Ultrasonic humidifiers use sound vibrations at frequencies higher than can be heard by humans (> 20,000 Hz) to generate aerosolized water also have potential for inducing sonochemical reactions for chemicals present in water. This research focuses on examining oxidants formed within ultrasonic humidifiers, as well as the oxidants effects of contaminants in water used in the systems. Hydroxyl radicals were found using DMPO as a spin trap. Caffeine and 17β-estradiol, as pharmaceutical contaminants of drinking water, were both emitted from the humidifier when present in the water reservoir and would enter breathing air. Emitted 17β-estradiol was found at 60% of the initial concentration filled in the ultrasonic humidifier after 480 minutes. Caffeine exhibited less degradation than 17β-estradiol. Degradation of both pharmaceuticals was attributed to ultrasonic processes, most likely oxidation with hydroxyl radicals produced. Bromide as a contaminant of the fill water was found to remain constant over time. / MS / Ultrasonic humidifiers carry health benefits from humidified air, but also have potential for chemical reactions within the systems that can impact human health. This research focuses on examining oxidants formed in ultrasonic humidifiers, as well as the degradation of contaminants in water used in the ultrasonic humidifiers. Hydroxyl radicals were found to be generated within the humidifier system. Caffeine and 17β-estradiol, a common estrogen, are possible contaminants in drinking water, which may be used to fill a humidifier. Both were introduced and emitted from the ultrasonic humidifier. Emitted 17β-estradiol was found at 60% of the initial concentration filled in the ultrasonic humidifier at the start of 8 hours. Degradation of both pharmaceuticals was attributed to ultrasonic processes, most likely oxidation with hydroxyl radicals produced.

L'élaboration de squelettes de pipéridinones et lactones a été accomplie de manière très efficace en alliant processus radicalaires et ioniques. La synthèse d'oximes SEM-protégées par un assemblage multicomposant radicalaire permet, après hydrolyse de la fonction oxime, d'obtenir rapidement un aldéhyde fonctionnalisé. Ce composé est ensuite transformé en lactone ou pipéridinone désirée par un processus ionique.Une approche minimisant le nombre d'étapes élémentaires a été développée autorisant ainsi un accès rapide et convenable à une grande diversité de structures. Ces processus peuvent impliquer jusqu'à cinq composants. / The construction of piperidinone and lactone scaffolds has been performed efficiently, combining radical and ionic processes. The synthesis of SEM-protected oximes by a multicomponent radical reaction enables, after hydrolysis of the oxime functional group, the access to a functionalized aldehyde. This compound is then converted into a lactone or a piperidinone by a ionic process.An approach minimizing the number of steps has been developed, thus allowing a rapid and convenient access to a large diversity of structures. These processes may involve up to five components.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Neveu du député Alphonse Baudin tué sur les barricades le 3 décembre 1851, Pierre Baudin (1863-1917) est un homme politique de la Troisième République insuffisamment reconnu aujourd’hui. Élu radical-socialiste au Conseil municipal de Paris en 1890, il y accomplit un parcours exemplaire au service de la défense des Droits de Paris. Rapporteur général du Budget pendant trois ans, il devient viceprésident du Conseil en 1895 et président en 1896, à moins de 33 ans. Député dès 1898, il est nommé, l’année suivante, à 36 ans, à peine, ministre des Travaux publics du cabinet Waldeck-Rousseau, le seul de son groupe politique. Il opte, en 1900, pendant son ministère, pour le siège de Belley, abandonnant le 11e arrondissement de la capitale. Dissident du combisme, il doit lutter contre les radicaux orthodoxes de son département pendant la période 1903-1905. Réélu aisément à la Chambre, en 1902 et 1906, il poursuit une belle carrière de journaliste entamée en 1890. Président de l’association des journalistes sportifs, en 1905, vice-président, en 1907, de l’association des journalistes parisiens (dont il sera l’éphémère président en 1915), administrateur hors pair, il est rapporteur général du budget à la Chambre en 1905 et 1906. P. Baudin est également un homme d’affaires à partir de 1906, en devenant - pendant un an - président de la banque franco-américaine et de la Société internationale des Écoles Berlitz de 1907 à 1913. Sénateur de l’Ain, en 1909, devenu briandiste, il est nommé, en 1910, ambassadeur extraordinaire en Argentine. De retour au Palais du Luxembourg, il se montre d’une rare activité, rapportant d’importants dossiers de politique étrangère notamment. Ministre de la Marine en 1913, il conduit, en 1915, une mission de propagande en Amérique latine. Patriote exigeant, il a dénoncé inlassablement la menace allemande jusqu’à son décès, par maladie, en 1917. / Pierre Baudin (1863-1917), was the nephew of Alphonse Baudin, a Deputy killed on the barricades on December 3rd 1851, and a French statesman. Although a popular political figure of the Third Republic, Pierre Baudin has not been given sufficient recognition today. As a radical-socialist, he was elected to the Paris Municipal Council in 1890. There, he defended, with remarkable skills, the Rights of the City of Paris. After serving as a General Budget Reporter for three years, he was elected Vice-President of the Council in 1895 and subsequently elected President, before the age of 33, in 1896. He entered the chamber as Deputy as early as 1898, and, as the only member of his party, he was appointed the following year, at the age of 36, Minister of Public Works in the Waldeck-Rousseau cabinet. During his ministry, he chose to relinquish Paris’s eleventh arrondissement and run for office in Belley. A dissident of the Combiste movement, he had to oppose the orthodox radicals in his département from 1903 to 1905. He was easily re-elected to the chamber in 1902 and 1906, however, and he was even able to pursue the career of a journalist that he had launched successfully in 1890. He was elected President of the French Association of Sports Journalists in 1905 and subsequently elected Vice-President of the Association of Parisian Journalists in 1907, which he briefly chaired in 1915, and as an administrator beyond compare, he was appointed General Budget Reporter at the chamber in 1905 and 1906. He also established himself as a businessman from 1906, becoming [the first] President of the French-American bank, but only for a year, and President of the International Society of the Berlitz schools from 1907 to 1913. Turned Briandiste, he was elected to the senate by the département of Ain in 1909, and, in 1910, he was appointed Ambassador Extraordinary in Argentina. Upon his return to the Palais du Luxembourg, he was very active in contributing key reports on foreign affairs to the senate. He was appointed Minister of Marine in 1913 and was charged with a propaganda mission in Latin America in 1915. A relentless patriot, Baudin never stopped warning his contemporaries against the German threat until his death, due to a serious illness, in 1917.

