- β-Lactamase triggered visual detection of bacteria using cephalosporin functionalized biomaterials
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We report the conjugation of a chromogenic cephalosporin β-lactamase (βL) substrate to polymers and integration into biomaterials for facile, visual βL detection. Identification of these bacterial enzymes, which are a leading cause of antibiotic resistance, is critical in the treatment of infectious diseases. The βL substrate polymer conjugate undergoes a clear to deep yellow color change upon incubation with common pathogenic Gram-positive and Gram-negative bacteria species. We have demonstrated the feasibility of formulating hydrogels with the βL substrate covalently tethered to a poly(ethylene glycol) (PEG) polymer matrix, exhibiting a visible color change in the presence of βLs. This approach has the potential to be used in diagnostic biomaterials for point-of-care detection of βL-producing bacteria, helping combat the spread of drug resistant microbes.
- Alkekhia, Dahlia,Hopson, Russel,Safford, Hannah,Shukla, Anita,Shukla, Shashank
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Read Online
- Synthesis of a Gold–Metal Oxide Core–Satellite Nanostructure for In Situ SERS Study of CuO-Catalyzed Photooxidation
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This work reports on an assembling–calcining method for preparing gold–metal oxide core–satellite nanostructures, which enable surface-enhanced Raman spectroscopic detection of chemical reactions on metal oxide nanoparticles. By using the nanostructure, we study the photooxidation of Si?H catalyzed by CuO nanoparticles. As evidenced by the in situ spectroscopic results, oxygen vacancies of CuO are found to be very active sites for oxygen activation, and hydroxide radicals (*OH) adsorbed at the catalytic sites are likely to be the reactive intermediates that trigger the conversion from silanes into the corresponding silanols. According to our finding, oxygen vacancy-rich CuO catalysts are confirmed to be of both high activity and selectivity in photooxidation of various silanes.
- Bai, Lu,Fan, Chenghao,Hu, Yanfang,Li, Yonglong,Liu, Jun,Shi, Faxing,Xie, Wei,Yang, Ling,Zhang, Kaifu,Zhao, Yaran
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Read Online
- Stepwise Mechanisms of the Aminolyses of 4-Nitrophenyl and 2,4-Dinitrophenyl O-Ethyl Dithiocarbonates in Aqueous Ethanol
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The reactions of the title substrates with a series of secondary alicyclic amines are subjected to a kinetic study in 44 wtpercent aqueous ethanol, at 25.0 deg C, ionic strength 0.2 M (maintained with KCl).Pseudo-first-order kinetics are found under amine excess.The order in amine obtained is one in the reactions of all amines.The Broensted-type plots for the overall second-order rate coefficients are biphasic with slopes β1 = 0.3 (high pKa), β2 = 0.95 (low pKa) for the aminolysis of the 4-nitro derivative, and β1 = 0.3 and β2 = 0.80 for the aminolysis of the dinitro compound; the pKa values at the curvature center are pK0a 9.8 and 9.5, respectively.From a comparison of these pK0a values with those found in the same reactions in water and the shapes of the Broensted-type plots, it is concluded that these reactions are stepwise, with the formation of a zwitterionic tetrahedral intermediate in the reaction pathway.
- Castro, Enrique A.,Munoz, Gabriel,Salas, Mirtha,Santos, Jose G.
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Read Online
- Rational design of fluorescent probes for targeted: In vivo nitroreductase visualization
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Nitroreductase (NTR) has been recognized as a biomarker for identifying the hypoxic status of cancers. Therefore, it is of high scientific interest to design effective fluorescent probes for tracking NTR activity. However, studies on elucidation of the structure-performance relationship of fluorescent probes and those providing valuable insight into optimized probe design have rarely been reported. Three BODIPY based fluorescent probes were made by conjugation of para-, ortho-, and meta-nitrobenzene to the BODIPY core via a thiolether bond, respectively. Our study revealed that the linkage and nitro substituent position significantly influence the capability of nitroreductase detection.
- Chen, Ji-An,Gao, Jie,Gu, Xianfeng,Li, Mimi,Tan, Jiahui,Yin, Xiaofan,Zhao, Zhen
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supporting information
p. 4744 - 4747
(2020/07/13)
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- Transition metal-free, chemoselective arylation of thioamides yielding aryl thioimidates or N-aryl thioamides
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Reactions of secondary thioamides with diaryliodonium salts under basic, transition metal-free conditions resulted in chemoselective S-arylation to provide aryl thioimidates in good to excellent yields. Equimolar amounts of thioamide, base and diaryliodonium salt were sufficient to obtain a diverse selection of products within short reaction times. Reactions with thiolactams delivered N-arylated thioamides in good yield at room temperature.
- Villo, Piret,Kervefors, Gabriella,Olofsson, Berit
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supporting information
p. 8810 - 8813
(2018/08/17)
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- SINGLE-STEP SYNTHESIS METHOD OF ARYL THIOL AND APPLICATION THEREOF
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The present invention relates to a single-step synthesis method of aryl thiol, and more specifically, to a method of synthesizing aryl thiol in a single-step by making aryl halide react with alkane dithiol in the presence of a transition metal catalyst. According to the present invention, a single-step synthesis method using the transition metal catalyst, the synthesis method which is capable of synthesizing aryl thiol from aryl halide at a high yield, can be provided. Various aryl halides may be applied to the synthesis method. Further, the synthesis method has advantages that an easily usable reagent may be used, operations are simple, and reactions can be performed under mild conditions. In addition, the synthesized aryl thiol may be used in the synthesis of advanced molecules such as diaryl sulfides and benzothiophenes.COPYRIGHT KIPO 2017
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Paragraph 0032; 0033; 0063; 0067-0070; 0073; 0075; 0076
(2017/09/02)
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- Phosphorus Pentasulfide Mediated Conversion of Primary Carbamates into Thiols
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In this paper, we report a method for the conversion of primary carbamates into thiols in the presence of phosphorus pentasulfide (P 2 S 5) in refluxing toluene. Presently, no method exists in the literature for conversion of carbamates into thiols and, to the best of our knowledge, it is the first report for this type of conversion. This method presents an indirect route for the conversion of alcohols into thiols via their carbamate derivatives that may be useful in the total synthesis of compounds containing a thiol functionality.
