- Light-Activated COS/H2S Donation from Photocaged Thiocarbamates
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Hydrogen sulfide (H2S) is an important biomolecule, and responsive chemical tools for its delivery are needed. Here, we utilize the photocleavable o-nitrobenzyl group to unmask caged thiocarbamates and to access photoactivated H2S releasing molecules. These donors function by the initial release of carbonyl sulfide (COS), which is quickly hydrolyzed to H2S by carbonic anhydrase (CA). Our investigations demonstrate that o-nitrobenzyl-caged thiocarbamates can serve as a donor platform for the bio-orthogonal stimulated release of COS/H2S.
- Zhao, Yu,Bolton, Sarah G.,Pluth, Michael D.
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- The matrix-isolation IR spectrum of the o-quinonoid intermediate in the photolysis of 2-nitrobenzyl methyl ether
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Photolysis of 2-nitrobenzyl methyl ether in Ar and N2 matrices at 12 K generated an intermediate with λmax at 430 nm, and which was itself photolabile at 430-460 nm. Matrix IR spectra, as well as the UV-visible absorption, were obtai
- Dunkin,Gebicki,Kiszka,Sanin-Leira
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- Photoresponsive micelles enabling codelivery of nitric oxide and formaldehyde for combinatorial antibacterial applications
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It is of particular interest to develop new antibacterial agents with low risk of drug resistance development and low toxicity toward mammalian cells to combat pathogen infections. Although gaseous signaling molecules (GSMs) such as nitric oxide (NO) and formaldehyde (FA) have broad-spectrum antibacterial performance and the low propensity of drug resistance development, many previous studies heavily focused on nanocarriers capable of delivering only one GSM. Herein, we developed a micellar nanoparticle platform that can simultaneously deliver NO and FA under visible light irradiation. An amphiphilic diblock copolymer of poly(ethylene oxide)-b-poly(4-((2-nitro-5-(((2-nitrobenzyl)oxy)methoxy)benzyl)-(nitroso)amino)benzyl methacrylate) (PEO-b-PNNBM) was successfully synthesized through atom transfer radical polymerization (ATRP). The resulting diblock copolymer self-assembled into micellar nanoparticles without premature NO and FA leakage, whereas they underwent phototriggered disassembly with the corelease of NO and FA. We showed that the NO- and FA-releasing micellar nanoparticles exhibited a combinatorial antibacterial performance, efficiently killing both Gram-negative (e.g., Escherichia coli) and Gram-positive (e.g., Staphylococcus aureus) bacteria with low toxicity to mammalian cells and low hemolytic property. This work provides new insights into the development of GSM-based antibacterial agents.
- Duan, Yutian,He, Kewu,Zhang, Guoying,Hu, Jinming
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- Intramolecular nucleophilic assistance in the solvolyses of benzyl derivatives: Solvolyses of o-nitrobenzyl bromide and tosylate
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The specific rates of solvolysis of onitrobenzyl p-toluenesulfonate (1) have been measured in a wide range of solvents. Comparison with the previously studied para-isomer (2) indicates very similar behaviour (dominant S N2 pathway) in solvents without fluoroalcohol content. With an appreciable fluoroalcohol component, the specific rates are considerably higher than those predicted based on the comparison with the solvolysis of 2 and intramolecular participation by the ortho-nitro group is implicated. Consistent with this postulate, in 97% 2,2,2-trifluoroethanol, the entropy of activation for the solvolysis is considerably less negative for 1 than for 2. Measurements in four representative solvents of the specific rates of solvolysis of the bromides led to kOTs/kBr ratios of 10 to 30, consistent with appreciable nucleophilic assistance (by either solvent or nitro group) in the rate-determining step. For the solvents with an appreciable fluoroalcohol content, an analysis using the extended Grunwald-Winstein equation shows a negligible sensitivity towards changes in solvent nucleophilicity and a low (m = 0.27 ± 0.02) sensitivity towards changes in solvent ionising power. The low m value may result from a favourable solvation of the leaving group being partially counterbalanced by an unfavourable solvation of the nucleophilic nitro group.