Ces dernières années, de plus en plus de composés organiques réfractaires et toxiques ont été détectés dans les eaux usées. Un bon nombre de ces polluants organiques sont difficilement dégradés par des traitements classiques. Les procédés d’oxydation avancée à base de radicaux sulfates (SR-AOP) sont apparus comme une méthode innovante dans le domaine de la décontamination oxydative des eaux polluées. Des études antérieures ont porté sur ces SR-AOP utilisant du peroxodisulfate (PS) ou du peroxomonosulfate (PMS) comme oxydants, en particulier des couples «métaux de transition et oxydants» (systèmes Fe (II)/PS, systèmes Ni(II)/PMS et Co (II))/PMS), où il a été confirmé que SO4•-·présentent des avantages (sélectivité) par rapport au radical hydroxyle (HO•) pour la décontamination des eaux usées contenant des polluants organiques.Dans cette thèse, nous avons généré des radicaux tels que le radical sulfite SO3•-, le radical sulfate SO4•-, le radical peroxomonosulfate SO5•- à partir d’ions métalliques (Cr(VI), le Co(II), le Fe(III)) capables d’activer le sulfite pour la dégradation des composés organiques. L'efficacité d'élimination et le mécanisme d'oxydation ont été étudiés et le rôle des espèces soufrées a été élucidé. / In recent years, more and more refractory and toxic organic compounds are detected in wastewater. Many of these organic pollutants can hardly be degraded by conventional water treatments. Sulfate radical based advanced oxidation process (SR-AOPs), have emerged as a promising method in the field of oxidative decontamination of polluted water. Past studies focused on this SR-AOPs with peroxydisulfate (PS) or peroxymonosulfate (PMS) as oxidants, especially the ‘transition metal + oxidants’ (i.e. Fe(II)/PS system, Ni(II)/PMS system and Co(II)/PMS system), which has been confirmed that SO4·− has advantages over HO in the decontamination of wastewater containing organic pollutants. In this PhD thesis, oxysulfur radicals including sulfite radical SO3·−, sulfate radical SO4·−, peroxymonosulfate radical SO5·− produced by transition metal ions such as Cr(VI), Co(II), Fe(III) activated sulfite were used to degrade organic compounds. The removal efficiency, the oxidation mechanism were examined, and and the role of sulfur species were elucidated.

