Guilherme Ferreira de Lima

Study of angiotensin-(1-7) vasoactive peptide and its β-cyclodextrin inclusion complexes : Complete sequence-specific NMR assignments and structural studies

We report the complete sequence-specific hydrogen NMR assignments of vasoactive peptide angiotensin-(1-7) (Ang-(1-7)). Assignments of the majority of the resonances were accomplished by COSY, TOCSY, and ROESY peak coordinates at 400MHz and 600MHz. Long-side-chain amino acid spin system identification was facilitated by long-range coherence transfer experiments (TOCSY). Problems with overlapped resonance signals were solved by analysis of heteronuclear 2D experiments (HSQC and HMBC). Nuclear Overhauser effects (NOE) results were used to probe peptide conformation. We show that the inclusion of the angiotensin-(1-7) tyrosine residue is favored in inclusion complexes with beta-cyclodextrin. QM/MM simulations at the DFTB/UFF level confirm the experimental NMR findings and provide detailed structural information on these compounds in aqueous solution.

Dynamical Discrete/Continuum Linear Response Shells Theory of Solvation: Convergence Test for NH4+ and OH- Ions in Water Solution Using DFT and DFTB Methods

A new dynamical discrete/continuum solvation model was tested for NH(4)(+) and OH(-) ions in water solvent. The method is similar to continuum solvation models in a sense that the linear response approximation is used. However, different from pure continuum models, explicit solvent molecules are included in the inner shell, which allows adequate treatment of specific solute-solvent interactions present in the first solvation shell, the main drawback of continuum models. Molecular dynamics calculations coupled with SCC-DFTB method are used to generate the configurations of the solute in a box with 64 water molecules, while the interaction energies are calculated at the DFT level. We have tested the convergence of the method using a variable number of explicit water molecules and it was found that even a small number of waters (as low as 14) are able to produce converged values. Our results also point out that the Born model, often used for long-range correction, is not reliable and our method should be applied for more accurate calculations.

Novel fluorescent lapachone-based BODIPY: synthesis, computational and electrochemical aspects, and subcellular localisation of a potent antitumour hybrid quinone

For the first time, a fluorescent lapachone-based BODIPY was synthesised and characterised by NMR and mass spectrometry. Computational and electrochemical aspects, as well as cytotoxic activity and subcellular localisation, were studied. Confocal microscopy experiments indicated that the probe was a specific mitochondria-staining agent. These in-detail analyses were useful in understanding the cytotoxic effects and mechanism of action of this novel hybrid compound. This molecule constitutes a promising prototype owing to its potential biological activities and the new strategies aimed at mechanistic investigations in cells and in vivo, and opens up an interesting avenue of research.

Quinone-Derived π-Extended Phenazines as New Fluorogenic Probes for Live-Cell Imaging of Lipid Droplets

We describe a new synthetic methodology for the preparation of fluorescent π-extended phenazines from the naturally-occurring naphthoquinone lapachol. These novel structures represent the first fluorogenic probes based on the phenazine scaffold for imaging of lipid droplets in live cells. Systematic characterization and analysis of the compounds in vitro and in cells led to the identification of key structural features responsible for the fluorescent behavior of quinone-derived π-extended phenazines. Furthermore, live-cell imaging experiments identified one compound (P1) as a marker for intracellular lipid droplets with minimal background and enhanced performance over the lipophilic tracker Nile Red.

Modeling the oxidation mechanism of pyrite and arsenopyrite – connection to acid rock drainage

Acid rock drainage (ARD) is hazardous to the environment and it is caused by the oxidation of sulfide minerals leading to the formation of acids and, consequently, enhancing the dissolution of the rocks. Therefore, ARD leads to the acidification of aquifers and mobilization of heavy metals in the environment. Sulfide minerals are the main source of noble metals such as copper and gold (besides zinc and lead), hence, ARD is the main environmental concern in the mining regions. Arsenopyrite is normally associated to other sulfide minerals. Its presence enhances the environmental problem since the poisoning arsenic is also released in the environment due to ARD phenomenon. In this chapter, the contribution of the computer modeling to the understanding of the oxidation mechanism of sulfide minerals is reviewed. The challenge for modeling such a complex reaction involving water and oxygen is highlighted. The effects of the pyrite/arsenopyrite interface to their oxidation mechanism are also discussed in the light of the recent reports.

Chapter 6:Surface reactivity of the sulfide minerals

Mineral and mining industries have been associated to environmental degradation and natural resources exploration. The hazardous acid mining drainage (AMD), usually caused by the exposition of sulfide minerals to the environment, is of great importance, responsible for acidifying aquifers and releasing heavy metals, hence affecting all biota living around it. AMD is caused by oxidation of sulfide minerals when exposed to the oxidant environment leading to the sulfate formation. The intricate oxidation mechanism is a subject of intense research. Recently, density functional methods have been applied to investigate the reactivity of the sulfide minerals towards their oxidation. On the other hand, the understanding of the leaching mechanism of chalcopyrite is also of technological importance since this mineral is the main source of copper in the world. In the present chapter, different methodologies in the DFT framework applied to study sulfide minerals are reviewed. Recent publications about the reconstruction of the surfaces, surface energies, adsorption processes and reaction mechanisms of the pyrite, arsenopyrite and chalcopyrite using different DFT approaches are discussed. Experimental evidences that support the theoretical results have also been presented. The importance of the development of molecular modeling approaches that permit the investigation of the mineral/water interface is strengthened in the present chapter.