Introdução a modelagem molecular de fármacos no curso experimental de química farmacêutica

Molecular Modeling is an important tool in drug design and it is very useful to predict biological activity from a library of compounds. A wide variety of computer programs and methods have been developed to visualize the tridimensional geometry and calculate physical properties of drugs. In this work, we describe a practical approach of molecular modeling as a powerful tool to study structure-activity relationships of drugs, including some antibacterials, hormones, cholinergic and adrenergic agents. At first, the students learn how to draw 3D structures and use them to perform conformational and molecular analysis. Thus, they compare drugs with similar pharmacological activity by superimposing one structure on the top of another and evaluate the geometry and physical properties.

Fixação de nitrogênio: estrutura, função e modelagem bioinorgânica das nitrogenases

Biological nitrogen fixation, catalyzed by nitrogenases, contributes about half of the nitrogen needed to global agriculture. For forty years synthetic chemists and theoreticians have tried to understand and model the structure and function of this important metalloenzyme. Ten years after the first report on the crystal structure of the MoFe protein, scientists still have not been able to synthesize a chemical equivalent of the FeMo cofactor nor the structure knowledge revealed the key to its catalytic activity. This paper with 104 references presents a review of the most relevant advances in chemical nitrogen fixation and their relation with the nitrogenases.

Cucurbitacinas e suas principais características estruturais

The cucurbitacins are highly oxygenated triterpenoid compounds found in several botanical families that show high toxicity and varied biological activities. This review presents the main cucurbitacins so far isolated and their key structural characteristics. It complements and updates the existing reviews on this subject.

Propriedades eletrônicas e estruturais do PbTiO3: teoria do funcional de densidade aplicada a modelos periódicos

Calculations based on density functional theory at the B3LYP hybrid functional level applied to periodic models have been performed to characterize the structural and electronic properties of PbTiO3. Two different slab terminations (PbO and TiO2) have been considered to obtain and discuss the results of band structure, density of states, charge distribution on bulk and surface relaxation. It is observed that the relaxation processes are most prominent for the Ti and Pb surface atoms. The electron density maps confirm the partial covalent character of the Ti-O bonds. The calculated optical band gap and other results are in agreement with experimental data.

Estudo de modelagem molecular de complexos ferriprotoporfirina-IX e quinolinocarbinolaminas antimaláricas: proposta de um farmacóforo

Quinine and quinidine are well-known 4-quinolinecarbinolamines that exhibit antimalarial activity, but, in contrast, their epimers 9-epiquinine and 9-epiquinidine are almost inactive. Literature data are conflicting in describing the 4-quinolinecarbinolamine interaction mode with the molecular target, the ferriprotoporphyrin IX [Fe(III)PPIX]. In the present paper, a pharmacophore is proposed based on the binding of the non-aromatic nitrogen to the iron atom. The 4-quinolinecarbinolamine antimalarials were superimposed on the pharmacophore under consideration and complexes with Fe(III)PPIX were constructed. Conformational analyses of the complexes were performed applying the MM+ molecular mechanics method. The analysis of the complexes showed that the proposed ligand mode is possible although it does not explain the activity differences between epimers. A discussion of the structural aspects is also provided.

Aspectos estruturais relacionados ao processo de troca iônica no niobato lamelar K4Nb6O17

The niobate with formula K4Nb6O17 has a layered structure formed by stacked negative sheets and exchangeable cations in the interlayer region. In this study we discuss some structural aspects related to the ion exchange in layered hexaniobate based on X-ray diffractometry and vibrational Raman spectroscopy data. Hexaniobate has two distinct interlayer regions and the potassium ions of one interlayer in particular are preferably exchanged by other cations, leading to an interstratified material.

Descrições estruturais cristalinas de zeólitos

Crystalline structures of zeolites can be studied using different representations: the internal symmetry obtained by X-Ray or neutron diffraction crystallography techniques or a systematic analysis of the basic structural units which can be arranged to build the geometries of each kind of zeolite. In this work the basic concepts of three building units, SBU (Secondary Building Units), SSU (Structural SubUnits) and PBU (Periodic Building Units) are presented. The properties of the resulting crystalline structures are discussed (pores, cavities, channels), describing the influence of each one of these properties in processes of physical-chemical interest. Representative case studies of known zeolite crystalline structures are also discussed in terms of their space group classification.

Propriedades estruturais e microestruturais de manganitas dopadas com cobre

We report a structural study on polycrystalline La0.86Sr0.14Mn1-y Cu yO3+delta samples (y = 0, 0.05, 0.10, 0.15, 0.20) using refinement of powder X-ray diffraction data and analysis of scanning electron microscopy images. It is found that the structure remains rhombohedral through the whole series, with a decrease in the average Mn-Mn bond distances, slight variations in Mn-O-Mn angle and reduction in the unit cell volume with increasing Cu amounts. The values of Mn-Mn distances suggest compact structures with d within ±1%. Scanning electron microscopy images reveal homogeneous microstructure in all samples, besides a trend for smaller grains and larger porosity with increasing Cu content.

Utilização de modelagem numérica para o estudo da dispersão de poluentes emitidos pela usina termoelétrica Presidente Médici

The purpose of the present study is to evaluate the atmospheric behavior in the dispersion of the pollutants SO2, PM10 and NOx emitted by the President Medici power plant in Candiota, RS. The RAMS atmospheric model was applied and the simulations were conducted from april in 20 to 24, 2004. The concentrations of the pollutants simulated by RAMS were compared with the data measured at the air quality monitoring stations. The results showed significant influence of the emissions generated by the power plant on the concentration of the pollutants.

