Estudo eletroquímico e químico-quântico da oxidação do antidepressivo tricíclico amitriptilina

This work presents the electrochemical and quantum chemical studies of the oxidation of the tricyclic antidepressant amitriptyline (AM) employing a carbon-polyurethane composite electrode (GPU) in a 0.1 mol L-1 BR buffer. The electrochemical results showed that the oxidation of AM occurs irreversibly at potentials close to 830 mV with the loss of one electron and one proton and is controlled by reagent and product adsorption. According to the PM3 results, the atom C16 is the region of highest probability for the oxidation of AM since it has the largest charge variation.

Análise teórica da interação de CO, CO2 e NH3 com ZnO

This paper presents a study of the interaction of small molecules with ZnO surfaces by means of theoretical methods. The AM1 semi-empirical method was used for optimizing the geometric parameters of adsorbed molecules. The optimized AM1 structures were used in the calculations of the ab initio RHF method with the 3-21G* basis set. The interaction of CO, CO2 and NH3 molecules were studied with (ZnO)22 and (ZnO)60 cluster models. We have analyzed the interaction energy, SCF orbital energies, Mulliken charges and the density of states (DOS).

Estudo experimental e teórico da redução de bases de Schiff derivadas da 3,3-difenilpropilamina

A series of seven Schiff bases have been synthesized from 3,3-diphenylpropilamine and substituted benzaldehydes. These imines were treated with NaBH4 in ethanol affording the corresponding amines in 98-55% yields. A molecular modeling study was performed with the Schiff bases in order to compare the theoretical parameters with the experimental results. The theoretical parameters were obtained by AM1 and PM3 semi-empirical methods. The analysis of charge, electron densities and LUMO coefficients suggested that the most favorable interactions should occur with Schiff bases containing electron-donating groups, in accordance with experimental yields, showing that the higher reactivity is due to higher electrophilic character of imine carbons.

On the application of knoevenagel condensation for the synthesis of benzylidene benzothiazine compounds and structural study

The synthesis and physico-chemical properties of new 6-acetylamino or 6-benzoyl-amino 2-benzylidene-4-methyl-4H-benzo[1,4]thiazin-3-ones and 6-benzoylamino or 6-nitro 2-benzylidene-4H-benzo[1,4]thiazin-3-ones are described. These benzylidene benzothiazine compounds were prepared by the Knoevenagel condensation with benzaldehydes. The configurations and conformations of benzylidene benzothiazine derivatives were optimised using the semi-empirical method AM1.

Uso de modelagem molecular no estudo dos conceitos de nucleofilicidade e basicidade

Molecular modeling enables the students to visualize the abstract relationships underlying theoretical concepts that explain experimental data on the molecular and atomic levels. With this aim we used the free software "Arguslab 4.0.1" (semi-empirical method) to study the reaction of 1-chloropropane with ethoxide in solution, known to lead to methyl propyl ether, through the S N2 mechanism, and propene, through the E2 mechanism. This tool allows users to calculate some properties (i. e. heat formation or electric charges) and to produce 3D images (molecular geometry, electrostatic potential surface, etc.) that render the comprehension of the factors underlying the reaction's progress, which are related to the structure of the reagents, and the process kinetic clearer and easier to understand by the students

Estudo teórico da interação existente entre a artemisinina e o heme

The purpose of this work is to study theoretically stereoelectronic aspects of the interaction between heme and artemisinin in the transitional heme-artemisinin complex. Through semi-empirical calculations using the PM3 method, the potential energy barrier of artemisinin rotation relative to heme in the heme-artemisinin complex was studied in vacuum and in the partially solvated state. The minimum heat of formation obtained for the complex with and without water molecules is -702.39 and -100.86 kcal mol-1, respectively, which corresponds to the dihedral angle C-Fe-O1-O2 of 43.93º and 51.90º around the iron-oxygen O1 bond, respectively. The water molecules bind to heme via 13 hydrogen bonds and O-H•••O and 6 C-H•••O interactions, which accounts for -67.23 kcal mol-1. It is observed that the inclusion of water molecules does not affect significantly the stability of the heme-artemisinin complex.

