<p>The aqueous solvation of metal ions is one of the long-standing and complex problems in chemistry, with implications for and applications in a broad range of biochemical and electrochemical systems, where water is the all-pervasive medium.</p><p>This thesis describes computer simulations of Al³⁺(<i>aq</i>), Fe²⁺(<i>aq</i>), Fe³⁺(<i>aq</i>) and Cu²⁺(<i>aq</i>). Various aspects of the solvation of these polyvalent metal ions in water are addressed, at different levels of theory, using Car-Parrinello molecular dynamics, classical molecular dynamics and quantum-mechanical cluster calculations. Polyvalent metal ions are particularly interesting because of their large influence on the solvent structure, dynamics and thermodynamics, as well as on the properties of the individual solvent molecules. Polyvalent metal ions in aqueous solution also constitute a challenging subject for computer simulations since a sophisticated interaction model is needed to incorporate the large many-body effects. </p><p>All the ion-water coordination figures in this thesis are octahedral, except in the Cu²⁺(<i>aq</i>) solution, where the ion is penta-coordinated with four equatorial neighbours in a plane and one axial neighbour located ~0.45 Å further out from the ion. The equatorial ion-water bonds have covalent character, while the axial water molecule is only electrostatically bound. For all the ions, the OD stretching frequencies of the first-shell water molecules are much more downshifted than in liquid water. In the case of Cu²⁺(<i>aq</i>), however, only the OD frequencies of the equatorial water molecules are downshifted with respect to bulk water whereas the OD frequencies of the axial water molecule are slightly upshifted. </p><p>Various limitations of the Car-Parrinello molecular dynamics simulations have been explored and compared, such as finite system-size effects and shortcomings in the electronic structure calculations. The Car-Parrinello simulations are found to give reasonable descriptions of the polyvalent metal ions in aqueous solution.</p>

Water is one of the most common compounds on earth and is essential for all biological activities. Water has, however, been a mystery for many years due to the large number of unusual chemical and physical properties, e.g. decreased volume during melting and maximum density at 4 °C. The origin of the anomalies behavior is the nature of the hydrogen bond. This thesis will presented an x-ray absorption spectroscopy (XAS) study to reveal the hydrogen bond structure in liquid water. The x-ray absorption process is faster than a femtosecond and thereby reflects the molecular orbital structure in a frozen geometry locally around the probed water molecules. The results indicate that the electronic structure of liquid water is significantly different from that of the solid and gaseous forms. The molecular arrangement in the first coordination shell of liquid water is actually very similar as the two-hydrogen-bonded configurations at the surface of ice. This discovery suggests that most molecules in liquid water have two-hydrogen-bonded configurations with one donor and one acceptor hydrogen bond compared to the four-hydrogen-bonded tetrahedral structure in ice. This result is controversial since the general picture is that the structure of liquid water is very similar to the structure of ice. The results are, however, consistent with x-ray and neutron diffraction data but reveals serious discrepancies with structures based on current molecular dynamics simulations. The two-hydrogen-bond configuration in liquid water is rigid and heating from 25 °C to 90 °C introduce a minor change in the hydrogen-bonded configurations. Furthermore, XAS studies of water in aqueous solutions show that ion hydration does not affect the hydrogen bond configuration of the bulk. Only water molecules in the close vicinity to the ions show changes in the hydrogen bond formation. XAS data obtained with fluorescence yield are sensitive enough to resolved electronic structure of water molecules in the first hydration sphere and to distinguish between different protonated species. Hence, XAS is a useful tool to provide insight into the local electronic structure of a hydrogen-bonded liquid and it is applied for the first time on water revealing unique information of high importance.

