- Cascade photocaging of diazeniumdiolate: A novel strategy for one and two photon triggered uncaging with real time reporting
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We report a new strategy, viz. cascade photocaging, for protecting diethylamine diazeniumdiolate (O2-position), a light sensitive molecule. Upon photolysis, the cascade photocage at first releases the light activatable linker (latent fluorophore) O2-caged diazeniumdiolate, which undergoes spontaneous 1,8-elimination, triggering the release of the diazeniumdiolate anion and the fluorophore.
- Behara, Krishna Kalyani,Rajesh,Venkatesh, Yarra,Pinninti, Bhaskar Rao,Mandal, Mahitosh,Singh, N. D. Pradeep
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- Synthesis and evaluation of “Ama-Flash”, a photocaged amatoxin prodrug for light-activated RNA Pol II inhibition and cell death
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Amanitin is used extensively as a research tool to inhibit RNA Pol II thereby implicating its role in mRNA transcription. Recently, amanitin has gained traction as a toxic payload for targeted therapy. Here we report the first-ever photocaged amanitin analog, that is non-toxic and can be pre-loaded into cells. Light provides a means to inhibit RNA Pol II and provoke cell death on-demand.
- Matinkhoo, Kaveh,Pryyma, Alla,Wong, Antonio A. W. L.,Perrin, David M.
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- Metal–Organic Framework-Encapsulated CoCu Nanoparticles for the Selective Transfer Hydrogenation of Nitrobenzaldehydes: Engineering Active Armor by the Half-Way Injection Method
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A novel armor-type composite of metal–organic framework (MOF)-encapsulated CoCu nanoparticles with a Fe3O4 core (Fe3O4@SiO2-NH2-CoCu@UiO-66) has been designed and synthesized by the half-way injection method, which successfully serves as an efficient and recyclable catalyst for the selective transfer hydrogenation. In this half-way injection approach, the pre-synthetic Fe3O4@SiO2-NH2-CoCu was injected into the UiO-66 precursor solution halfway through the MOF budding period. The formed MOF armor could play a role of providing significant additional catalytic sites besides CoCu nanoparticles, protecting CoCu nanoparticles, and improving the catalyst stability, thus facilitating the selective transfer hydrogenation of nitrobenzaldehydes into corresponding nitrobenzyl alcohols in high selectivity (99 %) and conversion (99 %) rather than nitro group reduction products. Notably, this method achieves the precise assembly of a MOF-encapsulated composite, and the ingenious combination of MOF and nanoparticles exhibits excellent catalytic performance in the selective hydrogen transfer reaction, implementing a “1+1>2” strategy in catalysis.
- Li, Yang,Li, Yu-Nong,Zheng, Jian-wei,Dong, Xiao-yun,Guo, Rong-xiu,Wang, Yi-ming,Hu, Ze-nan,Ai, Yongjian,Liang, Qionglin,Sun, Hong-bin
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- VP1 crystal structure-guided exploration and optimization of 4,5-dimethoxybenzene-based inhibitors of rhinovirus 14 infection
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Human rhinoviruses (HRV) are the predominant cause of common colds and flu-like illnesses, but are also responsible for virus-induced exacerbations of asthma and chronic obstructive pulmonary disease. However, to date, no drug has been approved yet for clinical use. In this study, we present the results of the structure-based lead optimization of a class of new small-molecule inhibitors that we previously reported to bind into the pocket beneath the canyon of the VP1 protein. A small series of analogues that we designed based on the available structure and interaction data were synthesized and evaluated for their potency to inhibit the replication of HRV serotype 14. 2-(4,5-Dimethoxy-2-nitrophenyl)-1-(4-(pyridin-4-yl)phenyl)ethanol (3v) was found to be a potent inhibitor exhibiting micromolar activity (EC50 Combining double low line 3.4 ± 1.0 μM) with a toxicity for HeLa cells that was significantly lower than that of our previous hit (LPCRW-0005, CC50 Combining double low line 104.0 ± 22.2 μM; 3v, CC50 > 263 μM).
