Stereoselective diversity-oriented solution and solid-phase synthesis of tetrahydroquinoline-based polycyclic derivatives

A diversity-oriented solution and solid-phase synthesis of tetrahydroquinoline-based tricyclic derivatives has been achieved from enantiomerically pure, natural product-like bicyclic scaffold. The solution synthesis of enantiopure bicyclic scaffold was developed by asymmetric hetero Michael reaction. Our approach for the synthesis of polycyclic derivatives utilized regio- and stereoselective hetero Michael reaction and ring-closing metathesis as key steps in solution and on solid phase.     

Symmetry numbers and chemical reaction rates

This article shows how to evaluate rotational symmetry numbers for different molecular configurations and how to apply them to transition state theory. In general, the symmetry number is given by the ratio of the reactant and transition state rotational symmetry numbers. However, special care is advised in the evaluation of symmetry numbers in the following situations: (i) if the reaction is symmetric, (ii) if reactants and/or transition states are chiral, (iii) if the reaction has multiple conformers for reactants and/or transition states and, (iv) if there is an internal rotation of part of the molecular system. All these four situations are treated systematically and analyzed in detail in the present article. We also include a large number of examples to clarify some complicated situations, and in the last section we discuss an example involving an achiral diasteroisomer.     

Electrochemically Induced Iron Release of Adsorbed Horse Spleen Ferritin: Quantitation of Iron Using Long Optical Path Length Thin‐Layer Spectroelectrochemistry

In this work, long optical path length thin‐layer electrochemical cell was constructed using indium‐tin oxide on glass as the electrode material. Iron release from ferritin adsorbed on the electrode was induced by applying a negative potential sweep in the presence of 1,10‐phenanthroline. The usefulness of spectroelectrochemistry as a means of determining the quantity of iron released from an adsorbed layer of ferritin is demonstrated.     

On the role of the conserved aspartate in the hydrolysis of the phosphocysteine intermediate of the low molecular weight tyrosine phosphatase

The usual rate-determining step in the catalytic mechanism of the low molecular weight tyrosine phosphatases involves the hydrolysis of a phosphocysteine intermediate. To explain this hydrolysis, general base-catalyzed attack of water by the anion of a conserved aspartic acid has sometimes been invoked. However, experimental measurements of solvent deuterium kinetic isotope effects for this enzyme do not reveal a rate-limiting proton transfer accompanying dephosphorylation. Moreover, base activation of water is difficult to reconcile with the known gas-phase proton affinities and solution phase pK(a)'s of aspartic acid and water. Alternatively, hydrolysis could proceed by a direct nucleophilic attack by a water molecule. To understand the hydrolysis mechanism, we have used high-level density functional methods of quantum chemistry combined with continuum electrostatics models of the protein and the solvent. Our calculations do not support a catalytic activation of water by the aspartate. Instead, they indicate that the water oxygen directly attacks the phosphorus, with the aspartate residue acting as a H-bond acceptor. In the transition state, the water protons are still bound to the oxygen. Beyond the transition state, the barrier to proton transfer to the base is greatly diminished; the aspartate can abstract a proton only after the transition state, a result consistent with experimental solvent isotope effects for this enzyme and with established precedents for phosphomonoester hydrolysis.     

Europium-sensitized luminescence determination of oxytetracycline in catfish muscle

An europium-sensitized time-resolved luminescence (TRL) method was developed to determine oxytetracycline (OTC) in cultivated catfish muscle. Extraction of OTC from fish muscle was performed with pH 4.0 ethylenediaminetetraacetic acid (EDTA)-McIlvaine buffer and clean up with hydrophilic-lipophilic balanced copolymer solid phase extraction (SPE) cartridges. The eluate was used without further concentration for TRL measurement in pH 9.0 micellar tris(hydroxylmethyl)aminomethane (TRIS) buffer. Cetyltrimethylammonium chloride (CTACl) was used as surfactant and EDTA as a co-ligand. The excitation and emission wavelengths were set at 388 and 615 nm, respectively. The linear dynamic range was 0-1000 ng g⁻¹ (R²=0.9995). The recovery was 92-112% in the fortification range of 50-200 ng g⁻¹ and the limits of detection (LOD) ranged from 3 to 7 ng g⁻¹. Incurred catfish samples were used to demonstrate the performance of the method around 100 ng g⁻¹, the European Union maximum residue level.     