- Maurya, Chandra Kant,Gupta, Pradeep Kumar
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p. 1649 - 1651
(2017/08/11)
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- Insight into the Mechanism of Reversible Ring-Opening of 1,3-Benzoxazine with Thiols
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The reversible ring-opening addition and fragmentation reaction of p-cresol-based N-phenylbenzoxazine with aliphatic and aromatic thiols was investigated in solvent-mediated and solvent-free reactions. Independently of the used thiol, N-phenylbenzoxazine and the thiols reacted to equilibrium with comparable amounts of reactants and products in aprotic solvent, whereas in protic solvent almost full conversions were reached. In contrast, thiol reactivity was a crucial factor in solvent-free reactions yielding fast and complete conversions for a more acidic thiol and balanced equilibrium concentrations in case of thiols with high pKa values. The strong influence of thiols with low pKa values emphasizes the relevance of the protonation step in the ring-opening reactions of 1,3-benzoxazines with thiols in absence of solvents where acidity predominates nucleophilicity. The reverse reactions, namely adduct dissociation and benzoxazine recovery, were successfully conducted at elevated temperatures and reduced pressure facilitated by the removal of the formed thiols yielding up to 95% recovered 1,3-benzoxazine. These results provide deeper understanding of the reversible ring-opening reaction mechanism of 1,3-benzoxazine with thiols.
- Urbaniak, Tobias,Soto, Marc,Liebeke, Manuel,Koschek, Katharina
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p. 4050 - 4055
(2017/04/27)
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- Silver-induced self-immolative Cl-F exchange fluorination of arylsulfur chlorotetrafluorides: Synthesis of arylsulfur pentafluorides
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A novel strategy for the synthesis of arylsulfur pentafluorides by silver carbonate-induced Cl-F exchange fluorination of arylsulfur chlorotetrafluorides is reported. This fluorination does not require any exogenous fluoride sources. Rather, the reaction proceeds via the self-immolation of the substrate Ar-SF4Cl.
- Cui, Benqiang,Jia, Shichong,Tokunaga, Etsuko,Saito, Norimichi,Shibata, Norio
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supporting information
p. 12738 - 12741
(2017/12/06)
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- Copper(II)-Catalyzed Single-Step Synthesis of Aryl Thiols from Aryl Halides and 1,2-Ethanedithiol
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A highly efficient transition metal-catalyzed single-step synthesis of aryl thiols from aryl halides has been developed employing copper(II) catalyst and 1,2-ethanedithiol. The key features are use of readily available reagents, a simple operation, and relatively mild reaction conditions. This new protocol shows a broad substrate scope with excellent functional group compatibility. A variety of aryl thiols are directly prepared from aryl halides in high yields. Furthermore, the aryl thiols are used in situ for the synthesis of more advanced molecules such as diaryl sulfides and benzothiophenes.
- Liu, Yajun,Kim, Jihye,Seo, Heesun,Park, Sunghyouk,Chae, Junghyun
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supporting information
p. 2205 - 2212
(2015/07/27)
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- Development of selective colorimetric probes for hydrogen sulfide based on nucleophilic aromatic substitution
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Hydrogen sulfide is an important biological signaling molecule and an important environmental target for detection. A major challenge in developing H2S detection methods is separating the often similar reactivity of thiols and other nucleophiles from H2S. To address this need, the nucleophilic aromatic substitution (SNAr) reaction of H2S with electron-poor aromatic electrophiles was developed as a strategy to separate H2S and thiol reactivity. Treatment of aqueous solutions of nitrobenzofurazan (7-nitro-1,2,3-benzoxadiazole, NBD) thioethers with H 2S resulted in thiol extrusion and formation of nitrobenzofurazan thiol (λmax = 534 nm). This reactivity allows for unwanted thioether products to be converted to the desired nitrobenzofurazan thiol upon reaction with H2S. The scope of the reaction was investigated using a Hammett linear free energy relationship study, and the determined ρ = +0.34 is consistent with the proposed SN2Ar reaction mechanism. The efficacy of the developed probes was demonstrated in buffer and in serum with associated submicromolar detection limits as low as 190 nM (buffer) and 380 nM (serum). Furthermore, the sigmoidal response of nitrobenzofurazan electrophiles with H2S can be fit to accurately quantify H2S. The developed detection strategy offers a manifold for H2S detection that we foresee being applied in various future applications.
- Montoya, Leticia A.,Pearce, Taylor F.,Hansen, Ryan J.,Zakharov, Lev N.,Pluth, Michael D.
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p. 6550 - 6557
(2013/07/26)
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- Photochemical reactivity of two gold(I) dinuclear complexes, cis/trans-(AupNBT)2dppee: Isomerization for the cis-(AupNBT) 2dppee isomer, radical substitution for trans-(AupNBT) 2dppee
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Two complexes, cis (1) and trans (2) (AupNBT)2dppee (pNBT = p-nitrobenzenethiol; dppee = bis(diphenylphosphino)ethylene) have been synthesized and characterized. X-ray diffraction studies reveal that cis-(AupNBT)2dppee has an intramolecular gold-gold distance of 3.0036(3) ? while the trans-(AupNBT)2dppee crystal is a dimer with an intermolecular gold-gold distance of 3.1201(4) ?. We have used UV-Vis spectroscopy, 1H NMR, and 31P {1H} NMR to investigate the photochemical reactivity of both complexes. In a range of organic solvents with λ > 230 nm cis-(AupNBT)2dppee readily isomerizes to the trans isomer. Under these same conditions, the trans isomer does not isomerize to cis-(AupNBT)2dppee, but undergoes a photochemical substitution reaction. In chlorinated solvents (CH 2Cl2, CH3Cl) trans-(AupNBT)2dppee reacts to form trans-(AuCl)2dppee (3) which crystallizes into an extended chain of molecules linked via intermolecular gold-gold distances of 3.0203(2) ?. TDDFT calculations support the observed experimental results. We propose that at high energies the reaction is initiated by chlorine radicals from direct photolysis of the solvent. At longer wavelengths the excited state of the metal complex is the photoactive species, abstracting a chlorine radical from the solvent.
- Foley, Janet B.,Herring, Angela,Li, Bo,Dikarev, Evgeny V.
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p. 300 - 310
(2013/01/13)
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- About the reaction of aryl fluorides with sodium sulfide: Investigation into the selectivity of substitution of fluorobenzonitriles to yield mercaptobenzonitriles via SNAr displacement of fluorine
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In this report we describe a simple synthesis of mercaptobenzonitriles from the reaction of fluorobenzonitriles with Na2S in DMF at room temperature and following direct treatment with Zn/HCl. Significantly, 2- and 4-fluorobenzonitriles substituted with chlorine or bromine, but not iodine, undergo selective substitution of fluorine at room temperature to yield synthetically useful halo-substituted mercaptobenzonitriles.