O presente trabalho é fruto de um percurso teórico que teve como objetivo buscar aproximações e realizar um diálogo entre Construtivismo Semiótico-Cultural e Esquizoanálise. Fazendo uso da noção de multiplicação dialógica, Guimarães (2010), verifiquei a possibilidade de acessar o campo intensivo/relacional denominado empirismo radical pelo campo do construtivista semiótico-cultural em Psicologia, e plano de imanência pelo campo esquizoanalítico. Ao fazê-lo, busquei viabilizar um diálogo a partir de uma tênue superfície de contato entre os diferentes campos de conhecimento. As noções de sistema semiaberto e rizoma e seu funcionamento em rede foram os propulsores desta pesquisa. Parti do dialogismo teórico-metodológico desenvolvido Marková (2003) colocando Construtivismo Semiótico-Cultural, Esquizoanálise e pesquisador nas posições de Ego-Alter-Objeto, respectivamente. Tal proposta direcionava-se para um árduo trabalho de construção de uma ponte entre os distintos posicionamentos de cada campo de conhecimento. Por outro lado fiz uma opção metodológica que permitisse buscar regiões de tensão entre as áreas sem a intensão de construir uma ponte entre elas. Tomando a metáfora trazida por Bruno Latour (2008), segundo a qual processos de construção de conhecimento podem se assemelhar ao trânsito sobre um rio, elaborei uma explanação sobre os campos de conhecimento. Uma das margens do rio correspondeu ao Construtivismo Semiótico-Cultural em Psicologia, e a outra margem à Esquizoanálise. Na primeira das margens, busquei apresentar dimensões da especificidade humana do Construtivismo Semiótico-Cultural nos campos dos construtivismos em psicologia explorando as noções de sistema semiaberto, self, subjetividade, cultura e construção social da realidade. Na segunda margem, me dirigi para as noções da filosofia da diferença, rizoma e subjetividade como multiplicidade. Adicionalmente explorei filósofos historicamente abordados por cada uma das margens, Leibniz, Hume, Bergson, para em seguida encontrar uma superfície de contato, que identifiquei como empirismo radical, construtivismo, e como plano de imanência, Esquizoanálise. A superfície de contato identificada possui como característica ser um campo relacional pré-pessoal que cria realidade por meio do entrelaçamento dos mais diversos elementos e de onde emergem as várias possibilidades de subjetividade e de mundo. A característica de entrelaçamento, como um tear que produz um tecido é encontrada tanto no pensamento de James, uma das bases do Construtivismo Semiótico-Cultural, como nas proposições de Deleuze e Guattari fundadores da Esquizoanálise. Encontrar essa superfície possibilitou a conclusão deste trabalho, embora considere que maiores aprofundamentos possam ser feitos no futuro, articulando outros aspectos histórico-filosóficos pertencentes a ambas as áreas de conhecimento e suas implicações para o avanço da noção de multiplicação dialógica, dentre outras noções fundamentais no campo da psicologia cultural / This work is the result of a theoretical course which aimed to seek approaches and achieve a dialogue between Semiotic-Cultural Constuctivism and Schizoanalysis. Making use of the notion of dialogic multiplication, Guimarães (2010) checked the possibility to access intensive / relational field called radical empiricism by the field of cultural-semiotic constructivism in psychology and immanence plane by equizoanalitic field. In doing so, I sought facilitate a dialogue from a tenuous contact surface between the different fields of knowledge. The notions of open ended system and rhizome and yours networking were the thrusters of this research. Go away from theorical-methodological dialogismo developed by Marková (2003) putting Semiotic-Cultural Constructivism, Schizoanalysis and researcher in positions Ego-Alter-Object respectively. Such a proposal directed to hard work of building a bridge between the different positions of each field of knowledge. On the other hand made a methodological option that allows searching regions of tension between the areas without the intention to build a bridge between them. Taking the metaphor brought by Bruno Latour (2008), whereby processes of knowledge building may resemble traffic over a river, elaborated an explanation of the fields of knowledge. A river banks corresponded to Semiotic-Cultural Constructivism in Psychology, and the other side to Schizoanalysis. At first the banks, sought to present dimensions of human specificity of Constructivist Semiotic-Cultural Constructivism in constructivism fields of psychology exploring the notions of openended system, self, subjectivity, culture and social construction of reality. In the second bank, I headed to the notions of philosophy of difference, rhizome and subjectivity as multiplicity Additionally philosophers explored historically addressed by each of the banks, Leibniz, Hume, Bergson, to then find a contact surface, which identified as radical empiricism, constructivism, and as the plane of immanence, Schizoanalysis. The surface contact has identified as being characteristic of a pre-personal relational field that creates reality through the interweaving of diverse elements which emerge and the various possibilities of subjectivity and world. The feature of entanglement, as a loom which produces a tissue is found both in the thought of James, one of the bases of Semiotic-Cultural Constructivism, as the propositions of Deleuze and Guattari founders of Schizoanalysis. Find the surface enabled the completion of this work, but believes that further insights can be made in the future, articulating other historical and philosophical aspects pertaining to both areas of knowledge and its implications for the development of the notion of dialogic multiplication, among other fundamental notions in field of psychology culture

