Ab initio study of the binding of Trichostatin A (TSA) in the active site of histone deacetylase like protein (HDLP)

Histone deacetylase (HDAC) inhibitors have recently attracted considerable interest because of their therapeutic potential for the treatment of cell proliferative diseases. An X-ray structure of a very potent inhibitor, Trichostatin A (TSA), bound to HDLP (an HDAC analogue isolated from Aquifex aeolicus), is available. From this structure, an active site model (322 atoms), relevant for the binding of TSA and structural analogues, has been derived, and TSA has been minimized in this active site at HF 3-21G* level. The resulting conformation is in excellent accordance with the X-ray structure, and indicates a deprotonation of the hydroxamic acid in TSA by His 131. Also, a water molecule was minimized in the active site. In addition to a similar deprotonation, in accordance with a possible catalytic mechanism of HDAC as proposed by Finnin et al. (M. S. Finnin, J. R. Donigian, A. Cohen, V. M. Richon, R. A. Rifkind and P. A. Marks, Nature, 1999, 401, 188-193), a displacement of the resulting OH- ion in the active site was observed. Based on these results, the difference in energy of binding between TSA and water was calculated. The resulting value is realistic in respect to experimental binding affinities. Furthermore, the mechanism of action of the His 131-Asp 166 charge relay system was investigated. Although the Asp residue in this motif is known to substantially increase the basicity of the His residue, no proton transfer from His 131 to Asp 166 was observed on binding of TSA or water. However, in the empty protonated active site, this proton transfer does occur.     

Evaluation of isothermal kinetic of sweetener

Summary Sulfonylureas are widely used for the treatment of non-insulin dependent diabetes mellitus. Glibenclamide belongs to the group of substituted arylsulfonylureas. Many representative of this group shows polymorphism. The purpose of this work was to investigate the thermal behaviour and compatibility between glibenclamide and some excipients using thermoanalytical techniques (TG-DTG/DSC). The thermal and isothermal kinetics data showed incompatibility between glibenclamide and magnesium stearate.     

Structural Analysis of Ti And Pb Citrate Using NMR and FT-Raman Signals and Quantum Mechanics Simulations

Titanium citrate and lead and titanium citrate were prepared by polymeric precursor method in aqueous solution. This citrate was analyzed by ¹H, ¹³C NMR and gHMBC–NMR (Hetero-nuclear multiple-bond correlation) to investigate the formation of the citrate complexs and influence of the Pb²⁺ ion in this complex. These complexs were characterized by interaction between Ti⁴⁺ ion and citric acid carboxyls. Quantum mechanic simulations in level ab initio were used to study the electronic structure and natural charges (NBO) to both the complexs. Such techniques indicated the formation of an octahedral complex with an arrangement similar to Ti atom in the crystalline structure of the PbTiO₃. A study using the technique FT-Raman made possible the confirmation of the interaction among the Ti⁴⁺ and Pb²⁺ ions with the citric acid carboxyls.     

Photochemistry of perfluoroacyl halides in the presence of O2 and CO

Photolyses of CF₃C(O)X and C₂F₅C(O)X (X=Cl, F) at 254 nm in the presence of O₂ yield the perfluorinated radicals C₂F₅O (C₂) and CF₃O (C₁), respectively. The C₂ radicals decompose to give CF₃ radicals:

C₂F₅O→CF₃+CF₂O

which, in turn, react with O₂ leading to the formation of C₁ radicals. When in addition to O₂, CO is present, the C₁ radicals react with it leading to its catalytic oxidation to CO₂. The trioxide CF₃OC(O)O₃C(O)OCF₃ was observed following the photolysis of all four halides in the presence of O₂ and CO.

The other radical partners coming from the initial step in the photolysis (XC(O)) as well as the products of their reaction with O₂ (XC(O)O_y, y=1, 2) do not react with CO but when X=F they lead to the formation of a new stable peroxy molecule with the formula CF₃OC(O)O₂C(O)F. Some of the properties of this new molecule, its stability and its IR features are presented in this work.     

Electrospray mass and tandem mass spectrometry of homologous and isomeric singly, doubly, triply and quadruply charged cationic ruthenated meso-(phenyl)m-(meta- and para-pyridyl)n (m + n = 4) macrocyclic porphyrin complexes

