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Knightletin is a novel, high quantum-yield, substituted coumarin in the group of fluorescent aminocoumarins. The molecule reveals the influence of a hydroxyl group on the aminocoumarin structure through its absorbance-fluorescence properties and interaction with several solvents. The substitution on the benzene ring of the coumarin affects electronic states, the molecular dipole moment and hydrogen bonding between vicinal groups as well as hydrogen bonding with solvents. This report describes the synthesis of knightletin, its absorbance-fluorescence characteristics in three solvents of varying polarity, and insights on its conformation from density functional theory modeling. The quantum yield of 0.81 in methanol is remarkable. The modeling indicates a ground state geometry with a pyramidal NH2 group interacting with the OH in an NH-donor hydrogen bond and predicts spectroscopic characteristics consistent with the experimental observations.

3-Aryl- and 3-heteroaryloxazolidin-2-ones, by virtue of the diverse pharmacologic activities exhibited by them after subtle changes to their appended substituents, are becoming increasingly important and should be considered privileged chemical structures. The iodocyclocarbamation reaction has been extensively used to make many 3-alkyl-5-(halomethyl)oxazolidin-2-ones, but the corresponding aromatic congeners have been relatively underexplored. We suggest that racemic 3-aryl- and 3-heteroaryl-5-(iodomethyl)oxazolidin-2-ones, readily prepared by the iodocyclocarbamation reaction of N-allylated N-aryl or N-heteroaryl carbamates, may be useful intermediates for the rapid preparation of potential lead compounds with biological activity. We exemplify this point by using this approach to prepare racemic linezolid, an antibacterial agent. Herein, we report the results of our systematic investigation into the scope and limitations of this process and have identified some distinguishing characteristics within the aryl/heteroaryl series. We also describe the first preparation of 3-aryloxazolidin-2-ones bearing new functionalized C-5 substituents derived from conjugated 1,3-dienyl and cumulated 1,2-dienyl carbamate precursors. Finally, we describe the utility of the iodocyclocarbamation reaction for making six-membered tetrahydro-3-aryl-1,3-oxazin-2-ones.

In the presence of commercially available chiral rhodium catalysts, a competitive benzylamination of racemic allyl carbonates, substituted with p-X-Ph groups, shows that the reaction proceeds faster with substituents (X) that are more electron-withdrawing. Mechanistic implications of these results are discussed.

Underlying the chemistry of unsubstituted 3-alkynals (i. e., 3-alkynals unsubstituted at the 2-position) is their tendency to rearrange to 2,3-dienals in which one of the carbon-carbon π bonds is c...

We report the application of recently developed microscopic models to estimate the apparent kinetic and thermodynamic parameters in a single molecule force spectroscopy study of the carbonic anhydrase enzyme and a complementary sulfonamide inhibitor. The most probable rupture force for the enzyme-inhibitor interaction shows a non-linear dependency on the log-loading rate. Estimates for the kinetic and thermodynamic parameters were obtained by fitting the non-linear dependency to linear cubic potential and cusp potential models and compared to the standard Bell-Evans model. The reliability of the estimated parameters was verified by modeling the experimental rupture force distributions by the theoretically predicted distributions at rupture. We also report that linkers that are attached to the enzyme and inhibitor show appreciable effects on the apparent kinetic and thermodynamic parameters.

In the presence of commercially available chiral rhodium catalysts, a competitive benzylamination of racemic allyl carbonates, substituted with p-X-Ph groups, shows that the reaction proceeds faster with substituents (X) that are more electron-withdrawing. Mechanistic implications of these results are discussed.

Photolysis of 1-(3-alkynoxy)-9,10-anthraquinones in deoxygenated methanol leads to moderate yields (35-45%) of 3-alkynals along with the unexpected formation of diacetals. Reaction of these 3-alkynals with Grignard and Wittig reagents occurs nearly quantitatively without rearrangement to their 2,3-dienal isomers.

