Pharmacophore Model of Cruzain Inhibitors

Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the most serious amongst the so-called neglected diseases in Latin America, specially in Brazil. So far there has been no effective treatment for the chronic phase of this disease. Cruzain is a major cysteine protease of T cruzi and it is recognized as a valid target for Chagas disease chemotherapy. The mechanism of cruzain action is associated with the nucleophilic attack of an activated sulfur atom towards electrophilic groups. In this report, features of a putative pharmacophore model of the enzyme, developed as a virtual screening tool for the selection of potential cruzain inhibitors, are described. The final proposed model was applied to the ZINC v.7 database and afterwards experimentally validated by an enzymatic inhibition assay. One of the compounds selected by the model showed cruzain inhibition in the low micromolar range.

Useful Strategies for Algal Volatile Analysis

The production of volatile organic compounds (VOC) by plants is well known. However, few scientific groups have studied VOC produced by green, brown and red algae. Headspace collection of volatiles and solid phase microextraction, as well as the traditional extraction by hydrodistillation combined with analytical chromatographic techniques (i.e., GC-MS), have significantly improved the investigation of VOC from plants and algae. The major volatile compounds found in seaweeds are hydrocarbons, terpenes, phenols, alcohols, aldehydes, ketones, esters, fatty acids and halogen or sulfur-containing compounds. This article presents an overview of VOC isolated from and identified in marine macro-algae. Focus is given to non-halogenated and non-sulfur volatile compounds, as well as strategies to analyze and identify algal VOC by GC-MS.

Saccharomyces cerevisiae coq10 null mutants are responsive to antimycin A

Deletion of COQ10 in Saccharomyces cerevisiae elicits a respiratory defect characterized by the absence of cytochrome c reduction, which is correctable by the addition of exogenous diffusible coenzyme Q(2). Unlike other coq mutants with hampered coenzyme Q(6) (Q(6)) synthesis, coq10 mutants have near wild-type concentrations of Q(6). In the present study, we used Q-cycle inhibitors of the coenzyme QH(2)-cytochrome c reductase complex to assess the electron transfer properties of coq10 cells. Our results show that coq10 mutants respond to antimycin A, indicating an active Q-cycle in these mutants, even though they are unable to transport electrons through cytochrome c and are not responsive to myxothiazol. EPR spectroscopic analysis also suggests that wild-type and coq10 mitochondria accumulate similar amounts of Q(6) semiquinone, despite a lower steady-state level of coenzyme QH(2)-cytochrome c reductase complex in the coq10 cells. Confirming the reduced respiratory chain state in coq10 cells, we found that the expression of the Aspergillus fumigatus alternative oxidase in these cells leads to a decrease in antimycin-dependent H(2)O(2) release and improves their respiratory growth.

Reactions of toluquinone - cyclopentadiene Diels -Alder epoxide adducts with nucleophiles under heterogeneous conditions

Toluquinone-cyclopentadiene Diels-Alder epoxide adducts react with sulfur and oxygen nucleophiles under heterogeneous conditions, leading to products resulting from the epoxide ring opening and from skeletal rearrangement, respectively. Pyrolysis of the sulfanyl adducts gave the new 3-sulfanyltoluquinones (1).

Effect of SO(2) on the Transport Properties of an Imidazolium Ionic Liquid and Its Lithium Solution

Transport coefficients have been measured as a function of the concentration of sulfur dioxide, SO(2), dissolved in 1-butyl-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)-imide, [BMMI][Tf(2)N], as well as in its lithium salt solution, Li[Tf(2)N]. The SO(2) reduces viscosity and density and increases conductivity and diffusion coefficients in both the neat [BMMI] [Tf(2)N] and the [BMMI][Tf(2)N]-Li[Tf(2)N] solution. The conductivity enhancement is not assigned to a simple viscosity effect; the weakening of ionic interactions upon SO(2) addition also plays a role. Microscopic details of the SO(2) effect were unraveled using Raman spectroscopy and molecular dynamics (MD) simulations. The Raman spectra suggest that the Li(+)-[Tf(2)N] interaction is barely affected by SO(2), and the SO(2)-[Tf(2)N] interaction is weaker than previously observed in an investigation of an ionic liquid containing the bromide anion. Transport coefficients calculated by MD simulations show the same trend as the experimental data with respect to SO(2) content. The MD simulations provide structural information on SO(2) molecules around [Tf(2)N], in particular the interaction of the sulfur atom of SO(2) with oxygen and fluorine atoms of the anion. The SO(2)-[BMMI] interaction is also important because the [BMMI] cations with above-average mobility have a larger number of nearest-neighbor SO(2) molecules.

Detailed analysis of the charge transfer complex N,N-dimethylaniline-SO(2) by Raman spectroscopy and density functional theory calculations

Although the amine sulfur dioxide chemistry was well characterized in the past both experimentally and theoretically, no systematic Raman spectroscopic study describes the interaction between N,N-dimethylaniline (DMA) and sulfur dioxide (SO(2)). The formation of a deep red oil by the reaction of SO(2) with DMA is an evidence of the charge transfer (CT) nature of the DMA-SO(2) interaction. The DMA -SO(2) normal Raman spectrum shows the appearance of two intense bands at 1110 and 1151 cm(-1), which are enhanced when resonance is approached. These bands are assigned to nu(s)(SO(2)) and nu(phi-N) vibrational modes, respectively, confirming the interaction between SO(2) and the amine via the nitrogen atom. The dimethyl group steric effect favors the interaction of SO(2) with the ring pi electrons, which gives rise to a pi-pi* low-energy CT electronic transition, as confirmed by time-dependent density functional theory (TDDFT) calculations. In addition, the calculated Raman DMA-SO(2) spectrum at the B3LYP/6-311++g(3df,3pd) level shows good agreement with the experimental results (vibrational wavenumbers and relative intensities), allowing a complete assignment of the vibrational modes. A better understanding of the intermolecular interactions in this model system can be extremely useful in designing new materials to absorb, detect, or even quantify SO(2). Copyright (C) 2009 John Wiley & Sons, Ltd.