- Kevill, Dennis N.,Kyong, Jin Burm
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- The early processes in the photochemistry of ortho-nitrobenzyl acetate
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The early processes in the de-caging of acetic acid from o-nitrobenzyl acetate (oNBAc) were studied by femtosecond techniques. Solutions of oNBAc in acetonitrile were excited by 260 nm laser pulses and the resulting spectroscopic changes probed by transient absorption and stimulated Raman spectroscopy. Absorption and Raman data give evidence of the formation of an aci-nitro species resulting from an intramolecular hydrogen transfer. The species is formed on the 1 ps and 1 ns time scale in equal amounts. The two processes are attributed to hydrogen transfers via a singlet and a triplet channel. The overall quantum yield of the aci-nitro formation is 0.1 matching the de-caging yield.
- Schmierer,Bley,Schaper,Gilch
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- Photocaged variants of the MunI and PvuII restriction enzymes
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Regulation of proteins by light is a new and promising strategy for the external control of biological processes. In this study, we demonstrate the ability to regulate the catalytic activity of the MunI and PvuII restriction endonucleases with light. We used two different approaches to attach a photoremovable caging compound, 2-nitrobenzyl bromide (NBB), to functionally important regions of the two enzymes. First, we covalently attached a caging molecule at the dimer interface of MunI to generate an inactive monomer. Second, we attached NBB at the DNA binding site of the single-chain variant of PvuII (scPvuII) to prevent binding and cleavage of the DNA substrate. Upon removal of the caging group by UV irradiation, nearly 50% of the catalytic activity of MunI and 80% of the catalytic activity of PvuII could be restored.(Figure Presented)
- Silanskas, Arunas,Foss, Michael,Wende, Wolfgang,Urbanke, Claus,Lagunavicius, Arunas,Pingoud, Alfred,Siksnys, Virginijus
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- Davis-Beirut Reaction: A Photochemical Br?nsted Acid Catalyzed Route to N-Aryl 2 H-Indazoles
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The Davis-Beirut reaction provides access to 2H-indazoles from aromatic nitro compounds. However, N-aryl targets have been traditionally challenging to access due to competitive alternate reaction pathways. Previously, the key nitroso imine intermediate w
- Kraemer, Niklas,Li, Clarabella J.,Zhu, Jie S.,Larach, Julio M.,Tsui, Ka Yi,Tantillo, Dean J.,Haddadin, Makhluf J.,Kurth, Mark J.
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supporting information
p. 6058 - 6062
(2019/08/20)
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- Supramolecular photochemistry of encapsulated caged: Ortho -nitrobenzyl triggers
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ortho-Nitrobenzyl (oNB) triggers have been extensively used to release various molecules of interest. However, the toxicity and reactivity of the spent chromophore, o-nitrosobenzaldehyde, remains an unaddressed difficulty. In this study we have applied the well-established supramolecular photochemical concepts to retain the spent trigger o-nitrosobenzaldehyde within the organic capsule after release of water-soluble acids and alcohols. The sequestering power of organic capsules for spent chromophores during photorelease from ortho-nitrobenzyl esters, ethers and alcohols is demonstrated with several examples.
- Kamatham, Nareshbabu,Raj, A. Mohan,Givens, Richard S.,Da Silva, José P.,Ramamurthy
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p. 2411 - 2420
(2019/10/21)
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- Synthesis and photochemical studies of 2-nitrobenzyl-caged N-hydroxysulfonamides
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Recently, N-hydroxysulfonamides (RSO2NHOH) caged by photolabile protecting groups have attracted significant interest as potential photoactive nitroxyl (HNO) donors. The selectivity of the desired HNO generation pathway from photocaged N-hydroxysulfonamides versus a competing pathway involving O-N bond cleavage is dependent on the specific photodeprotection mechanism of the phototrigger. We present a new class of photocaged N-hydroxysulfonamides incorporating the well-established o-nitrobenzyl photoprotecting group, including a derivative incorporating an additional carbonate linker. Photodecomposition of o-NO2Bn-ON(H)SO2CF3 and the corresponding 2-nitro-4,5-dimethoxybenzyl analog generated the desired HNO and CF3SO2- as a minor pathway, with competing photoinduced O-N bond cleavage to release CF3SO2NH2 as the major photodecomposition pathway. Photolysis of the corresponding -SO2CH3 analogs resulted in O-N bond cleavage only. The presence of the o-nitro substituent was shown to be essential for photoactivity. Photorelease of the parent HNO donor CH3SO2NHOH was observed as the major product upon irradiation of o-NO2Bn-OC(O)ON(H)SO2CH3, with the desired HNO release and O-N bond cleavage occurring as minor pathways. Photoproduct quantum yields for each species have been determined by actinometry. The effect of solvent, pH and air on the mechanism of photodecomposition was studied for o-NO2Bn-ON(H)SO2CH3. The ratio of the solvents in the solvent mixture (CH3CN and phosphate buffer, pH 7.0), the pH of the aqueous component of the buffer, and the presence of oxygen did not affect the amount of each photoproduct and the observed rate constant for O-N bond cleavage. Possible mechanisms for the various pathways are proposed.
