An experimental and theoretical approach on oxidative metabolism of paracetamol was applied for the pharmaceutical chemistry learning. Classical reactions, functional group identification, structural parameter, and chemical reactivity using frontier orbitals and Fukui index were used explaining the main products between N-acetyl-p-benzosemiquinone (NAPQI) and thiolic compounds. The chemoprotection mechanisms by N-acetyl-cysteine on high dosage of paracetamol are consistent with theoretical and experimental results. The methods also described the relationship between the chemical reactivity of quinone-imine system and the induced-toxicity of paracetamol by Michael reaction. These results can be applied in experimental pharmaceutical chemistry teaching.

The molecular mechanism of cytoprotective effect on human erythrocytes of aminophenol and salicylates associated derivatives was related to their antioxidant capacity. The oxidative hemolysis induced by water-soluble free-radical initiator 2,2’-azobis-(2-amidine-propane)-dihydrochloride (AAPH) was inhibited by drug candidates named benzaminophen (BZL), salicytamide or 5-acetamide-salicylic acid (ASL), and salibenzamide or 5-benzamide-salicylic acid (BSL) when compared to their parents salicylic acid (SAC) and acetaminophen (ACP). Trolox (TLX) was the most powerful compound and used as positive control. BZL showed a potent effect followed by ACP > BSL > ASL. SAC did not show protective effect in any evaluated concentrations. These results are in accordance with the molecular mechanism by using theoretical calculation of single electron transfers (SET), hydrogen atom transfers (HAT), and sequential proton loss electron transfer (SPLET) by means of DFT/B3LYP/6-31++G(d,p) level of theory. [1,5] Hydrogen shift between carboxyl and phenol moieties and electronic properties related to pKa and other physical-chemical properties can be involved. The molecular association approach provides protective compounds more effective than SAC.

The preparation, characterization, theoretical calculations and biological application of four RuII complexes with 2-picolinate (pic), 2,2’-bipyridine (bipy) and P-P as ligands [P-P = 1,1-bis(diphenylphosphino)methane (dppm-1), 1,2-bis(diphenylphosphino)ethane (dppe-2), 1,3-bis(diphenylphosphino)propane (dppp-3) or 1,1’-bis(diphenylphosphino)ferrocene (dppf-4)], is here presented. The complexes 1-4, with general formula [Ru(pic)(P-P)(bipy)]PF6, were characterized by elemental analysis and by infrared (IR), UV-Vis, nuclear magnetic resonance (NMR 1H and 13P{1H}) spectroscopies, cyclic voltammetry and X-ray crystallography technique. Additionally, preliminary in vitro tests against human breast (MDA-MB-231) and murine ascitic sarcoma 180 (S180) tumor cell lines were carried out, and compared with cisplatin, a reference drug. The drug concentration at which 50% of the cells are viable relative to the control (IC50) values found for complexes 1, 2, 3 and 4 against MDA-MB-231 tumor cells were around 14.6, 7.6, 3.3 and 0.4 µM, respectively, while against S180 tumor cells these complexes showed IC50 values of 71.9, 31.3, 11.2 and 3.5 µM, respectively. Therefore, the complexes were more active against MDA-MB-231 than S180.

In this work, we tested a linear interpolation approach in order to select polarization functions (exponents) to be used with Gaussian basis sets. The Gaussian primitive functions were generated here for Ga to Kr and also for Sc to Cu. The general contraction method was used for the construction of contracted Gaussian basis sets of 6Z and 7Z quality. Polarization functions were added to the contracted bases by explicit optimization and also by interpolation of exponents. The performance of the contracted basis sets, augmented with polarization functions obtained by interpolation, was tested with molecular configurations interaction single and double excitations (CISD) and density functional theory (DFT) calculations for the systems Se, Se2, Se6, Ge2, CrH and FeH. The outcomes obtained in this work with interpolated polarization functions agreed very well with the ones augmented with polarization functions obtained by explicit optimization. The interpolation methodology presented here is useful to generate polarization functions for any Gaussian basis set in different series of atoms of the periodic table.

Acetaminophen or paracetamol is a widely used analgesic and antipyretic drug and appears to be safe if used at normal therapeutic doses, but in large doses produce liver and / or kidney damage in humans and experimental animals. Prostaglandin endoperoxide synthase (PGES) and cytochrome P-450 are the key enzymes in humans as they are responsible for the analgesic and toxicity effects of paracetamol, respectively. At present, the development of new derivatives still has few impacts on clinical applications of safe compounds. Thus, in this work are discussed, a series of approaches on the design and development of acetaminophen derivatives. Some efforts were realized in our own research group.

