No description available.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1948. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves [124]-125).

The introduction to this thesis examines the importance of N-dealkylation in pharmaceutical studies and considers the scope of microbial transformations and their possible role in effecting N-dealkylation. The experimental section is in eight parts, Chapters 2 and 3 are concerned with the screening of selected Pseudomonads, Streptomyces and fungi for their ability to N-dealkylate drug molecules. The development of qualitative analytical techniques is also detailed. A 'model' transformation system in which the alkaloid codeine is N-demethylated by C. echinulata was selected. Chapter 4 describes quantitative transformation studies in chemically defined growth media with the model transformation system. The effect of growth media components on codeine transformation is investigated and parameters which may influence microbial transformations, such as substrate concentration, are optimised. In Chapter 5, factors likely to affect the transformation process are characterised. These include microbial growth, carbon source depletion, extracellular protein levels and cell lysis. Chapter 6 investigates the feasibility of batch culture transformations in laboratory fermenters and examines the effect of culture pH on N-demethylation. Chapter 7 describes experiments with resting cells, and cell-free extracts prepared from C. echinulata aimed at establishing the type of catabolic regulation operative during transformations and the optimum pH, temperature and cofactor requirements for the N-dealkylation reaction. Studies using specific enzyme inhibitors, in an attempt to characterise the N-demethylase enzyme system, are also reported. Investigations into the microbial transformation of diazepam, a substrate with low aqueous solubility, are described in Chapter 8. Various pharmaceutical solubilisation techniques are investigated in an attempt to increase the diazepam solubility and transformation. The effect of two different fungal growth forms on diazepam transformation is also examined. Chapter 9 examines the effect of structural variations in the codeine molecule on N-demethylation and ability of C. echinulata to cleave more complex N-alkyl functions in 6,7, benzomorphans. In the discussion, the data are considered with reference to current microbial transformation literature and are compared to mammalian biotransformations utilising similar pathways.

A series of mononuclear boron halides of the type LBX2 (LH = N-phenyl-3,5-di-tbutylsalicylaldimine,X = Cl (2), Br (3)) and LBX ( LH2 = N-(2-hydroxyphenyl)-3,5-di-tbutylsalicylaldimine,X = Cl (7), Br (8); LH2 = N-(2-hydroxyethyl)-3,5-di-tbutylsalicylaldimine,X = Cl (9), Br (10); LH2= N-(3-hydroxypropyl)-3,5-di-tbutylsalicylaldimine,X = Cl (11), Br (12)) were synthesized from their borate precursorsLB(OMe)2 (1) (LH = N-phenyl-3,5-di-t-butylsalicylaldimine ) and LB(OMe) (LH2 = N-(2-hydroxyphenyl)-3,5-di-t-butylsalicylaldimine (4), N-(2-hydroxyethyl)-3,5-di-tbutylsalicylaldimine(5), N-(3-hydroxypropyl)-3,5-di-t-butylsalicylaldimine (6)). Theborate precursors, 1, 4 - 6, in turn, were prepared by refluxing the corresponding ligandsLH or LH2 with excess B(OMe)3. The boron halide compounds were air- and moisturesensitiveand compound 7 on hydrolysis gave the oxo-bridged compound 13 thatcontained two seven-membered boron heterocycles. The boron halide compoundsdealkylated trimethyl phosphate in stoichiometric reactions to produce methyl halide andunidentified phosphate materials. Compounds 8 and 12 were found to be the mosteffective dealkylating agents. Compound 8 on reaction with t-butyl diphenyl phosphinateproduced a unique boron phosphinate compound LB(O)OPPh2 (14) containing a terminalphosphinate group. Compounds 1-14 were characterized by 1H, 13C, 11B, 31P NMR, IR,MS, EA and MP. Compounds 5, 6, 11, 12 and 13 were also characterized by singlecrystalX-ray diffraction.The alkane elimination reaction between Salen(tBu)H2 ligands and diethylaluminumbromide was used to prepare the four Salen aluminum bromide compounds,salen(tBu)AlBr (15) (salen = N,N'-ethylenebis(3,5-di-tert-butylsalicylideneimine)),salpen(tBu)AlBr (16) (salpen = N,N'-propylenebis(3,5-di-tert-butylsalicylideneimine)),salben(tBu)AlBr (17) (salben = N,N'-butylenebis(3,5-di-tert-butylsalicylideneimine)) andsalophen(tBu)AlBr (18) (salophen = N,N'-o-phenylenenebis(3,5-di-tertbutylsalicylideneimine)).The compounds contained five-coordinate aluminum either in adistorted square planar or a trigonal bipyramidal environment. The bromide group inthese compounds could be displaced by triphenylphosphine oxide or triphenyl phosphateto produce the six-coordinate cationic aluminum compounds [salen(tBu)Al(Ph3PO)2]Br(19), [salpen(tBu)Al(Ph3PO)2]Br (20), [salophen(tBu)Al(Ph3PO)2]Br (21) and[salophen(tBu)Al{(PhO)3PO}2]Br (22). All the compounds were characterized by 1H,13C, 27Al and 31P NMR, IR, mass spectrometry and melting point. Furthermore,compounds 15, 16, 17, 18, 20, 21 and 22 were structurally characterized by single-crystalX-ray diffraction. Compounds 15, 17 and 18 dealkylated a series of organophosphates instoichiometric reaction by breaking the ester C–O bond. Also, they promoted thedealkylation reaction between trimethyl phosphate and added boron tribromide.Stoichiometric reaction of compound 15 with trimethyl phosphate produced thealuminophosphinate compound salen(tBu)AlOP(O)Ph2 (23). Compound 16 on reactionwith tributyl phosphate produced the aluminophosphate compound[salpen(tBu)AlO]2[(BuO)2PO]2 (24). Compounds 23 and 24 were characterized by singlecrystalX-ray diffraction and spectroscopically.