- Zhou, Yang,Bharadwaj, Vinay,Rahman, Mohammad S.,Sampson, Paul,Brasch, Nicola E.,Seed, Alexander J.
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- Phototriggered Release of a Transmembrane Chloride Carrier from an o-Nitrobenzyl-Linked Procarrier
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While there have been many studies on synthetic chloride carriers and a recent application for apoptotic cell death, so far, the proposed huge potential of these systems in targeting cancer has not been realized due to their cytotoxicity to healthy cells. Herein, we describe the development of an indole-2-carboxamide receptor as an efficient membrane chloride carrier while the corresponding o-nitrobenzyl-linked derivative is a procarrier of the ion. Photoirradiation of the procarrier in liposomes results in release of the active carrier with up to 90 % transport efficiency. Such photorelease of the carrier also works within cancer cells, resulting in efficient cell killing. Such photocleavable procarriers have great potential as a photodynamic therapy to combat various types of cancers.
- Salunke, Swati Bansi,Malla, Javid Ahmad,Talukdar, Pinaki
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supporting information
p. 5354 - 5358
(2019/03/21)
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- ENZYMATICALLY-RELEASABLE ARYL DIAZONIUM SPECIES
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Triazabutadiene molecules and methods of use of triazabutadiene molecules, for example methods and compositions for yielding an aryl diazonium species from a triazabutadiene molecule, e.g., a protected aryl diazonium species in the form of a triazabutadiene. In some embodiments, an enzyme catalyzes the reaction yielding the aryl diazonium species from the triazabutadiene molecule. As an example, the methods and compositions herein may be used for delivery of drugs.
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Paragraph 00124
(2018/09/28)
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- Synthesis of Di(hetero)arylamines from Nitrosoarenes and Boronic Acids: A General, Mild, and Transition-Metal-Free Coupling
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The synthesis of di(hetero)arylamines by a transition-metal-free cross-coupling between nitrosoarenes and boronic acids is reported. The procedure is experimentally simple, fast, mild, and scalable and has a wide functional group tolerance, including carbonyls, nitro, halogens, free OH and NH groups. It also permits the synthesis of sterically hindered compounds.
- Roscales, Silvia,Csák?, Aurelio G.
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supporting information
p. 1667 - 1671
(2018/03/23)
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- Photodegradable self-assembling PAMAM dendrons for gene delivery involving dendriplex formation and phototriggered circular DNA release
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For effective gene delivery, structural degradation of synthetic carriers is crucial to the release of nucleic acids on the transfection time scale. In this study, we have synthesized the amphiphilic dendritic scaffolds with a photolabile o-nitrobenzyl (o-NB) group that can enable the structural decomposition and controlled release of nucleic acids under active light stimulation. The amphiphilic counterpart composed of a lipophilic cholesterol and a hydrophilic poly(amido amine) (PAMAM) dendron allows the self-assembly into a core-shell-like pseudodendrimer above the critical aggregation concentration (CAC) of approximately 20 μM. On the basis of electrostatic interaction, the polycationic pseudodendrimers are capable of forming stable complexes with polyanionic cyclic reporter genes under low charge excess values, suggesting substantial binding affinity of the dendron assembly toward circular DNA. Because the o-NB group in the dendritic structure undergoes efficient photolytic cleavage, an in vitro test shows that thus-formed "dendriplexes" are readily dissociated under 365 nm light irradiation, causing effective dendron degradation accompanied by DNA release. This photochemical strategy provides an opportunity to control gene binding and release in a spatiotemporal manner.
