2021/10/01)
Precise therapy has become prevalent in clinical practice owing to its accurate and efficient targeting treatment of diseases. Such treatments involving polymersomes as carriers have great potential to lesion sites without damage to normal tissues. However, due to the inherent thick hydrophobic layer of polymersomes, an instantaneous release response to external stimuli remains a challenge. To tackle this challenge, here, we report on the synthesis and applications of azobenzene-containing photochromic vesicles as delivery vectors. These vesicles are assembled from small-molecule amphiphiles that have been developed to provide a fast response and promote instantaneous release due to molecular size reduction compared with macromolecular polymersomes. After cross-linking, the stability of vesicles under a physiological environment is notably enhanced. By varying UV and visible light irradiation, the “gate” of vesicles can be opened and closed reversibly for the controlled release of capsuled cargoes. In vitro experiments display that the vesicles can be applied to load cysteamine for eliminating excess reactive oxygen. The synthesized vesicles here show high performance in controlled and instantaneous release in cells both in time and space. By our approach, oxidative damage to cellular biomolecules can be substantially reduced.
Phenylimino Indolinone: A Green-Light-Responsive T-Type Photoswitch Exhibiting Negative Photochromism
Buma, Wybren Jan,Crespi, Stefano,Di Donato, Mariangela,Doria, Sandra,Feringa, Ben L.,Hilbers, Michiel F.,Kiss, Ferdinand L.,Simeth, Nadja A.,Stindt, Charlotte N.,Szymański, Wiktor,Toyoda, Ryojun,Wesseling, Sammo
supporting information, p. 25290 - 25295 (2021/10/25)
Imines are photoaddressable motifs useful in the development of new generations of molecular switches, but their operation with low-energy photons and control over isomer stability remain challenging. Based on a computational design, we developed phenylimino indolinone (PIO), a green-light-addressable T-type photoswitch showing negative photochromism. The isomerization behavior of this photoactuator of the iminothioindoxyl (ITI) class was studied using time-resolved spectroscopies on time scales from femtoseconds to the steady state and by quantum-chemical analyses. The understanding of the isomerization properties and substituent effects governing these photoswitches opens new avenues for the development of novel T-type visible-light-addressable photoactuators based on C=N bonds.
Selective Mild Oxidation of Anilines into Nitroarenes by Catalytic Activation of Mesoporous Frameworks Linked with Gold-Loaded Mn3O4 Nanoparticles
Armatas, Gerasimos S.,Daikopoulou, Vassiliki,Koutsouroubi, Eirini D.,Lykakis, Ioannis N.,Skliri, Euaggelia
, (2021/11/01)
This work reports the synthesis and catalytic application of mesoporous Au-loaded Mn3O4 nanoparticle assemblies (MNAs) with different Au contents, i. e., 0.2, 0.5 and 1 wt %, towards the selective oxidation of anilines into the corresponding nitroarenes. Among common oxidants, as well as several supported gold nanoparticle platforms, Au/Mn3O4 MNAs containing 0.5 wt % Au with an average particle size of 3–4 nm show the best catalytic performance in the presence of tert-butyl hydroperoxide (TBHP) as a mild oxidant. In all cases, the corresponding nitroarenes were isolated in high to excellent yields (85–97 %) and selectivity (>98 %) from acetonitrile or greener solvents, such as ethyl acetate, after simple flash chromatography purification. The 0.5 % Au/Mn3O4 catalyst can be isolated and reused four times without a significant loss of its activity and can be applied successfully to a lab-scale reaction of p-toluidine (1 mmol) leading to the p-nitrotulene in 83 % yield. The presence of AuNPs on the Mn3O4 surface enhances the catalytic activity for the formation of the desired nitroarene. A reasonable mechanism was proposed including the plausible formation of two intermediates, the corresponding N-aryl hydroxylamine and the nitrosoarene.
Photochromic Evaluation of 3(5)-Arylazo-1 H-pyrazoles
Rustler, Karin,Nitschke, Philipp,Zahnbrecher, Sophie,Zach, Julia,Crespi, Stefano,K?nig, Burkhard
, p. 4079 - 4088 (2020/04/09)
The desire to photocontrol molecular properties ranging from materials to pharmacology using light as an external trigger with high spatiotemporal resolution led to the development of a broad range of photochromic scaffolds. Among them, azobenzenes are synthetically well accessible and show excellent fatigue resistance. Their photochromic properties vary with the substitution pattern and for different heteroarenes. However, the photochromism of 3(5)-substituted-1H-pryazoles has not yet been investigated, although this compound class offers interesting possibilities of metal ion coordination and hydrogen bond formation via its NH moiety. Herein, we present the results of an experimental and computational investigation of arylazo-3(5)-arylazo-1H-pyrazoles. To elucidate their properties, solvent and substitution effects on their light absorption, thermal half-lives, photostationary states, fatigue, and quantum yields were determined.
Photoswitchable Conjugated Oligoelectrolytes for a Light-Induced Change of Membrane Morphology
Bazan, Guillermo C.,Leifert, Dirk,Limwongyut, Jakkarin,Mikhailovsky, Alexander A.,Moreland, Alex S.
supporting information, p. 20333 - 20337 (2020/09/07)
The synthesis of a new conjugated oligoelectrolyte (COE), namely DSAzB, is described, which contains a conjugated core bearing a diazene moiety in the center of its electronically delocalized structure. Similar to structurally related phenylenevinylene-based COEs, DSAzB readily intercalates into model and natural lipid bilayer membranes. Photoinduced isomerization transforms the linear trans COE into a bent or C-shape form. It is thereby possible to introduce DSAzB into the bilayer of a cell and disrupt its integrity by irradiation with light. This leads to controlled permeabilization of membranes, as demonstrated by the release of calcein from DMPG/DMPC vesicles and by propidium iodide influx experiments on S. epidermidis. Both experiments support that the permeabilization is selective for the light stimulus, highly efficient, and repeatable. Target-selective and photoinduced actions demonstrated by DSAzB may have broad applications in biocatalysis and related biotechnologies.
