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dc.contributor.authorRocha, Sheisi Fonseca Leite da Silva
dc.date.accessioned2023-12-22T03:05:02Z-
dc.date.available2023-12-22T03:05:02Z-
dc.date.issued2014-04-15
dc.identifier.citationRocha, Sheisi Fonseca Leite da Silva. Desenvolvimento de um modelo empírico de predição da atividade de inibidores da Urease utilizando o método Semi-Empírico PM6. 2014. [73 f.]. Dissertação (Programa de Pós-Graduação em Química) - Universidade Federal Rural do Rio de Janeiro, [Seropédica - RJ] .por
dc.identifier.urihttps://rima.ufrrj.br/jspui/handle/20.500.14407/14724-
dc.description.abstractA urease é uma enzima importante para as pesquisas relacionadas com a agricultura, meio ambiente e medicina. Ela catalisa a reação de hidrólise da uréia para formar amônia e carbamato, o qual se decompõe espontaneamente, produzindo uma segunda molécula de amônia e dióxido de carbono, provocando um significativo aumento do pH da solução. Com o objetivo de desenvolver modelos de predição da atividade de inibidores da urease, estudou-se inicialmente a multiplicidade de spin da enzima, que contém dois íons Ni(II), e o estado de protonação do oxigênio localizado entre estes íons. Os resultados indicaram que o sistema é melhor representado pelo estado tripleto ou quinteto e o oxigênio localizado entre os íons de níquel provavelmente é um íon hidroxila. A partir destes resultados, a construção dos modelos se baseou em propostas da literatura sobre o uso de ciclos termodinâmicos para se calcular a energia livre de interação entre ligantes e enzimas. No presente estudo, foram combinados termos referentes à entalpia de interação entre o inibidor e a enzima, a energia livre de Gibbs necessária para o inibidor passar do meio aquoso para o interior da enzima e as perdas entrópicas devido a restrições rotacionais após a interação do mesmo com a enzima para se obter funções de correlação com constantes inibitórias (Ki) obtidas experimentalmente. A quantificação destes parâmetros para alguns derivados do ácido fosfínico da literatura nos possibilitou o desenvolvimento de um modelo para determinação da atividade com boa correlação com dados experimentais (r=0,92). Este modelo foi utilizado na predição da atividade relativa de novas dialquilfosforilidrazonas, sintetizadas pelo grupo de síntese de organofosforados da UFRRJ. Foi possível identificar quais compostos são os mais promissores da série proposta e quais fatores devem ser alterados para otimizar o perfil de inibição da urease.por
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES, Brasil.por
dc.formatapplication/pdf*
dc.languageporpor
dc.publisherUniversidade Federal Rural do Rio de Janeiropor
dc.rightsAcesso Abertopor
dc.subjectOrganofosforadospor
dc.subjectModelo de energia livrepor
dc.subjectMétodo semi-empíricopor
dc.subjectUreaseeng
dc.subjectOrganophosphorus compoundseng
dc.subjectFree energy modelseng
dc.subjectSemi-empirical methodeng
dc.titleDesenvolvimento de um Modelo Empírico de Predição da Atividade de Inibidores da Urease utilizando o Método Semi-Empírico PM6por
dc.typeDissertaçãopor
dc.description.abstractOtherUrease is an important enzyme for the research in agriculture, environment and medicine. This enzyme catalyzes the hydrolysis of urea to ammonia and carbamate, which decomposes spontaneously, yielding a second molecule of ammonia, causing a significant increase of pH solution. In order to develop theoretical models for the prediction of activities of urease inhibitors, we initially studied the enzyme’s spin multiplicity, which contains two Ni(II) íons, and the state of protonation of the oxygen located between the nickel ions. The results indicate that the system is best represented by the triplet or quintet state and the oxygen atom located between the nickel ions, probably is a hydroxyl ion. Based on these results, the construction of the models was based on literature proposals about the use of thermodynamic cycles for the calcultation of the free energy of binding between ligands and enzymes. In the present work, parameters such as the interaction enthalpy, the Gibbs free energy required for the inhibitor to go from the aqueous phase to the interior of the enzyme and the entropic losses associated to the freezing of bonds after the binding of the inhibitors to the enzyme were used to develop correlations with the measured experimental Ki values. The quantification of these parameters for some phosphinic acids derivatives from the literature allowed us to obtain a good empirical model for the correlation between experimental activity data and the theoretical parameters (r=0.92). The model was employed for the prediction of the relative activity of a series of new proposed compounds by the organophosphorous synthesis group of UFRRJ. It was possible to identify which compounds are the most promising and which are the main factors that should be modified in order to optimize the urease inhibition profile by these compounds.eng
dc.contributor.advisor1Sant'Anna, Carlos Mauricio Rabello de
dc.contributor.advisor1ID827232227-72por
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/2087099684752643por
dc.contributor.referee1Bauerfeldt, Glauco Favilla
dc.contributor.referee2Machado, Sérgio de Paula
dc.creator.ID122348897-74por
dc.creator.Latteshttp://lattes.cnpq.br/4206525243279971por
dc.publisher.countryBrasilpor
dc.publisher.departmentInstituto de Ciências Exataspor
dc.publisher.initialsUFRRJpor
dc.publisher.programPrograma de Pós-Graduação em Químicapor
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