A semi-automatic computerized method to measure baroreflex-mediated heart rate responses that reduces interobserver variability

Arterial baroreflex sensitivity estimated by pharmacological impulse stimuli depends on intrinsic signal variability and usually a subjective choice of blood pressure (BP) and heart rate (HR) values. We propose a semi-automatic method to estimate cardiovascular reflex sensitivity to bolus infusions of phenylephrine and nitroprusside. Beat-to-beat BP and HR time series for male Wistar rats (N = 13) were obtained from the digitized signal (sample frequency = 2 kHz) and analyzed by the proposed method (PRM) developed in Matlab language. In the PRM, time series were low-pass filtered with zero-phase distortion (3rd order Butterworth used in the forward and reverse direction) and presented graphically, and parameters were selected interactively. Differences between basal mean values and peak BP (deltaBP) and HR (deltaHR) values after drug infusions were used to calculate baroreflex sensitivity indexes, defined as the deltaHR/deltaBP ratio. The PRM was compared to the method traditionally (TDM) employed by seven independent observers using files for reflex bradycardia (N = 43) and tachycardia (N = 61). Agreement was assessed by Bland and Altman plots. Dispersion among users, measured as the standard deviation, was higher for TDM for reflex bradycardia (0.60 ± 0.46 vs 0.21 ± 0.26 bpm/mmHg for PRM, P < 0.001) and tachycardia (0.83 ± 0.62 vs 0.28 ± 0.28 bpm/mmHg for PRM, P < 0.001). The advantage of the present method is related to its objectivity, since the routine automatically calculates the desired parameters according to previous software instructions. This is an objective, robust and easy-to-use tool for cardiovascular reflex studies.

Manual and semi-automatic quantification of in vivo ¹H-MRS data for the classification of human primary brain tumors

In vivo proton magnetic resonance spectroscopy (¹H-MRS) is a technique capable of assessing biochemical content and pathways in normal and pathological tissue. In the brain, ¹H-MRS complements the information given by magnetic resonance images. The main goal of the present study was to assess the accuracy of ¹H-MRS for the classification of brain tumors in a pilot study comparing results obtained by manual and semi-automatic quantification of metabolites. In vivo single-voxel ¹H-MRS was performed in 24 control subjects and 26 patients with brain neoplasms that included meningiomas, high-grade neuroglial tumors and pilocytic astrocytomas. Seven metabolite groups (lactate, lipids, N-acetyl-aspartate, glutamate and glutamine group, total creatine, total choline, myo-inositol) were evaluated in all spectra by two methods: a manual one consisting of integration of manually defined peak areas, and the advanced method for accurate, robust and efficient spectral fitting (AMARES), a semi-automatic quantification method implemented in the jMRUI software. Statistical methods included discriminant analysis and the leave-one-out cross-validation method. Both manual and semi-automatic analyses detected differences in metabolite content between tumor groups and controls (P < 0.005). The classification accuracy obtained with the manual method was 75% for high-grade neuroglial tumors, 55% for meningiomas and 56% for pilocytic astrocytomas, while for the semi-automatic method it was 78, 70, and 98%, respectively. Both methods classified all control subjects correctly. The study demonstrated that ¹H-MRS accurately differentiated normal from tumoral brain tissue and confirmed the superiority of the semi-automatic quantification method.

Febrifugine derivative antimalarial activity: quantum mechanical predictors

Plasmodium falciparum resistant strain development has encouraged the search for new antimalarial drugs. Febrifugine is a natural substance with high activity against P. falciparum presenting strong emetic property and liver toxicity, which prevent it from being used as a clinical drug. The search for analogues that could have a better clinical performance is a current topic. We aim to investigate the theoretical electronic structure by means of febrifugine derivative family semi-empirical molecular orbital calculations, seeking the electronic indexes that could help the design of new efficient derivatives. The theoretical results show there is a clustering in well-defined ranges of several electronic indexes of the most selective molecules. The model proposed for achieving high selectivity was tested with success.

Analysis of the structural and electronic properties of 1-(5-Hydroxymethyl - 4 -[ 5 - (5-oxo-5-piperidin-1-yl-penta-1,3dienyl)-benzo[1,3]dioxol-2-yl] -tetrahydro-furan-2-yl)-5-methyl-1H-pyrimidine-2,4dione molecule

The structural and electronic properties of 1-(5-Hydroxymethyl - 4 -[ 5 - (5-oxo-5-piperidin- 1 -yl-penta- 1,3 -dienyl)-benzo [1,3] dioxol- 2 -yl]-tetrahydro -furan-2 -yl)-5-methy l-1Hpyrimidine-2,4dione (AHE) molecule have been investigated theoretically by performing density functional theory (DFT), and semi empirical molecular orbital calculations. The geometry of the molecule is optimized at the level of Austin Model 1 (AM1), and the electronic properties and relative energies of the molecules have been calculated by density functional theory in the ground state. The resultant dipole moment of the AHE molecule is about 2.6 and 2.3 Debyes by AM1 and DFT methods respectively, This property of AHE makes it an active molecule with its environment, that is AHE molecule may interacts with its environment strongly in solution.

Model for subchannel friction factors and flow redistribution in wire-wrapped rod bundles

The fuel element of LMFBR consists of a bundle of rods wrapped with an helical wire as spacer, surrounded by an hexagonal duct. In the present work, a semi-empirical model is developed to calculate bundle average and subchannel based friction factors and flow redistribution. The obtained results were compared to experimental data and they were considered satisfactory for wide range of geometrical parameters.