The aqueous solvation of metal ions is one of the long-standing and complex problems in chemistry, with implications for and applications in a broad range of biochemical and electrochemical systems, where water is the all-pervasive medium. This thesis describes computer simulations of Al3+(aq), Fe2+(aq), Fe3+(aq) and Cu2+(aq). Various aspects of the solvation of these polyvalent metal ions in water are addressed, at different levels of theory, using Car-Parrinello molecular dynamics, classical molecular dynamics and quantum-mechanical cluster calculations. Polyvalent metal ions are particularly interesting because of their large influence on the solvent structure, dynamics and thermodynamics, as well as on the properties of the individual solvent molecules. Polyvalent metal ions in aqueous solution also constitute a challenging subject for computer simulations since a sophisticated interaction model is needed to incorporate the large many-body effects. All the ion-water coordination figures in this thesis are octahedral, except in the Cu2+(aq) solution, where the ion is penta-coordinated with four equatorial neighbours in a plane and one axial neighbour located ~0.45 Å further out from the ion. The equatorial ion-water bonds have covalent character, while the axial water molecule is only electrostatically bound. For all the ions, the OD stretching frequencies of the first-shell water molecules are much more downshifted than in liquid water. In the case of Cu2+(aq), however, only the OD frequencies of the equatorial water molecules are downshifted with respect to bulk water whereas the OD frequencies of the axial water molecule are slightly upshifted. Various limitations of the Car-Parrinello molecular dynamics simulations have been explored and compared, such as finite system-size effects and shortcomings in the electronic structure calculations. The Car-Parrinello simulations are found to give reasonable descriptions of the polyvalent metal ions in aqueous solution.

The thesis is a summary and discussion of eight papers. During the last decades, precipitation has become increasingly acidic due to the extensive use of fossil fuels. In areas of poorly buffered bedrocks, e.g. Scandinavia, northeastern United States, this phenomenon has resulted in elevated amounts of Al(III) being leached into streams and lakes. Recent findings reveal that these elevated Al-concentrations could cause fish death and decreasing forest production. In the present thesis, the importance of taking naturally occurring substances into consideration when discussing Al(III) in natural waters, is emphasized. On the basis of a chemical characterization of relevant ligand classes in a natural water, the complex formation between Al^+, hydroxide ions and the inorganic ligand carbonic acid, the low-molecular weight organic ligand citric acid and the high-molecular weight model substances gallic acid, 1,2-dihydroxynaphtha-lene-4-sulfonate, 1,2-naphthoquinone-4-sulfonate, pyrocatechol and salicylic acid were investigated. The investigations were performed as series of Potentiometrie titrations and data were processed by means of the least-squares computer program LETAGROPVRID using a technique called pqr-analysis, permitting an unbiased search for complex model (and corresponding equilibrium constants) to be made. In most systems studied, the complexation at high ligand excesses can be described by a series of mononuclear complexes AIL-AIL^. Tentatively, the whole series consists of octahedrally coordinated (water and ligand oxygens) AI(III). At lower ligand excesses, the significance and in some cases even predominance of ternary mono- and polynuclear hydroxo complexes is demonstrated. In two of the systems, binary aluminium hydroxo species are evaluated. The potential importance of the substances with respect to Al-com-plexation in natural waters are indicated in a number of model calculations. The solubility of the clay mineral kaolinite is calculated as a function of -lg[H+] and ligand concentration. It is shown that citric acid, gallic acid, 1,2-dihydroxynaphthalene-4-sulfonate, pyrocatechol and salicylic acid contribute quite significant to the total solubilities, even at very low concentrations. As a complement and background to the equilibrium studies, the corrosion rate for one of the naturally occurring Al-bearing minerals, corundum, is reported. In this investigation, performed with a leach-ant solution of ground-water composition, an experimental technique was employed which made it possible to divide the corrosion into chemical and mechanical losses. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1983</p> / digitalisering@umu

