Síntese, caracterização e reatividade de complexos modelo para as PAPs gálio substuídas

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas. Programa de Pós-Graduação em Química.Enzimas são moléculas protéicas que possuem forma tridimensional globular. Algumas enzimas têm sido estudadas para o desenvolvimento de novas drogas contra uma variedade de doenças, incluindo osteoporose, câncer, fibrose cística e depressão. Além disso, são de grande interesse como substâncias que podem ser utilizadas no combate ao terrorismo bem como na bioremediação, visto que, modificadas podem degradar gases organofosforados tóxicos e pesticidas. Aqui descreve-se a síntese e caracterização de 4 complexos binucleares inéditos de FeCu com ligantes derivados do H2bpbpmp contendo grupos substituintes metila, nitro, di-terc-butil e bromo. As estruturas cristalinas de dois complexos foram obtidas e revelaram que estes são isosestruturais. Os complexos sintetizados foram testados na hidrólise do substrato 2,4-bis-dinitrofenilfosfato e apresentram acelerações entre 10 e 15 mil em comparação a reação não catalisada. Estudos preliminares utilizando o triéster 2,4-dinitrofenil dietil fosfato foram realizados. Baseado nos estudos de reatividade realizados foi possível propor que o nucleófilo responsável pela catálise do substrato 2,4-BDNPP mediada pelos complexos de FeCu seja diferente daquele proposto para a série de complexos análogos de FeZn já descrita anteriormente e semelhante àquele que foi proposto recentemente para a fosfatase ácida púrpura extraída da batata doce (FeMn PAP)

Catalase vs Peroxidase Activity of a Manganese(II) Compound: Identification of a Mn(III)-(μ-O)2-Mn(IV) Reaction Intermediate by Electrospray Ionization Mass Spectrometry and Electron Paramagnetic Resonance Spectroscopy

Herein, we report reactivity studies of the mononuclear water-soluble complex [Mn(II)(HPClNOL)(η1-NO3)(η2-NO3)] 1, where HPClNOL ) 1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol, toward peroxides (H2O2 and tertbutylhydroperoxide). Both the catalase (in aqueous solution) and peroxidase (in CH3CN) activities of 1 were evaluated using a range of techniques including electronic absorption spectroscopy, volumetry (kinetic studies), pH monitoring during H2O2 disproportionation, electron paramagnetic resonance (EPR), electrospray ionization mass spectrometry in the positive ion mode [ESI(+)-MS], and gas chromatography (GC). Electrochemical studies showed that 1 can be oxidized to Mn(III) and Mn(IV). The catalase-like activity of 1 was evaluated with and without pH control. The results show that the pH decreases when the reaction is performed in unbuffered media. Furthermore, the activity of 1 is greater in buffered than in unbuffered media, demonstrating that pH influences the activity of 1 toward H2O2. For the reaction of 1 with H2O2, EPR and ESI(+)-MS have led to the identification of the intermediate [Mn(III)Mn(IV)(μ- O)2(PClNOL)2]+. The peroxidase activity of 1 was also evaluated by monitoring cyclohexane oxidation, using H2O2 or tert-butylhydroperoxide as the terminal oxidants. Low yields (<7%) were obtained for H2O2, probably because it competes with 1 for the catalase-like activity. In contrast, using tert-butylhydroperoxide, up to 29% of cyclohexane conversion was obtained. A mechanistic model for the catalase activity of 1 that incorporates the observed lag phase in O2 production, the pH variation, and the formation of a Mn(III)-(μ-O)2-Mn(IV) intermediate is proposed

Novel 2-(R-phenyl)amino-3-(2-methylpropenyl)-[1,4]-naphthoquinones: synthesis, characterization, electrochemical behavior and antitumor activity

