Reactivity of 2-methyl-4-(1-pyrrolidinyl)-2H-1,2-benzothiazine 1,1-dioxide towards p-toluenesulphonyl azide

The 2-methyl-2H-1,2-benzothiazin-4-(3H)-one 1,1 dioxide ( 2 ), obtained according to a new, one-pot method, is transformed into the pyrrolidino enamine 3 . Reaction of p-toluenesulphonyl azide with 3 gives, via an unstable triazoline adduct which loses nitrogen, the two isomeric tosylamino derivatives 4 and 5 . The structures have been assigned by exhaustive nmr analysis and some aspects on their formation and chemical behaviour are discussed.     

Molecular switches of fluorescence operating through metal centred redox couples

Three-component molecular systems (redox active subunit)-spacer-(light-emitting fragment) can operate as fluorescence switches, following the alternate addition of an oxidizing agent and a reducing agent (or the adjustment of the potential of the working electrode in an electrolysis experiment). The redox active subunit typically consists of a metal centred redox couple (M⁽ⁿ⁺¹⁾⁺/Mⁿ⁺), encircled by a macrocyclic receptor, and switching efficiency requires that one of the two oxidation states quenches the proximate fluorophore and the other does not. Four ON/OFF systems, based on either the Cu^II/Cu^I or Ni^III/Ni^II couple, will be discussed. The nature of the quenching process responsible for the OFF state, either electron transfer or energy transfer, is related to the length and to the flexibility-rigidity of the spacer.     

Harmonic oscillator tensors in contact transformation theory

The application of contact transformation theory to the perturbed harmonic oscillator is reexamined in the light of the harmonic oscillator tensors previously presented. It is found that the recasting of the formalism of this problem in terms of harmonic oscillator tensors results in great simplifications, most of which stem from the introduction of the additional algebraic quantum numbers (l, m). The order of magnitude of each fragment of the Hamiltonian is easily recognizable, and the diagonal and nondiagonal parts contained therein are readily identifiable. The determination of the contact transformation operator is reduced to a simple formula. First, an analysis is made for a single mode of vibration, and it is subsequently extended to a multimode case. The perturbed diatomic vibrator is presented as an example.     

Geographical traceability of West Liguria extravirgin olive oils by the analysis of volatile terpenoid hydrocarbons

This study aimed at evaluating if the volatile terpenoid hydrocarbons of extravirgin olive oils from West Liguria, a North Italy region, could trace their geographical origin. If terpenoid hydrocarbons were individually considered, three compounds, i.e. alpha-copaene, alpha-muurolene and alpha-farnesene, allowed building a simple decision tree and discriminating oils produced in West Liguria from oils produced in other Mediterranean regions. Moreover, the multivariate analysis allowed building West Liguria class-models with high predictive ability, confirming the fundamental role of the volatile terpenoid hydrocarbons for the geographical characterisation of West Liguria oils.     

The hydrogen salicylate ion as ligand. Complex formation equilibria with dioxouranium (VI), neodymium (III) and lead (II)

The complexation equilibria of the hydrogen salicylate ion, HL(-), have been studied, at 25 degrees C, by potentiometric measurements with a glass electrode in 1 M NaClO4 for uranyl and Nd(III) ions and in 3 M NaClO4 for Pb(II) ion. The ligand concentration (CL) was varied between 10(-3) and 0.05 M. In the system with U(VI) the concentrations ranged between: 10(-3) < or = [U(VI)] < or = 0.01 M, 0.5 < or = CL /[U(VI)] < or = 10 and 10(-2) < or = [H+] < or = 10(-5) M; for neodymium system: 2 x 10(-3) < or = [Nd(III)] < or = 0.01, 1 < or = CL /[Nd(III)] < or = 10 and 10(-2) < or = [H+] < or = 10(-7) M; for lead system: 10(-3) < or = [Pb(II) < or = 3 x 10(-3), 1 < or = CL /Pb(II)] < or = 2 and 10(-5) < or = [H+] < or = 10(-7.3) M. The experimental data have been explained with the formation of UO2HL+, UO2L, UO2(OH)L(-), (UO2)2(OH)L2(-) UO2(HL)L(-), NdHL(2+), NdL(+), Nd(OH)L, PbHL(+), PbL and PbL2(2-). Equilibrium constants are given for the investigated ionic media and at infinite dilution.     