- Lai, Yu-Sen,Kao, Chai-Lin,Chen, Ya-Pei,Fang, Chia-Chia,Hu, Chao-Chin,Chu, Chih-Chien
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p. 2601 - 2608
(2016/03/22)
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- COMPOUND AND PHOTOBASE GENERATOR COMPRISING THE COMPOUND
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PROBLEM TO BE SOLVED: To provide a novel compound suitable as a photobase generator, the compound capable of keeping high basicity for a long time by ultraviolet irradiation. SOLUTION: A novel compound is suitable as a photobase generator forming a polycyclic condensed aromatic ring represented by α-methyl-8-nitronaphthalenyloxycarbonylpiperidine, α-methyl-8-nitronaphthalenyloxycarbonyltetramethylguanidine, α-methyl-8-nitronaphthalenyloxycarbonylbispiperidinoguanidine. COPYRIGHT: (C)2015,JPOandINPIT
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Paragraph 0102-0104
(2016/12/16)
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- Photobase generators derived from trans-o-coumaric acid for anionic UV curing systems without gas generation
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Anionic UV curing systems of poly(glycerol methacrylate) and/or poly[3-(methacryloyloxy)propyltrimethoxysilane] are obtained using novel photobase generators (PBGs) derived from trans-o-coumaric acid. These PBGs decompose into amines and coumarins by UV i
- Arimitsu, Koji,Takemori, Yuri,Nakajima, Atsushi,Oguri, Ayaka,Furutani, Masahiro,Gunji, Takahiro,Abe, Yoshimoto
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p. 1174 - 1177
(2015/04/14)
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- Wavelength-selective cleavage of o-nitrobenzyl and polyheteroaromatic benzyl protecting groups
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Evaluation of the wavelength-selective cleavage of five photolabile protecting groups from two different families has been performed. Alanine, as a model bifunctional target molecule was masked at the amino terminal with o-nitrobenzyl group and at the carboxylic terminal with benzyl-type nitrogen and oxygen polyheteroaromatics, namely acridine, (thioxo)benzocoumarin and a coumarin built on the julolidine nucleus. The photosensitivity of the corresponding alanine conjugates was studied at selected wavelengths with HPLC/UV and 1H NMR monitoring. The release of the fully deprotected molecule could be achieved by sequential irradiation in variable irradiation times, which were dependent on the heteroaromatic group used.
- Piloto, Ana M.,Costa, Susana P.G.,Gon?alves, M. Sameiro T.
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p. 650 - 657
(2014/02/14)
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- A tetraphenylethene-based caged compound: Synthesis, properties and applications
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A tetraphenylethene-based caged compound (TPE-C) is designed and synthesized. TPE-C is non-fluorescent either in solution or in aggregated state, but its emission can be induced to emit strong cyan emission in the aggregated state by UV irradiation. This property enables TPE-C to be applied in photo-patterning and anti-counterfeiting related areas. This journal is the Partner Organisations 2014.
- Yu, Chris Y. Y.,Kwok, Ryan T. K.,Mei, Ju,Hong, Yuning,Chen, Sijie,Lam, Jacky W. Y.,Tang, Ben Zhong
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supporting information
p. 8134 - 8136
(2014/07/21)
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- Acid and base catalyzed Davis-Beirut reaction: Experimental and theoretical mechanistic studies and synthesis of novel 3-amino-2H-indazoles
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The Davis-Beirut reaction, which provides an efficient synthesis of 2H-indazoles and, subsequently, indazolones, is shown to proceed rapidly from o-nitrosobenzaldehyde and primary amines under both acid and base catalysis. Experimental and theoretical evi
- Avila, Belem,Harrison, Jason G.,Tantillo, Dean J.,Kurth, Mark J.,El-Dakdouki, Mohammad H.,Haddadin, Makhluf J.,Nazer, Musa Z.
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p. 6475 - 6478,4
(2012/12/12)
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- Nitrosation of aryl and heteroaryltrifluoroborates with nitrosonium tetrafluoroborate
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Organotrifluoroborates have emerged as an alternative to toxic and air- and moisture-sensitive organometallic species for the synthesis of functionalized aryl and heteroaryl compounds. It has been shown that the trifluoroborate moiety can be easily converted into a variety of different substituents in a late synthetic stage. In this paper, we disclose a mild, selective, and convenient method for the ipso-nitrosation of organotrifluoroborates using nitrosonium tetrafluoroborate (NOBF4). Aryl- and heteroaryltrifluoroborates were converted into the corresponding nitroso products in good to excellent yields. This method proved to be tolerant of a broad range of functional groups.