Novel 2-(R-phenyl)amino-3-(2-methyl-propenyl)-[1,4]-naphthoquinones (R = H, 4-OMe, 4-Ferrocenyl, 4-Me, 3-Me, 4-I, 3-I, 4-CN, 3-CN, 4-NO2 and 3-NO2) derived from nor-lapachol [2-hydroxy-3-(2-methylpropenyl)-1,4-naphthoquinone] were obtained in good yields. Their structures were proposed on the basis of a single crystal X-ray diffraction study (R = OMe, 2b), ¹H and 13C NMR studies and calculations using the B3LYP functional and the 6-311+G(2d,p) basis set. The half-wave potentials of the aminonaphthoquinones and ¹H NMR chemical shifts of the 3-propenyl hydrogen in 2a-k show good correlation with the substituent Hammett constants on the phenylamino ring. The antitumor assays showed promising activity for substrate methoxy-nor-lapachol 1 and the 4-ferrocenyl derivative 2c.Novas 2-(R-fenil)amino-3-(2-metilpropenil)-[1,4]-naftoquinonas (R = H, 4-OMe, 4-Ferrocenil, 4-Me, 3-Me, 4-I, 3-I, 4-CN, 3-CN, 4-NO2 e 3-NO2) derivadas do nor-lapachol [2-hidroxi-3-(2-metilpropenil)-1,4-naftoquinona] foram obtidas em bons rendimentos. A estrutura dos compostos foi proposta com base em estudos de difração de raios-X (R = OMe, 2b), dados de RMN de ¹H e 13C e cálculos teóricos utilizando o funcional B3LYP e a base 6-311+G(2d,p). Os potenciais de meia-onda das aminonaftoquinonas e o deslocamento químico do hidrogênio da cadeia 3-propenil dos compostos 2a-k mostraram boa correlação com as constantes de Hammett dos substituintes presentes no anel fenileno. A avaliação da citotoxicidade evidenciou atividade antitumoral promissora para o substrato metóxi-nor-lapachol 1 e o derivado 4-ferrocenil 2c.169178Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Síntese e reatividade de complexos biomiméticos para as fostatases ácidas púrpuras

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas. Programa de Pós-Graduação em Química

THEORETICAL STUDY OF THE BINUCLEAR COMPLEXES OF MANGANESE (II) WITH LIGAND 2-HYDROXYBENZYLGLYCINE, POSSIBLES MIMICS FOR CATECHOL OXIDASE

This work applies the Density Functional Theory (DFT) to study binuclear complexes of Mn2+ with the ligand 2-hydroxibenzilglycine and its substituted derivatives. The results showed the isomer 2 with multiplicity 11-ete as the most stable between all the structures and multiplicities obtained. Then, the most stable complex with the -OCH3, -Br, -Cl and -NO2 substituents were analyzed. Finally, the absolute hardness and the percentage of LUMO orbital participation for the substituted complexes were evaluated. Among them, the complexes with -NO2, -H, -Br groups were more likely to play the catalytic activity, respectively

Estudo espectroscópico de compósito obtido da reação no estado sólido entre um complexo mononuclear de vanádio(IV) e caulinita

The use of probes, such as paramagnetic species diluted in diamagnetic materials in EPR spectroscopy, and mathematical tools such, as the Kubelka-Munk function in DRUV-VIS spectroscopy are strategies in the analysis of complex mixtures of solid materials. The results obtained here show that the solid state reaction between the complex, [VO(acac)(BMIMAPY)] [ClO4], BMIMAPY = [(bis(1-methylimidazole-2-yl)methyl)(2-(pyridyl-2-yl)ethyl) amine] and acac = acetilacetonate, with kaolinite turns possible to obtain anisotropic EPR spectrum of the complex with a reasonable level of resolution. The study by DRUV-VIS using the method of second derivative mode of the Kubelka-Munk function revealed new complex structural arrangements, a solid hitherto unknown

Química Nova

p. 257-261The use of probes, such as paramagnetic species diluted in diamagnetic materials in EPR spectroscopy, and mathematical tools such, as the Kubelka-Munk function in DRUV-VIS spectroscopy are strategies in the analysis of complex mixtures of solid materials. The results obtained here show that the solid state reaction between the complex, [VO(acac)(BMIMAPY)] [ClO4], BMIMAPY = [(bis(1-methylimidazole-2-yl)methyl)(2-(pyridyl-2-yl)ethyl) amine] and acac = acetilacetonate, with kaolinite turns possible to obtain anisotropic EPR spectrum of the complex with a reasonable level of resolution. The study by DRUV-VIS using the method of second derivative mode of the Kubelka-Munk function revealed new complex structural arrangements, a solid hitherto unknown