Thesis (Ph. D.)--Washington State University, May 2010. / Title from PDF title page (viewed on June 9, 2010). "Department of Chemistry." Includes bibliographical references.

Orientador: Gilbert Bannach / Banca: Eder Tadeu Gomes Cavalheiro / Banca: Flavio Junior Caires / O Programa de Pós Graduação em Ciência e Tecnologia de Materiais, PosMat, tem caráter institucional e integra as atividades de pesquisa em materiais de diversos campi / Resumo: A síntese e caracterização de complexos do fármaco anti-inflamatório não esteroide sulindaco (sulin) com os íons lantanídeos (Ln3+) La3+, Ce3+, Pr3+, Nd3+, Gd3+, Tb3+ e Ho3+ no estado sólido são descritas neste trabalho. A caracterização dos complexos foi realizada empregando a termogravimetria-calorimetria exploratória diferencial simultânea acoplada ao espectrômetro de FTIR (TG-DSC-FTIR), DSC-fotovisual, titulação complexométrica com EDTA e análise elementar, além de utilização de difração de raios X pelo método do pó e espectroscopia vibracional de refletância na região do infravermelho com transformada de Fourier (FTIR). Os métodos termoanalíticos foram utilizados para verificar a decomposição térmica, estabilidade térmica, entalpia de desidratação, entre outras propriedades e juntamente com a titulação complexométrica e a análise elementar, foi possível determinar a estequiometria dos complexos como [Ln(sulin)3]XH2O. Através do espectro de infravermelho pode-se sugerir que o sulindaco está coordenado aos íons lantanídeos de modo bidentado e em ponte pelo grupo carboxilato. Os testes de citotoxicidade e de atividades anti-inflamatória dos compostos sintetizados demonstraram que os complexos, em geral, possuem comportamento muito semelhante ao do fármaco. Contudo, os resultados, sugerem que complexo [Gd(sulin)3] apresenta potencial para um melhoramento farmacológico / Abstract: Synthesis and characterization of complexes of the anti-inflammatory drug nonsteroidal sulindac (sulin) with the lanthanide ions (Ln3+) La3+, Ce3+, Pr3+, Nd3+, Gd3+, Tb3+ and Ho3+ in the solid state area described in this work. The characterization of the pharmaceutical and the complexes was performed using simultaneous thermogravimetry-differential scanning calorimetry (TG-DSC), differential scanning calorimetry-photovisual (DSC-photovisual), coupled thermogravimetry-infrared spectroscopy (TG-FTIR) analyses, complexometric titranion with EDTA and elemental analysis, and also use of X-ray diffraction by the powder method and vibrational spectroscopy reflectance in the infrared Fourier transform spectroscopy (FTIR). The thermal analysis results provided information concerning the thermal stability, dehydration and the thermal behavior of the compounds and along with the compleximetric titration and elemental analysis, it was possible to determine the stoichiometry of the complex as [Ln(sulin)3]XH2O. The spectroscopic results suggest that the ligand sulindac coordinates through the carboxylate group to the metals as a bidentatebrinding ligand. Tests for cytotoxicity and anti-inflammatory activity of the synthesized compounds demonstrated tha the complexes in general have very similar behavior in comparison to the drug. However, the results suggest that [Gd(sluin)3] has potential for pharmacological improvement / Mestre