Sampling and convergence in free energy calculations of protein-ligand interactions: The binding of triphenoxypyridine derivatives to factor Xa and trypsin

The binding of a set of 10 triphenoxypyridine derivatives to two serine proteases, factor Xa and trypsin, has been used to analyze factors related to sampling and convergence in free energy calculations based on molecular dynamics simulation techniques. The inhibitors investigated were initially proposed as part of the Critical Assessment of Techniques for Free Energy Evaluation (CATFEE) project for which no experimental results nor any assessment of the predictions submitted by various groups have ever been published. The inhibitors studied represent a severe challenge for explicit free energy calculations. The mutations from one compound to another involve up to 19 atoms, the creation and annihilation of net charge and several alternate binding modes. Nevertheless, we demonstrate that it is possible to obtain highly converged results (+/- 5-10 kJ/mol) even for such complex multi-atom mutations by simulating on a nanosecond time scale. This is achieved by using soft-core potentials to facilitate the creation and deletion of atoms and by a careful choice of mutation pathway. The results show that given modest computational resources, explicit free energy calculations can be successfully applied to realistic problems in drug design.     

Calculation of the free energy of solvation for neutral analogs of amino acid side chains

The ability of the GROMOS96 force field to reproduce partition constants between water and two less polar solvents (cyclohexane and chloroform) for analogs of 18 of the 20 naturally occurring amino acids has been investigated. The estimations of the solvation free energies in water, in cyclohexane solution, and chloroform solution are based on thermodynamic integration free energy calculations using molecular dynamics simulations. The calculations show that while the force field reproduces the experimental solvation free energies of nonpolar analogs with reasonable accuracy the solvation free energies of polar analogs in water are systematically overestimated (too positive). The dependence of the calculated free energies on the atomic partial charges was also studied.     

Novel heteroaromatic-based multi-branched dyes with enhanced two-photon absorption activity

The first examples of heterocycle-based multi-branched dyes with efficient two-photon absorption (TPA) activity are reported; the novel chromophores exhibit large TPA cross sections (as high as 1600 x 10(-50) cm4 s photon(-1) molecule(-1), measured with 150 fs laser pulses at 800 nm); a strong cooperative enhancement in the branched systems with respect to the one-dimensional sub-units is found.     

High-performance liquid chromatographic determination of acetone in blood and urine in the clinical diagnostic laboratory.

A method for the determination of acetone in plasma or urine by high-performance liquid chromatography (HPLC) was developed. Plasma specimens are deproteinized with acetonitrile (1:1, v/v) 2,4-dinitrophenylhydrazine (DNPH) is added to the supernatant or to filtered urine samples, similarly treated with acetonitrile (2:1, v/v) to prevent crystallization of the synthesized phenylhydrazone. An aliquot (20 microliters) of the reaction mixture was subjected to HPLC at ambient temperature using a reversed-phase Pecosphere 3 x 3 C18 column with acetonitrile-water (45:55, v/v) as eluent at a flow-rate of 1 ml/min and detection at 365 nm. Hydroxyacetone and acetoacetate phenylhydrazone derivatives do not interfere. The identification of acetone by its retention time was confirmed by comparison with a laboratory-synthesized acetone DNPH derivative. The concentration of acetone, eluted within 3 min, was determined by the peak-height method. The detection limit was 0.034 mmol/l; the relative standard deviations were less than 5% within run (n = 20) and less than 10% between run (n = 20).     

Wide Oscillation Finite Time Blow Up for Solutions to Nonlinear Fourth Order Differential Equations

We give sufficient conditions for local solutions to some fourth order semilinear ordinary differential equations to blow up in finite time with wide oscillations, a phenomenon not visible for lower order equations. The result is then applied to several classes of semilinear partial differential equations in order to characterize the blow up of solutions including, in particular, its applications to a suspension bridge model. We also give numerical results which describe this oscillating blow up and allow us to suggest several open problems and to formulate some related conjectures.