- Taldone, Tony,Patel, Pallav D.,Patel, Hardik J.,Chiosis, Gabriela
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supporting information; experimental part
p. 2548 - 2551
(2012/06/15)
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- Aminolysis of S-4-nitrophenyl X-substituted thiobenzoates: Effect of nonleaving-group substituents on reactivity and mechanism
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A kinetic study is reported for aminolysis of S-4-nitrophenyl X-substituted thiobenzoates 3a-g in 80 mol % H2O/20 mol % DMSO at 25.0 ± 0.1 °C. Thiol esters 3a-g are 7.8-47.6 fold more reactive than the corresponding oxygen esters (i.e., 4-nitrophenyl X-substituted benzoates 1a-g). Such reactivity order appears to be in accordance with the expectation that 4-nitrothiophenoxide in 3a-g is a better nucleofuge than 4-nitrophenoxide in 1a-g since the former is 2.64 pKa units less basic than the latter. Hammett plot for the reactions of 3a-g exhibit poor correlation coefficients (R2 = 0.977-0.986) with negative deviation by substrates possessing an electrondonating group (EDG), while the Yukawa-Tsuno plots result in excellent linear correlation (R2 = 0.995-0.997) with ? = 0.93-1.23 and r = 0.57-0.67, indicating that the negative deviation shown by substrates possessing an EDG is caused by ground-state stabilization through resonance interactions but not due to a change in ratedetermining step upon changing the nonleaving-group substituent X. The p value increases as the incoming amine becomes more basic and more reactive, indicating that the RSP is not operative in the current reactions.
- Im, Li-Ra,Jeon, Sang-Eun,Um, Ik-Hwan
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experimental part
p. 1153 - 1157
(2011/11/12)
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- Copper-catalyzed coupling of thiourea with aryl iodides: The direct synthesis of aryl thiols
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A general, economical and efficient protocol for the direct copper-catalyzed coupling of thiourea with aryl iodides is developed and it will be potentially applied in large-scale industry as a preferred process.
- Qiao, Shu,Xie, Kun,Qi, Junsheng
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scheme or table
p. 1441 - 1443
(2011/01/04)
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- A general and efficient approach to aryl thiols: Cul-catalyzed coupling of aryl iodides with sulfur and subsequent reduction
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A Cul-catalyzed coupling reaction of aryl iodides and sulfur powder takes place in the presence of K2CO3 at 90 °C. The coupling mixture is directly treated with NaBH4 or triphenylphosphine to afford aryl thiols in good to
- Jiang, Yongwen,Qin, Yuxia,Xie, Siwei,Zhang, Xiaojing,Dong, Jinhua,Ma, Dawei
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supporting information; scheme or table
p. 5250 - 5253
(2009/12/28)
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- A comparison of commercial microwave reactors for scale-up within process chemistry
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Seven commercially available microwave reactors designed for limited scale-up have been investigated using a highly reliable and robust reaction (the Newman-Kwart rearrangement). The use of a single reaction has enabled the comparison to be made across the range of different reactor types and scales. Overall, all reactors gave reliable scale-up from small scale, and performance equivalent to one another on large scale. A more detailed comparison between them is given in the concluding section.
- Moseley, Jonathan D.,Lenden, Philip,Lockwood, Mark,Ruda, Katinka,Sherlock, Jon-Paul,Thomson, Anthony D.,Gilday, John P.
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- Kinetics and mechanism of the reactions of S-4-nitrophenyl 4-methylthiobenzoate with secondary alicyclic amines and pyridines
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The reactions of the title substrate with a series of six secondary alicyclic amines and a series of eight pyridines are subjected to a kinetic investigation in 44 wt% ethanol-water, at 25.0°C, and an ionic strength of 0.2 mol · dm-3. Under amine excess pseudo first-order rate coefficients (kobs) are obtained. Plots of kobs against free amine concentration at constant pH are linear, with the slope (k N) independent of pH. The Bronsted-type plots (log k N against pKa of the conjugate acids of the amines) are non-linear, with the curvature center located at pKa (pX a0) 9.7 and 9.4, for the reactions of secondary alicyclic amines and pyridines, respectively. The plots are consistent with a zwitterionic tetrahedral intermediate (T±) on the reaction path and a change in rate-determining step. The greater pKa0 value for secondary alicyclic amines than pyridines is explained by the greater nucleofugality from T± of secondary alicyclic amines compared to isobasic pyridines. These pKa0 values are lower than those found for the reactions of S-4-nitrophenyl 4-Y-substituted thiolbenzoates (Y = H, Cl, NO2) with the corresponding amine series. These results indicate that electron donation from the non-leaving group in T ± favors leaving group expulsion from T± relative to amine expulsion. Copyright
- Castro, Enrique A.,Aguayo, Raul,Bessolo, Jorge,Santos, Jose G.
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p. 555 - 561
(2007/10/03)
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- Mechanistic studies of la3+- And Zn2+-catalyzed methanolysis of aryl phosphate and phosphorothioate triesters. Development of artificial phosphotriesterase systems
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The methanolyses of a series of O,O-diethyl O-aryl phosphates (2,5) and O,O-diethyl S-aryl phosphorothioates (6) promoted by methoxide and two metal ion systems, (La3+)2(-OCH3)2 and 4:Zn2+:-OCH3 (4 = 1,5,9- triazacyclododecane) has been studied in methanol at 25°C. Bronsted plots of the log k2 values vs. sspKa for the phenol leaving groups give βlg values of -0.70. -1.43 and -1.12 for the methanolysis of the phosphates and -0.63, -0.87 and -0.74 for the methanolysis of the phosphorothioates promoted by the methoxide, La 3+ and Zn2+ systems respectively. The kinetic data for the metal-catalyzed reactions are analyzed in terms of a common mechanism where there is extensive cleavage of the P-XAr bond in the rate-limiting transition state. The relevance of these findings to the mechanism of action of the phosphotriesterase enzyme is discussed. The Royal Society of Chemistry 2005.
- Liu, Tony,Neverov, Alexei A.,Tsang, Josephine S.W.,Brown, R. Stan
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p. 1525 - 1533
(2007/10/03)
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- A general and efficient method for the synthesis of silyl-protected arenethiols from aryl halides or triflates
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An improved palladium-catalyzed synthesis of silyl-protected arenethiols has been developed. This method is particularly useful because of its experimental simplicity, high generality and high level of functional group toleration. The first synthesis of enantiomerically pure [2.2]paracyclophane-4- thiol was realized employing this method.