- Da Costa, Laurène,Roche, Manon,Scheers, Els,Coluccia, Antonio,Neyts, Johan,Terme, Thierry,Leyssen, Pieter,Silvestri, Romano,Vanelle, Patrice
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- Photocaged and Mixed Photocaged Bioreversible-Protected ATP Derivatives as Tools for the Controlled Release of ATP
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Adenosine triphosphate (ATP) is known as the universal energy source for cellular processes, in addition, ATP also plays an important role in inflammation and cell signaling. Extracellular ATP binds to purinergic receptors and initiates further immune responses. To investigate these processes in-depth and to understand the complex mechanism of purinergic signaling, chemical tools are necessary. Here we present the synthesis of different photocaged ATP derivatives and the investigation of the light-induced release of ATP depending on the different synthesized photocleavable protecting groups based on the 2-nitrobenzyl moiety. Furthermore, we also present the synthesis of a mixed protected ATP-derivative as an example for a novel class of lipophilically caged nucleoside triphosphates. This new type of compounds is protected with a highly lipophilic non-toxic bio-removable acyloxybenzyl group and a photocleavable group. This combination may allow both passive cell uptake and controlled release of ATP by irradiation with non-harmful UV light.
- Jeschik, Nils,Meier, Chris,Schneider, Tobias
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supporting information
p. 6776 - 6789
(2020/11/23)
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- Stabilization of High Oxidation State Upconversion Nanoparticles by N-Heterocyclic Carbenes
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The stabilization of high oxidation state nanoparticles by N-heterocyclic carbenes is reported. Such nanoparticles represent an important subset in the field of nanoparticles, with different and more challenging requirements for suitable ligands compared to elemental metal nanoparticles. N-Heterocyclic carbene coated NaYF4:Yb,Tm upconversion nanoparticles were synthesized by a ligand-exchange reaction from a well-defined precursor. This new photoactive material was characterized in detail and employed in the activation of photoresponsive molecules by low-intensity near-infrared light (λ=980 nm).
- M?ller, Nadja,Rühling, Andreas,Lamping, Sebastian,Hellwig, Tim,Fallnich, Carsten,Ravoo, Bart Jan,Glorius, Frank
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supporting information
p. 4356 - 4360
(2017/04/03)
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- Erlotinib derivative with antitumor activity, and preparation method and application thereof
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The invention discloses an erlotinib derivative with antitumor activity, and a preparation method and application thereof, and belongs to the technical field of synthesis of antitumor active medicine. The method has the main technical scheme that the erlotinib derivative with antitumor activity has a structure formula shown as the accompanying drawing, wherein R is phenyl, p-methylphenyl, m-nitrophenyl, o-chlorphenyl or o-hydroxy benzon phenyl. The invention also discloses a concrete synthesis process of the erlotinib derivative with antitumor activity and application of the erlotinib derivative with antitumor activity to preparation of liver cancer treatment medicine. The erlotinib molecules are modified and are structurally connected with a series of different 1,2,3-triazole groups; the synthesized erlotinib derivative is subjected to anti-tumor activity test; the test result shows that the compound has high inhibition activity on liver cancer HepG2 cells.
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Paragraph 0029; 0030; 0031
(2017/08/29)
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- Photobase generators liberating two bases by absorbing one photon and their application to photosensitive materials
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We propose a photobase generator (PBG) that liberates two bases by absorbing one photon. Phototriggered decarboxylation proceeds first to generate one base, and subsequently the unstable reaction intermediate is thermally decarboxylated to generate another base. It was found that the photosensitivity of poly(glycidyl methacrylate) films containing the PBG is much higher than that of films containing a conventional PBG that generates one base by absorbing one photon.
- Arimitsu, Koji,Maruyama, Yuya,Furutani, Masahiro
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supporting information
p. 1194 - 1196
(2015/09/21)
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- Photolysis of ortho-nitrobenzylic derivatives: The importance of the leaving group
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Quantum yields for the photoinduced release of seven different commonly used leaving groups (LGs) from the o-nitroveratryl protecting group were measured. It was found that these quantum yields depend strongly on the nature of the LGs. We show that the quantum efficiency with which the LGs are released correlates with the stabilization that these LGs provide to o-nitrobenzyl-type radicals because radical stabilizing groups weaken the C-H bond that is cleaved in the photoinduced hydrogen atom transfer step, and hence lower the barrier for this process. At the same time these substituents lower the endothermicity of the thermal hydrogen atom transfer and thus increase the barrier for the reverse process, thereby enhancing the part of the initially formed aci-nitro intermediates which undergo cyclization (which ultimately leads to LG release). Radical stabilization energies computed by DFT methods are thus a useful predictor of the relative efficiency with which LGs are photoreleased from o-nitrobenzyl protecting groups.