- Molander, Gary A.,Cavalcanti, Livia N.
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experimental part
p. 4402 - 4413
(2012/06/18)
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- UV-induced fluorescence recovery and solubility modulation of photocaged conjugated oligomers
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This article describes photoactivatable conjugated oligomers that show both increased fluorescence quantum yield and pH-dependant solubility upon irradiation with UV light. Sonogashira coupling between ester-substituted phenylacetylenes and alkoxy-substituted diiodo phenylene-vinylenes yielded conjugated phenylene-ethynylene/phenylene-vinylene oligomers. Oligomers with nitrobenzyl ester moieties had quenched fluorescence in polar solvents; UV irradiation restored their quantum yield of fluorescence to that of corresponding alkyl ester-substituted oligomers. These photocaged oligomers also exhibited UV-induced changes in solubility consistent with photogeneration of carboxylic acids. This approach is therefore effective at tuning the properties of conjugated organics with light after traditional synthetic operations, and has potential for use in photoactivatable fluorophores or solution-processable multilayer devices.
- Pawle, Robert H.,Eastman, Victoria,Thomas, Samuel W.
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scheme or table
p. 14041 - 14047
(2012/06/01)
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- Photoprocesses of molecules with 2-nitrobenzyl protecting groups and caged organic acids
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The 308 nm photoinduced formation of the nitroso product and the intermediacy of the aci-nitro form(s) were studied for a series of 2-nitrobenzyl alkyl and aryl esters (1a-4e) and bis-(nitrophenyl)methyl acetates (5a-6b) by time-resolved UV-vis spectroscopy. A triplet state appears as major transient, when 2-nitrobenzyl derivatives 1 are substituted by 4,5-dimethoxy (2) and 4,5-methylenedioxy (3/4) groups. This triplet of charge transfer character is, however, not part of the route via the aci-nitro into the 2-nitroso form. The activation energy and preexponential factor of the longest lifetime component (τaci), i.e. the major part of the aci-nitro decay, were determined. The carboxylic acids as leaving groups have rather small effects on τaci. An additional nitrated phenyl ring in α-position (5) leads generally to shorter τaci value. Otherwise, the photogeneration of nitroso products is similar. The quantum yield (Φd) varies only moderately with structure, the yield of the aci-nitro form and Φd are correlated and little affected by solvent properties.
- Bley, Filiz,Schaper, Klaus,Goerner, Helmut
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p. 162 - 171
(2008/09/18)
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- Photocleavage of o-nitrobenzyl ether derivatives for rapid biomedical release applications
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The externally controlled cleavage of covalently linked prodrugs, proteins, or solid-phase formulation vehicles offers potential advantages for controlled drug or gene delivery. A series of o-nitrobenzyl ester compounds (1-8) were synthesized to allow a systematic study of photolability. The o-nitrobenzyl ester was strictly required for photolability, while imido esters were not photolabile. The degradation kinetics of 1-o-phenylethyl ester was an order of magnitude faster than that of o-nitrobenzyl ester. Tosylate, phosphate, and benzoate derivatives of 1-o-nitrophenylethyl displayed similar photolability (>80% decomposition within 10 min at 3.5 mW/cm2 at 365 nm). O-o-Nitrobenzyl O′,O″-diethyl phosphate displayed the fastest decomposition at photoirradiation condition (3.5 mW/cm2, 365 nm) suitable for biological systems. We report the synthesis and photo-decomposition of 1-o-nitrophenylethyl derivatives amenable for the creation of photolabile prodrugs or formulation particles for drug depots, DNA condensation, or tissue engineering applications.
- Kim, Moon Suk,Diamond, Scott L.
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p. 4007 - 4010
(2007/10/03)
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- N,N-bond-forming heterocyclization: Synthesis of 3-alkoxy-2H-indazoles
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A one-step heterocyclization of o-nitrobenzylamines to 3-alkoxy-2H- indazoles is reported. The electronic nature of the nitrophenyl group, the steric and electronic nature of the R1-functionalized benzylic amine, and the nature of the alcoholic solvent affect the efficiency of this heterocyclization reaction (~40-90%).
- Mills, Aaron D.,Nazer, Musa Z.,Haddadin, Makhluf J.,Kurth, Mark J.
