Síntese e caracterização de complexos ditiocarbamatos de Sn(IV), In(III), Ga(III) e metais de transição: decomposição térmica e perfil farmacológico in vitro

• Main Author: Daniele Cristiane Menezes
• Other Authors: Geraldo Magela de Lima
• Format: Others
• Language: Portuguese
• Published: Universidade Federal de Minas Gerais 2008
• Online Access: http://hdl.handle.net/1843/SFSA-7SFQXX

=== This work presents three complementary fields, approaching the synthesis of dithiocarbamate organotin(IV) complexes, in special, moreover Ga(III), In(III) and some transition metals. Preparation of solid tin sulphides was investigated through thermal decomposition in different temperatures of Sn(IV) precursors by MOD technique, metal-organic Decomposition. Besides, the in vitro pharmacologic profile, mainly antifungal, exhibited for organotin derivatives, is presented. In the Chapter 1, some perspectives in relation to the coordination inorganic chemistry are shown, approaching the obtaining of new materials starting from ideal metal-organic precursors as well as aspects of the potential biological activity exhibited by metallic complexes. In addition, the chapter presents some particularities exhibited by dithiocarbamate ligands class, focus of the present work. Concerning to the Chapter 2, the preparation of ligands is shown: pyrrolidine ([NH4{S2CN(CH2)4}]); diethyl ([Na{S2CN(C2H5)2}]); n-propylethanol ([Na{S2CN(CH2CH2CH3)CH2CH2OH}]) and tert-butylethane ([CH2CH2S2CN(CH3)3]) dithiocarbamates; used as reagents in reactions for synthesis of Sn(IV), In(III), Ga(III), Cu(II), Ni(II), Ag(I) and Co(III) complexes. The mentioned dithiocarbamate ligands were characterized by elemental analysis; infrared and nuclear magnetic resonance (1H e 13C) spectroscopies. In addition, the structures of n-propylethanol and tert-butylethane dithiocarbamates were determined by X-ray crystallography. In Chapter 3 are described the synthesis and characterization of tin(IV) compounds with pyrrolidine and diethyl dithiocarbamates ligands: [Sn{S2CN(CH2)4}2Cl2] (1), [Sn{S2CN(CH2)4}2Ph2] (2), [Sn{S2CN(CH2)4}Ph3] (3), [Sn{S2CN(CH2)4}2Bu2] (4), [Sn{S2CN(CH2)4}Cy3] (5), [Sn{S2CN(C2H5)2}2Cl2] (6), [Sn{S2CN(C2H5)2}2Ph2] (7), [Sn{S2CN(C2H5)2}Ph3] (8), [Sn{S2CN(C2H5)2}3Ph] (9) and [Sn{S2CN(C2H5)2}Cy3] (10), with Ph, Bu and Cy corresponding to phenyl, butyl and ciclohexyl groups, respectively. These compounds were characterized by elemental analysis; Xray electron probe microanalysis; infrared, multinuclear magnetic resonance (1H, 13C and 119Sn) and 119Sn Mössbauer spectroscopies as well as by X-ray crystallography for 2 and 4. In additional way, the preparation of complexes contends several metals with sodium npropylethanol dithiocarbamate is related in Chapter 4: [In{S2CN(CH2CH2OH)CH3CH2CH2}3] (11), [Ga{S2CN(CH2CH2OH)CH3CH2CH2}3] (12), [Cu{S2CN(CH2CH2OH)CH3CH2CH2}2] (13), [Ni{S2CN(CH2CH2OH)CH3CH2CH2}2] (14) and [Ag{S2CN(CH2CH2OH)CH3CH2CH2}] (15). The crystal structure of copper derivative was elucidated by X-ray diffraction. Moreover, all complexes were characterized by elemental analysis; atomic absorption spectrophotometry; infrared, nuclear magnetic resonance (1H and 13C) and electron paramagnetic (for compound 13) spectroscopies. Thermal decomposition experiments in N2 were carried out for both serial organotin(IV) compounds, containing pyrroline and diethyl dithiocarbamates, in order to prepare tin sulphides Síntese e caracterização de complexos ditiocarbamatos: Decomposição térmica e perfil farmacológico in different temperatures, as shown in Chapter 5. All pyrolysis products were characterized by elemental analysis; X-ray; electron probe microanalysis; 119Sn Mössbauer, ultraviolet-visible and Raman spectroscopies; multinuclear magnetic resonance (1H, 13C and 119Sn) and 119Sn Mössbauer spectroscopies; X-ray powder diffraction and scanning electron microscopy. Precursors 4, 7, 8 and 9 yielded SnS at 350ºC. Precursor 6 afforded SnS e Sn2S3 at 450 and 900ºC, respectively, and the results indicate the formation of a mixture of SnS e Sn2S3 for remaining precursors. In Chapter 6, an in vitro pharmacology study exhibited for dithiocarbamate organotin complexes is presented. The compounds have been tested against pathogen Candida species, such as Candida albicans (ATCC 18804), Candida tropicalis (ATCC 750) and resistant Candida albicans collected from HIV-positive Brazilian patients with oral candidiasis. In addition, the inhibitory activity of these compounds is shown against phytopatogenic fungi, Neurospora crassa and Colletotrichum graminicola. Results involving the antibacterial action of these compounds against Staphylococcus aureus also are presented. The activity of all compounds cited was investigated by agar diffusion method and minimal inhibitory concentrations, MIC (g mL-1). The effect of compounds was performed on the cellular activity of the yeast cultures. Changes in mitochondrial function have not been detected. However, all drugs reduced ergosterol and sterols biosynthesis. Preliminary studies on DNA integrity indicated that the compounds do not cause gross damaging on yeast DNA. === O presente trabalho aborda a síntese e caracterização de novos complexos ditiocarbamatos de Sn(IV), primordialmente, além de Ga(III), In(III) e alguns metais de transição. Estudos de decomposição térmica envolvendo os complexos de Sn(IV) foram conduzidos visando a preparação de sulfetos sólidos através da técnica de Decomposição de Precursores Metalorgânicos, MOD (Metal-organic Decomposition). Além disso, relata-se o perfil farmacológico in vitro, sobretudo antifúngico, exibido por derivados de Sn(IV) contendo os ligantes mencionados. Derivados pirrolidino e dietilditiocarbamatos de Sn(IV) foram submetidos a experimentos de decomposição térmica, via MOD, em temperaturas variadas sob atmosfera inerte de N2, objetivando a preparação de sulfetos de estanho. Os produtos de pirólise obtidos neste processo foram caracterizados por técnicas variadas e alguns derivados mostraram-se precursores adequados de sulfeto de estanho(II), SnS, a 350ºC. Por outro lado, o perfil farmacológico em potencial exibido pelos derivados ditiocarbamatos de Sn(IV) sintetizados no decorrer do trabalho é mostrado. São apresentadas as atividades destes compostos frente a espécies de C. albicans e C. tropicalis. Em especial, relata-se a ação destes compostos frente a uma cepa de C. albicans resistente a antifúngicos disponíveis no mercado, isolada a partir da cavidade bucal de pacientes HIV-soropositivos com candidíase oral. Além disso, é mostrada a ação inibitória dos compostos contendo o metal em questão frente a fungos fitopatógenos como Colletotrichum graminicola e Neurospora crassa. Resultados envolvendo a ação antibacteriana dos derivados de Sn(IV) citados frente a Staphylococcus aureus também são descritos. As atividades dos compostos organoestânicos em questão foram investigadas pelos métodos de difusão em ágar e da determinação dos valores da concentração inibitória mínima (CIM), em gmL-1. Além disso, uma investigação mais detalhada a respeito do possível mecanismo de ação antifúngica exibida por estes complexos frente a C. albicans é descrita a partir das análises da função respiratória celular, do material genético (DNA e RNA) e de lipídios presentes na membrana desta levedura. Os resultados sugerem que a ação antifúngica destes derivados esteja intimamente ligada a uma diminuição dos níveis de esteróis presentes na membrana plasmática celular, alvo terapêutico provável da atividade.