Baylis-Hillman reactions of N-tosyl aldimines and aryl aldehydes with 3-methylpenta-3,4-dien-2-one

The attempted Baylis-Hillman reactions of N-tosyl aldimines and aryl aldehydes with 3-methylpenta-3,4-dien-2-one gave the corresponding Baylis-Hillman adducts 3 and 6 in moderate to good yields in the presence of DMAP in DMSO, respectively. In the case of the aza-Baylis-Hillman reactions of N-tosyl aldimines with 3-methylpenta-3,4-dien-2-one catalyzed by PBu3, the corresponding aza-Baylis-Hillman derivatives 4 and 5 were formed at the same time.     

Addition of grignard reagents to aryl acid chlorides: an efficient synthesis of aryl ketones

[chemical reaction: see text]. Direct addition of Grignard reagents to acid chlorides in the presence of bis[2-(N,N-dimethylamino)ethyl] ether proceeds selectively to provide aryl ketones in high yields. A possible tridentate interaction between Grignard reagents and bis[2-(N,N-dimethylamino)ethyl] ether moderates the reactivity of Grignard reagents, preventing the newly formed ketones from nucleophilic addition by Grignard reagents.     

A zwitterion of 1,5‐bis­(2‐hydroxy­benzamido)‐3‐aza­pentane: a two‐dimensional hydrogen‐bonding network involving dimers

The title compound, 2‐{N‐[2‐(2‐hydroxy­benzamido)ethyl­ammonio­ethyl]amino­carbon­yl}phenolate, C₁₈H₂₁N₃O₄, crystallizes in a zwitterionic form as a result of inter­molecular proton transfer and possesses a negatively charged phenolate group and a protonated amino group. The 2‐hydroxy­benzamide and 2‐(amino­carbonyl)­phenolate moieties attached to the two ends of the C—C—N—C—C backbone adopt a cis conformation in relation to this backbone. All N‐ and O‐bound H atoms are involved in hydrogen‐bond formation; the zwitterions are first linked into head‐to‐tail dimers, which are further organized into a two‐dimensional network parallel to the crystallographic bc plane.     

Use of the tubulin bound paclitaxel conformation for structure-based rational drug design

A new computational docking protocol has been developed and used in combination with conformational information inferred from REDOR-NMR experiments on microtubule bound 2-(p-fluorobenzoyl)paclitaxel to delineate a unique tubulin binding structure of paclitaxel. A conformationally constrained macrocyclic taxoid bearing a linker between the C-14 and C-3'N positions has been designed and synthesized to enforce this "REDOR-taxol" conformation. The novel taxoid SB-T-2053 inhibits the growth of MCF-7 and LCC-6 human breast cancer cells (wild-type and drug resistant) on the same order of magnitude as paclitaxel. Moreover, SB-T-2053 induces in vitro tubulin polymerization at least as well as paclitaxel, which directly validates our drug design process. These results open a new avenue for drug design of next generation taxoids and other microtubule-stabilizing agents based on the refined structural information of drug-tubulin complexes, in accordance with typical enzyme-inhibitor medicinal chemistry precepts.     

Rigorous information-theoretic derivation of quantum-statistical thermodynamics. II

Part I of the present work outlined the rigorous application of information theory to a quantum mechanical system in a thermodynamic equilibrium state. The general formula developed there for the best-guess density operator \(\hat \rho\) was indeterminate because it involved in an essential way an unspecified prior probability distribution over the continuumD _H of strong equilibrium density operators. In Part II mathematical evaluation of \(\hat \rho\) is completed after an epistemological analysis which leads first to the discretization ofD _H and then to the adoption of a suitable indifference axiom to delimit the set of admissible prior distributions. Finally, quantal formulas for information-theoretic and thermodynamic entropies are contrasted, and the entire work is summarized.     

Separation of metal ions by capillary electrophoresis

A number of experimental parameters have been optimized for the separation of 26 metal ions, including alkali, alkaline earth, transition and lanthanide metal ions. Experimental parameters that were evaluated included nature of indirect-detection reagent, pH of electrolyte, concentration of complexing agent and nature of the surface of the capillary; unbonded and C₁ and C₁₈ bonded phases were studied. In addition the effect of internal diameter on linearity and signal-to-noise ratio was examined, and separation efficiency was determined for a variety of experimental conditions. Detection limits (signal-to-noise RATIO = 3) were ca. 1 μg/ml for the lanthanides, ca. 0.6 μg/ml for transition and alkaline earth ions and ca. 0.1–0.8 μg/ml for alkali metal ions. The average relative standard deviations of were 3.7, 5.1 and 2.5% on unbonded, C₁ and C₁₈ capillaries, respectively. Whereas conventional regression analysis suggested that the calibration curves were linear over the range of 1·10⁻⁵ to 4·10⁻⁴ mol/l, sensitivity plots showed that the results were actually linear to within 6% only over the range of 2.5·10⁻⁵ to 4·10⁻⁴ mol/l.     