Total synthesis of (±) zoapatanol: a stereospecific synthesis of a key intermediate

The development of a stereospecific synthesis of a key intermediate in the synthesis of (±)-zoapatanol from the Weiland-Miescher ketone is described.     

Solution- and solid-phase synthesis of natural product-like tetrahydroquinoline-based polycyclics having a medium size ring

A solid-phase synthesis of tetrahydroquinoline-derived polycyclic 4, having a medium size ring with an enamide functionality, was achieved from tetrahydroquinoline derivative 3 in five steps with overall 40-45% yield. An enantiopure, tetrahydroquinoline-derived beta-amino ester, 1, was converted into compound 2 that has a free phenolic hydroxyl group as an anchoring site for solid-phase synthesis. The solid-phase worked well for this sequence, in which the synthesis of the unsaturated eight-membered enamide lactam was obtained by a ring-closing metathesis approach. Compound 4 is a novel, natural product-like polycyclic derivative that could further be utilized in library generation for developing small molecule chemical probes.     

The mass spectra of (trimethylstannyl)x methanes: Occurrence of tin-carbon double bonds

The mass spectra of (Me₃Sn)_nCH_4?n, where n varies from 1 to 4, (Me₃Sn)₂CClX, where X equals H, Cl, Br or I, together with some tetraalkyltin compounds and Me₃SnCCl₃, are presented. Comparisons with mass spectra of the silicon analogs¹ show a large number of similarities, including the appearance of allylic ions which require Group IV metal to carbon π-bonding. Multiple rearrangements are observed with the halogenated tin compounds which bring the α-halogen into direct bonding with the tin atom.     

Volumes of activation for the reactions of Pentacyanocobaltate(III) Complexes in aqueous solution

The volumes of activation in cm³ mol^?1 for the aquation of Co(CN)₅X^3? were determined at 40°C and μ = 1 M (NaClO₄) to be + 7.8 ± 0.5 for X = Cl^?, + 7.6 ± 0.6 for X = Br^?, + 14.0 ± 0.7 for X = I^?, and + 16.8 ± 0.5 for X = N₃^? (0.1 M HClO₄), respectively. The volumes of activation for the aquation of Co(CN)₅Cl^3? at μ = 0.1 M are + 10.0 ± 0.6 cm³ mol^?1 and ± 9.1 ± 0.3 cm³ mol^?1 at 40°C and 25°C, respectively. The corresponding values for the anation of Co(CN)₅OH₂^2? (at 40°C) and μ = 1 M by Br^?, I^?, and NCS^? are +8.4 ± 1.0, +9.4 ± 1.6, and +8.2 ± 0.9 cm³ mol^?1, respectively. These data are discussed in terms of a dissociative (D) mechanism.     

Molecular dynamics studies of melting and solid-state transitions of ammonium nitrate

Molecular dynamics simulations are used to calculate the melting point and some aspects of high-temperature solid-state phase transitions of ammonium nitrate (AN). The force field used in the simulations is that developed by Sorescu and Thompson [J. Phys. Chem. A 105, 720 (2001)] to describe the solid-state properties of the low-temperature phase-V AN. Simulations at various temperatures were performed with this force field for a 4 x 4 x 5 supercell of phase-II AN. The melting point of AN was determined from calculations on this supercell with voids introduced in the solid structure to eliminate superheating effects. The melting temperature was determined by calculating the density and the nitrogen-nitrogen radial distribution functions as functions of temperature. The melting point was predicted to be in the range 445 +/- 10 K, in excellent agreement with the experimental value of 442 K. The computed temperature dependences of the density, diffusion, and viscosity coefficient for the liquid are in good agreement with experiment. Structural changes in the perfect crystal at various temperatures were also investigated. The ammonium ions in the phase-II structure are rotationally disordered at 400 K. At higher temperatures, beginning at 530 K, the nitrate ions are essentially rotationally unhindered. The density and radial distribution functions in this temperature range show that the AN solid is superheated. The rotational disorder is qualitatively similar to that observed in the experimental phase-II to phase-I solid-state transition.