Neste trabalho, foi investigado o efeito do tamanho do abrasivo e do pH do meio na resistência ao desgaste abrasivo do aço H-13 com matriz martensítica e do aço Hadfield com matriz austenítica. Ensaios de abrasão foram realizados utilizando o equipamento roda de borracha a úmido, variando o tamanho do abrasivo entre 0,15 e 2,40 mm e o pH do meio entre 5,5 e 12,8. As microestruturas dos materiais estudados foram analisadas utilizando microscopia óptica, as superfícies de desgaste e as partículas de desgaste foram analisadas em microscópio eletrônico de varredura. A macrodureza e a microdureza, antes e após os ensaios, foram obtidas utilizando durômetro Vickers. A topografia da região central da superfície de desgaste foi obtida utilizando Perfilometria 3D, visando obter valores de profundidade de penetração do abrasivo. Os resultados mostraram que o aço Hadfield é mais resistente do que o aço H-13 em todos os valores de pH e tamanhos de abrasivo utilizados. Para os dois materiais, a perda de massa aumenta linearmente até um tamanho crítico de abrasivo (TCA) e, após este, a mesma continua a aumentar, mas com uma intensidade menor. Para os dois materiais e para todos os tamanhos de abrasivo, o aumento do pH do meio resultou em menores perdas de massa, sendo este efeito maior para os dois menores tamanhos de abrasivo. Para maiores valores de pH, foram observadas menores profundidades de penetração do abrasivo. A microdureza da superfície de desgaste do aço H-13 sofreu um pequeno aumento com o aumento do tamanho do abrasivo enquanto que para o aço Hadfield esse aumento foi mais intenso. A análise das partículas de desgaste mostraram que, para todas as condições ensaiadas, os debris do aço H-13 tinham duas morfologias, contínuas e descontínuas enquanto que os cavacos do aço Hadfield foram sempre descontínuos. Para os dois materiais, foram observados dois micromecanismos de desgaste, sendo eles microcorte e microsulcamento. Por fim, os resultados apresentados neste trabalho sugerem que a análise de desempenho do aço Hadfield em serviço deve considerar o pH do meio bem como a granulometria do abrasivo em contato. / In this work, the effects of abrasive particle size and pH value of the aqueous solution on abrasive wear resistance of the H-13 steel with martensitic matrix and the Hadfield steel with austenitic matrix were investigated. Abrasive wear tests, using a wet rubber wheel abrasion tester, were carried out using abrasive sizes between 0.15 and 2.40 mm and pH values of the aqueous solution between 5.5 and 12.8. The microstructures of the materials studied were analyzed by optical microscopy and the wear surfaces and wear particles were analyzed by scanning electron microscopy. The hardness and microhardness before and after the tests were measured using a Vickers hardness tester. The topography of the middle of wear scars, were obtained by a noncontact 3D profiler in order to measure the depth of abrasive penetrations.The results show that the Hadfield steel is more wear resistant than the H-13 steel at all pH values and abrasive sizes conditions tested. For both materials, mass loss increases linearly up to a critical abrasive size, and after this the mass loss continues to increase, but with a lower intensity. Moreover, for both materials and all the abrasive sizes, increases in the pH values of the aqueous solution resulted in lower mass losses, and this effect is greater for the two smaller grain sizes. For higher pH values, lower depths of penetration of abrasive were observed. The microhardness in the wear scar surface of the H-13 steel presented a slight increase with the abrasive size, while for the Hadfield steel, this microhardness increases in a more intense form with the abrasive size. The analysis of the wear particles showed that, for all test conditions, the chips of H-13 steel has two types of morphologies, continuous or discontinuous, and for Hadfield steel only discontinuous. For both materials, two abrasive wear micromechanisms were observed, microcutting and microploughing. Finally, the results presented in this work suggest that the wear performance analysis of the Hadfield steel, to be used in an abrasive environment, must consider the effects of pH of the aqueous solution and particle size.