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p. 2687 - 2689
(2007/10/03)
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- Photochemical Reaction Mechanisms of 2-Nitrobenzyl Compounds: Methyl Ethers and Caged ATP
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The mechanism of methanol photorelease from 2-nitrobenzyl methyl ether (1) and 1-(2-nitrophenyl)ethyl methyl ether (2), and of ATP release from adenosine-5′-triphosphate-[P3-(1-(2-nitrophenyl)-ethyl)] ester ('caged ATP', 3) was studied in various solvents by laser flash photolysis with UV-vis and IR detection. In addition to the well-known primary aci-nitro transients (A, λmax ≈ 400 nm), two further intermediates preceding the release of methanol, namely the corresponding 1,3-dihydrobenz[c]isoxazol-1-ol derivatives (B) and 2-nitrosobenzyl hemiacetals (C), were identified. The dependencies of the reaction rates of A-C on pH and buffer concentrations in aqueous solution were studied in detail. Substantial revision of previously proposed reaction mechanisms for substrate release from 2-nitrobenzyl protecting groups is required: (a) A novel reaction pathway of the aci-tautomers A prevailing in buffered aqueous solutions, e.g., phosphate buffer with pH 7, was found. (b) The cyclic intermediates B were identified for the first time as the products formed by the decay of the aci-tautomers A in solution. A recently proposed reaction pathway bypassing intermediates B (Corrie et al. J. Am. Chem. Soc., 2003, 125, 8546-8554) is shown not to be operative. (c) Hemiacetals C limit the release rate of both 1 (pH 8) and 2 (pH 10). This observation is in contrast to a recent claim for related 2-nitrobenzyl methyl ethers (Corrie et al.). Our findings are important for potential applications of the 2-nitrobenzyl protecting group in the determination of physiological response times to bioagents ('caged compounds').
- Il'ichev, Yuri V.,Schwoerer, Markus A.,Wirz, Jakob
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p. 4581 - 4595
(2007/10/03)
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- Biomolecular labeling
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A method for using an organic compound to label polynucleotides is described. The method utilizes an organic compound including an oligonucleotide, and electrophilic active site, an active complex, and a phosphate binding site. The oligonucleotide has a sequence that is complimentary to a specific region of a polynucleotide. This facilitates labeling of DNA or RNA at a specific site in its sequence. The active site consists of a stable precursor, and only becomes reactive upon activation. Leaving and protecting functional groups may be attached to the active site in order to facilitate the formation of a stable precursor and subsequent activation. The active complex may be a drug, polypeptide or a reporter molecule such as an isotope or fluorescing compound. The phosphate binding sites may be any functional group capable of forming ionic bonds with phosphate oxygens. Nucleotide labeling using this compound does not interfere with a polynucleotide sequence. The described method for utilizing this compound may be performed in situ. Latent reactivity is utilized to make the reaction chemically specific, alkylating only phosphodiester groups on the polynucleotide. A lactonization reaction traps the trialkylphosphate in a stable form.
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- Novel photoacid generators for photodirected oligonucleotide synthesis
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Photodirected oligonucleotide synthesis uses either direct or indirect light-dependent 5′-deprotection. Both have been reported to give lower stepwise synthetic yields than conventional methods. The deficiency appears to be due to incomplete deprotection at the oligonucleotide 5′-position and, additionally in the case where photodirection is indirect and uses photogenerated photoacid to effect 5′-detritylation, the depurinating effects of strong acid. We have developed novel photosensitive-2-nitrobenzyl esters that on irradiation with near UV light generate α-chloro-substituted acetic acids, such as trichloroacetic acid, which are widely and successfully used in conventional solid-phase oligonucleotide synthesis. α-Phenyl-4,5-dimethoxy-2-nitrobenzyltrichloroacetate and α-phenyl-4,5-dimethoxy-2,6-dinitrobenzyltrichloroacetate showed appropriate photochemical characteristics and were used for photodirected synthesis of a variety of oligonucleotides, including (T)5, TATAT, TGTGT, (T)10, (AT)5, (CT)5 (GT)5 and (TGCAT)2 on a modified Millipore Expedite DNA synthesizer. The outcomes were compared with those obtained by use of directly added trichloroacetic acid (conventional synthesis). The stepwise yields for the two methods were essentially identical.
- Serafinowski, Pawel J.,Garland, Peter B.
