Reduction of iron by decarboxylation in the formation of magnetite nanoparticles.

The process of formation of magnetite nanoparticles has been investigated by liquid chromatography and mass spectroscopy in the liquid phase decomposition of either Fe(III) acetylacetonate with decanoic acid or Fe(III) decanoate. In both cases, the dissociation into radicals of the iron carboxylate bonds provides the reduction of the Fe(III) cations and the oxygen atoms required for the formation of the mixed-valence inverse spinel magnetite structure. A reaction mechanism is proposed. It is also shown that the reaction of free decanoic acid with the Fe(III) cations in solution promotes the growth of faceted particles at the reflux temperature of the solvent (ca. 280 °C), while, under the same conditions, the stepwise decomposition of the Fe(III) decanoate generates smaller and pseudo-spherical particles. The latter also yields faceted particles when the temperature is increased above that of the total decomposition of the salt. Magnetic measurements make evident that the reaction starting from Fe(III) acetylacetonate yields nanoparticles with higher magnetization and lower spin disorder, due to the improved regularity of the surface crystal structure. The starting conditions for the decarboxylation process thus affect the morphology and magnetic properties of the resulting nanoparticles.

Stable radical cores: a key for bipolar charge transport in glass forming carbazole and indole derivatives.

Stable radical adducts of the TTM series bearing carbazolyl or indolyl fragments show bipolar transport properties with mobility values among the highest detected in glassy small molecules. Bipolarity is attributed to the radical character, while the heterocyclic ring confers the adducts the glassy morphological states and the non-dispersive regimes for charge transport.

Differential behavior of amino-imino constitutional isomers in nonlinear optical processes.

A detailed study of the "blocked" amino-imino tautomers derived from N-acridine-substituted 2-aminobenzothiazole--and their effect on the nonlinear optical response--is presented. The synthesis, characterization, and nonlinear optical properties of these frozen tautomers, namely, N-methyl-N-(2-nitroacridin-6-yl)-2-aminobenzothia-zole and 3-methyl-N-(7-nitroacridin-3-yl)-2-iminobenzothiazole, are reported. A theoretical model based on valence-bond theory is also proposed and used to analyze the effects of the nuclear configuration corresponding to each frozen tautomer structure. In the present case, the aromatic form and the allylic-anion-like system of the -N-C-N- group inherent to each isomer are crucial for understanding and analyzing the different responses of each "blocked" tautomer.

Multiple interactions in the self-association of porphyrin discotic mesogens.

The conformational preferences and the self-associational behaviors of two hemin-derived porphyrin compounds, a tetramethyl ester and a liquid crystalline tetrakis(3,5-didodecyloxyphenyl)ester, have been studied by UV/vis and (1)H NMR spectroscopy in solution. Results indicate that the 3,5-didodecyloxyphenyl units play an important role in both the conformational and the self-associational behaviors of the mesomorphic tetraester. In the monomeric, nonassociated species, the two propionic 3,5-didodecyloxyphenyl esters establish mutual CH/pi interactions that restrict the fluctuative behavior of the chains. In the dimeric, self-associated species, intermolecular CH/pi interactions occur in addition to the pi-pi stacking of the porphyrin cores. The temperature-dependent addition of side CH/pi interactions to the pi-pi stacking of the porphyrin rings accounts for the observed tightening and for the slower dynamics of the dimeric structure. The relationship between the self-associational behavior and the mesomorphism of the hemin-derived porphyrin tetraesters is also discussed.

Taking advantage of the radical character of tris(2,4,6-trichlorophenyl)methyl to synthesize new paramagnetic glassy molecular materials.

This paper describes the synthesis of the novel bis[4-(N-carbazolyl)-2,6-dichlorophenyl](2,4,6-trichlorophenyl)methyl radical (2*) and tris[4-(N-carbazolyl)-2,6-dichlorophenyl]methyl radical (3*). A Friedel-Crafts reaction on [4-(N-carbazolyl)-2,6-dichlorophenyl)bis(2,4,6-trichlorophenyl]methyl radical (1*), 2*, and 3* leads to the introduction of acyl chains in the 3- and 6-positions of the carbazolyl moiety without impairment of the radical character of the molecule to give radicals 5*, 6*, and 7*. All of these novel radical adducts are thermally stable, 5* and 6* being amorphous solids by differential scanning calorimetry. Electron paramagnetic resonance spectra of them show a multiplet at low temperature due to the electron-coupling with six aromatic hydrogens. They show electrochemical amphotericity being reduced and oxidized to their corresponding stable anionic and cationic species, respectively. These radical adducts have luminescent properties covering the red spectral band of the emission with high intensities.

Perturbation of the dimer interface of triosephosphate isomerase and its effect on Trypanosoma cruzi.

BACKGROUND: Chagas disease affects around 18 million people in the American continent. Unfortunately, there is no satisfactory treatment for the disease. The drugs currently used are not specific and exert serious toxic effects. Thus, there is an urgent need for drugs that are effective. Looking for molecules to eliminate the parasite, we have targeted a central enzyme of the glycolytic pathway: triosephosphate isomerase (TIM). The homodimeric enzyme is catalytically active only as a dimer. Because there are significant differences in the interface of the enzymes from the parasite and humans, we searched for small molecules that specifically disrupt contact between the two subunits of the enzyme from Trypanosoma cruzi but not those of TIM from Homo sapiens (HTIM), and tested if they kill the parasite. METHODOLOGY/PRINCIPAL FINDINGS: Dithiodianiline (DTDA) at nanomolar concentrations completely inactivates recombinant TIM of T. cruzi (TcTIM). It also inactivated HTIM, but at concentrations around 400 times higher. DTDA was also tested on four TcTIM mutants with each of its four cysteines replaced with either valine or alanine. The sensitivity of the mutants to DTDA was markedly similar to that of the wild type. The crystal structure of the TcTIM soaked in DTDA at 2.15 A resolution, and the data on the mutants showed that inactivation resulted from alterations of the dimer interface. DTDA also prevented the growth of Escherichia coli cells transformed with TcTIM, had no effect on normal E. coli, and also killed T. cruzi epimastigotes in culture. CONCLUSIONS/SIGNIFICANCE: By targeting on the dimer interface of oligomeric enzymes from parasites, it is possible to discover small molecules that selectively thwart the life of the parasite. Also, the conformational changes that DTDA induces in the dimer interface of the trypanosomal enzyme are unique and identify a region of the interface that could be targeted for drug discovery.