M. Tech. (Department of Chemistry, Faculty of Applied and Computer Sciences), Vaal University of Technology. / Removal of wastewater pollutants is urgent as they are continuously defiling the limited freshwater resources, affecting the ecosystem, aquatic and terrestrial life. Carbon nanotubes-based adsorbent materials are effective for removal of wastewater pollutants owing to their large specific surface area. Surface modification of carbon nanotubes (CNTs) can mediate specific pollutant adsorption and increase CNTs colloidal stability and chemical reactivity. Heavy metal pollution of wastewater is one of the major threats, as this metals can be toxic to humans when present at certain concentrations in drinking water. This study report the synthesis of chlorine functionalized and nitrogen doped carbon nanotubes (ClNCNTs) loaded with iron oxide nanoparticles and their use as adsorbents for Pb2+ ions in aqueous solutions. Carbon nanomaterials that are functionalized with chlorine and doped with nitrogen were successfully synthesized. This was done through pyrolysis of a mixture of dichlorobenzene and acetonitrile (in a 1:1 volume ratio) over 10% Fe-Co/CaCO3 bi-metallic catalyst via chemical vapour deposition (CVD) method. Addition of chlorine and nitrogen to the CNTs was to enable defect and disorder creation on the surface of the nanotubes which is envisaged to create nucleation sites on the their surface for better adhesion of the iron oxide nanoparticles. Different loadings of magnetite (Fe3O4) nanoparticles on the surface of the ClNCNTs was achieved using a co-precipitation method. The synthesized materials were charaterized by Raman spectroscopy, Transmission electron microscopy (TEM), Powder X-ray diffraction (PXRD) spectroscopy, Thermal gravimetric analysis (TGA), Brunauer Emmett and Teller (BET) and X-ray photoelectron spectroscopy (XPS). Highly defected CNTs, some with hollow and others with bamboo-compartments due to nitrogen inclusion were obtained. The effect of metal salt concentration in wt.% (10, 20, 30 and 53 wt.%) was investigated. The increase in wt.% loading has resulted in an increase in surface area, and a decrease in thermal stability as a result of defected Fe3O4/ClNCNTs. In addition, agglomeration was observed at 30 and 53 wt.% loading, due to large amount of iron present. The identity of the Fe3O4 nanoparticles was confirmed by PXRD and XPS with two iron peaks deconvoluted at 725.6 eV and 721 eV respectively. The percentage loading of the Fe3O4 nanoparticles at the surface of the ClNCNTs was affirmed by TGA analysis, where the residual mass obtained from TGA were closely related to the mass percentages added. Different nitrogen environments namely, the quatenary, pyridinic, pyrollic and nitrogen oxides were also observed, whilst chlorine could not be deconvoluted because it was present in very limited amount probably it was masked by the iron oxide nanoparticle. Thus, a 20 wt.% Fe3O4/ClNCNTs was chosen as an optimum, due to uniform distribution of spherical nanopaticles observed along the radial length of ClNCNTs that had an average size of 10 ± 4.5 nm. The synthesized ClNCNTs and a nanocomposite made from a 20 wt.% Fe3O4/ClNCNTs were applied in the removal of Pb2+ ions from aqueous solution. The results obtained showed that a nanocomposite made from a 20 wt.% Fe3O4/ClNCNTs had a better adsorption capacity of 17.0 mg/g as compared with 14.8 mg/g for ClNCNTs.

No description available.