Síntese, avaliação biológica e modelagem molecular de arilfuranos como inibidores da enzima tripanotiona redutase

Trypanosoma cruzi is a protozoan parasite that causes a severe disease (Chagas'disease) in Central and South America. The currently available chemotherapeutic agents against this disease are still inadequate. The enzyme trypanothione reductase (TR) is considered a validated molecular target for the development of new drugs against this parasite. In this regard, a series of arylfurans based on 2,5-bis-(4-acetamidophenyl)furan was synthesized and tested for their in vitro inhibitory activity against TR. Molecular modeling studies of putative enzyme-inhibitor complexes revealed a possible mechanism of interaction. From synthesized compounds, a benzylaminofuran derivative was found to be more active than the lead compound.

Constituintes químicos de Parmotrema lichexanthonicum Eliasaro & Adler: isolamento, modificações estruturais e avaliação das atividades antibiótica e citotóxica

From the lichen Parmotrema lichexantonicum were isolated the depsidone salazinic acid, the xanthone lichexanthone, and the depside atranorin. The two major compounds, salazinic acid and lichexanthone, were selected for structure modifications. Salazinic acid afforded O-alkyl salazinic acids, some of them potentially cytotoxic against tumor cell lines (HCT-8, SF-295 and MDA/ MB - 435). From lichexanthone were obtained norlichexanthone, 3-O-methylnorlichexanthone, 3-O-methyl-6-O-prenylnorlichexanthone, 3,6-di-O-prenyl-norlichexanthone, 3,6-bis[(3,3-dimethyloxyran-2-il)methoxy]-1-hydroxy-8-methyl-9H-xanten-9-one and 3,6-bis[3-(dimethylamine)propoxy]-1-hydroxy-8-methyl-9H-xanten-9-one. The last compound was the most active against S. aureus.

Estudos espectroscópicos e estruturais dos polímeros de coordenação 2D, ∞[Tb(DPA)(HDPA)] e ∞[Gd(DPA)(HDPA)]

This paper presents the synthesis of the coordination polymers ∞[Ln(DPA)(HDPA)] (DPA=2,6-pyridinedicarboxylate; Ln= Tb and Gd), their structural and spectroscopic properties. The structural study reveals that the ∞[Ln(DPA)(HDPA)] has a single Ln+3 ion coordinated with two H2DPA ligands in tridentade coordination mode, while two others H2DPA establish a syn-bridge with a symmetry-related Ln3+, forming a two-dimensional structure. The spectroscopic studies show that ∞[Tb(DPA)(HDPA)] compound has high quantum yield (q x≈ 50.0%), due to the large contribution of radiative decay rate. Moreover triplet level is localized sufficiently over the emitter level 5D4 of theTb3+ ion, avoiding a retrotransference process between these states.

Proteínas quinases: características estruturais e inibidores químicos

Protein kinases are one of the largest protein families and they are responsible for regulation of a great number of signal transduction pathways in cells, through the phosphorylation of serine, threonine, or tyrosine residues. Deregulation of these enzymes is associated with several diseases including cancer, diabetes and inflammation. For this reason, specific inhibition of tyrosine or serine/threonine kinases may represent an interesting therapeutic approach. The most important types of protein kinases, their structural features and chemical inhibitors are discussed in this paper. Emphasis is given to the small-molecule drugs that target the ATP-binding sites of these enzymes.

Metodologia AGOA: a modelagem de clusters de hidratação no complexo aziridina···ácido fluorídrico

We present a theoretical study of solvent effect on C2H5N···HF hydrogen-bonded complex through the application of the AGOA methodology. By using the TIP4P model to orientate the configuration of water molecules, the hydration clusters generated by AGOA were obtained through the analysis of the molecular electrostatic potential (MEP) of solute (C2H5N···HF). Thereby, it was calculated the hydration energies on positive and negative MEP fields, which are maxima (PEMmax) and minima (PEMmin) when represent the -CH2- methylene groups and hydrofluoric acid, respectively. By taking into account the higher and lower hydration energy values of -370.6 kJ mol-1 and -74.3 kJ mol-1 for PEMmax and PEMmin of the C2H5N···HF, our analysis shows that these results corroborate the open ring reaction of aziridine, in which the preferential attack of water molecules occurs at the methylene groups of this heterocyclic.

Correlação entre parâmetros da cinética de intumescimento com características estruturais e hidrofílicas de hidrogéis de poliacrilamida e metilcelulose

In this paper, the effects of acrylamide (AAm), methylcellulose (MC) contents, pH and ionic strength on kinetic, network and hydrophilic properties of polyacrylamide and methylcellulose hydrogels were investigated. The hydrogels were characterized by evaluating of network [average molecular weight between crosslinks (M C), crosslink density (q) and the number of elastically effective chains (Ve)], and kinetic parameters [diffusional exponent (n), diffusion constant (k) and diffusion coefficient (D)]. Such properties were controlled by adjusting of the AAm, MC contents, pH and ionic strength factors. Due to high hydrophilicity and fast water-uptake, the PAAm-MC hydrogels can be considered as materials for potential applications in agricultural fields, mainly in controlled release of water or pesticides.