Red organic light-emitting radical adducts of carbazole and tris(2,4,6-trichlorotriphenyl)methyl radical that exhibit high thermal stability and electrochemical amphotericity.

Synthesis and characterization of new carbazolyl derivatives with a pendant stable radical of the TTM (tris-2,4,6-trichlorophenylmethyl radical) series are reported. The EPR spectra, electrochemical properties, absorption spectra, and luminescent properties of these radical adducts have been studied. All of them show electrochemical amphotericity being reduced and oxidized to their corresponding stable charged species. The luminescence properties of them cover the red spectral band of the emission. The luminescence of the electron-rich carbazole adducts shows the donor-acceptor nature of the excited state. On the other hand, the EPR parameters of these radical adducts show an imperceptible variation with the substituents in the carbazole.

Structural differences in triosephosphate isomerase from different species and discovery of a multitrypanosomatid inhibitor.

We examined the interfaces of homodimeric triosephosphate isomerase (TIM) from eight different species. The crystal structures of the enzymes showed that a portion of the interface is markedly similar in TIMs from Trypanosoma cruzi (TcTIM), Trypanosoma brucei, and Leishmania mexicana and significantly different from that of TIMs from human, yeast, chicken, Plasmodium falciparum, and Entamoeba histolytica. Since this interfacial region is central in the stability of TcTIM, we hypothesized that it would be possible to find agents that selectively affect the stability of TIMs from the three trypanosomatids. We found that 6,6'-bisbenzothiazole-2,2' diamine in the low micromolar range causes a desirable irreversible inactivation of the enzymes from the three trypanosomatids and has no effect on the other five TIMs. Thus, the data indicate that it is possible to find compounds that induce selective inactivation of the enzymes from three different trypanosomatids.

Visible second-harmonic light generated from a self-organized centrosymmetric lattice of nanospheres.

We designed and fabricated a centrosymmetric material where one may be able to consider an efficient quadratic nonlinear interaction. We followed a solid phase-supported organic synthesis methodology to covalently bind a large number of highly nonlinear molecules to the surface of polystyrene nanospheres. Such chemically modified optically nonlinear latex spheres, when suspended in water, are seen to perfectly self-organize into a centrosymmetric lattice. Taking advantage of the nonlinear interaction located at the sphere-water interface and the photonic crystal properties of the fabricated material we were able to generate second-harmonic light visible to the naked eye.

Inactivation of triosephosphate isomerase from Trypanosoma cruzi by an agent that perturbs its dimer interface.

We characterized by crystallographic, calorimetric and biochemical methods the action of a low molecular weight compound, 3-(2-benzothiazolylthio)-1-propanesulfonic acid (compound 8) that binds to the dimer interface of triosephosphate isomerase from Trypanosoma cruzi (TcTIM) and thereby abolishes its function with a high level of selectivity. The kinetics of TcTIM inactivation by the agent and isothermal titration calorimetry experiments showed that the binding of two molecules of the compound per enzyme is needed for inactivation. The binding of the first molecule is endothermic, and that of the second exothermic. Crystals of TcTIM in complex with one molecule of the inactivating agent that diffracted to a resolution of 2A were obtained. The compound is at the dimer interface at less than 4A from residues of the two subunits. Compound 8 is more effective at low than at high protein concentrations, indicating that it perturbs the association between the two TcTIM monomers. Calorimetric and kinetic data of experiments in which TcTIM was added to a solution of the inactivating agent showed that at low concentrations of the compound, inactivation is limited by binding, whereas at high concentrations of the agent, the events that follow binding become rate-limiting. The portion of the interface of TcTIM that binds the benzothiazole derivative and its equivalent region in human TIM differs in amino acid composition and hydrophobic packing. Thus, we show that by focusing on protein-protein interfaces, it is possible to discover low molecular weight compounds that are selective for enzymes from parasites.

Highly specific inactivation of triosephosphate isomerase from Trypanosoma cruzi.

We searched for molecules that selectively inactivate homodimeric triosephosphate isomerase from Trypanosoma cruzi (TcTIM), the parasite that causes Chagas' disease. We found that some benzothiazoles inactivate the enzyme. The most potent were 3-(2-benzothiazolylthio)-propanesulfonic acid, 2-(p-aminophenyl)-6-methylbenzothiazole-7-sulfonic acid, and 2-(2-4(4-aminophenyl)benzothiazole-6-methylbenzothiazole-7-sulfonic acid. Half-maximal inactivation by these compounds was attained with 33, 56, and 8 microM, respectively; in human TIM, half-maximal inactivation required 422 microM, 3.3 mM, and 1.6 mM. In TcTIM, the effect of the benzothiazoles decreased as the concentration of the enzyme was increased. TcTIM has a cysteine (Cys 15) at the dimer interface, whereas human TIM has methionine in that position. In M15C human TIM, the benzothiazole concentrations that caused half-maximal inactivation were much lower than in the wild type. The overall findings suggest that the benzothiazoles perturb the interactions between the two subunits of TcTIM through a process in which the interface cysteine is central in their deleterious action.