Propagations- und Terminierungsgeschwindigkeitskoeffizienten radikalischer Polymerisationen in w&auml;ssriger L&ouml;sung wurden durch Pulslaser-induzierte Polymerisationen und durch chemisch initiierte Polymerisationen bestimmt. Pulslaser-induzierte Polymerisationen wurden von <i>N</i>,2&#8209;Dimethylprop&#8209;2&#8209;enamid, <i>N</i>,<i>N</i>&#8209;Dimethylprop&#8209;2&#8209;enamid, 2&#8209;Methylprop&#8209;2&#8209;enamid und Prop&#8209;2&#8209;enamid durchgef&uuml;hrt. Anschlie&szlig;ende Analyse der Produkte mittels Gr&ouml;&szlig;enausschlusschromatographie erm&ouml;glichte die Bestimmung der Propagationsgeschwindigkeitskoeffizienten. Die beobachtete &Auml;nderung des Propagationsgeschwindigkeitskoeffizienten mit der Monomerkonzentration kann durch die St&auml;rke, mit der innere Rotationen und Vibrationen im &Uuml;bergangszustand des Propagationsschritts gehindert sind, erkl&auml;rt werden. Die Abh&auml;ngigkeit der St&auml;rke der Hinderung von der Monomerkonzentration l&auml;sst sich zur&uuml;ckf&uuml;hren auf sich mit steigendem Monomeranteil verst&auml;rkende intermolekulare Wechselwirkungen der &Uuml;bergangszustandsstruktur mit solvatisierenden Molek&uuml;len. Zur Bestimmung der Aktivierungsvolumina und der Arrhenius-Aktivierungsenergien der Propagation wurden Druck und Temperatur von Umgebungsdruck bis 2&nbsp;000&nbsp;bar beziehungsweise von 10&nbsp;&deg;C bis 80&nbsp;&deg;C variiert. Sowohl die Aktivierungsenergie als auch der Betrag des Aktivierungsvolumens sind im Fall von 2&#8209;Methylprop&#8209;2&#8209;enamid gr&ouml;&szlig;er verglichen mit <i>N</i>,<i>N</i>&#8209;Dimethylprop&#8209;2&#8209;enamid. Diese Beobachtung kann dem Umstand, dass <i>N</i>,<i>N</i>&#8209;Dimethylprop&#8209;2&#8209;enamid keine &alpha;&#8209;Methylgruppe aufweist, zugeschrieben werden. Beide Aktivierungsparameter sind im Fall von <i>N</i>,2&#8209;Dimethylprop&#8209;2&#8209;enamid denen des <i>N</i>,<i>N</i>&#8209;Dimethylprop&#8209;2&#8209;enamid &auml;hnlich. Dies ist unerwartet, da <i>N</i>,2&#8209;Dimethylprop&#8209;2&#8209;enamid eine &alpha;&#8209;Methylgruppe aufweist. Unterschiede zwischen beiden Monomeren hinsichtlich der Konformation der Kohlenstoff&ndash;Kohlenstoff-Doppelbindung relativ zur Kohlenstoff&ndash;Sauerstoff-Doppelbindung k&ouml;nnten diese Beobachtung erkl&auml;ren.<br> Zur Bestimmung von Terminierungsgeschwindigkeitskoeffizienten wurde die Polymerisation durch einen einzelnen Laserpuls initiiert und der Monomer-zu-Polymer-Umsatz anschlie&szlig;end mittels zeitaufgel&ouml;ster Nahinfrarotspektroskopie verfolgt. Die Zeitaufl&ouml;sung ist auf 0.33&nbsp;&mu;s verbessert worden. Wiederholte Einstrahlung von Laserpulsen in Kombination mit nahinfrarotspektroskopischer Analyse liefert Terminierungsgeschwindigkeitskoeffizienten als Funktion des Grades des Monomerumsatzes. Untersuchungen der Terminierungskinetik von Prop&#8209;2&#8209;enamid, 2&#8209;Methylprop&#8209;2&#8209;enamid, <i>N</i>,2&#8209;Dimethylprop&#8209;2&#8209;enamid, <i>N</i>,<i>N</i>&#8209;Dimethylprop&#8209;2&#8209;enamid und 1&#8209;Vinylpyrrolidin&#8209;2&#8209;on wurden, aufgrund des besseren Signal-Rausch-Verh&auml;ltnisses bei hohen Dr&uuml;cken, bei 2&nbsp;000&nbsp;bar durchgef&uuml;hrt. Weitere Messungen wurden im Fall der meisten Prop&#8209;2&#8209;enamide bei Dr&uuml;cken von 500&nbsp;bar, 1&nbsp;000&nbsp;bar und 1&nbsp;500&nbsp;bar durchgef&uuml;hrt. Die dadurch erhaltenen Aktivierungsvolumina k&ouml;nnen zur Absch&auml;tzung des Terminierungsgeschwindigkeitskoeffizienten bei Umgebungsdruck verwendet werden. Die Aktivierungsvolumina der Terminierungsgeschwindigkeitskoeffizienten