Ten homologous or isomeric singly, doubly, triply and quadruply charged cationic macrocyclic complexes I-Va, bn+ (n = 1-4) formed by the coordination of [Ru(bipy)2Cl]+ to the pyridyl N-atoms of a series of meso-(phenyl)m-(meta or para-pyridyl)n-porphyrins (m + n = 4) were transferred to the gas phase and structurally characterized by electrospray ionization (ESI) mass (MS) and tandem mass (MS/MS) spectrometry. Previously known to be stable in solution and in the solid state, I-Va, bn+ are found to constitute also a new class of stable, long-lived multiply charged gas-phase ions with spatially separated charge sites. Increasing intramolecular electrostatic repulsion from Ia, b+ to IVa, b3+ facilitates in-source and tandem collision-induced dissociation (CID). However, for the quadruply charged ions Va, b4+, electrostatic repulsion is alleviated mainly by ion pairing with the CF3SO3- counterion forming the salt clusters [Va,b/CF3SO3]3+ and [Va,b/(CF3SO3)2]2+ with reduced charge states. Ion-pairing that yields [IVa,b/CF3SO3]2+ is also observed as a minor ESI process for the triply charged ions IVa, b3+. The gaseous ions I-Va, bn+ (n = 2, 3 or 4) dissociate by sequential 'charge partitioning' with the formation of two cationic fragments by the release of [Ru(bipy)2Cl]+. The meta (a) and para (b) isomers and the positional isomers II2+ and III2+ display nearly identical ESI-MS and ESI-MS/MS spectra. ESI-MS/MS of I-Va, bn+ shows that the Ru-py(P) is, intrinsically, the weakest bond since this bond breaks preferentially upon CID.     

Thermal studies of pre-formulates of metronidazole obtained by spray drying technique

Compatibility studies between active drugs and excipients are substantial in the pharmaceutical technology. The objective of the present work was to develop pre-formulated mixtures of metronidazole (MT) obtained by spray drying (SPDR) and their thermoanalytical characterization. Dynamic and isothermal TG, conventional DSC and DSC coupled to a photovisual system were used. DSC experiments with both techniques confirmed the homogeneity of the conventional and pre-formulated mixtures. The TG data made possible the comparison the thermal stability of the different mixtures. Similar thermal stabilities were found of the conventional and pre-formulated mixtures, with slower particles sizes of MT.     

The Effects of Beating,Web Forming and Sizing on the Surface Energy of <Emphasis Type="Italic">Eucalyptus globulus</Emphasis> Kraft Fibres Evaluated by Inverse Gas Chromatography

In this work attention has been focused on the effects of papermaking beating, web forming and sizing operations on the physical/chemical surface properties of bleached Eucalyptus globulus kraft fibres. Inverse gas chromatography (IGC) was used to determine the dispersive component of surface tension (γ_s^d) as well as the acidic/basic character (according to the Lewis concept) of the solid surfaces (pulp fibres and pulp handsheets). The results have shown that the main effect of beating is to increase the fibre's Lewis acidic character. Web forming caused a strong decrease in γ_s^d and significant increments in the adhesion works of both acidic and basic probes, lowering the ratio between the two. Nevertheless, the surface of handsheets still exhibited a dominant acidic character. The sizing operation did not change the dispersive component of the surface tension significantly but decreased the difference between the adhesion works of the acidic and basic probes, rendering the handsheet surface less Lewis acidic and more Lewis basic. Thus, although internal sizing is expected to strongly influence liquid spreading at the paper surface and liquid penetration of the fibre's network, it is concluded that beating and web forming lead to important changes in the surface energetic properties of the Eucalyptus globulus kraft fibres.     

Microgravimetric study of electrochemically controlled nucleophilic addition of sulfite to polyaniline

The sulfonation of polyaniline (PANI) films by nucleophilic addition of sulfite ion has been controlled through the polymer oxidation state under electrochemical control. The process was monitored by in situ electrochemical quartz crystal microbalance (EQCM), and the polymer oxidation was accomplished by electrode potential steps in sulfite aqueous solutions. The nucleophilic addition of sulfite to PANI only takes place on the oxidized polymer. From the ratio of added mass to the injected charge, the degree of sulfonation has been obtained with a yield as high as 50%. It has been observed that the ion-exchange mechanism during the oxidation-reduction process in the resulting sulfonated polymer is analogous to the polymer produced by electrophilic sulfonation of polyaniline or by copolymerization of aniline with aminosulfonic acids, unlike the ionic exchange observed for unmodified PANI.     

Stereochemistry and dynamic behavior of some synthetic “angular” profisetinidin tetraflavanoid derivatives

The structure and stereochemistry of four synthetic “angular” tetraflavanoid-condensed tannin derivatives are examined by high-resolution variable temperature ¹H NMR. spectroscopy, and hence correlated with their dynamic behavior. Three “angular” oligomers exist as stable rotational isomers at ambient temperatures, thus contrasting with the mobility about their interflavanoid bonds of most natural profisetinidin “trimeric” and “tetrameric” homologs. A “linear” tetraflavanoid analog results from one of these regioselectively controlled condensations.     

Development and validation of a high-performance liquid chromatographic method for the determination of clomazone residues in surface water

A method is described for the determination of clomazone residues in surface water by high-performance liquid chromatography with UV detection. The method involves solid-phase extraction with C18 extraction tubes. Clomazone was separated on a C18 column with a mobile phase of methanol-water (65:35, v/v) at pH 4.0 and a flow-rate of 1.0 ml/min. After optimization of the extraction and separation conditions, the method was validated. The method developed can be used for determination of clomazone in surface water, at the limit of 0.1 mcirog/l set by the European Union drinking water directive, with a 400-fold preconcentration.