INTRODUÇÃO: O câncer de próstata é responsável por 15% dos casos novos de câncer que acometem os homens e pela 5ª causa de morte. As técnicas minimamente invasivas, sobretudo a cirurgia robótica tornou-se a técnica comumente empregada nos Estados Unidos. Muitos artigos tentam demonstrar a curva de aprendizado necessária para a estabilização dos resultados, mas a implementação de novas tecnologias passa por diversos desafios, além da avaliação de seus resultados e dos custos, o que em países em desenvolvimento pode ter um importante impacto no sistema de saúde. OBJETIVO: Avaliar a curva de aprendizado da prostatectomia radical laparoscópica robótica assistida (PRRA) para o tratamento do câncer de próstata, de acordo com a continência urinária, a potência sexual, o tempo cirúrgico e o controle oncológico. MÉTODOS: Duzentos pacientes com neoplasia de próstata localizada submetidos à PRRA por um único cirurgião foram divididos em quatro grupos de acordo com a sequência das cirurgias. Foram avaliados os dados intra-operatórios, como: tempo cirúrgico, perda sanguínea estimada e as margens cirúrgicas. Também durante o pósoperatório foram avaliadas a potência (IIEF) e a continência (ICIQ). RESULTADOS: Os pacientes apresentaram idade média de 60,6 anos (59,72-61,61), volume prostático ao toque retal de 40 gramas e valor do PSA 6,95 ng/ml (5,79-8,10) semelhantes em todos os grupos (p > 0,05). A biópsia prostática pré-operatória mostrou diferença no escore de Gleason e no tamanho da próstata, sendo que o escore 6 foi menos frequente no grupo 4, representado por 23 pacientes (46%) e no grupo 1, com 39 pacientes (78%) (p < 0,01). Já o tamanho prostático avaliado pelo USTR foi de 39,6 gramas (29,75-48,7) no grupo 4 e 30,5 gramas (23,0-38,15) no grupo 2. A curva de aprendizado estabelecida demonstrou uma diminuição no tempo cirúrgico de 157 minutos (145-170) no grupo 1, para 132 minutos (119-140) no grupo 2 (p < 0,01). A perda sanguínea estimada também se reduziu aproximadamente pela metade: de 395 ml (250-500) no grupo 1, para 200 ml (150-250) no grupo 3 (p < 0,01). As margens positivas reduziram de 16% para apenas 8%, mas se mostraram estatisticamente semelhantes (p=0,236). A capacidade de penetração com doze meses praticamente dobrou de 38% (19 pacientes) no grupo 1 para 80% (40 pacientes) no grupo 4 (p=0,003). A continência avaliada com um ano mostrou-se melhor no grupo 4 (98%) quando comparado aos pacientes do grupo 1 (94%) (p=0,001). As complicações foram estatisticamente semelhantes entre os quatro grupos (p = 0,668). A análise da recidiva bioquímica não demonstrou diferença (p > 0,05). CONCLUSÕES: A curva de aprendizado da PRRA é variável de acordo com o parâmetro a ser avaliado, e apesar do equipamento e da tecnologia, à medida que se aumenta a experiência do cirurgião, melhores resultados são obtidos. O tempo de cirurgia e o sangramento estabilizaram-se, respectivamente, após 50 e 100 PRRA. A potência e a continência, por sua vez, estabilizaram-se após 150 PRRA. É importante ressaltar que o controle oncológico necessita de um período de acompanhamento mais longo para ser avaliado / BACKGROUND: Prostate cancer is responsible for 15% of new cases of male cancer and is the fifth leading cause of death. Minimally invasive and mainly, robotic surgery technique became the technique most widely utilized in the United States. Many articles have tried to demonstrate the required learning curve to achieve the plateau. Although, new techniques implementation go through many challenges besides the evaluation of its results, costs also became an issue, which may impact in developing countries health system. OBJECTIVE: We aim to evaluate the learning curve of robot-assisted radical prostatectomy (RARP) for the treatment of prostate cancer, according to continence, potency, surgical time and oncologic control. METHODS: Two hundred patients with localized prostate cancer that underwent RARP by a single surgeon were divided into four groups according to its surgical sequence. Intraoperative data, such as surgical time, estimated blood loss and margins were recorded. Also postoperative functional parameters as continence and potency were gathered using validated questionnaires (ICIQ and IIEF). RESULTS: Patients mean age were 60.6 years (59.72- 61.61), mean prostate volume at digital rectal examination was 40 grams and PSA value 6.95 ng/ml (5.79-8.10) were similar in all groups (p > 0.05). Pre-operative prostate biopsy showed difference in Gleason score and prostate size. Gleason score 6 was less frequent in group 4, 23 patients (46%), than group 1, 39 patients (78%)(p <0.01) and prostate size at TRUS was 39.6 grams (29.75- 48.7) in group 4 and 30.5 grams (23.0- 38.15) in group 2. The established learning curve showed a reduction on surgical time from 157 minutes (145-170) in group 1 to 132 minutes (119-140 min) in group 2 (p < 0.01). The estimated blood loss also decreased almost to half, from 395 ml (250-500) in group 1 to 200 ml (150-250) in group 3 (p < 0.01). Positive margins decreased from 16% to only 8 %, but were statistically similar (p=0.236). Nineteen patients (38%) could have sexual intercourse at an year after the surgery, in the first group but latest, in the fouth group, it doubled to 40 patients (80%) (p=0.003). Also continence improved in group 4(98%) when compared with group 1 (94%) (p=0.001). Complications were similar between groups (p=0.668). Biochemical recurrence also showed no difference (p > 0.05). CONCLUSIONS: Therefore, the learning curve of the RARP is variable according to the evaluated parameter and obviously, despite the equipment and technology, the increase of surgical experience the best the outcome. Surgery time plateau were achieved at 50 RARP, estimated blood loss stabilized after 100 surgeries, sexual function and urinary continence after 150 RARP. Cancer control requires a longer follow-up period for review

N,N,N\',N \'-tetrametil-p-fenilenodiamina (TMPD) catalisa a autoxidação de coenzimas piridínicos (NADH, NADPH) e modelos (ClBCH ,ClPCH ) ao cátion piridínico com rendimentos de 80-100%. A velocidade destas reações mostrou dependência de primeira ordem com respeito à concentração da 1,4-dihidronicotinamida e de meia ordem em relação às concentrações de O2 e TMPD. Estes dados cinéticos e testes com captadores de ion superóxido e superóxido dismutase indicam que os radicais HO&#8226;2 oriundos da autoxidação lenta do TMPD promovem a oxidação da dihidronicotinamida numa reação em cadeia; no término os radicais HO&#8226;2 se aniquilam por dismutação. O mecanismo proposto também é confirmado (1º) pela razão kC-H/kC-D=2,3 quando se substitui um dos hidrogênios do C4 de ClBCH por deutério, (2º) pelas idênticas velocidades iniciais em H2O e D2O, (3º) pelo valor da Ea = 10 kcal/mol na autoxidação do NADH e (4º) pelo aumento da velocidade de pH = 7,8 a pH 6,5. TMPD também promove a autoxidação do derivado 5, 6-hidratado (PHTN) da dihidronicotinamida ao cátion piridínico (ClPC+) apenas de fosfato ou arsenato estão presentes. O ClPC+ nã o se forma a partir do ClPCH em equilíbrio com o PHTN. Muito provavelmente se forma a partir do intermediário fosforilado no C6 por oxidação no C4 seguida de eliminação de fosfato. Quando PHTN e ClPCH foram oxidados pelo sistema O2/TMPD na presença de fosfato de piridínio ou de tetra-n-butilamônio em meio piridínico houve formação de pirofosfato, isolado por cromatografia de papel e por resina de troca aniônica. Adicionando-se ADP de tetra-n-butilamôneo ao sistema, constatou-se a formação de pirofosfato e de ATP com rendimentos mínimos de 5% e 3% , respectivamente. Por outro lado se a mistura de reação contém AMP de tetra-n-butilamôneo pôde-se verificar a formação de pirofosfato, ADP e ATP com rendimento total de 28% de \"ligações ricas\". A reação estudada foi proposta como modelo para síntese de ATP no sítio I da cadeia respiratória. / N,N,N\',N\'-tetramethyl-p-phenylenediamine (TMPD) catalyses the autoxidation of the pyridine coenzymes and of their models to the pyridinium form (80-100% yields). The first arder dependence of the rate upon the dihidronicotinamide concentration and half order upon both the O2 and TMPD concentrations, indicates that the relatively slow autoxidation of TMPD is the source of free radicals: dihydronicotinamide autoxidizes by the HO&#8226;2 chain mechanism and in the termination step the HO&#8226;2 radicals decay by dismutation. Such a mechanis is also supported by the inhibitory effects of cathecol, a scavenger of the HO&#8226;2 radical, and of superoxide dismutase, an enzyme which accelerates the dismutation of the O-2/ HO&#8226;2 species. The mecanism is further supported by (1) kC-H/kC-D=2,3 for substitution in 1-benzyl-1,4-dihydronicotinamide (ClBCH), (2) identical rates in H2O and D2O buffers, (3) Ea = 10 kcal/mole in the autoxidation of NADH and (4) the increase in rate from pH 7,8 to 6,5. TMPD promotes also the autoxidation of 1-n-propyl-6-hydroxy-1,4,5,6 - tetrahydronicotinamide (PHTN) to the 1-propyl-3-carboxamidopyridinium cation (ClPC+) provided phosphate ar arsenate are present. ClPC+ originates not from 1-n-propyl-1,4-dihydronicotinamide (ClPCH) in equilibrium with PHTN but most certainly from a C6 phosphorylated intermediate by oxidation at C4 and loss of phosphate. When PHTN an ClPCH were oxidated by the system O2/TMPD in the presence of pyridinium phosphate or tetra-n-butylammonium phosphate in pyridineas solvent, formation of pyrophosphate occurred. Pyrophosphate was isolated and identified by paper and ionic exchange resin chromatography. If tetra-n-butylammonium ADP is also present in the system, one can observe the formation of both pyrophosphate and ATP (5% and 3% minimum yields, respectively). In the presence of tetra-n-butylammonium AMP there, formation of pyrofosphate, ADP and ATP occurs. The total yield of energy rich bond is 28%. We suggest that the reaction is a model for the generation of the first ATP in the respiratory chain.