In this study, the chemistry stability of hydroquinone (HQ) was evaluated according to its effects in redox properties and compared to kojic acid (KA). The HQ oxidation was more inhibited by N-acetylcysteine (NAC) than ascorbic acid (AA). These results were elucidated using theoretical methods at the DFT/B3LYP level of theory. All electronic parameters were related between antioxidant performance and highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), HOMO-LUMO value gap (GAP), ionization potential (IP), and phenol or enol bond dissociation energy (BDEOH) values. However, the interactions between HQ and NAC cannot be related by changing of these electronic parameters. Therefore the high calculated values for electron transfer can be associated to NAC due to polarizability or chelation properties of sulfur moiety.

In the present article the theoretical calculation of thermodynamic parameters for the two main precipitation agents, potassium 2-ethylhexanoate and t-octylamine, employed by the pharmaceutical industry to obtain potassium clavulanate for clinical use, is described. The results obtained using the standard thermochemistry calculation in the Gaussian package and by calculation of the reactivity indexes of the reagents and products are compared. The calculated thermodynamic parameters indicate that the reactivity indexes present a better correlation with the experimentally obtained percentage yield. In addition, a series of additional precipitation agents that are also used in industrial procedures to obtain potassium clavulanate for clinical use, were compared. This was done to verify if any present, a priori, better properties than potassium 2-ethylhexanoate or t-octylamine. The consistency of the reactivity indexes calculated clearly suggests that the methodology employed can be used to screen future precipitation agents for possible use in the production of potassium clavulanate.

In this work we show that structure-activity relationship studies are of great importance in modern chemistry and biochemistry. In order to obtain a significant correlation, it is crucial that appropriate descriptors be employed. Thus, quantum chemical calculations are an attractive source of new molecular descriptors which can, in principle, express all the electronic and geometric properties of molecules and their interactions with the biological receptor.

The present work describes how a group of chemistry graduate students have improved their teaching skills by teaching extension courses. It is suggested that future teachers have much to be gained by sharing the insights they have whilst teaching with their peers and students. This work explores the implications in teaching and learning and the relationship between teachers and students. This relationship requires mutual respect of ideas as well as continuous critical evaluation in both directions.

The aim of this article is to provide the understanding of the chemical world that underlies everything around us by introducing basic chemical concepts and their everyday applications. The specific topics presented were selected according to their relevance and their ability to be presented as an exhibition. This format is based on the visual effects that help the public to see abstract descriptions in a concrete form. In addition, a soundtrack is used to stimulate the affective intelligence and relax the public. According to the results obtained here, we can conclude that chemical demonstrations, combined with music, help the presentation of scientific topics and motivate and facilitate the "chemistry communication".

Um estudo sobre os impactos ambientais causados por atividades agrícolas e industriais, ao longo da bacia do rio Mogi Guaçu, foi realizado neste trabalho. A concentração de alguns metais (Fe, Cd, Cu, Cr, Zn, Ni, Pb e Mn) foi determinada em quinze estações de coleta de sedimentos e em dois períodos diferentes: chuvoso (Março/2001) e seco (Junho/2001). Os métodos de reconhecimento de padrões PCA e HCA foram utilizados para agrupar as amostras coletadas em São Paulo e em Minas Gerais e obter informações relevantes sobre as possíveis fontes de contaminação do rio Mogi Guaçu de acordo com o período de coleta das amostras. As análises quimiométricas realizadas, utilizando as amostras coletas em Março/2001 e em Junho/2001, indicaram que somente a concentração de Cd, Cu, Cr e Pb discrimina as amostras coletadas em São Paulo das amostras coletadas em Minas Gerais. A influência do período de coleta também foi analisada e os resultados obtidos indicaram que a concentração de quatro metais (Cd, Cr, Zn e Mn) foi importante para discriminar as amostras coletadas em Março/2001 das amostras coletadas em Junho/2001. De forma geral, a concentração dos metais estudados se apresenta em altos níveis em todas as estações de coleta e este fato caracteriza um ambiente com alto grau de contaminação causada, principalmente, por atividades antropogênicas.

A study on the environmental impacts caused by agricultural and industrial activities along the Mogi Guaçu river basin was carried out. Concentrations of some metals (Fe, Cd, Cu, Cr, Zn, Ni, Pb and Mn) were determined for fifteen collection stations in two different seasons: rainy (March/2001) and dry (June/2001). Pattern recognition methods (Principal Component Analysis and Hierarchical Cluster Analysis) were used to group samples collected in São Paulo and Minas Gerais and obtain relevant information on possible polluting sources of the Mogi Guaçu river according to the collection season of the samples. A chemometric analyses performed using samples collected in March/2001 and June/2001 indicated that only the concentrations of Cd, Cu, Cr and Pb discriminate samples collected in São Paulo from those collected in Minas Gerais. The influence of the collection season was also analysed and the results indicated that four metals (Cd, Cr, Zn and Mn) were important to discriminate samples collected in March/2001 (rainy season) from those collected in June/2001 (dry season). We verified that the concentrations of the metals studied are at high levels in all collection stations and this fact characterizes an environment with a high degree of contamination caused mainly by anthropogenic activities.