Made available in DSpace on 2016-01-13T13:27:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-07-28. Added 1 bitstream(s) on 2016-01-13T13:32:38Z : No. of bitstreams: 1 000855142.pdf: 2602801 bytes, checksum: 3d3b585e85a9cfc362e0b0d136af6d71 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A síntese e caracterização de complexos do fármaco anti-inflamatório não esteroide sulindaco (sulin) com os íons lantanídeos (Ln3+) La3+, Ce3+, Pr3+, Nd3+, Gd3+, Tb3+ e Ho3+ no estado sólido são descritas neste trabalho. A caracterização dos complexos foi realizada empregando a termogravimetria-calorimetria exploratória diferencial simultânea acoplada ao espectrômetro de FTIR (TG-DSC-FTIR), DSC-fotovisual, titulação complexométrica com EDTA e análise elementar, além de utilização de difração de raios X pelo método do pó e espectroscopia vibracional de refletância na região do infravermelho com transformada de Fourier (FTIR). Os métodos termoanalíticos foram utilizados para verificar a decomposição térmica, estabilidade térmica, entalpia de desidratação, entre outras propriedades e juntamente com a titulação complexométrica e a análise elementar, foi possível determinar a estequiometria dos complexos como [Ln(sulin)3]XH2O. Através do espectro de infravermelho pode-se sugerir que o sulindaco está coordenado aos íons lantanídeos de modo bidentado e em ponte pelo grupo carboxilato. Os testes de citotoxicidade e de atividades anti-inflamatória dos compostos sintetizados demonstraram que os complexos, em geral, possuem comportamento muito semelhante ao do fármaco. Contudo, os resultados, sugerem que complexo [Gd(sulin)3] apresenta potencial para um melhoramento farmacológico / Synthesis and characterization of complexes of the anti-inflammatory drug nonsteroidal sulindac (sulin) with the lanthanide ions (Ln3+) La3+, Ce3+, Pr3+, Nd3+, Gd3+, Tb3+ and Ho3+ in the solid state area described in this work. The characterization of the pharmaceutical and the complexes was performed using simultaneous thermogravimetry-differential scanning calorimetry (TG-DSC), differential scanning calorimetry-photovisual (DSC-photovisual), coupled thermogravimetry-infrared spectroscopy (TG-FTIR) analyses, complexometric titranion with EDTA and elemental analysis, and also use of X-ray diffraction by the powder method and vibrational spectroscopy reflectance in the infrared Fourier transform spectroscopy (FTIR). The thermal analysis results provided information concerning the thermal stability, dehydration and the thermal behavior of the compounds and along with the compleximetric titration and elemental analysis, it was possible to determine the stoichiometry of the complex as [Ln(sulin)3]XH2O. The spectroscopic results suggest that the ligand sulindac coordinates through the carboxylate group to the metals as a bidentatebrinding ligand. Tests for cytotoxicity and anti-inflammatory activity of the synthesized compounds demonstrated tha the complexes in general have very similar behavior in comparison to the drug. However, the results suggest that [Gd(sluin)3] has potential for pharmacological improvement / FAPESP: 13/04096-2

Nowadays the necessity for designing and synthesizing novel imaging agents increases rapidly. The long wavelength, and thus, low energy, of excitation and emission, and the good specificity and stability are examples of essential characteristics of ideal diagnostic and therapeutic agents. In this work, the synthesis and photophysical studies of metal complexes for biological applications were performed and evaluated, and it contained the development of (a) a porphyrin probe for imaging and treatment and (b) a tripodal thermal sensor for imaging. The research and study of the two cases of complex is analyzed in the second and third chapters, respectively, which follow the introduction or literature review to the diagnostic and/ or therapeutic agents which is given with examples in the first chapter. The scope of the main project, which is analysed in the second chapter, was the development and synthesis of a porphyrin-based bio-probe capable of bacterial fluorescence imaging. The porphyrin moiety of a complex is also able to generate singlet oxygen and this effect can be used for treatment purposes (PDT, Photodynamic Therapy). Thus, the complex can act as a diagnostic and therapeutic (anti-bacterial in this case) agent simultaneously. A probe with such a dual capability is known as theranostic agent. A theranostic agent is crucial for the enhancement and expansion of personalised medicine. The studies and physical measurements of the proposed, synthesised porphyrin complex have proved its capability to be used as a theranostic probe. Furthermore, after coupling the porphyrin moiety firstly with a small protein part (ampetoid: antimicrobial peptoid) and secondly with a radionuclide (Gallium-68), the in vitro and in vivo studies have to be performed. The aim of the project analysed in the third chapter was the development of a thermal sensor. Coordination of a tripodal ligand with a mixture of two lanthanides in various ratios was achieved and the photophysical measurements of the resulted complexes were evaluated. Lanthanide metals were chosen due to their unique photophysical properties that they offer when they are connected to an organic chomophoric ligand. Additionally, the preferred final luminophore product would obey a thermostable structure over a wide temperature range and it would be capable of effectively sensing the alterations in temperature. These properties were true for the ratio 99.5:0.5 for Terbium: Europium, and thus, the complex with such a consistency clarified the final product. Furthermore, the highly promising results after repeatedly photophysical (especially emission) measurements could conclude that the complex can be served as an ideal thermal sensor. Additional emission measurements at higher temperatures have to be done in order to confirm the ability of the proposed thermal sensor to be used for bio-imaging purposes. In conclusion, two-kind of metal complexes for biological applications were synthesized and their photophysical properties were assessed. Both the bulky porphyrin complex and the smaller tripodal ligand have shown promising results for their proposed applications. Of course, a more detailed assessment is required to verify their capability.