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p. 962 - 965
(2007/10/03)
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- Peptide-small molecule hybrids via orthogonal deprotection-chemoselective conjugation to cysteine-anchored scaffolds. A model study
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(formula presented) The feasibility of an orthogonal deprotection - conjugation protocol, holding the promise of libraries of functionally diverse chemical probes attached to cysteine-anchored peptide scaffolds, has been explored with a model system. The
- Smith III, Amos B.,Savinov, Sergey N.,Manjappara, Uma V.,Chaiken, Irwin M.
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p. 4041 - 4044
(2007/10/03)
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- Wavelength-selective cleavage of photolabile protecting groups
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The selective photocleavage of protecting groups using monochromatic light is described. Some groups were found to react faster than others at 254 nm, whereas this trend was reversed at 419 nm. This behavior was preserved in solution mixtures of both grou
- Bochet
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p. 6341 - 6346
(2007/10/03)
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- Non-photochemical rearrangements of o-nitrobenzyl compounds
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Three rearrangements of 2-nitrobenzyl compounds with increasingly complex structural changes are described. The first is a remarkably facile conversion of 2-nitrobenzyl triflate to 2-nitrosobenzaldehyde. The second is an unexpected formation of 1-acetyl-2
- Corrie, John E. T.,Gradwell, Michael J.,Papageorgiou, George
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p. 2977 - 2982
(2007/10/03)
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- Formation of o-nitrosobenzaldehyde from hydrolysis of o-nitrobenzyl tosylate. Evidence of intramolecular nucleophilic interaction
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Hydrolysis of o-nitrobenzyl tosylate in CH3CN:H2O (1:1, v/v) gave o- nitrobenzyl alcohol and o-nitrosobenzaldehyde in 1.8 : 1 ratio. Formation of o-nitrosobenzaldehyde indicates that the nitro group participates in the leaving of the tosylate group. o-Nitrosobenzaldehyde was reduced by biological thiols to give o-aminobenzaldehyde. Reaction of o- nitrosobenzaldehyde with 1 tool of benzylamine afforded 3-(N- benzylamino)anthranil (or its tautomer) as a major product.
- Chen, Ling-Jen,Burka, Leo T.
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p. 5351 - 5354
(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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- 2-Nitrobenzyl quaternary ammonium derivatives photoreleasing nor-butyrylcholine in the microsecond time range
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2-Nitrobenzyl derivatives of nor-butyrylcholine (N,N-dimethylaminoethyl butyrate) were synthesized and characterized as photolabile inhibitors of butyrylcholinesterase, displaying the required photofragmentation kinetics for rapid release of the enzyme substrate, nor-butyrylcholine.
- Peng, Ling,Wirz, Jakob,Goeldner, Maurice
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p. 2961 - 2964
(2007/10/03)
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- Synthesis and characterization of photolabile compounds releasing noracetylcholine in the microsecond time range
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The rapid and efficient photochemical release of noracetylcholine 2, an analogue of the neurotransmitter acetylcholine, from its precursor 1 makes this probe well-suited for a dynamic study of the mechanism of hydrolysis of acetylcholine by acetylcholinesterase. The nitrobenzyl derivative 1, the most promising candidate for time-resolved crystallographic studies of this rapid enzyme, displays the required photo-fragmentation kinetics in the microsecond time-range and inhibitory properties oacetylcholinesterase.
- Peng,Wirz,Goeldner
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p. 398 - 400
(2007/10/03)
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- Synthesis and characterization of photolabile choline precursors as reversible inhibitors of cholinesterase: Release of choline in the microsecond time range
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Three o-nitrobenzyl ether derivatives of choline (compounds A-C) were synthesized as photolabile cholinesterase inhibitors in order to study the mechanism of choline release from the enzyme active site. The key step of the synthesis was a simple and efficient Lewis acid-catalyzed opening of dioxolane rings derived from o-nitrobenzaldehyde and o-nitroacetophenone. Laser flash photolyses of compounds A-C were analyzed by UV spectroscopy, HPLC, and an enzymatic assay for choline. The quantum yields of photoconversion were determined, and the kinetics of choline release were analyzed by studying the decay of the transient aci-nitro intermediate at 405 nm.The observed rates varied considerably in function of both pH and the substituent at the α-benzylic position. Furthermore, we demonstrated that all three compounds possessed reversible inhibitory properties on both purified Torpedo acetylcholinesterase and purified human plasma butyrylcholinesterase. Compound A, O-[1-(2-nitrophenyl)ethyl]choline iodide, which displayed the highest quantum yield (0.27) and the most rapid photolysis rate (6.8 x 104 s-1 at pH 6.5), represents therefore an interesting tool for the study of the fast process of choline release from cholinesterases by time-resolved Laue crystallography.