Peroxinitrito é um potente agente oxidante, nitrante e nucleofilico formado in vivo pela reação difusional do radical ânion superóxido com óxido nítrico, cuja produção exacerbada em situações de estresse oxidativo e nitrosativo pode resultar em danos a biomoléculas e estruturas sub-celulares. Por outro lado, vários compostos carbonílicos reativos tais como acroleína e compostos &#945;-dicarbonílicos são descritos como citotóxicos e genotóxicos, pois reagem com biomoléculas aminadas resultando em perda de funções nativas, situação esta denominada de \"estresse carbonílico\". Dentre os metabólitos &#945;-dicarbonílicos, altamente suscetíveis a adições nucleofílicas, destacam-se o biacetilo, derivado do metabolismo hepático de etanol e contaminante de alimentos, e metilglioxal e glioxal, ambos catabólitos de glicose, proteínas e lipídios acumulados em doenças relacionadas ao envelhecimento. Neste trabalho, observou-se que, em tampão fosfato normalmente aerado de pH próximo à neutralidade, (i) estes três compostos sofrem adição nucleofílica de peroxinitrito com constantes de velocidade de segunda ordem uma a três ordens de grandeza acima dos valores relatados para compostos monocarbonílicos (k2 &#8776; 4-100 M-1s-1); (ii) os sistemas biacetilo ou metilglioxal/peroxinitrito consomem o oxigênio dissolvido com produção de acetato ou acetato e formiato, respectivamente, via radical acetila capaz de acetilar histidina, lisina e 2\'-desoxiguanosina se adicionados à mistura reacional; e (iii) o sistema glioxal/peroxinitrito gera sucessivamente radical formila e radical formilhidroperoxila, cujo desproporcionamento a formiato e gás carbônico é acompanhado da emissão de luz no infra-vermelho próximo (&#955;max = 1270 nm), atribuída a oxigênio molecular no estado singlete (O21&#916;g) (Reação de Russell). Estes estudos evidenciam que a reação de metabólitos &#945;-dicarbonílicos com peroxinitrito gera radicais livres e embasam a hipótese de que possam contribuir para a acetilação radicalar, não-enzimática intracelular, de proteínas (epigenética) e DNA, portanto potencialmente implicadas na fisiologia e patologia do envelhecimento e desordens metabólicas, nas quais a participação de espécies reativas de oxigênio, nitrogênio e compostos carbonílicos foi relatada. Deve-se ainda notar que a descoberta de acetilação radicalar de biomoléculas por metabólitos &#945;-dicarbonilicos e peroxinitrito prepara o caminho para a identificação de novas reações químicas de biomoléculas, não catalisadas por enzimas, que possam eventualmente revelar novos biomarcadores teciduais em doenças adquiridas e inatas. / Peroxynitrite is a strong biological oxidant, nitrating and nucleophilic agent, formed by the diffusion-controlled reaction of the superoxide anion radical with nitric oxide, whose exacerbated production in oxidative and nitrosative stress leads to chemical damage to biomolecules and sub-cellular structures. On the other hand, various reactive carbonyl compounds like acrolein and &#945;-dicarbonyls are reportedly cytotoxic and genotoxic for their ability to react with amino biomolecules resulting in loss of native functions, a situation named \"carbonyl stress\". Among very reactive &#945;-dicarbonyls highly prone to nucleophilic additions, we highlight biacetyl, a hepatic alcohol metabolite and food contaminant, and methylglyoxal and glyoxal, both catabolites of glucose, proteins and lipids that accumulate in ageing-related disorders. Here, we report that, in normally aerated phosphate buffer near the physiological pH, (i) these three dicarbonyls undergo nucleophilic addition of peroxynitrite whose second order rate constants are one to three orders of magnitude than those documented for monocarbonyls (k2 &#8776; 4-100 M-1s-1); (ii) the biacetyl or methylglyoxal/peroxynitrite systems consume the dissolved oxygen yielding the acetate anion or acetate plus formate anion, respectively, from acetyl radical intermediate which was found to acetylate added histidine, lysine and 2\'-deoxyguanosine; and (iii) the glyoxal/peroxynitrite system ultimately generate formyl radical and formylperoxyl radical, whose dismutation to formate and carbonic oxide is accompanied by near infrared monomol emission (&#955;max = 1270 nm) characteristic of singlet molecular oxygen (O21&#916;g) (Russell reaction). Our studies strongly attest that the reaction of &#945;-dicarbonyls with peroxynitrite release free radicals that can potentially contribute for the radical, non-enzymatic acetylation of proteins (epigenetics) and DNA bases possibly implicated in the ageing physiopathology and metabolic disorders, where participation of reactive oxygen, nitrogen and carbonyl species is well recognized. Also noteworthy is that our findings may pave the way to the discovery of novel biochemical reactions whose products can eventually be useful as biomarkers of acquired and innate maladies.