The cyclopropylmethyl and (trans-2-phenylcyclopropyl)methyl radical clocks were used to estimate the lifetimes of triplet state biradicals formed from substituted 1-alkoxy-9,10-anthraquinones by photoexcitation and subsequent 1,5-hydrogen atom transfer. Irradiation (350 nm) of 1-(cyclopropylmethoxy)-2-methyl-9,10-anthraquinone (1cp) in argon-purged methanol generated the primary anthrahydroquinone product (2). Upon exposure to air, 2 was rapidly converted to cyclopropanecarboxaldehyde and 1-hydroxy-2-X-9,10-anthraquinone (3). In contrast, irradiation of 1-{(trans-2-phenylcyclopropyl)methoxy}-2-benzyl-9,10-anthraquinone (1pcp) under similar conditions produced only small amounts of 3 and the corresponding aldehyde, trans-(2-phenylcyclopropyl)carboxaldehyde. In addition, products resulting from rearrangement of the 1,5-biradical to a homoallylic 1,8-biradical were also obtained. Using the known rate constant for the rearrangement of the phenylcyclopropylmethyl radical to the homoallylic radical and the obse...

A cobaltocenium label was covalently attached to two antidepressants, nortriptyline and desipramine, via an amide linkage, and also to the hydrazine derivative of the biologically important compound biotin (vitamin H), again via an amide linkage. Analytically pure samples of these new cobaltocenium salts could be obtained by chromatography on silica gel followed by elution with aqueous acetone solutions containing sodium chloride (NaCl). These positively charged cobaltocenium ions preconcentrate in a polyanionic Nafion film coated on a glassy carbon surface, albeit at different concentration levels. One factor which seems to influence the amount of cobaltocenium ion that enters the film is polarity since the cobaltocenium ion containing the rather polar biotin preconcentrates at the lowest level in the relatively hydrophobic Nafion. Square-wave voltammograms of Nafion films containing these cobaltocenium cations exhibit a one-electron, reversible, reduction wave at approximately −1.1 V (vs Ag/AgCl) with peak currents that are sufficiently large to permit detection of 10−8 M quantities of these substances in the bulk solution.

A Nafion film-modified electrode has been used as an electroanalytical sensor to detect a drug containing a cationic redox label by square wave voltammetry. A tracer, composed of the model drug amphetamine covalently attached to a cobaltocenium redox label, was synthesized and used in a competitive immunoassay technique. In this assay, only the positively charged tracer not vound to the antibody preconcentrated in the anionic film. Consequently, it was not necessary to separate free from antibody-bound labeled amphetamine, thereby allowing the assay to be carried out in homogeneous media at the electrode surface

A nitroxide label was covalently attached to amphetamine and two antidepressants, nortriptyline and desipramine, by forming an amide linkage between the amino group on each of these compounds and 3-carboxyl-2,2,5,5-tetramethyl-1-pyrrolidinyloxy. This nitroxide label was also attached to be biologically important compound biotin, but a spacer group, N,N'-dimethyl-1,6-hexanediamine, was needed to male two amide linkages between the carboxylic acids on the nitroxide and biotin. These nitroxide-labeled substances undergo a one-electron reversible oxidation between 0.5 and 0.6 V (vs. Ag/AdCl) at a naked glassy carbon (GC) elecrode and between 0.3 and 0.4 V at a GC electrode coated with a polyanionic film of Nafion

Recently developed microscopic models by Dudko et al. were used to estimate the apparent kinetic and thermodynamic parameters in a single molecule force spectroscopy study of the carbonic anhydrase enzyme and a sulfonamide inhibitor. The most probable rupture force for the enzyme-inhibitor interaction demonstrates a nonlinear dependency on the log-loading rate. Estimates for the kinetic and thermodynamic parameters were obtained by fitting the nonlinear dependency to linear cubic potential and cusp potential models and compared to the Bell-Evans model. The reliability of the estimated parameters was verified by modeling the experimental rupture force distributions by the theoretically predicted distributions at rupture. We also report that an increase in the inhibitor tether length has a significant effect on the apparent kinetic and thermodynamic parameters while extending the length of the linkers which attach the enzyme to the surface has a minimal effect.

The photochemistry of a variety of 1-alkoxy- and 1-(benzyloxy)-9,10-anthraquinones in methanol has been examined. In the absence of oxygen the primary photoproducts of these reactions are 9,10-anthrahydroquinones with MeOCH 2 O and ArCH(OMe)O groups at the 1-position, respectively. Quenching studiens established the multiplicity of the excited state to be triplet. Deuterium isotope effects, substituent effects, and solvent polarity studies support a mechanism in which a biradical intermediate is formed by an intramolecular δ-hydrogen atom transfer that occurs in one step but not a reaction pathway in which the hydrogen atom transfer is accomplished in two discrete steps via separate electron and proton transfers. Apparent rate constants for the disappearance of 1-(p-XPhCH 2 O)-2-methyl-9,10-anthraquinone (X=H, Cl, CH 3 , NO 2 , OCH 3 , CF 3 , and CN) were measured and found to vary by a factor of 3.4 from the largest (X=NO 2 ) to the smallest (X=OCH 3 ). Captodative interactions account for the small differences in these rate constants