- Kreis, Michael,Braese, Stefan
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p. 313 - 319
(2007/10/03)
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- Biomimetic thiolate alkylation with zinc pyrazolylbis(thioimidazolyl)borate complexes
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The NS2ZnX coordination in thiolate-alkylating zinc enzymes is reproduced in (tripod)ZnX complexes with substituted pyrazolylbis(thioimidazolyl)borate tripod ligands. Intermediate (tripod)Zn nitrates and perchlorates are converted into (tripod) Zn thiolates, including the biologically relevant homocysteinate. Methylation with CH3I converts these to (tripod)ZnI and the corresponding thioethers CH3SR, including methionine. A kinetic investigation has shown the alkylations to be intramolecular SN2 processes that take place at the zinc-bound thiolates. They are considerably faster for the (NS2)Zn thiolates than for the (N2S)- and (N3)Zn-thiolates with similar pyrazolylborate-derived tripod ligands, in agreement with Nature's choice of an NS2 donor set for zinc. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
- Ibrahim, Mohamed M.,He, Guosen,Seebacher, Jan,Benkmil, Boumahdi,Vahrenkamp, Heinrich
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p. 4070 - 4077
(2007/10/03)
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- Method of decomposing organophosphorus compounds
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Methods and kits for decomposing organophosphorus compounds in non-aqueous media at ambient conditions are described. Insecticides, pesticides, and chemical warfare agents can be quickly decomposed to non-toxic products. The method comprises combining the organophosphorus compound with a non-aqueous solution, preferably an alcohol, comprising metal ions and at least a trace amount of alkoxide ions. In a first preferred embodiment, the metal ion is a lanthanum ion. In a second preferred embodiment, the metal ion is a transition metal.
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- Chemoselective protection of thiols versus alcohols and phenols. The Tosvinyl group
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The conjugate addition of aliphatic and aromatic thiols to ethynyl p-tolyl sulphone (tosylacetylene) has been managed to afford Tosvinyl derivatives chemoselectively (in the presence of oxygen nucleophiles) and stereoselectively (isomers Z) in practically quantitative yields. The conditions of choice are: catalytic amounts of Et3N (only 0.5-1.0 mol%), a reaction temperature around 0°C and, for the less acidic thiols, CF3CH2OH or CH3CN/CF3CH2OH as the solvent. Thus, N-Boc-Cys-OMe has been quantitatively protected as its S-Tosvinyl derivative in the presence of N-Boc-Ser-OMe and N-Boc-Tyr-OMe. This novel protecting group is stable to several basic and acidic conditions; its removal is achieved at rt by treatment with an excess of pyrrolidine or at 0°C with alkanethiolate ions.
- Arjona, Odón,Medel, Rocío,Rojas, Jenny,Costa, Anna M.,Vilarrasa, Jaume
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p. 6369 - 6373
(2007/10/03)
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- Kinetic investigation of the reactions of S-4-nitrophenyl 4-substituted thiobenzoates with secondary alicyclic amines in aqueous ethanol
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The reactions of S-4-nitrophenyl 4-X-substituted thiobenzoates (X = H, Cl, and NO2: 1, 2, and 3, respectively) with a series of secondary alicyclic amines (SAA) were subjected to a kinetic investigation in 44 wt % ethanol-water, at 25.0 °C and an ionic strength of 0.2 M (KCl). The reactions were followed spectrophotometrically by monitoring the release of 4-nitrobenzenethiolate anion at 420-425 nm. Under excess amine, pseudo-first-order first-order rate constants (kobsd) are obtained for all reactions. The plots of kobsd vs [SAA] at constant pH are linear with the slope (kN) independent of pH. The statistically corrected Bronsted-type plots (log kN/q vs pKa + log p/q) for the reactions of 1 and 2 are nonlinear with slopes at high pK a, β1 = 0.27 and 0.10, respectively, and slopes at low pKa, β2 = 0.86 and 0.84, respectively. The Bronsted curvature is centered at pKa (pKa 0) 10.0 and 10.4, respectively. The reactions of SAA with 3 exhibit a linear Bronsted-type plot of slope 0.81. These results are consistent with a stepwise mechanism, through a zwitterionic tetrahedral intermediate (Ti±). For the reactions of 1 and 2, there is a change in rate-determining step with amine basicity, from T± breakdown to products at low pKa, to T± formation at high pKa. For the reactions of 3, breakdown to products of T ± is rate limiting for all the SAA series (pKa 0 > 11). The increasing pKa0 value as the substituent in the acyl group becomes more electron withdrawing is attributed to an increasing nucleofugality of SAA from T±. The greater pKa0 value for the reactions of SAA with 1, relative to that found in the pyridinolysis of 2,4-dinitrophenyl benzoate (pK a0 = 9.5), is explained by the greater nucleofugality from T± of the former amines, compared to isobasic pyridines, and the greater leaving ability from T± of 2,4-dinitrophenoxide relative to 4-nitrobenzenethiolate.
- Castro, Enrique A.,Bessolo, Jorge,Aguayo, Raul,Santos, Jose G.
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p. 8157 - 8161
(2007/10/03)
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- Aryl monosulphides and symmetrical disulphides based second order nonlinear optical chromophores with transparency in the visible
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A series of aryl monosulphides and disulphides have been synthesized and characterized. Their molecular hyperpolarizability (β) has been measured in solution with the hyper-Rayleigh Scattering technique and also calculated by semiempirical AM1 method. The trend in the observed and calculated values of first hyperpolarizability of these compounds has been found to be in good agreement. These compounds show moderate β values and excellent transparency in the visible region.
- Sudharsanam, Ramanathan,Chandrasekaran, Srinivasan,Das, Puspendu Kumar
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p. 1763 - 1766
(2007/10/03)
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- Rates of reductive elimination of substituted nitrophenols from the (indol-3-yl)methyl position of indolequinones
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A series of indolequinones bearing substituted nitrophenols on the (indol-3-yl)methyl position was synthesised. The nitrophenol leaving groups were appropriately substituted to give a wide range (4 units) in phenolic pKa value. The rate of redu
- Swann,Moody,Stratford,Patel,Naylor,Vojnovic,Wardman,Everett
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p. 1340 - 1345
(2007/10/03)
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- Reductions using LiCl/NaBH4: A rapid and efficient cleavage of organic disulfides to mercaptans
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A practical and novel reagent system LiCl/NaBH4 is used for the reductive cleavage of organic disulfides to mercaptans under mild conditions, in excellent yields.
- Rajaram,Purushothama Chary,Iyengar
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p. 622 - 624
(2007/10/03)
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- A rapid and efficient cleavage of organic disulfides to mercaptans using ZrCl4/NaBH4
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A practical and cheaper reagent system ZrCl/NaBH4 is used for the reductive cleavage of organic disulfides to mercaptans under mild conditions, in excellent yields.
- Purushothama Chayr,Rajaram,Iyengar
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p. 3905 - 3911
(2007/10/03)
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- Galactosylation of thiol group by beta-galactosidase.