O presente trabalho procurou investigar influência da presença de proteínas do soro do leite na atividade antioxidante da vanilina e ácido vanílico frente ao radical DPPH&bull; e a espécie de ferro hipervalente ferrilmioglobina MbFe(IV)=O em meio simulando o trato gastrointestinal. A constante de associação (KA) entre a vanilina e a &beta;-lactoglobulina (BLG) foi determinada utilizando-se as técnicas de espectroscopia de emissão molecular (KA = 400 &plusmn; 12&middot;102 L&middot;mol-1) e microcalorimétria (KA = 5,6&plusmn;0,3&middot;102 L&middot;mol-1) ambas em tampão fosfato com CH+ = 10-7,4 mol&middot;L-1 e força iônica 0,32 (NaCl). Para a interação entre a vanilina e albumina de soro bovino (BSA) encontrou-se o valor de 340 &plusmn; 13&middot;102 L&middot;mol-1 em meio de tampão fosfato com CH+ = 10-6,4 mol&middot;L-1 e força iônica 0,32 (NaCl), obtido por espectroscopia de emissão molecular. Constatou-se pela técnica de microcalorimetria que a complexação possui caráter exotérmico e as contribuições de interações hidrofóbicas para a complexação são fracas. A reatividade da vanilina e ácido vanílico com o radical DPPH&bull; foi investigada em meio de emulsão aquosa Tween-20&reg; com CH+ = 10-2,0 mol&middot;L-1. Os resultados obtidos demonstraram que a vanilina não pode ser considerada um bom antioxidante frente ao DPPH&bull; (k298 = 1,42&plusmn;0,04&middot;10-1 L&middot;mol-1&middot;s-1), no entanto, o ácido vanílico apresentou maior reatividade frente ao radical DPPH&bull; (k298 = 17,1&plusmn;0,3 &middot;10-1 L&middot;mol-1&middot;s-1). A presença das proteínas BLG e BSA nas reações de redução do radical DPPH&bull; pela vanilina e ácido vanílico conduziu a um efeito antagônico na constante de velocidade de reação. Os parâmetros termodinâmicos do estado de transição da reação com DPPH&bull; apresentaram valores relativamente altos de entalpia de ativação e moderados valores de entropia de ativação: &Delta;H&Dagger;298 = 34,0 &plusmn; 0,3 kJmol-1 para a vanilina e 46,2 &plusmn; 0,1 kJmol-1 no complexo com BSA e 51,0 &plusmn; 0,6 kJ&middot;mol-1 no complexo com BLG, valores negativos de entropia &Delta;S&Dagger;298 = -147,4 &plusmn; 0,9 J&middot;mol-1&middot;K-1, -105,3 &plusmn; 0,5 J&middot;mol-1&middot;K-1 e -90 &plusmn; 2 J&middot;mol-1&middot;K-1 respectivamente. Os valores de entalpia e entropia de ativação encontrados para o ácido vanílico foram: &Delta;H&Dagger;298= 19,6 &plusmn; 0,2 kJ&middot;mol-1, 10,2 &plusmn; 0,03 kJ&middot;mol-1 e 37,6 &plusmn; 0,3 kJ&middot;mol-1 para os complexos com BSA e BLG respectivamente e valores negativos de entropia &Delta;S&Dagger;298=-174 &plusmn; 0,5 J&middot;mol-1&middot;K-1, -206,0 &plusmn; 0,1 J&middot;mol-1&middot;K-1 e -116 &plusmn; 1 J&middot;mol-1&middot;K-1. A partir destes valores de entalpia e entropia de ativação o mecanismo de redução do radical DPPH&bull; foi atribuído a um processo de abstração de átomo de hidrogênio (HAT/PCET). A reação de desativação da espécie MbFe(IV)=O pela vanilina apresentou constante de velocidade de k298 = 57&plusmn;1 L&middot;mol-1&middot;s-1 sendo superior quando comparada ao ácido vanílico k298 = 15&plusmn;1 L&middot;mol-1&middot;s-1, fato este atribuído as cargas totais, negativa, do redutor e da proteína nas presentes condições experimentais. Observa-se um efeito antagônico da complexão da vanilina pelas proteínas na atividade antioxidante frente à ferrilmioglobina, onde o efeito reduziu, mas não impediu a reação de transferência de elétrons por esfera-externa à longa distância. Em contrapartida, a presença das proteínas BLG e BSA não influenciaram a reatividade do ácido vanílico frente à espécie MbFe(IV)=O. Os parâmetros de ativação encontrados para a reação de redução da MbFe(IV)=O com a vanilina apresentaram valores de &Delta;H&Dagger;298 = 58,8 &plusmn; 0,3 kJmol-1 e &Delta;S&Dagger;298 = -14 &plusmn; 1 J&middot;mol-1&middot;K-1, &Delta;H&Dagger;298 = 45,5 &plusmn; 0,3 kJ&middot;mol-1 e &Delta;S&Dagger;298 = -60 &plusmn; 1 J &middot;mol-1&middot;K-1, &Delta;H&Dagger;298 = 68,6 &plusmn; 0,4 kJ&middot;mol-1 e &Delta;S&Dagger;298 = 17 &plusmn; 1 J &middot;mol-1&middot;K-1 para vanilina \"livre\", complexo com BSA, e complexo com BLG respectivamente. Para a redução com ácido vanílico foram determinados os seguintes valores de entalpia e entropia de ativação: &Delta;H&Dagger;298 = 41,8 &plusmn; 0,2 kJ&middot;mol-1 e &Delta;S&Dagger;298 = -82,4 &plusmn; 0,7 J&middot;mol-1&middot;K-1, &Delta;H&Dagger;298 = 37,7 &plusmn; 0,3 kJ&middot;mol-1 e &Delta;S&Dagger;298 = -96 &plusmn; 1,0 J&middot;mol-1&middot;K-1, &Delta;H&Dagger;298 = 53,5 &plusmn; 0,2 kJ&middot;mol-1 e &Delta;S&Dagger;298 = -44 &plusmn; 1,0 J&middot;mol-1&middot;K-1 