A variety of hydroxy- and methoxy-substituted 2-(acetoxymethyl)9,10-anthraquinones were reduced electrochemically and with dithionite in 50% aqueous CH 3 CN buffers over a wide pH range. Substituent effects upon the reductive cleavage process were determined by measuring rate constants for those acetates that react cleanly with dithionite at pH 8

In this communication, we report on the interaction landscape of an active site-specific enzyme-inhibitor complex by single-molecule force spectroscopy. Electrostatic immobilization was employed to orient a carbonic anhydrase enzyme on a positively charged surface so its active site is pointing upward. This approach to immobilization effectively increases the number of specific interactions measured between the zinc ion of the active site on carbonic anhydrase and a sulfonamide inhibitor tethered to an atomic force microscope (AFM) probe. Further, it reduces the time required for data collection and thereby minimizes the possible mechanical damage to the probe and contamination of the enzyme surface. The rupture force measured at various loading rates is interpreted in terms of a single energy barrier for the carbonic anhydrase enzyme-sulfonamide inhibitor complex from which the kinetic and thermodynamic parameters were estimated on the basis of microscopic models and were compared to the Bell-Evans model. The dissociation rate for the enzyme-inhibitor complex was found to be significantly faster (~35 times) than the natural spontaneous dissociation rate.

In this work, monolayers of metal complexes were covalently attached to the surface of carbon electrodes with the goal of binding monolayers of histidine-tagged proteins with a controlled molecular orientation and a maintained biological activity. In this novel method, which is simple, versatile, and efficient, the covalent attachment was accomplished in a single step by the electrochemical reduction of aryl diazonium ions that were substituted with a nitrilotriacetic (NTA) or an imminodiacetic (IDA) ligand at the para position. The transient aryl radicals that were generated in the reduction were grafted to the surfaces of glassy carbon, highly oriented pyrolitic graphite, and graphite-based screen-printed electrodes, producing dense monolayers of the ligands. The NTA- and IDA-modified electrodes were shown to efficiently chelate Cu(II) and Ni(II) ions. The presence of the metal was established using X-ray photoelectron spectroscopy and electrochemistry. Surface coverages of the ligands were indirectly determined from the electroactivity of the copper(II) complex formed on the electrode surface. Studies on the effect of electrodeposition time and potential showed that, at sufficiently negative potentials, the surface coverage reached a saturating value in less than 2 min of electrodeposition time, which corresponds to the formation of a close-packed monolayer of ligand on the electrode surface. Once loaded with a metal ion, the modified electrode was able to bind specifically to histidine-tagged proteins such as the horseradish peroxidase (His-HRP) or to an enhanced, recombinant green-fluorescent protein via its N-terminal hexahistidine tail. In the case of His-HRP, the amount of active enzyme specifically immobilized by metal-chelating binding was determined from the analysis of electrocatalytic currents using cyclic voltammetry. The electrochemical grafting makes it possible to accurately controlled and electronically address the amount of deposited ligand on the conductive surfaces of carbon electrodes with any size and shape.

A substituted anthraquinone (AQ), previously shown to photochemically generate benzaldehyde in methanol solution, was attached to a commercially available resin via an 11 carbon tether and an amide bond. Photolysis of the polymer-bound AQ with visible or 350 nm UV light resulted in the formation of benzaldehyde in yields of 50-55% as determined by HPLC. The phenolic positions in the polymer were then alkylated using benzyl bromide and 1-iodo-3-(4-nitrophenyl)propane in a coupling reaction with K(2)CO(3) as a base and a solution-phase proton shuttle. Photolysis of these alkylated polymers resulted in the formation of benzaldehyde (54-89%) and 3-(4-nitrophenyl)-propanal (58-67%). The yields of both aldehydes dropped considerably with subsequent realkylation and photolysis, and the polymer beads began to show signs of deterioration. This is the first time that aldehydes have been made photochemically on a solid-supported phase.