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beta-Galactosidase catalyzed beta-galactosylation not only of a hydroxyl group but also of a thiol group in the condensation reaction of D-galactose and 2-mercaptoethanol. The thio-galactosylation product was confirmed as 2-hydroxyethyl S-beta-D-galactoside on the bases of fast atom bombardment mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance spectorometry. Aspergillus oryzae beta-galactosidase hydrolyzed p-nitrophenyl S-beta-D-galactoside most rapidly among several beta-galactosidases and produced the thio-galactosylation product most efficiently. The Penicillim multicolor enzyme was as effective as the A. oryzae enzyme. However the enzymes from Escherichia coli, Saccharomyces fragilis, Kluyveromyces lactis, and Bacillus circulans galactosylated hydroxyl groups predominantly to produce O-galactoside. The thio-galactoside was synthesized most effectively at a 2-mercaptoethanol concentration of about 1.25 M. Galactose concentration at 0.8-2.8 M did not affect the synthetic yield of the thiogalactoside so greatly.
- Nakano,Shizuma,Kiso,Kitahata
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p. 735 - 740
(2007/10/03)
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- Oxidative cleavage of S-Arylmercaptoacetic acids by pyridinium chlorochromate: Kinetic and correlation analysis
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Kinetics of oxidation of 24 S-Arylmercaptoacetic acids (SAMA) by pyridinium chlorochromate (PCC) have been studied in acid medium. The product of oxidation is the corresponding thiophenol. The rate data of meta- and para-substituted acids have been correlated well with σI, σ°R values and the meta-compounds correlate well with F,R values. The reaction constants are negative and of smaller magnitudes. Further, the ortho-substituted acids show a good correlation with triparametric equation involving Taft's σI and σ°R and charton's steric parameter v. There is no considerable steric contribution to the total orthosubstituent effect. Based on these observations, the mechanism involving the formation of protonated arylsulfinylacetic acid intermediate, followed by an intramolecular rearrangement leading to the product thiophenol has been proposed.
- Kabilan,Girija,Rajagopal
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p. 683 - 688
(2007/10/03)
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- Hydrolysis and aminolysis of alkyl xanthate esters and cellulose analogues
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The hydrolysis and aminolysis of a series of S-substituted O-alkylxanthate esters was studied in 20% v/v aqueous methanol at 35°C. The pH-rate profiles of the hydrolyses showed water and hydroxide-ion-catalyzed reactions. The reaction of 2,4-dinitrophenyl cellulose xanthate (CelXDNP) and p-nitrobenzyl cellulose xanthate (CelXNB) with polyalanine and lysozyme produced a covalent bond between the polypeptide and the cellulose matrix, as shown by solid-state 13C NMR. However, the nature of the bonding could not be identified. The reaction of nucleophiles (H2O, OH-, RNH2) and xanthic esters was consistent with an addition-elimination mechanism through a tetrahedral intermediate. Bronsted plots against the pKa of the nucleophile (βnu) or the nucleofuge of the substrate (βlg) were used to characterize the rate-determining step. The pKa values of the nucleophiles ranged between -1.74 and 15.74, and for the nucleofuges, they were in the range of 10.50-0.92. For nucleophiles with pKa values up to about 10, βlg was 0.10-0.15, and βnu changed from 0.48 to 0.35 for the strongest electron-withdrawing nucleofuge. It was concluded that the water-catalyzed hydrolyses, and also aminolyses with moderately basic amines, occur with rate-determining formation of the tetrahedral intermediate. For strong bases such as hydroxide ion, the disappearance of the intermediate becomes the slowest step. The reaction of cellulose xanthic esters with external nucleophiles as hydroxide ion and amines shows simple first-order kinetics and is slower than alkyl or sugar xanthates, probably due to the diffusion effect through the tight cybotactic region of cellulose.
- Humeres, Eduardo,Soldi, Valdir,Klug, Marilene,Nunes, Mauricea,Oliveira, Celia M.S.,Barrie, Patrick J.
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p. 1050 - 1056
(2007/10/03)
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- General acid catalysis of the reversible addition of thiolate anions to cyanamide
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The addition of aromatic thiols (pKa = 2.6-6.5) to cyanamide to give the isothiourea is subject to general-acid catalysis of the addition of thiolate anions by tertiary ammonium ions, with α = 0.26 and 0.31 (±0.07) for the addition of thiophenol and 4-nitrothiophenol, respectively. The Bronsted coefficients and a small solvent isotope effect of kH2O/kD2O = 1.6 for catalysis by 4-morpholinoethanesulfonic acid (MES) buffer and for the uncatalysed addition of thiophenol are consistent with significant movement of a hydron in the transition state. The conclusion that the reaction proceeds through a basic asymmetric intermediate in the absence of catalysis is supported by the similar rate constants for the addition of thiophenolate anion to cyanamide and to N,N-dimethylcyanamide, which cannot tautomerize to the carbodiimide. The reaction has a central transition state in which S-C bond formation takes place with βnuc = 0.55. It is concluded that the mechanism of catalysis involves partial transfer of a hydron to the cyano nitrogen atom in the transition state.
- Dalby, Kevin N.,Jencks, William P.
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p. 1555 - 1563
(2007/10/03)
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- Solvent effects on reactions of hydroxide and oximate ions with phosphorus(V) esters
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Second-order rate constants of reactions of OH-, 2,3-butanedionemonooximate and 2-hydroxybenzaldoximate ions with aryl phosphate, phosphinate and thioarylphosphinate esters go through minima with decreasing water content of aqueous acetonitrile, tert-butyl alcohol and N-methyl-2-pyrrolidone. For reactions in H2O-MeCN the solvent effects are analyzed in terms of activity coefficients of the anionic nucleophiles and transition states. In the drier solvents partial desolvation of the nucleophiles increases rates. Nucleophilicities of several oximates and inorganic anions are compared in water.
- Bunton, Clifford A.,Gillitt, Nicholas D.,Kumar, Anurag
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p. 221 - 228
(2007/10/03)
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- Structure - reactivity correlation in the reactions of pyrrolidine with O-ethyl S-aryl dithiocarbonates in aqueous ethanol
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The reactions of pyrrolidine with O-ethyl S-(X-phenyl) dithiocarbonates (X = 4-methyl, 4-methoxy, H, 4-chloro, 4-nitro, 2,4-dinitro, and 2,4,6-trinitro) are subjected to a kinetic study in 44 wt% aqueous ethanol, 25.0°C, and ionic strength 0.2 M (maintained with KCl). Pseudo-first-order kinetics are found under amine excess. Linear plots of the pseudo-first-order rate coefficient against concentration of free-base pyrrolidine are obtained for all the reactions, nucleophilic rate coefficient (kN) being the slope of such plots. The Bronsted-type plot (log kN vs. pKa for the leaving group) is linear with slope β1g = -0.2, which is consistent with a mechanism through a tetrahedral intermediate (T±) where its formation is rate determining. The β1g value is very similar to that found in the same reactions in water. There is a great difference in the mechanism of the reactions of O-ethyl S-phenyl dithiocarbonate with pyrrolidine (order one in amine) and piperidine (complex order in amine) in aqueous ethanol, and this is attributed to a greater nucleofugality from T± of piperidine rather than pyrrolidine.