para vanilina \"livre\", complexo com BSA, e complexo com BLG respectivamente. / The present study evaluate the influence of the presence of whey proteins in the antioxidant activity of vanillin and vanillic acid towards the DPPH&bull; radical species and the hypervalent iron species ferrylmyoglobin, MbFe(IV)=O under conditions simulating the gastrointestinal tract. The association constant (KA) between vanillin and &beta;- lactoglobulin (BLG) was obtained using molecular emission spectroscopy (KA = 400 &plusmn; 12&middot;102 L&middot;mol-1) and microcalorimetric titration (KA = 5.6&plusmn;0.3&middot;102 L&middot;mol-1) both in phosphate buffer CH + = 10-7.4 mol&middot;L -1 and ionic strength 0.32 (NaCl). For the interaction between vanillin and bovine serum albumin (BSA) it was founded value of 340 &plusmn; 13&middot;102 L&middot;mol-1 in phosphate buffer with CH+ = 10-6,4 mol&middot;L-1 and ionic strength 0.32 (NaCl), as obtained by molecular emission spectroscopy. It was founded by microcalorimetry tritation that the complexation has a exothermic character and the contributions of hydrophobic interactions for complexation are weak. The reactivity of vanillin and vanillic acid toward DPPH&bull; radical was studied in aqueous emulsion using Tween-20&reg; with CH + = 10-2.0 mol&middot;L-1. The results show that vanillin can not be considered a good antioxidant (k298 = 1.42&plusmn;0.04&middot;10-1 L&middot;mol-1&middot;s-1), however vanillic acid show higher reactivity than vanillin towards the radical DPPH&bull; (k298 = 17.1&plusmn;0.3&middot;10-1 L&middot;mol-1&middot;s-1). The presence of the proteins BLG and BSA in the reduction reactions of the DPPH&bull; radical by vanillin and vanillic acid led to an antagonic effect in the reaction rate constant. The thermodynamic parameters for the transition state of the reaction with DPPH&bull; showed relatively high values of enthalpy of activation and moderately negative entropy of activation: &Delta;H&Dagger;298= 34.0 &plusmn; 0.3 kJmol-1 for vanillin and 46.2 &plusmn; 0.1 kJmol-1 for complex with BSA and 51.0 &plusmn; 0.6 kJ&middot;mol-1 for complex with BLG, negatives values of entropy &Delta;S&Dagger;298 = -147.4 &plusmn; 0.9 J&middot;mol-1&middot;K-1, -105.3 &plusmn; 0.5 J&middot;mol-1&middot;K-1 and -90 &plusmn; 2 J&middot;mol-1&middot;K-1 respectively. The values of enthalpy and entropy of activation found for vanillic acid were: &Delta;H&Dagger;298 = 19.6 &plusmn; 0.2 kJ&middot;mol-1, 10.2 &plusmn; 0.03 kJ&middot;mol-1 and 37.6 &plusmn; 0.3 kJ&middot;mol-1 for BSA and BLG respectively and negative values of entropy &Delta;S&Dagger;298 = -174 &plusmn; 0.5 J&middot;mol-1&middot;K-1, -206.0 &plusmn; 0.1 J&middot;mol-1&middot;K-1 and -116 &plusmn; 1 J&middot;mol-1&middot;K-1. From these values of enthalpy and entropy of activation the mechanism of radical DPPH&bull; reduction was assigned to a process of hydrogen atom transfer (HAT/PCET). The deactivation reaction of the MbFe(IV)=O species by vanillin shown rate constant of k298 = 57&plusmn;1 L&middot;mol-1&middot;s-1, which it is higher than vanillic acid k298 = 15&plusmn;1 L&middot;mol-1&middot;s-1. This fact is assigned to the total negative charges of the reductor and the protein under the experimental conditions. It is observed an antagonistic effect of the complexation of vanillin by proteins in the antioxidant activity, in which the effect diminish, but not avoid the long range electron transfer by out-sphere reaction. On the other hand, the presence of BLG and BSA do not affect the reactivity of vanillic acid towards the MbFe(IV)=O species. The activation parameters found for the reduction of MbFe(IV)=O by vanillin revealed values of &Delta;H&Dagger;298 = 58.8 &plusmn; 0.3 kJmol-1 and &Delta;S&Dagger;298 = -14 &plusmn; 1 J&middot;mol-1&middot;K-1, &Delta;H&Dagger;298 = 45.5 &plusmn; 0.3 kJ&middot;mol-1 e &Delta;S&Dagger;298 = -60 &plusmn; 1 J &middot;mol-1&middot;K-1, &Delta;H&Dagger;298 = 68.6 &plusmn; 0.4 kJ&middot;mol-1 and &Delta;S&Dagger;298 = 17 &plusmn; 1 J &middot;mol-1&middot;K-1 for free vanillin, complex with BSA and complex with BLG respectively. For the reduction by vanillic acid it were with the following values of enthalpy and entropy of activation: &Delta;H&Dagger;298 = 41.8 &plusmn; 0.2 kJ&middot;mol-1 and &Delta;S&Dagger;298 = -82.4 &plusmn; 0.7 J&middot;mol-1&middot;K-1, &Delta;H&Dagger;298 = 37.7 &plusmn; 0.3 kJ&middot;mol-1 and &Delta;S&Dagger;298 = -96 &plusmn; 1.0 J&middot;mol-1&middot;K-1, &Delta;H&Dagger;298 = 53.5 &plusmn; 0.2 kJ&middot;mol-1 and &Delta;S&Dagger;298 = -44 &plusmn; 1.0 J&middot;mol-1&middot;K-1 for free vanillin, complex with BSA and complex with BLG respectively.