Submitted by Beatriz Aline Riga null (beatriz_aline16@hotmail.com) on 2017-03-15T18:07:31Z No. of bitstreams: 1 Riga Rocha, B. A._me_sjrp.pdf: 4397938 bytes, checksum: 97cd69af09e5df0e1dcc372a541946c2 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2017-03-21T16:17:50Z (GMT) No. of bitstreams: 1 rocha_bar_me_sjrp.pdf: 4397938 bytes, checksum: 97cd69af09e5df0e1dcc372a541946c2 (MD5) / Made available in DSpace on 2017-03-21T16:17:50Z (GMT). No. of bitstreams: 1 rocha_bar_me_sjrp.pdf: 4397938 bytes, checksum: 97cd69af09e5df0e1dcc372a541946c2 (MD5) Previous issue date: 2017-02-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Neste trabalho objetivou-se a síntese e caracterização de oito complexos de cobalto(II) que fossem aptos a atuarem como agentes controladores na Polimerização Radicalar Mediada por Cobalto do monômero acetato de vinila. Através da modulação da esfera de coordenação destes complexos com a alteração dos efeitos estéricos e eletrônicos promovidos pela coordenação de ligantes α-diiminas, buscou-se estabelecer parâmetros para propor a forma como estes complexos mediam a CMRP do referido monômero. Os complexos foram divididos em dois grupos, objetivando uma avaliação mais eficiente da forma como os efeitos estéricos e eletrônicos interferem na capacidade controladora dos mesmos. Após a variação sistemática das proporções molares entre complexo, iniciador e monômero encontrou-se na proporção [Co]/[AIBN]/[VAc] = 1/3,25/542 os resultados mais satisfatórios deste trabalho. O uso de DMSO fora prejudicial para os complexos 2a-c, porém fez com que os complexos 2d-h apresentassem melhorias, reduzindo seus valores de polidispersidade e aumentando as massas moleculares dos polímeros. O complexo 2b fora escolhido como o melhor controlador do grupo do efeito estérico, por reunir em si as características estérias e eletrônicas que o fizeram apresentar os menores valores de polidispersidade (Đmáx = 1,43). Com relação ao grupo de complexos do efeito eletrônico, fora o complexo 2f que, devido à maior estabilidade estrutural conferida ao complexo por seu substituinte cicloexil, apresentara as menores polidispersidades de seu grupo, entre 1,12 e 1,58. / This work aimed the synthesis and characterization of eight cobalt(II) complexes which could be able to act as controlling agents in vinyl acetate radical polymerization mediated by cobalt. By modulating the coordination sphere of these complexes, modifying the steric and electronic effects offered by the α-diimine ligands, we sought to establish parameters to propose how these complexes mediate the CMRP of vinyl acetate. The complexes were split in two groups in way to assess efficiently how the electronic and steric effects can affect the controlling capacity of the CoII(α-diimine).A systematic variation of the molar ratio such as [Co]/[initiator] and [Co]/[monomer] made it possible to choose [Co]/[initiator]/[monomer] = 1/3.25/542 as the ratio that provided certain level of control. The addition of DMSO was detrimental to the complexes 2a-c, but caused an improvement to the activity of complexes 2dh, reducing their polydispersity values and increasing the molecular weights of the polymers. Complex 2b was chosen as the best controller of the steric effect group, its steric and electronic characteristics made possible to reach the lowest polydispersity of its group (Đmax = 1.43).Regarding to the group of complexes of the electronic effect, it was the complex 2f that had the smallest polydispersity of its group, between 1.12 and 1.58, due to the greater structural stability conferred to the complex by its cyclohexyl substituent.

Photodynamic therapy (PDT) is a non-invasive treatment of cancer with an advantage of having localized photo-activation of the drug at the targeted tumor cells leaving the healthy cells unaffected by the photo-toxicity of the PDT agent. Organic molecules and 4d/5d metal complexes have been extensively studied for their DNA cleavage activity and photo-cytotoxicity in UV and/or visible light. The photoactivity of the current PDT drugs is due to reactive singlet oxygen species. To address the hypoxic nature within neoplasia and to get a realistic scenario to build model and potent PDT agents, attempts have been made in this thesis work to design and synthesize new cobalt and copper complexes having a variety of ancillary ligands and planar phenanthroline bases showing efficient visible light-induced anaerobic plasmid DNA cleavage activity. The disulfide and thiol compounds are known to generate thyil radical in anaerobic medium in presence of some electron donating solvent. To exploit this chemistry of the sulfur anion radical as a reactive species damaging DNA under light irradiation, we have prepared copper(II) complexes of bis(2-hydroxybenzylamino-ethyl)disulfide and D-penicillaminedisulfide and characterized. The complexes are moderate binders to calf thymus DNA and exhibit plasmid DNA cleavage activity in red light. Near-IR light-induced double-strand DNA cleavage activity is observed for the complexes having 3,3' -dithiodipropionic acid and phenanthroline bases. These complexes show lethal double strand breaks in SC DNA responsible for the inhibition in DNA repair mechanism in the cells thus becoming potent candidates as transcription inhibitors. The work has been extended to achieve better visible light-induced plasmid DNA cleavage activity and UV light-induced photocytotoxicity using a more bio-compatible metal ion, viz. cobalt(II) with the same ligand system and enhancement in the photocytotoxicity is observed. To investigate the role of the disulfide ancillary ligands, complexes of salicylideneaminothiophenol bound to the copper(II) are prepared and the complexes show significant plasmid DNA cleavage activity in red light. Finally, ternary cobalt(III) phenanthroline base complexes are prepared to study their DNA cleavage activity in red light and photo-cytotoxicity in UV light. The complexes show efficient plasmid DNA cleavage activity in red light, significant cytotoxicity in UV light, low dark cytotoxicity, and protein (BSA, lysozyme) cleavage activity in UV light. The mechanistic aspects of the photo-induced DNA and protein cleavage activity of the complexes have been studied. A dual involvement of the charge transfer and d-d band is observed in the photosensitization process leading to generation of reactive oxygen species. In summary, the thesis work presents cobalt and copper complexes having thiolate and disulfide moieties that are designed and synthesized as new photodynamic therapeutic agents showing anaerobic DNA cleavage activity in red light and photocytotoxicity. The present study opens up new strategies for designing and developing cobalt and copper based photosensitizers for their potential photochemotherapeutic applications under hypoxic reaction conditions. References: Lahiri, D. et al., J Chern. Sci, 2010, 122, 321-333; Inorg. Chern., 2009, 48, 339-349; Dalton Trans. 2010,39,1807-1816; Polyhedron, 2010, 29, 2417-2425.