- Castro,Cabrera,Santos
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p. 113 - 117
(2007/10/03)
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- Potassium fluoride on alumina: Synthesis of O-aryl N,N-dimethylthiocarbamates and their rearrangement into S-aryl N,N-dimethylthiocarbamates under microwave irradiation
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A series of O-aryl N,N-dimethyl thiocarbamates have been prepared by the reaction of dimethylthiocarbamoyl chloride with phenols absorbed on potassium fluoride on alumina. The rearrangement of O-aryl N,N-dimethylthiocarbamate into S-aryl N,N-dimethylthiocarbamate under microwave irradiation was also studied. The use of conductive support like graphite or silicon carbide allow these rearrangements although the O-aryl N,N-dimethylthiocarbamates have very low dielectric lost.
- Villemin, Didier,Hachemi, Messaoud,Lalaoui, Mekki
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p. 2461 - 2471
(2007/10/03)
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- Oxidative Cleavage of S-Arylmercaptoacetic Acids by Sodium Perborate: Kinetic and Correlation Study
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Kinetics of oxidation of twenty six S-arylmercaptoacetic acids (SAMA) (I) by sodium perborate (PB) have been studied in acid medium.The product of oxidation is the corresponding thiophenol.The rate data of meta- and para-substituted acids have been correlated with DSP equations.While the para-compounds correlate well with ?I and ?0R values, the meta-compounds correlate well with ?I and ?-R values.The reaction constants are negative and of smaller magnitudes.Further, the ortho-substituted acids show a good correlation with a triparametric equation involving Taft's ?I and ?0R and Charton's steric parameter ν.There is a considerable steric contribution to the total ortho-substituent effect.Based on these observations, mechanism involving the formation of protonated arylsulfinylacetic acid intermediate, followed by an intramolecular rearrangement leading to the product thiophenol has been proposed.
- Kabilan, S.,Pandiarajan, K.,Krishnasamy, K.,Sankar, P.
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p. 443 - 452
(2007/10/02)
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- Kinetic Studies of the Reactions of Some Phenyl Aryl Sulfides with Aliphatic Amines in Dimethyl Sulfoxide: the Mechanism of Base Catalysis
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The reaction of n-butylamine, pyrrolidine and piperidine with 4'-R-phenyl 2,4,6-trinitrophenyl sulfides (R = H, Me, Br, NO2), 4a-d, result in the rapid formation of ?-adducts by attack at the unsubstituted 3-position; rate and equilibrium data are reported and substituent effects examined. Attack by amine at the 1-position of of 4a-d, phenyl 2,4-dinitronaphthyl sulfide 9, and phenyl 2,6-dinitro-4-trifluoromethyl sulfide 11, results in displacement of the phenylthio group.The substitutions by butylamine show a first order dependence on the amine concentration indicating that nucleophilic attack is rate determining.However the substitutions by pyrrolidine are subject to general base catalysis and it is argued that here the rate limiting step is deprotonation of the initially formed zwitterionic intermediate.
- Chamberlin, Rachel A.,Crampton, Michael R.
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p. 425 - 432
(2007/10/02)
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- Kinetic and Equilibrium Studies of ?-Adduct Formation and Nucleophilic Substitution in the Reactions of Hydroxide Ions with 2,4,6-Trinitrophenyl Sulfides and Ethers
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Kinetic and equlibrium data are reported for reaction of hydroxide ions in 20/80 DMSO/water (v/v) with a series of 4'-substituted phenyl 2,4,6-trinitrophenyl sulfides, 1, and with ethyl thiopicrate, 2, ethyl picrate, 3, phenyl picrate, 4, and 1,3,5-trinitrobenzene, 5.In each case a rapid reaction is observed involving reversible hydroxide addition at an unsubstituted ring-position.In the case of 1-4 this is followed by slower, irreversible attack at the 1-position leading to the formation of picric acid.The Hammett ρ value for equilibrium addition of hydroxide to the 3-position of 1 is 0.98, and the ρ value for rate constants for attack at the 1-position is 0.62.The results are discussed in terms of the electronic and steric effects of the 1-substituents.Comparison of 1-5 indicates that changing from an OR to SR group introduces additional steric crowding.However for the reactions studied changing from R = Et to R = Ph has little steric consequence.
- Chamberlin, Rachel,Crampton, Michael R.,Knight, Roland L.
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p. 2986 - 2998
(2007/10/02)
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- Kinetics and Mechanism of the Acid-Catalysed Hydrolysis of Benzaldehyde Diaryl Thioacetals and of Benzaldehyde S-Aryl, S-Ethyl Acetals in Aqueous Perchloric Acid
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The effects on the rate of hydrolysis of changes in aryl substituents, acid concentration, temperature, and solvent isotope, show that the acid-catalysed hydrolyses of five benzaldehyde diaryl thioacetals and three benzaldehyde S-aryl, S-ethyl acetals in 2-7 mol dm-3 aqueous perchloric acid proceed via essentially A1 mechanisms.The pattern of the substituent effects found for the leaving, and remaining, S-aryl groups is similar to that found previously for leaving and remaining groups in O,O- and O,S-acetals.
- Ali, Muhammad,Satchell, Derek P. N.
