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Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-15T13:39:52Z No. of bitstreams: 1 Mauro Gomes da Silva.pdf: 2235103 bytes, checksum: 2f7922e62d0e9e6cd2bbc309f61aa8f1 (MD5) / Made available in DSpace on 2017-02-15T13:39:52Z (GMT). No. of bitstreams: 1 Mauro Gomes da Silva.pdf: 2235103 bytes, checksum: 2f7922e62d0e9e6cd2bbc309f61aa8f1 (MD5) Previous issue date: 2012-03-14 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / In the present study ten 2,3-diyne-1,4-naphthoquinone derivatives were synthesized by Sonogashira coupling reaction between the 2,3-dibromo-1,4- naphthoquinone and several functionalized terminal alkynes using a catalytic complex of palladium (II) and CuI. Alkynes are among phenylacetylene, 1-ethyl-4- methoxybenzene, 2-methyl-3-butyn-2-ol, 1-ethynyl-1-cyclohexanol, 4-pentyn-2-ol, 4- pentyn-1-ol, 1-pentyne, 1-hexyne, 1-octyne and 1-decyne. The yields of products obtained ranged 15 to 55%. The enediynes having hydroxyl groups, in their structures such as 2,3-di(3-hydroxy-3-methylbut-1-yn-1-yl)-, 2,3-di[(1- hydroxycyclohexyl)ethynyl]- and 2,3-di(5-hydroxypent-1-yl)-1,4-naphthoquinone were subjected to acetylation reaction using acetic anhydride and montmorillonite clay K- 10 under sonication, thereby obtaining three new enediyne derivatives with yields ranging from 56 to 71%. The compounds were all characterized by 1H NMR and 13C NMR spectra, IR and MS-LC. These compounds containing the 1,4-naphthoquinone nucleus and acetylenic substituents in the quinonoid ring form a enediyne system (Z-3-ene-1,5-diyne) highly reactive, possibly subject to Bergman cycloaromatization, with potential antitumor activity. The enediynes underwent evaluation of the cytotoxic potential against three tumor cell lines, OVCAR-8 (ovarian adenocarcinoma - human), PC-3M (metastatic prostate cancer - human), NCI-H358M (bronchoalveolar lung carcinoma - human), presenting, in general, satisfactory results for inhibition of cell growth. The compound 2,3-di(3-hydroxy-3-methylbut-1-yn-yl)-1,4-naphthoquinone where said among the substances analyzed by presenting a lower IC50 (˂ 2 μg/mL) for three cell lines tested, which is characterized as a potent cytotoxic agent. / No presente trabalho foram obtidos dez derivados 2,3-diino-1,4- naftoquinonas, entre estes sete são inéditos na literatura, empregando a reação de acoplamento de Sonogashira entre o 2,3-dibromo-1,4-naftoquinona e diversos alquinos terminais funcionalizados, utilizando um complexo catalítico de paládio (II) e CuI. Entre os alquinos estão o fenilacetileno, o 4-metoxifenilacetileno, o 2-metil-3- butin-2-ol, o 1-etinil-1-cicloexanol, o 4-pentin-2-ol, o 4-pentin-1-ol, o 1-pentino, o 1- hexino, o 1-octino e o 1-decino. Os rendimentos dos produtos obtidos variaram entre 15-55%. Os enediinos que possuem grupos hidroxilas presentes em suas estruturas, como o 2,3-di(3-hidroxi-3-metilbut-1-in-il)-, o 2,3-di[(1-hidroxicicloexil)etinil]- e o 2,3- di(5-hidroxipent-1-il)-1,4-naftoquinona, foram submetidos à reação de acetilação utilizando anidrido acético e argila montmorillonita K-10 em ultrassom, obtendo assim, três novos derivados enediinos com rendimentos que variaram de 56-71%. Os compostos obtidos foram todos caracterizados por espectros de RMN 1H e RMN 13C, LC-MS e IV. Estes compostos contendo o núcleo 1,4-naftoquinona e substituintes acetilênicos no anel quinônico formam um sistema enediino (Z-3-eno-1,5-diino) altamente reativo, possivelmente sujeito a cicloaromatização de Bergman, com potencial atividade antitumoral. Os enediinos foram submetidos à avaliação do potencial citotóxico em três linhagens de células tumorais, OVCAR-8 (adenocarcinoma de ovário – humano), PC-3M (carcinoma de próstata metastático – humano), NCI-H358M (carcinoma bronquioalveolar de pulmão – humano, apresentando, no geral, resultados satisfatórios para inibição do crescimento celular. O composto 2,3-di(3-hidroxi-3-metilbut-1-in-1-il)-1,4-naftoquinona se destacou dentre as substâncias analisadas por apresentar menor CI50 (˂ 2 μg/mL) para as três linhagens de células testadas, o que o caracteriza como potente agente citotóxico.

<p>High resolution tandem mass spectrometry (MSⁿ) coupled with various separation techniques, such as high-performance liquid chromatography (HPLC) and gas chromatography (GC), is widely used to analyze mixtures of unknown organic compounds. In a mass spectrometric analysis, analytes of interest are at first transferred into the gas phase, ionized (protonated or deprotonated) and introduced into the instrument. Tandem mass spectrometric experiments may then be used to gain insights into structure and reactivity of the analyte ions in the gas phase. The tandem mass spectral data are often compared to those reported in external databases. However, the tandem mass spectra obtained for protonated analytes may be markedly different from those in external databases because protonation site manifested during a mass spectrometric experiment can be affected by the ionization technique, ionization solvents and condition of the ion source. This thesis focuses on investigating the effects of instrumental conditions and analyte concentrations on the protonation sites of 4-aminobenzoic acid. Reactivities of radical species were also investigated. A modified bracketing method was developed and proton affinities of a series of mono- and biradicals of pyridine were measured. In another study, a <i>para</i>-benzyne analog was generated in both solution and the gas phase and its reactivities towards various neutral reagents in the gas phase were compared to those in solution.</p> <p> Chapter 2 discusses the fundamental aspects of the instruments used in this research. In chapter 3, the effects of residual moisture in linear quadrupole ion trap on the protonation sites of 4-aminobenzoic acid are considered. Chapter 4 focuses on the use of gas-phase ion-molecule reactions with trimethoxymethylsilane (TMMS) for the identification of the protonation sites of 4-aminobenzoic acid. Further, the effects of analyte concentration on the protonation sites of 4-aminobenzoic acid are considered. Chapter 5 introduces a modified bracketing method for the experimental determination of proton affinities of a series of pyridine-based mono- and biradicals. In chapter 6, successful generation of <i>para</i>-benzynes in solution is discussed. The reactivity of a <i>para</i>-benzyne analog, 1,4-didehydrophenazine, is compared to its reactivity in the gas phase.</p>