- Peng,Goeldner
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p. 185 - 191
(2007/10/03)
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- Photochemistry of (2-nitrophenyl)diazomethane studied by the matrix isolation technique. (Nitrophenyl)carbene to (carboxylphenyl)nitrene rearrangement by successive reduction of the nitro group with the carbenic center
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Irradiation (λ > 350 nm) of (2-nitrophenyl)diazomethane (1) matrix-isolated in Ar at 10 K provided 2-nitrosobenzaldehyde (3) presumably as a result of intramolecular oxygen migration in (2-nitrophenyl)carbene (2). Upon further irradiation (λ > 350 nm), 3 was decomposed to give a mixture of 2,1-benzisoxazol-3(1H)-one (4) and carbonylcyclopentadiene imine (5) along with CO2. The oxazolone (4) underwent decarboxylation to give 5 upon irradiation with shorter wavelength light (λ > 300 nm) but not at longer wavelength (λ > 350 nm), suggesting 4 is not the direct precursor for 5 in the photolysis of 3. Irradiation (λ > 350 nm) of (4-n-butyl-2-nitrophenyl)diazomethane (1b) under similar conditions resulted in the formation of carbonyloximinocyclohexadienylidene (7) which then produced the oxazolone (4b) and the imine (5b) upon further irradiation, suggesting that a 1,4-biradical generated as a result of abstraction of H at the ortho position by the photoexcited nitroso group was involved in the reaction of 3 forming 4. (2-Carboxyphenyl)nitrene (9) generated by 1,4-OH shift in the 1,4-biradical was postulated as an intermediate leading to 5, and this was actually demonstrated by independent generation of 9 by the photolysis of 2-azidobenzoic acid (8).
- Tomioka, Hideo,Ichikawa, Naoki,Komatsu, Kazunori
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p. 8045 - 8053
(2007/10/02)
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- Photogeneration of Organic Bases from o-Nitrobenzyl-Derived Carbamates
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The design of novel photoprecursors of organic bases and the steric and electronic factors that control their quantum-efficient transformation into free amines or diamines have been investigated. The basic design involves the protection of amines with photolabile [(o-nitrobenzyl)oxy]carbonyl groups or α-substituted analogues. The resulting protected amines owe their light sensitivity to the classical o-nitrobenzyl photorearrangement and cleanly liberate free amine in both the solid state and in solution upon irradiation with UV light below 400 nm. Several designs were explored in which the structure of the photoactive center was varied systematically to investigate the influence of various steric and electronic effects. In all cases, the practical potential of these photoactive carbamates as organic sources of photogenerated base was evaluated by product analysis of solution photolysates, by determination of their solid-state quantum efficiencies, and by measurement of their thermal properties. For example, the quantum efficiency of various carbamates for cyclohexylamine photogeneration at 254 nm ranged from 0.11 to 0.62 depending on both α-substituent and o-nitro substitution patterns, confirming the importance of both steric and electronic considerations. Similar results were obtained with other base photoprecursors and all showed good thermal stabilities.
- Cameron, James F.,Fréchet, Jean M. J.
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p. 4303 - 4313
(2007/10/02)
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- PHOTOACTIVABLE FLUOROPHORES. 1. SYNTHESIS AND PHOTOACTIVATION OF o-NITROBENZYL-QUENCHED FLUORESCENT CARBAMATES
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The synthesis and photoactivation of a new type of fluorescent probe, the photoactivable fluorophore (PAF) are described.The PAFs described in this paper consist of fluorescent aromatic amines coupled to substituted nitrobenzyl quenching chromophores via a carbamate linkage.Photoactivation occurs by an intramolecular photo-redox reaction, converting the o-nitrosobenzaldehyde hemiacetal which fragments with loss of CO2 to liberate the fluorescent amine.Photoactivation quantum yields also are reported.
- Cummings, Richard T,Krafft, Grant A.
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