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p. 1825 - 1828
(2007/10/02)
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- Toxin-targeted design for anticancer therapy. I: Synthesis and biological evaluation of new thioimidate heterobifunctional reagents
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In an effort to obtain a more potent and specific immunotoxin for cancer therapy, we designed a series of heterobifunctional linkers characterized by a thioimidate group linked to a S-acetyl thiol (4, 5) or substituted aryldithio group (6-10). These ligands were synthesized by a Pinner-type process from the corresponding nitrile derivatives obtained by thiol- disulphide exchange reaction, reaction with substituted benzene-sulphenyl chloride, or other known procedures. To check the reagent of choice for immunoconjugate preparation, we studied thioldisulphide exchange kinetics between the intermediate nitrile derivatives and cysteine. Among the tested aryldithio derivatives (6-10), we selected ethyl 3-(4-carboxamido- phenyldithio)propionthioimidate (CDPT, 9) for further studies. By analyzing the rate of incorporation of the linkers 4, 5, and 9 in a model immunoglobulin G protein, we found similar results with CDPT 9 and ethyl S- acetyl 3-mercaptopropionthioimidate ester hydrochloride (AMPT, 5) because both reagents showed a linear correlation between the number of introduced thiol groups and factors such as time and protein and reagent concentrations. Comparison of the two acetylthio-derivative ligands 4 and 5 showed that AMPT 5 was more stable toward deacetylation than ethyl S-acetyl 2- mercaptopropionthioimidate ester hydrochloride (AMAT, 4). By comparing the kinetic and biological parameters of seven new thioimidate linkers, we found that two of these (CDPT and AMPT) could be superior ligands for protein- protein conjugation. They offer advantages over the commercially available compounds, such as minimal perturbation of the protein structure, controlled reactivity, and good stability.
- Delprino,Giacomotti,Dosio,Brusa,Ceruti,Grosa,Cattel
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p. 506 - 512
(2007/10/02)
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- Structure-Reactivity Relationships in the Aminolysis of O-Ethyl S-Aryl Dithiocarbonates in Aqueous Solution
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The reactions of O-ethyl S-(X-phenyl) diothiocarbonates (X = p-Cl, p-Me, and p-MeO) with a series of secondary alicyclic amines and those of the same substrates and analogous derivatives (X = H, p-NO2, 2,4-(NO2)2 with pyrrolidine are subjected to a kinetic study in water, 25.0 deg C, ionic strength 0.2 M (KCl).The reactions of piperidine and pyrrolidine show second-order kinetics (first order in amine) with the formation of a zwitterionic tetrahedral intermediate (T+/-) as the rate-determining step.The reactions of the other amines exhibit orders in amine differentfrom one, compatible with the presence of an anionic intermediate (T-), resulting from a kinetically important proton transfer from T+/- to the amine.The rate of this proton transfer is faster than that of expulsion of arylthiolate from T+/- (k2) as evidenced by the estimation of these rate coefficients.The rate constants for formation of T+/- (k1) are obtained experimentally, and those for amine expulsion from T+/- (k-1) are estimated.Equations for k1 and k-1 are derived as functions of the basicity of the amine and leaving (aryl thiolate) groups.Comparison of the k-1 and k2 values found in the present reactions with those obtained in the aminolysis of aryl dithioacetates shows that substitution of Me by EtO as the "acyl" group of the zwitterionic tetrahedral intermediate destabilizes this species.
- Castro, Enrique A.,Cubillos, Maria,Ibanez, Fernando,Moraga, Inge,Santos, Jose G.
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p. 5400 - 5404
(2007/10/02)
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- A facile, high-yielding method for the conversion of halides to mercaptans
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An efficient, high-yield, one-pot preparation of alkyl and activated aryl mercaptans is presented. The method relies on sodium thiophosphate displacement of the halide, followed by mild hydrolysis of the intermediate phosphorothioate.
- Bieniarz,Cornwell
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p. 939 - 942
(2007/10/02)
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- Kinetics and Mechanism of the Aminolysis of 4-Nitrophenyl Dithioacetate
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The reaction of the title substrate with a series of secondary alicyclic amines has been the subject of a kinetic study in aqueous solution, 25 deg C, ionic strength 0.2 M (KCl).With the amine in excess, pseudo-first-order rate constants (k(obsd)) are observed.The order in amine varies from 1 to 2 depending on the basicity of the amine and reaction conditions.A reaction scheme is deduced on the basis of the existence of zwitterionic (T(+/-)) and anionic (T(-)) tetrahedral intermediates.Proton transfer from T(+/-) to an amine or base (to yield T(-)) seems to compete with 4-nitrothiophenoxide (NPS(-)) expulsion from T(+/-).The pKa of T(+/-) and all the rate microconstants of the scheme are estimated.The rates of expulsion of NPS(-) and amine from T(+/-) are smaller than those from analogous T(+/-) formed in the aminolyses of O-ethyl S-(4-nitrophenyl)dithiocarbonate and 4-nitrophenyl thiolacetate.It is claimed that substitution of Me by RO (R = alkyl) or S(-) by O(-) in T(+/-) destablizes this intermediate.
- Castro, Enrique A.,Ibanez, Fernando,Santos, Jose G.,Ureta, Carmen
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p. 7024 - 7028
(2007/10/02)
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- Kinetics and Mechanism of the Aminolysis of O-Ethyl S-Aryl Ditihiocarbonates
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The reactions of O-ethyl S-phenyl dithiocarbonate (1) and O-ethyl S-(p-nitrophenyl dithiocarbonate (2) with a series of secondary alicyclic amines, namely, piperidine, piperazine, 1-(β-hydroxyethyl)piperazine, morpholine, 1-formylpiperazine, and (with 2 only) piperazinium ion, are subject to a kinetic study at several pH values.The reaction leads to the corresponding thiocarbamates and thiophenols (measured as thiophenoxide ion by UV-vis spectrophotometry).Pseudo-first-order rate coefficients (kobsd) are found throughout (amine excess).The kinetics are first order in amine for the reactions of 2.The plots of kobsd vs for the reaction of 1, except with 1-formylpiperazine, are linear, but near the origin they are curved, showing a more complex rate equation.The reaction of 1 with 1-formylpiperazine shows a second-order dependence on the amine.No dependence on pH of the second-order rate constant values is observed.The findings are well-accommodated by a mechanistic model involving reversible nucleophilic attack on the thiocarbonyl group, two tetrahedral intermediates, 3 and 4, and a deprotonation step.The Bronsted-type plots obtained are linear (β1 = 0.22) for the reaction of 1 and curved for 2 (β1 = 0.2 and β2 = 0.8).The Bronsted-type plot obtained with the rate constants for amine expulsion from 3 is linear with β-1 = -0.67 and -0.54 for the reactions of 1 and 2, respectively.