- Solomek, Tomas,Mercier, Sebastien,Bally, Thomas,Bochet, Christian G.
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experimental part
p. 548 - 555
(2012/06/30)
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- Synthesis and in vitro antibacterial activity of gemifloxacin derivatives containing a substituted benzyloxime moiety
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A series of novel gemifloxacin (GMFX) derivatives containing a substituted benzyloxime moiety with remarkable improvement in lipophilicity were synthesized. The target compounds evaluated for their in vitro antibacterial activity against representative strains. Our results reveal that most of the target compounds have considerable potency against all of the tested Gram-positive strains including MRSA and MRSE (MIC: 90: 1 μg/mL) is 8-fold more active than GMFX, and 2-fold more active than GMFX and moxifloxacin against MRSE clinical isolates (MIC90: 4 μg/mL). Crown Copyright
- Feng, Lianshun,Lv, Kai,Liu, Mingliang,Wang, Shuo,Zhao, Jing,You, Xuefu,Li, Sujie,Cao, Jue,Guo, Huiyuan
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p. 125 - 136
(2012/11/07)
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- Synthesis and biological activity of pyridopyridazin-6-one p38α MAP kinase inhibitors. Part 2
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This manuscript concludes the Structure Activity Relationship (SAR) on the pyridazinone scaffold and identifies a compound with subnanomolar p38α activity and 24 h coverage in the rat arthritis efficacy model.
- Tynebor, Robert M.,Chen, Meng-Hsin,Natarajan, Swaminathan R.,O'Neill, Edward A.,Thompson, James E.,Fitzgerald, Catherine E.,O'Keefe, Stephen J.,Doherty, James B.
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p. 5971 - 5975
(2012/11/07)
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- Wavelength-orthogonal photolysis of neurotransmitters in vitro
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Irradiation of a mixture of 4-methoxyphenacyl-caged (S)-glutamate and 4,5-dimethoxy-2-nitrobenzyl-caged γ-amino butyric acid (GABA) on neurons, at ~260 nm, evokes selective photorelease of (S)-glutamate (Glu) whereas photolysis at 405 nm causes selective photorelease of GABA.
- Stanton-Humphreys, Megan N.,Taylor, Ruth D. T.,McDougall, Craig,Hart, Mike L.,Brown, C. Tom A.,Emptage, Nigel J.,Conway, Stuart J.
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supporting information; body text
p. 657 - 659
(2012/02/02)
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- Low power, biologically benign NIR light triggers polymer disassembly
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Near infrared (NIR) irradiation can penetrate up to 10 cm deep into tissues and be remotely applied with high spatial and temporal precision. Despite its potential for various medical and biological applications, there is a dearth of biomaterials that are responsive at this wavelength region. Herein we report a polymeric material that is able to disassemble in response to biologically benign levels of NIR irradiation upon two-photon absorption. The design relies on the photolysis of the multiple pendant 4-bromo7-hydroxycoumarin protecting groups to trigger a cascade of cyclization and rearrangement reactions leading to the degradation of the polymer backbone. The new material undergoes a 50% Mw loss after 25 s of ultraviolet (UV) irradiation by single photon absorption and 21 min of NIR irradiation via two-photon absorption. Most importantly, even NIR irradiation at a biologically benign laser power is sufficient to cause significant polymer disassembly. Furthermore, this material is well tolerated by cells both before and after degradation. These results demonstrate for the first time a NIR sensitive material with potential to be used for in vivo applications.