Adsorptive stripping measurements of germanium(IV) in the presence of pyrogallol

The adsorptive stripping voltammetric determination of germanium(IV) based on the adsorptive accumulation of the germanium(IV)-pyrogallol complex on a hanging mercury drop electrode is reported. The reduction current of the adsorbed germanium complex is measured by differential-pulse cathodic stripping voltammetry. The peak potential is at -0.42 V vs. Ag AgCl (saturated KCL). The effects of various parameters (ligand concentration, supporting electrolytic composition and concentration, accumulation potential and collection time) on the response are discussed. With controlled accumulation for 3 min, the detection limit is 1.2 x 10(-9) M germanium. The relative standard deviation (at 1.2 x 10(-8) M germanium) is 3.6%. Possible interferences are evaluated. The applicability of the method to the determination of germanium(IV) in ore samples was also successfully carried out.     

Reactions of hydrazoic acid on TiO2 nanoparticles: an experimental and computational study

This article reports the results of a computational and experimental study on the reaction of hydrazoic acid, HN3, adsorbed on 15-20 nm TiO2 particle films. Experimentally, FTIR spectra of HN3(a) have been measured by varying HN3 dosage, UV irradiation time and surface annealing temperature. Three sharp peaks, related to v(a)(NNN) of HN3(a) and N3(a) with different configurations in the 2000-2200 cm(-1) region, and a broad band absorption, related to associated and isolated HN(a) and HO(a) adsorptions in the 3000-3800 cm(-1) region, have been detected. Computationally, molecular structures, vibrational frequencies and adsorption energies of possible adsorbates including HN3 and its derivatives, N3, N2, NH, and H, have been predicted by first-principles calculations based on the density functional theory (DFT) and the pseudopotential method. On the basis of the experimental and computational results, the peak appeared at 2075 cm(-1), which increases at a faster rate with HN3 exposure time, is attributed to a stable adsorbate, N3-Ti(a), with the predicted adsorption energy, E(ads) = 13 kcal/mol. The peak at 2118 cm(-1), which survives at the highest surface temperature in the heating experiment, is attributable to the most stable adsorbate, Ti-N2N(H)-O(a) with E(ads) = 36 kcal/mol. The peak at 2170 cm(-1), which vanishes most readily in all of the aforementioned experiments, is related to less stable molecular adsorbates, end-on HN3-Ti(a) with E(ads) = 5 kcal/mol and side-on HN(N2)-Ti(a) with E(ads) = 8 kcal/mol. A potential energy diagram for the formation of various absorbates with their transition states has been established for the HN3/TiO2 system. On the basis of the predicted desorption energies, the four most stable products of the HN3 reaction on TiO2 are H-O(a), 118 kcal/mol; HN-O(a), 85 kcal/mol; Ti-N2N(H)-O(a), 36 kcal/mol; and N3-O(a), 19 kcal/mol.     

The determination of trace amounts of tin by flow-injection hydride generation atomic-absorption spectrometry with on-line ion-exchange separation and preconcentration

A hydride generation atomic-absorption spectrometric (AAS) method with flow-injection (FI), aimed at developing a practical routine assay for the determination of tin in food digests, is described. In order to modify the sample matrix and to achieve optimized and reproducible conditions for the hydride generation reaction, the analyte is initially converted into its chlorostannate-complex thereby allowing it to be separated and preconcentrated on-line on an incorporated micro-column packed with a strongly basic anion exchanger and subsequently to be eluted by diluted nitric acid under strictly controlled conditions. Optimum acidic conditions for the FI hydride generation AAS system was found to be 0.01-0.05M nitric acid. At a consumption of 2.7-ml sample volume, aspirated by time-based injection, the procedure resulted in an enrichment factor of 3.5 and yielded a detection limit of 0.08 microg/l. (3sigma) at a sampling frequency of 72/hr. The precision was 2.5% rsd at the 10 microg/l. level. Potential interferents, such as Ni(II), Co(II), Zn(II) and Fe(III) could, at a Sn level of 10 microg/l., be tolerated at an excess of 1000 times without impairing the assay, while a 100-1000-fold excess of Cu(II) decreased the signal by 10-15%. Recoveries in the range 94-102% were obtained for canned food sample digests spiked with 10 microg/l. Sn.