- Cabrera, Mauricio,Castro, Enrique A.,Salas, Mirtha,Santos, Jose G.,Sepulveda, Patricia
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p. 5324 - 5328
(2007/10/02)
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- Structure-Reactivity Correlations in the Aminolysis of Phenyl and p-Nitrophenyl Thiolacetates
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Second-order rate constants (kN) for the nucleophilic reactions of piperidine, morpholine, piperazine, and N-substituted piperazines with the title substrates are reported in water, at 25 deg C, ionic strength 0.2 M (maintained with KCl).The Broensted-type plot obtained for the aminolysis of phenyl thiolacetate is linear while that for the p-nitrophenyl derivative (NPTA) is curved, with the center of curvature at pKa=10.5 (pKa0).According to these results the most likely mechanism involves a zwitterionic tetrahedral intermediate (T+/-), for which decomposition to products is the rate-limiting step for all the reactions, except that of NPTA with piperidine.For this reaction the formation of T+/- is rate determining.A semiempirical equation based on the above hypothesis accounts for the Broensted-type curve obtained in the aminolysis of NPTA.Estimation of the microscopic rate constants involved, in a possible more general reaction scheme and evaluation of the pKa's of T+/- indicate that expulsion of the leaving group of the substrate from T+/- is faster than deprotonation of T+/- by a base, precluding therefore the formation of an anionic tetrahedral intermediate.The fact that pKa0=10.5 for the NPTA reactions means that an (hypothetical) amine of pKa=10.5 leaves T+/- as readily as p-nitrothiophenoxide ion (pKa=4.6).From these and other data it is calculated that the nucleofugality from T+/- of an amine of pKa=4.6 is ca. 3*104 times larger than that of p-nitrothiophenoxide ion.The estimated pKa0 values for the aminolysis of (hipothetical) aryl acetates with leaving groups of pKa=4.6 and 6.5 (the same pKa as thiophenol) are pKa0=8.0 and 9.0, respectively, which gives nucleofugality ratios (a given amine/aryl oxide ion) from the oxy T+/- smaller than those from the corresponding sulfur T+/-.It is claimed that expulsion of ArS- from T+/- is only slightly slower than that of an isobasic ArO- from the oxy T+/-.Therefore, the above results indicate that the "push" provided by ArS in T+/- to expel a given amine is much stronger than that exerted by an isobasic ArO in the oxy T+/-.Activation parameters are reported for the reactions of the title substrates with piperidine, piperazine, and N-formylpiperazine.
- Castro, Enrique A.,Ureta, Carmen
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p. 2153 - 2159
(2007/10/02)
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- Elimination reactions of β-Cyano Thioethers: Evidence for a Carbanion Intermediate and a Change in Rate-Limiting Step
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The addition reactions of thiol anions to form adducts with acrylonitrile (1), 1-chloroacrylonitrile (2), and fumaronitrile (3) and the corresponding elimination reactions were examined in aqueous solution, generally containing 8.3percent Me2SO at 25 deg C.Deuterium exchange into the methanethiol and thiosalicylate adducts of 1 is faster than elimination.Deuterium exchange causes biphasic kinetics for elimination reactions in D2O of the p-nitrothiophenol, but not of the pentafluorothiophenol, adducts 1 and 2.The kinetic solvent deuterium isotope effects of knHOH/knDOD = 2.0 for addition of thiosalicylate to form 3 and 1.1-1.2 for addition of β-mercaptoethanol and thioacetic acid anions to form 1 are smaller than the product discrimination isotope effects of kH/kD = 3.2, 2.8 and 3.2 for these reactions.These differences show that the reactions proceed through a carbanion intermediate that is protonated faster than it expels basic thiol anions.These results exclude a concerted mechanism for addition-elimination with a concurrent, separate exchange reaction.The solvent kinetic deuterium isotope effect is 3.9 for the addition of thionitrobenzoate dianion to form 3.Buffer catalysis of elimination becomes more significant with more acidic leaving groups and is larger for 3 than for 1 with a given leaving group.The results show that the rate-limiting step changes from addition-elimination of the thiol anion to proton transfer with decreasing pKa of the thiol; the same change is favored by addition of CN to the α-position for a given thiol.The effect of the α-CN group is attributed to conjugation with the developing double bond in the transition state for elimination.The Broensted slope is β = 0.90 for rate-limiting deprotonation of the pentafluorothiophenol adduct 3 and Broensted-type plots against the pKa of the leaving group have slopes of β1g = -0.25 and -0.54 for predominantly rate-limiting deprotonation and leaving group expulsion, respectively.
- Fishbein, James C.,Jencks, William P.
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p. 5075 - 5086
(2007/10/02)
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- Elimination Reactions of β-Cyano Thioethers: Internal Return and the Lifetime of the Carbanion Intermediate
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The E1cB elimination reaction of the pentafluorothiophenol adduct of fumaronitrile (3) in water containing 8.3percent Me2SO shows strong buffer catalysis and primary deuterium isotope effects of kH/kD = 4-5.In contrast, hydrogen exchange of the methanethiol adduct of 3 shows little or no buffer catalysis.There is no incorporation of deuterium that gives an inverse solvent isotope effect in the buffer-catalyzed elimination of the thionitrobenzoate adduct of 3 in D2O and H2O, although thiol anion expulsion is partly rate limiting for this reaction.These observations are consistent with internal return of the abstracted proton from the protonated buffer base that is competitive with the expulsion of leaving groups with pKa > 4.The primary deuterium isotope effects for elimination catalyzed by hydroxide ion are kH/kD = 4.9 +/- 0.4, 4.2 +/- 0.1, 4.2 +/- 0.3, and 3.1 +/- 0.1 for the pentafluorothiophenol and thionitrobenzoate adducts of 3, the N-methyl-2-mercaptopyridinium ion adduct of acrylonitrile (1), and the pentafluorothiophenol adduct of chloroacrylonitrile (2), respectively.These isotope effects are significantly larger than values of kH/kD = 2.6 +/- 0.3, 2.2 +/- 0.1, and 2.1 +/- 0.1 for buffer-catalyzed elimination from the adducts of 1 and 3.They are also larger than (1) the primary isotope effects of kH/kD = 2.5 +/- 0.3, 2.3 +/- 0.2, and 2.3 +/- 0.2 for the p-nitrothiophenol adducts of 1 and 3 and the thiophenol adduct of 2 that were obtained from the biphasic kinetics for elimination of these compounds in D2O and (2) the product discrimination isotope effects of ca. 3 for the addition of thiol anions to 1 and 3.These observations are consistent with the formation of an unstable carbanion intermediate that undergoes competitive reprotonation by solvent, k-1, exchange of the abstracted proton with the bulk solvent, ks, and elimination, k2.Ratios of k-1/ks and k-1/k2 that were obtained from the results give values of k-1 ca. 1E11 s-1 and k2 = 1E10-1E13 s-1, assuming a value of ks = 1E11 s-1.Estimated pKa values in aqueous solution include 26.8 for NCCH2CH2SPh, 22.0 for NCCH(Cl)CH2SPhNO2, and 23.2 for NCCH2CH(CN)SCH3.
- Fishbein, James C.,Jencks, William P.
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p. 5087 - 5095
(2007/10/02)
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