- Fomina, Nadezda,McFearin, Cathryn L.,Sermsakdi, Marleen,Morachis, Jose M.,Almutairi, Adah
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scheme or table
p. 8590 - 8597
(2012/03/12)
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- Wavelength-controlled orthogonal photolysis of protecting groups
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The selective control of a chemical process by the use of an electromagnetic wave has been a challenging goal for several decades. In this article, we describe for the first time the use of a monochromatic light beam to differentiate two different reactive centers. A direct application of this concept is found in the chemistry of protecting groups. Two different photolabile protecting groups were tuned to be responsive to a specific wavelength (e.g., 254 or 420 nm). Using derivatives of the 2-nitroveratryl fragment (such as 10, sensitive at 420 nm) and 3′,5′-dimethoxybenzoin fragment (such as 4, sensitive at 254 nm), it was shown that energy transfer phenomena did not erode the selectivity. Both the inter- and the intramolecular cases were studied and showed selectivities within the synthetically useful range. Hence, we could replace the traditional chemical orthogonality by a chromatic orthogonality.
- Blanc, Aurelien,Bochet, Christian G.
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p. 5567 - 5577
(2007/10/03)
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- Nitrobenzyl-based photosensitive phosphoramide mustards: Synthesis and photochemical properties of potential prodrugs for cancer therapy
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Several nitrobenzyl-based photosensitive phosphoramide mustards were synthesized. The nitrobenzyl moiety was structurally varied to find the most promising prodrug candidates in respect to photorelease and activity of the alkylating species. The synthesis of these compounds proved to be applicable even in regard to compounds with additional functionalization. The target molecules 13a,b to 14 exhibited the expected red shift in their absorption spectra maximum compared to the parent nitrobenzyl moiety. As seen by UV and 31P NMR spectroscopy, the phosphoramide mustard was quickly liberated upon irradiation with mercury arc lamps. Assaying the structurally different prodrugs on their alkylating activity showed that compounds 13b and 14, derived from secondary benzyl alcohols, are promising prodrug candidates. Their water solubility and the possibility of attaching macromolecules are encouraging vis-a-vis future investigations on their in vitro cytotoxicity.
- Reinhard, Robert,Schmidt, Brigitte F.
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p. 2434 - 2441
(2007/10/03)
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- Intramolecular [2 + 2] cycloaddition of ketenimines with imines. Synthesis and chemical behaviour of azeto[2,1-b]quinazolines
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Azeto[2,1-b]quinazolines 5 have been prepared by the novel intramolecular [2 + 2] cycloaddition reaction of ketenimines with imines. The applicability and limitations of the synthetic methodology, and explorations on the reactivity of compounds 5 are discussed.
- Alajarin, Mateo,Molina, Pedro,Vidal, Angel,Tovar, Fulgencio
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p. 13449 - 13472
(2007/10/03)
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- Multisubstituted 1-hydroxy-9-acridones with anticancer activity
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The present invention provides a compound having the structure: STR1 The present invention also provides a method for synthesizing a compound having the above-identified structure as well as the intermediate compounds produced according to that method. The present invention further provides a pharmaceutical composition comprising the above compounds. Lastly, the present invention provides a method of inhibiting growth of tumor cells.
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- Synthesis of Photolabile "Precursors" of Amino Acid Neurotransmitters
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The synthesis of photolabile precursors of the neurotransmitters for the aspartic acid, glutamic acid, glycine, and γ-aminobutyric acid receptors are reported.These compounds are designed for the rapid, photochemically initiated release of the neurotransmitter.The importance of rapidly photolyzed, inert (toward a neuronal receptor) precursors of neurotransmitters is in chemical kinetic investigations of the reactions involving the neuronal receptors.In the past, such studies have been hampered because of the insufficient time resolution of the available techniques.A photolyzable precursor of carbamoylcholine, an amino-group-containing analogue of acetylcholine, has been used previously to make measurements of currents flowing through the acetylcholine receptor channel within 100 μs.
- Wilcox, Mary,Viola, Randall W.,Johnson, Katherine W.,Billington, Andrew P.,Carpenter, Barry K.,et al.
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p. 1585 - 1589
(2007/10/02)
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- Acidic o-nitroaromatics as photoinhibitors of polymerization in positive working films
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A photopolymerizable coating composition comprising (1) a nongaseous, ethylenically unsaturated, polymerizable compound, (2) a specified acidic o-nitroaromatic compound, and (3) an organic, radiation-sensitive, free-radical generating system which is useful for making a positive or negative polymeric image on a substrate.
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