Laponite clay modified electrodes (LCME) have been used to detect trace amounts of neutral or cationic organometallic substances, including ferrocene (Fc) and cobaltocenium (Cc+), two molecules covalently attached to cobaltocenium, and a molecule labelled by ferrocene (N-amphetaminecarbonylferrocene) as an electroactive organic test species. During an ion-exchange preconcentration step, the cationic species (cobaltocenium derivatives) are collected in the laponite film from their dilute solutions under open-circuit conditions whereas the procationic species (ferrocene derivatives) are collected in their cationic form by applying a positive potential. Quantification of the surface bound cations is then carried out by applying a negative scan using voltammetry or square wave voltammetry. In the case of the two molecules labelled by Cc+, a detection limit of 4 × 10−8 mol l−1 and a linear calibration range from 1 × 10−7 to 2 × 10−5 mol l−1 are obtained reproducibly by using a new LCME for each measurement. Conversely with small redox molecules such as ferrocene and cobaltocenium, the same LCME can be used repeatedly because applying a negative potential leads to the exclusion of the resulting neutral molecule which can be rinsed efficiently from the film.

The hydroboration-oxidation of alkenes is an important route to alcohols and therefore receives considerable treatment in standard organic textbooks. These authors present their findings of an example (an alkene that undergoes the hydroboration oxidation process) that displays both regiochemistry and stereochemistry.

A program offered biannually during the days between Christmas and New Year's Day that attempts to attract capable secondary students to chemistry.

Etude de la reduction des acetoxy-2 et trifluoroacetoxy-2 anthraquinones (prealablement preparees a partir de methyl-2 anthraquinone) sur une electrode de carbone dans le DMF-LiClO 4 . Mecanismes

The electrochemical oxidation of NADH to NAD+ was reexamined using aqueous buffers and a glassy carbon electrode. Using cyclic voltammetry, it was shown that NAD+ was an inhibitor of the oxidation process. This makes the reaction self-inhibited and that accounts for several anomalous observations which were previously made. In the presence of excess NAD+, the NADH oxidation is first-order in NADH. Rate limiting one-electron transfer in an ECE mechanism is indicated. Previous chronoamperometric data which indicated that NADH+ had a lifetime of about 10 ms, were also reinterpreted. It was shown that the previous result was achieved only if the electrode surface was precoated. Therefore, the result cannot be used to calculate the lifetime of NADH+ . It is suggested, however, that this lifetime is less than 1 μs.

Synthese des benzyloxycarbonylamino-4 butyrate d'[anthraquinone-9,10yl-2methyle] et [anthraquinone-9,10yl-2methoxycarbonylamino]-4 butyrate de benzyle. Etude par voltammetrie cyclique de la reduction electrochimique de ces 2 composes (deprotection du GABA)

Reduction sur une electrode a disque de carbone vitreux dans DMF-LiClO 4 de cyclobuta [j] cyclohepta [de] naphtalene en son derive dihydro

L'oxydation electrochimique du zinc bis(O,O-diethyl phosphorodithioate-S,S') (1a) et du zinc bis[O,O-bis(methyl-1 ethyl) phosphorodithioate-S,S'] (1b) dans CH 3 CN, en presence d'une electrode de carbone vitreux, par voltammetrie cyclique, donne des vagues irreversibles avec des potentiels de pic de +1,5 V (ecs). L'oxydation a potentiel constant de 1a, a +1,4 V donne l'O,O,O,O-tetraethyl thioperoxydiphosphate suivant un processus a 2 electrons. Donnees, aussi, sur l'influence du bis-(methoxycarbonyl)-ferrocene

L'oxydation electrochimique du zinc bis(O,O-diethyl phosphorodithioate-S,S') (1a) et du zinc bis[O,O-bis(methyl-1 ethyl) phosphorodithioate-S,S'] (1b) dans CH 3 CN, en presence d'une electrode de carbone vitreux, par voltammetrie cyclique, donne des vagues irreversibles avec des potentiels de pic de +1,5 V (ecs). L'oxydation a potentiel constant de 1a, a +1,4 V donne l'O,O,O,O-tetraethyl thioperoxydiphosphate suivant un processus a 2 electrons. Donnees, aussi, sur l'influence du bis-(methoxycarbonyl)-ferrocene

Reaction sur des alkyl-2 methoxy-1 et dimethoxy-1,8 anthraquinones. Obtention des hydroxy-anthraquinones correspondantes. Etude du mecanisme par effet isotopique