von <i>N</i>,2&#8209;Dimethylprop&#8209;2&#8209;enamid und von Prop&#8209;2&#8209;enamid belaufen sich auf 12.4&nbsp;cm³&middot;mol^&minus;1 beziehungsweise 14.3&nbsp;cm³&middot;mol^&minus;1. Das Aktivierungsvolumen im Fall von <i>N</i>,<i>N</i>&#8209;Dimethylprop&#8209;2&#8209;enamid (4.9&nbsp;cm³&middot;mol^&minus;1) ist kleiner als erwartet. Terminierungsgeschwindigkeitskoeffizienten von 1&#8209;Vinylpyrrolidin&#8209;2&#8209;on konnten f&uuml;r einen gro&szlig;en Bereich der Anfangsmonomerkonzentration und des Grades des Monomerumsatzes erhalten werden. Diese Daten erm&ouml;glichen eine detaillierte Analyse der Parameter, die zur Beschreibung der Monomerumsatzabh&auml;ngigkeit des Terminierungsgeschwindigkeitskoeffizienten verwendet werden. Es wird angenommen, dass der Terminierungsgeschwindigkeitskoeffizient innerhalb des untersuchten Monomerumsatzbereichs durch Segment-, Translations- und Reaktionsdiffusion kontrolliert ist.<br> Im Fall von <i>N</i>,<i>N</i>&#8209;Dimethylprop&#8209;2&#8209;enamid und 1&#8209;Vinylpyrrolidin&#8209;2&#8209;on wurden dynamische Viskosit&auml;ten von Monomer&ndash;Wasser-Gemischen bei Umgebungsdruck bestimmt, um das Verst&auml;ndnis der Terminierungskinetik zu erleichtern. F&uuml;r diese beiden Monomere wurde durch Pulslaser-induzierte Polymerisation eine gro&szlig;e Anzahl von Terminierungsgeschwindigkeitskoeffizienten in Abh&auml;ngigkeit von der Anfangsmonomerkonzentration erhalten.<br> Zur Bestimmung des Terminierungsgeschwindigkeitskoeffizienten von Prop&#8209;2&#8209;enamid in Abh&auml;ngigkeit vom Monomerumsatz wurden chemisch initiierte Polymerisationen bei Umgebungsdruck durchgef&uuml;hrt. Die erhaltenen Werte stimmen gut mit Daten &uuml;berein, die mit Hilfe von Pulslaser-induzierten Polymerisationen ermittelt wurden.<br> Untersuchungen der bin&auml;ren Copolymerisation von 1&#8209;Vinylpyrrolidin&#8209;2&#8209;on und Natriumacrylat zeigten einen ausgepr&auml;gten Einbau von Natriumacrylat in das gebildete Copolymer. Dies wurde mittels Kernspinresonanzspektroskopie gemessen. Die Monomerreaktivit&auml;tsverh&auml;ltnisse wurden mit Hilfe der Lewis&ndash;Mayo-Gleichung bestimmt.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / This work involved the preparation and characterization of an inclusion complex of Trimethoprim (TMP) a drug used in the treatment of infections and hydroxypropylgamma- cyclodextrin (HP-γ-CD). Owing to the low aqueous solubility of this drug, high dosages are required to provide a satisfactory therapeutic effect, although this also brings severe side effects to some patients. Thus here we aimed to increase the TMP aqueous solubility in order to potentially reduce the side effects by complexation in a CD derivative. Prior to the inclusion study, some relevant physiochemical parameters of the drug such as pKa, solubility in several pH values as well as absorption coefficient were determined. The inclusion complex has been prepared by the suspension method and collected by lyophilization. Primary evidence of the inclusion of TMP in HP-γ-CD was provided by the increase of the solubility in presence of HP -γ - CD, from the phase-solubility diagram obtained at different temperatures and pH values. The apparent stability constants K 1:1 for the complex formed at different temperatures and pH values were found strongly depend on the conditions, being higher at low pH. A 1:1 stoichiometry was suggested for the complex both from the phase-solubility diagram and from the continuous variation method Additional evidences of the inclusion were provided by thermal analysis (DSC), which suggested that TMP is not present in the sample as an isolated crystalline solid. The XRD analysis evidenced the loss of the TMP crystalline character in the complex, which is commonly observed for CD complexes but may be also a consequence of the lyophilization process. The presence of bands characteristic of both species was observed in the infrared spectrum of the complex. Although differences observed in the relative intensities cannot directly evidence complex formation, they don t exclude this possibility. Direct evidence of TMP inclusion in the CD cavities were given from 1H-1H bidimensional ROESY spectrum, which also showed that the inclusion mode involves penetration of the trimethoxyphenyl group in HP-γ-CD. / Este trabalho envolveu a preparação e caracterização de complexo de inclusão entre Trimetoprim (TMP), substância utilizada no tratamento de infecções, em hidroxipropil- γ-ciclodextrina (HP-γ-CD), objetivando o aumento da solubilidade aquosa do convidado. A baixa solubilidade do TMP torna necessário o uso de altas dosagens, causando diversos efeitos colaterais, que em testes futuros poderão ser reduzidos pelo aumento da solubilidade do mesmo. Determinaram-se, inicialmente, alguns parâmetros físico-químicos do fármaco e, posteriormente, preparou-se o complexo do mesmo em HP-γ-CD pelo método da suspensão. A ocorrência de inclusão foi evidenciada através do aumento da solubilidade do convidado em presença de HP-γ-CD, nos estudos do diagrama de solubilidade de fases em diferentes temperaturas e pH. Obteve-se, ainda a partir destes estudos, valores de 220,7 M-1 a 20oC e 144,7M-1 a 25oC e 55410 M-1 para pH 4,0; 2188 M-1 para pH 7,0 e 123 M-1 para pH 9,0 para a constante de associação do complexo, demonstrando interações relativamente fortes. A estequiometria 1:1 para o complexo foi sugerida tanto a partir do diagrama de solubilidades quanto pelo método das variações contínuas. Evidências adicionais da inclusão foram propiciadas por calorimetria diferencial de varredura (DSC), que sugeriu que o TMP não se encontra como um sólido isolado. As análises dos difratogramas obtidos mostraram perda do padrão de ordenamento cristalino do TMP quando comparado ao difratograma do complexo, o que pode também ter resultado do processo de liofilização. A partir da análise por espectroscopia infravermelho, observou-se a presença de bandas de ambas as espécies (hospedeiro e convidado) no espectro da amostra HP-γ-CD/TMP coletada por liofilização. Contudo, diferenças observadas quanto a intensidades relativas e mascaramento de bandas não evidenciam diretamente a formação do complexo, porém não excluem tal possibilidade. De acordo com os resultados de espectroscopia de RMN 1H-1H bidimensional (ROESY), ficou evidenciada a inclusão do TMP na cavidade da HP-γ-CD, mostrando adicionalmente que a entrada na cavidade se dá através do grupo trimetoxifenila.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / This work involved the preparation and characterization of an inclusion complex of Trimethoprim (TMP) a drug used in the treatment of infections and hydroxypropylgamma- cyclodextrin (HP-γ-CD). Owing to the low aqueous solubility of this drug, high dosages are required to provide a satisfactory therapeutic effect, although this also brings severe side effects to some patients. Thus here we aimed to increase the TMP aqueous solubility in order to potentially reduce the side effects by complexation in a CD derivative. Prior to the inclusion study, some relevant physiochemical parameters of the drug such as pKa, solubility in several pH values as well as absorption