The ability of a deprotonated aza-crown ether to allow isolation of soluble lanthanide and yttrium complexes has been investigated. A convenient route to these complexes has been demonstrated by the protonolysis reactions of Ln[(N(SiMe₃)₂]₃ with 4,13-diaza-18-crown-6. NMR spectroscopy and X-ray crystallography revealed a C₂V structure consisting of a basket shaped geometry. The successful protonolysis route has been extended to the preparation of stable alkyls, dialkyls, and alkyl cations of yttrium and zirconium stabilized by deprotonated aza- crown macrocycles. A yttrium, alkyl complex containing deprotonated diaza-18-crown-6 has been prepared by the protonolysis route. The thermal stability and reactivity of this complex were investigated. This alkyl reacts with terminal alkynes to produce a complex equilibrium between the colourless monomeric and dimeric alkynides and a purple Z-butatrienediyl (ie.RC=C=C=CR²⁻) coupling product. NMR studies demonstrate that electron poor alkynes favour coupling and that the carbon-carbon double bond forming process is readily reversible at room temperature. The flexibility of the deprotonated diaza-crown ligand is apparent from the isolation of both cis and trans-zirconium dibenzyl complexes from the protonolysis of tetrabenzyl zirconium with 4,13-diaza-18-crown-6. The structure of both isomers were investigated by NMR spectroscopy and X-ray crystallography. Both the cis and trans-isomers cleanly converted to the stable cation either by protonolysis with [n-Bu₃NH]⁺[BPh₄]⁻ or by alkyl abstraction with B(C₆F₅)₃. The reactivity of the alkyl cation derived from the reaction with B(C₆F₅)₃ was investigated. The reaction of this cation with t-BuNC gave a vinylamide complex following a 1,2-proton rearrangement of an initially formed iminoacyl. Two members of the still rare yttrium dialkyl class of compounds were isolated using monoanionic, deprotonated aza-crown ethers as supporting ligation. The dialkyl complexes were synthesized by protonolysis of Y(CH₂SiMe₃)₃(THF)₂ with either aza-18-crown-6 or aza-15-crown-5. NMR and X-ray analyses of the yttrium dialkyl supported by aza-18-crown-6 indicates a trans-dialkyl geometry while NMR analysis of the aza-15-crown-5 analog indicates a cis-dialkyl geometry. Reaction of the trans-dialkyl complex with CO afforded a trans-dienolate complex formed by the migration of SiMe₃. Alkyl abstraction from the trans-dialkyl complex using B(C₆F₅)₃ allowed generation of the first yttrium, alkyl cation. / Graduate

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No description available.

Galactitol and cis,cis,cis-1,3,5-cyclohexanetriol are polyols that are ideal examples of model compounds for ligands with lanthanide ions as they have their hydroxyl groups in favourable steric arrangement. Several complexes were synthesised with both lanthanide chloride and lanthanide nitrate salts with galactitol, and a variety of structures, both polymeric and monomeric, were observed. In all these complexes, galactitol acted as a bridging molecule between the lanthanide ions. A notable difference was the lanthanum chloride–galactitol complex that showed both chloride and galactitol bridging. The lanthanide nitrate salts formed only polymeric complexes with galactitol. Not all of the complexes showed nitrate ions coordinated to the metal centre, and in the neodymium nitrate– galactitol complex, which shows both monodentate and bidentate coordination of the nitrate groups. The coordination of the nitrate ions was confirmed using both XRD and IR analysis. Two complexes with lanthanide chloride salts and cis,cis,cis-1,3,5-cyclohexanetriol were synthesised and analysed. Lanthanum chloride formed a polymeric complex, which showed extensive chloride bridging between the metal centres. Praseodymium chloride formed a dimeric complex. All complexes were analysed with single-crystal X-ray diffraction, 1H NMR, 13C NMR and IR spectroscopy.

No description available.

No description available.