Fluid dynamic modelling and simulation of circulating fluidized bed reactors: importance of the interface turbulence transfer

The main objective of this work is to analyze the importance of the gas-solid interface transfer of the kinetic energy of the turbulent motion on the accuracy of prediction of the fluid dynamic of Circulating Fluidized Bed (CFB) reactors. CFB reactors are used in a variety of industrial applications related to combustion, incineration and catalytic cracking. In this work a two-dimensional fluid dynamic model for gas-particle flow has been used to compute the porosity, the pressure, and the velocity fields of both phases in 2-D axisymmetrical cylindrical co-ordinates. The fluid dynamic model is based on the two fluid model approach in which both phases are considered to be continuous and fully interpenetrating. CFB processes are essentially turbulent. The model of effective stress on each phase is that of a Newtonian fluid, where the effective gas viscosity was calculated from the standard k-epsilon turbulence model and the transport coefficients of the particulate phase were calculated from the kinetic theory of granular flow (KTGF). This work shows that the turbulence transfer between the phases is very important for a better representation of the fluid dynamics of CFB reactors, especially for systems with internal recirculation and high gradients of particle concentration. Two systems with different characteristics were analyzed. The results were compared with experimental data available in the literature. The results were obtained by using a computer code developed by the authors. The finite volume method with collocated grid, the hybrid interpolation scheme, the false time step strategy and SIMPLEC (Semi-Implicit Method for Pressure Linked Equations - Consistent) algorithm were used to obtain the numerical solution.

Delayed Schwann cell and oligodendrocyte remyelination after ethidium bromide injection in the brainstem of Wistar rats submitted to streptozotocin diabetogenic treatment

Schwann cell disturbance followed by segmental demyelination in the peripheral nervous system occurs in diabetic patients. Since Schwann cell and oligodendrocyte remyelination in the central nervous system is a well-known event in the ethidium bromide (EB) demyelinating model, the aim of this investigation was to determine the behavior of both cell types after local EB injection into the brainstem of streptozotocin diabetic rats. Adult male Wistar rats received a single intravenous injection of streptozotocin (50 mg/kg) and were submitted 10 days later to a single injection of 10 µL 0.1% (w/v) EB or 0.9% saline solution into the cisterna pontis. Ten microliters of 0.1% EB was also injected into non-diabetic rats. The animals were anesthetized and perfused through the heart 7 to 31 days after EB or saline injection and brainstem sections were collected and processed for light and transmission electron microscopy. The final balance of myelin repair in diabetic and non-diabetic rats at 31 days was compared using a semi-quantitative method. Diabetic rats presented delayed macrophage activity and lesser remyelination compared to non-diabetic rats. Although oligodendrocytes were the major remyelinating cells in the brainstem, Schwann cells invaded EB-induced lesions, first appearing at 11 days in non-diabetic rats and by 15 days in diabetic rats. Results indicate that short-term streptozotocin-induced diabetes hindered both oligodendrocyte and Schwann cell remyelination (mean remyelination scores of 2.57 ± 0.77 for oligodendrocytes and 0.67 ± 0.5 for Schwann cells) compared to non-diabetic rats (3.27 ± 0.85 and 1.38 ± 0.81, respectively).

Mathematical modeling of microwave dried celery leaves and determination of the effective moisture diffusivities and activation energy

Celery (Apium graveolens L. var. secalinum Alef) leaves with 50±0.07 g weight and 91.75±0.15% humidity (~11.21 db) were dried using 8 different microwave power densities ranging between 1.8-20 W g-1, until the humidity fell down to 8.95±0.23% (~0.1 db). Microwave drying processes were completed between 5.5 and 77 min depending on the microwave power densities. In this study, measured values were compared with predicted values obtained from twenty thin layer drying theoretical, semi-empirical and empirical equations with a new thin layer drying equation. Within applied microwave power density; models whose coefficient and correlation (R²) values are highest were chosen as the best models. Weibull distribution model gave the most suitable predictions at all power density. At increasing microwave power densities, the effective moisture diffusivity values ranged from 1.595 10-10 to 6.377 10-12 m2 s-1. The activation energy was calculated using an exponential expression based on Arrhenius equation. The linear relationship between the drying rate constant and effective moisture diffusivity gave the best fit.

Estudo químico-computacional da reatividade de aziridinona e diaziridinona através de cálculos semi-empíricos

The results of semiempirical molecular orbital calculations performed on aziridinone and diaziridinone employing the MNDO, AM1, and PM3 molecular models are presented. The AM1 method, which best reproduces ground-state molecular properties, is used to calculate electronic parameters and the use of these parameters for the evaluation of reactivity is discussed.