This paper aims to discuss and reflect about the use of computers in the teaching of Quantum Chemistry. A course on Computational Quantum Chemistry concentrating on Medicinal Chemistry projects was developed for undergraduate and graduate students. The results showed that students got more motivated and involved when there is an articulation between theory and practice. This work presents an alternative way to teach Theoretical Chemistry using projects.

Métodos quimiométricos (estatísticos) são empregados para classificar um conjunto de compostos derivados de neolignanas com atividade biológica contra a Paracoccidioides brasiliensis. O método AM1 (Austin Model 1) foi utilizado para calcular um conjunto de descritores moleculares (propriedades) para os compostos em estudo. A seguir, os descritores foram analisados utilizando os seguintes métodos de reconhecimento de padrões: Análise de Componentes Principais (PCA), Análise Hierárquica de Agrupamentos (HCA) e o método de K-vizinhos mais próximos (KNN). Os métodos PCA e HCA mostraram-se bastante eficientes para classificação dos compostos estudados em dois grupos (ativos e inativos). Três descritores moleculares foram responsáveis pela separação entre os compostos ativos e inativos: energia do orbital molecular mais alto ocupado (E HOMO), ordem de ligação entre os átomos C1'-R7 (L14) e ordem de ligação entre os átomos C5'-R6 (L22). Como as variáveis responsáveis pela separação entre compostos ativos e inativos são descritores eletrônicos, conclui-se que efeitos eletrônicos podem desempenhar um importante papel na interação entre receptor biológico e compostos derivados de neolignanas com atividade contra a Paracoccidioides brasiliensis.

Chemometric (statistical) methods are employed to classify a set of neolignan compounds with activity against Paracoccidioides brasiliensis. The AM1 (Austin Model 1) method was used to calculate a set of molecular descriptors (properties) of the neolignan compounds under study. The descriptors were further analyzed using Principal Components Analysis (PCA), Hierarchical Cluster Analysis (HCA) and K-Nearest Neighbor (KNN) chemometric methods. The PCA and HCA methods were quite efficient to classify the compounds into two groups (active and inactive) and three descriptors were found to be important in the classification: the highest occupied molecular orbital energy (E HOMO), the bond order between C1'-R7 atoms (L14) and the bond order between C5' -R6 atoms (L22). The three variables responsible for the separation between active and inactive compounds are all electronic descriptors, therefore we can conclude that electronic effects should have an important role when one is trying to understand the activity of neolignan compounds against Paracoccidioides brasiliensis.

Um conjunto de dezoito compostos de neolignanas com atividade antiesquistossomose foi estudado com o método semi-empírico PM3 e outros métodos teóricos com o intuito de avaliar algumas propriedades (variáveis ou descritores) moleculares selecionadas e correlacioná-las com a atividade biológica. Análise exploratória dos dados (análise de componentes principais, PCA, e análise hierárquica de agrupamentos, HCA), análise discriminante (DA) e o método KNN foram utilizados na obtenção de possíveis correlações entre os descritores calculados e a atividade biológica em questão e na predição da atividade antiesquistossimose de algumas moléculas teste. Os descritores moleculares responsáveis pela separação entre os compostos ativos e inativos foram: energia de hidratação (HE), refratividade molecular (MR) e carga sobre o átomo C19 (Q19). Estes descritores fornecem informações a respeito do tipo de interação que pode ocorrer entre os compostos e seu respectivo receptor biológico. Após a construção do modelo para compostos ativos e inativos, os métodos PCA, HCA, DA e KNN foram empregados em um estudo de predição. Foram estudados 10 novos compostos e somente 5 deles foram classificados como ativos contra esquistossomose.

A set of eighteen neolignan derivative compounds with anti-schistosomiasis activity was studied by using the quantum mechanical semi-empirical method PM3 and other theoretical methods in order to calculate selected molecular properties (variables or descriptors) to be correlated to their biological activities. Exploratory data analysis (principal component analysis, PCA, and hierarchical cluster analysis, HCA), discriminant analysis (DA) and the Kth nearest neighbor (KNN) method were employed for obtaining possible relationships between the calculated descriptors and the biological activities studied and predicting the anti-schistosomiasis activity of new compounds from a test set. The molecular descriptors responsible for the separation between active and inactive compounds were: hydration energy (HE), molecular refractivity (MR) and charge on the C19 carbon atom (Q19). These descriptors give information on the kind of interaction that can occur between the compounds and their respective biological receptor. The prediction study was done with a new set of ten derivative compounds by using the PCA, HCA, DA and KNN methods and only five of them were predicted as active against schistosomiasis.