coefficient were determined. The inclusion complex has been prepared by the suspension method and collected by lyophilization. Primary evidence of the inclusion of TMP in HP-γ-CD was provided by the increase of the solubility in presence of HP -γ - CD, from the phase-solubility diagram obtained at different temperatures and pH values. The apparent stability constants K 1:1 for the complex formed at different temperatures and pH values were found strongly depend on the conditions, being higher at low pH. A 1:1 stoichiometry was suggested for the complex both from the phase-solubility diagram and from the continuous variation method Additional evidences of the inclusion were provided by thermal analysis (DSC), which suggested that TMP is not present in the sample as an isolated crystalline solid. The XRD analysis evidenced the loss of the TMP crystalline character in the complex, which is commonly observed for CD complexes but may be also a consequence of the lyophilization process. The presence of bands characteristic of both species was observed in the infrared spectrum of the complex. Although differences observed in the relative intensities cannot directly evidence complex formation, they don t exclude this possibility. Direct evidence of TMP inclusion in the CD cavities were given from 1H-1H bidimensional ROESY spectrum, which also showed that the inclusion mode involves penetration of the trimethoxyphenyl group in HP-γ-CD. / Este trabalho envolveu a preparação e caracterização de complexo de inclusão entre Trimetoprim (TMP), substância utilizada no tratamento de infecções, em hidroxipropil- γ-ciclodextrina (HP-γ-CD), objetivando o aumento da solubilidade aquosa do convidado. A baixa solubilidade do TMP torna necessário o uso de altas dosagens, causando diversos efeitos colaterais, que em testes futuros poderão ser reduzidos pelo aumento da solubilidade do mesmo. Determinaram-se, inicialmente, alguns parâmetros físico-químicos do fármaco e, posteriormente, preparou-se o complexo do mesmo em HP-γ-CD pelo método da suspensão. A ocorrência de inclusão foi evidenciada através do aumento da solubilidade do convidado em presença de HP-γ-CD, nos estudos do diagrama de solubilidade de fases em diferentes temperaturas e pH. Obteve-se, ainda a partir destes estudos, valores de 220,7 M-1 a 20oC e 144,7M-1 a 25oC e 55410 M-1 para pH 4,0; 2188 M-1 para pH 7,0 e 123 M-1 para pH 9,0 para a constante de associação do complexo, demonstrando interações relativamente fortes. A estequiometria 1:1 para o complexo foi sugerida tanto a partir do diagrama de solubilidades quanto pelo método das variações contínuas. Evidências adicionais da inclusão foram propiciadas por calorimetria diferencial de varredura (DSC), que sugeriu que o TMP não se encontra como um sólido isolado. As análises dos difratogramas obtidos mostraram perda do padrão de ordenamento cristalino do TMP quando comparado ao difratograma do complexo, o que pode também ter resultado do processo de liofilização. A partir da análise por espectroscopia infravermelho, observou-se a presença de bandas de ambas as espécies (hospedeiro e convidado) no espectro da amostra HP-γ-CD/TMP coletada por liofilização. Contudo, diferenças observadas quanto a intensidades relativas e mascaramento de bandas não evidenciam diretamente a formação do complexo, porém não excluem tal possibilidade. De acordo com os resultados de espectroscopia de RMN 1H-1H bidimensional (ROESY), ficou evidenciada a inclusão do TMP na cavidade da HP-γ-CD, mostrando adicionalmente que a entrada na cavidade se dá através do grupo trimetoxifenila.