Pesticides have been used to control various types of pests, including plants and insects, for thousands of years, however the impact of exposure to these toxic chemicals, with respect to environmental and health consequences, is not fully understood. Two pesticides of interest, molinate and dieldrin, have been shown to cause neurotoxicity in humans, but their mechanisms of toxicity are still unknown. In order to better understand how exposure to these chemicals can cause toxicity, the structure-activity relationship (SAR) was defined to determine how specific changes to the structure of each pesticide affects the toxicity profiles of each of these compounds. Results of this study demonstrated that oxidation of molinate to molinate sulfoxide, and then further to molinate sulfone, a more potent inhibitor of aldehyde dehydrogenase. The sulfone metabolite is capable of covalently modifying the active-site cysteine residue of aldehyde dehydrogenase, accounting for the observed enzyme inhibition. These results indicate that the compound responsible for the toxicity from molinate exposure is not the parent compound, but rather one of the sulfoxidation metabolites. When the SAR of dieldrin was investigated with respect to a Parkinson's disease model, it was determined that the compounds that were previously found to be the least potent insecticides were the most toxic with respect to dopaminergic cells. Each of the compounds tested was observed to disrupt dopamine metabolism in accordance with their toxicity profiles in dopaminergic cells. In combination, these results implicate important structural features responsible for the toxicity with respect to Parkinson's disease. This information is critical for the development of new pesticides, and will be important to increase the selective toxicity for insects while minimizing adverse/off-target effects. This can lead to the development of safer, more effective pesticides that will be essential for future environmental and human health.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / O presente trabalho ilustra o desenvolvimento de uma rota sintÃtica para a obtenÃÃo de uma meso-metaloporfirina, a partir de uma meso-porfirina base livre, macromolÃcula derivada do LÃquido da Casca da Castanha de Caju (LCC), subproduto do agronegÃcio do caju. A obtenÃÃo dessas espÃcies seguida de estudos preliminares da modificaÃÃo da superfÃcie do eletrodo de ouro com a meso-metaloporfirina de cobre com aplicaÃÃo para sensor de NO (Ãxido NÃtrico) tambÃm compÃe os objetivos desse trabalho. A partir do processo de metalaÃÃo,foi sintetizada uma meso-metaloporfirina utilizando Cu (II) como centro metÃlico, a partir da macromolÃcula base livre, e testes voltamÃtricos foram realizados utilizando o eletrodo de ouro, em meio de diclorometano e PTBA 0,1 mol L-1, obtido a 100 mV s-1.Estudos foram realizados a cerca do comportamento eletroquÃmico dos filmes formados em presenÃa de NO em meio aquoso de Na2SO4 0,5 mol L-1 obtendo o voltamograma cÃclico para o eletrodo de ouro modificado com a porfirina de cobre(II) na detecÃÃo de NO e foi observado no voltamograma para NO sobre uma intensidade de corrente 7,6 vezes maior comparada à do pico observado para o mesmo processo do NO na superfÃcie de ouro nÃo modificado demonstrando elevado potencial para aplicaÃÃo como sensor eletroquÃmico. Outra metodologia eletroanalÃtica foi desenvolvida para a obtenÃÃo de um biossensor, baseado em uma enzima, glutationa-S-transferase (GST), para determinaÃÃo do pesticida molinato, um herbicida prÃ-emergente, em amostras reais de Ãgua de campos de arrozais da cidade do Porto, em Portugal. A construÃÃo deste biossensor baseou-se a imobilizaÃÃo de GST em um eletrodo de carbono vÃtreo (GCE), atravÃs da ligaÃÃo covalente glutaraldeÃdo-amino-silano (APTES/GA). O princÃpio deste biossensor consistiu no processo de inibiÃÃo da GST promovida pelo molinato. A curva de calibraÃÃo foi obtida por meio da tÃcnica de voltametria de pulso diferencial (VPD) variando a concentraÃÃo do pesticida entre 1,01x10-6 â 4,20x10-5 mol L-1 apresentando um limite de detecÃÃo (LD) de 0,064 mg L-1. O biossensor baseado na GST foi aplicado para quantificar o molinato nas amostras de Ãgua das lavouras de arrozais. Os resultados obtidos com este biossensor foram comparados com aqueles obtidos por HPLC e nÃo houve diferenÃas estatisticamente significativas comprovando, entÃo, que a metodologia desenvolvida foi precisa no nÃvel de concentraÃÃo estudada. / This study illustrates the development of synthetic route will be obtaining meso-metalloporphyrin, from porphyrin meso-free base macromolecule derived from Shell Liquid Cashew Nut (CNSL), byproduct of cashew agribusiness. Obtaining these species followed by preliminary studies of surface modification of gold electrode with copper meso-metalloporphyrin with application to sensor of NO (Nitric Oxide) also composed the objectives of this work. From metalation process, was synthesized by meso-metalloporphyrin using Cu (II) the a metal to center, from the macromolecule free base, and voltametric tests were carried out using the gold electrode in the middle of dichloromethane and TBAP 0,1 mol L-1, obtained at 100 mV s-1. Studies have been conducted about the electrochemical behavior of the films formed in the presence of NO in aqueous Na2SO4 0,5 mol L-1 the cyclic voltammogram obtained will be the gold electrode modified with porphyrin to copper (II) the detection of NO and voltammogram was observed in about one NO to current intensity 7,6 times larger compared to the peak observed for the same process of NO in unmodified gold surface showing high potential for application as an electrochemical sensor. Electroanalytical another methodology was developed will be obtaining the biosensor, based on an enzyme, glutathione-S-transferase (GST), will be determining the pesticide molinate, the real daily pre-emergent herbicide in samples of to water of paddy fields City Porto, in Portugal. The construction of this biosensor was based on the immobilization of GST in glassy carbon electrode (GCE) by covalent glutaraldehyde-amino-silane (APTES/GA). The principle of this biosensor consisted of the process promoted by inhibition of GST molinate. The calibration curve was obtained by the technique of differential pulse voltammetry (DPV) varying the concentration of the pesticide between 1,01 x10-6 to 4,20 x10-5 mol L-1 having a limit of detection (DL) of 0,064 mg L-1. The biosensor based on GST was applied to quantify the molinate in water samples of paddy crop. The results obtained with this biosensor were compared with those obtained by HPLC and no statistically significant differences proving therefore that the developed methodology has been studied in terms of concentration.