Development of a heavy metal sorption system through the P=S functionalization of coconut (Cocos nucifera) fibers

Lignocellulosic residues are interesting materials for the production of heavy metal adsorbents for aquatic systems. Whole fibers taken from coconut (Cocos nucifera) husks were functionalized with the thiophosphoryl (P=S) group by means of the direct reaction with CI(3)P=S, (CH(3)O)(2)CIP=S or (CH(3)CH(2)O)(2)CIP=S in order to obtain an adsorptive system for `soft` metal ions, particularly Cd(2+). These functionalized fibers (FFs) were characterized by means of elemental analysis, infrared spectroscopy, thermal analysis and acid-base titration. Adsorption isotherms for Cd(2+) fitted the Langmuir model, with binding capacities of 0.2-5 mmol g(-1) of FF at 25 degrees C. (C) 2009 Elsevier Ltd. All rights reserved.

Exploring new molecular species on the (1)[H, Se, F] singlet potential energy surface: Energetics, structures, IR spectra, and heats of formation

Structural, energetic, and vibrational properties of new molecular species, HSeF and HFSe, the associated transition state, and dissociation fragments are investigated using a state-of-the-art theoretical approach, CCSD(T)/CBS. HSeF is a normal covalently bonded molecule 38.98 kcal mol (1) more stable than the complex HF-Se, which shows an unusual structure with a central fluorine atom and a bond angle of 101.8 degrees.A barrier (Delta G(#)) of 49.01 kcal mol (1) separates the two species. Vibrational frequencies are also quite distinct. Heats of formation are evaluated for the diatomic fragments and HSeF. Final Delta(f)H values depend on the experimental accuracy of those of Se(g) and H(2)Se. (c) 2009 Elsevier B.V. All rights reserved.

Isomers on the [H, S(2), Cl] potential energy surface: A high level investigation

This study reports a systematic state-of-the-art characterization of new sulfur-chlorine species on the [H, S(2), Cl] potential energy surface. Coupled cluster theory singles and doubles with perturbative contributions of connected triples, using the series of correlation consistent basis sets with extrapolations to the complete basis set limit (CBS), were employed to quantify the energetic quantities involved in the isomerization processes on this surface. The structures and vibrational frequencies are unique for some species and represent the most accurate investigation to date. These molecules are potentially a new route of coupling the sulfur and chlorine chemistries in the atmosphere, and conditions of high concentration of H(2)S (HS) like in volcanic eruptions might contribute to their formation. Also an assessment of the MP2/CBS approach relative to CCSD(T)/CBS provides insights on the expected performance of MP2/CBS on the characterization of polysulfides, and also of more complex systems containing disulfide bridges. (C) 2009 Elsevier B.V. All rights reserved.

Thionicotinamide SAM on Gold: Adsorption Studies and Electroactivity

STM and impedance results of the self-assembled monolayer (SAM) formed with thionicotinamide (TNA) on gold indicate the presence of defects that increase with the immersion time of the electrode in the TNA solution affecting the SAM electroactivity toward the electron transfer reaction of the cytochrome e metalloprotein and [Fe(CN)(6)](4-) and [Ru(NH(3))(6)](3+) complexes. It was observed that this electroactivity was also affected by the pH of the electrolyte solution. SERS and STM data indicate sulfur coordination to the surface with contribution of the NH(2) group. From the dependence of the TNA surface coverage on the temperature and concentration in solution, thermodynamic parameters of adsorption were determined.

Practical synthesis of chiral beta-telluro amines by ring-opening reaction of aziridines

A set of chiral beta-tellurium amines and their selenium and sulfur-containing derivatives have been efficiently synthesized in good to excellent yields via the ring-opening reaction of chiral aziridines by chalcogen nucleophilic species. (C) 2008 Elsevier B.V. All rights reserved.

Electronic structure and spectra of a new molecular species: SI. A theoretical contribution

A high level theoretical approach is used to characterize for the first time a manifold of doublet and quartet A + S and Omega states correlating with the first two dissociation channels of an as yet experimentally unknown molecular species, SI, sulfur monoidide. A set of spectroscopic constants is determined, including vibrationally averaged spin-orbit coupling constants, vibrationally averaged dipole moments, and dissociation energies. The transition dipole moment function for the spin-forbidden transition a (4)Sigma -X (2)Pi, and the associated radiative lifetimes were also evaluated. Two possibilities to detect transitions experimentally and to derive spectroscopic constants are suggested. (C) 2011 Elsevier B. V. All rights reserved.

Hydrochalcogenation of activated olefines. Synthesis of functionalized dialkylchalcogenides

Alkanethiols, selenols and tellurols are generated in situ by reaction of elemental sulfur, selenium and tellurium with commercial alkyllithiums, followed by reaction with deoxygenated water. The alkanechalcogenols react in situ with activated ole. ns in a Michael- type addition reaction. (c) 2008 Elsevier B. V. All rights reserved.

Organotellurides as precursors of reactive organometallics

Reaction of organotellurides with easily available organometallics leads to a fast and clean tellurium/metal exchange reaction, allowing the preparation of a range of functionalized organometallics with C-sp(3), C-sp(2), and C-sp hybridization carbanionic centers. Some synthetic applications of the tellurium/metal exchange reactions are discussed.