No description available.

Dynamic isomerization of diethylstilbestrol (DES) makes it difficult to ascertain the active estrogen between its E and Z isomers. An indirect approach has been used in this project to identify the active estrogen. Methoxylated E- and Z-DES (13 and 14) and 9,10-diethylphenanthrene-3,6-diol (15), a closed ring analog of Z-DES, were synthesized and tested for their estrogenicity. The estrogenicity of 13 is higher than that of 14 and 15, which indicates that E-DES is more estrogenic than Z-DES. Dimethylstilbestrol (16), another analog of DES, was also synthesized and tested. Its estrogenicity is lower than that of DES. Non-estrogenic analogs of bisphenol-A were designed based on the observation that (15) is far less estrogenic than DES. Closed ring analogs of bisphenol-A, 3,6-dihydroxy-9,9-dimethylfluorene (34), 2,6-dihydroxy-9,9-dimethylfluorene (35), and 2,7-dhydroxy-9,9-dimethylfluorene (36) were synthesized and they were found to have little or no estrogenicity. An open ring analog of bisphenol-A, 2-(3-hydroxyphenyl)-2-(4-hydroxyphenyl)propane (33) was also synthesized and its estrogenicity is much lower than that of bisphenol-A. Polycarbonate of 36 was also synthesized and its glass transition temperature was measured using differential scanning calorimetry (DSC). Glass transition temperature of polycarbonate of 36 was found to be 199.92 oC, which is about 50o higher than that of bisphenol-A polycarbonate (150 oC). This indicates that polycarbonate of 36 forms a harder plastic than bisphenol-A polycarbonate. Compounds 2,8-dihydroxy-5,5-dioxo-dibenzothiophene (69) and 2,8-dihydroxydibenzothiophene (70) were also synthesized and were tested as non-estrogenic alternatives for bisphenol-S and bisphenol sulfide, respectively. Compound 69 and 70 were found to be less estrogenic than bisphenol-S and bisphenol sulfide respectively agreeing with our hypothesis. Iodane/quaternary ammonium halide in nitromethane was utilized to explore aromatic bromination, N-nitrosation-dealkylation, and benzoate ester formation from benzylamines. Koser's reagent was found to be a suitable iodane for aromatic bromination reaction, whereas for N-nitrosation-dealkylation, IBX gave the best yields. Further, for N-nitrosation-dealkylation reaction, the halides of quaternary ammonium salts play a crucial role. The effectiveness of halides follows F- > Cl- > Br- ~ I-. The lack of N-nitrosation-dealkylation and ester formation in the absence of nitromethane indicates that nitromethane is playing an essential role as well. Yields of benzoate ester from benzyl amines were low (~22%). Optimization experiments will be performed in the future. Plausible reaction mechanisms for these reactions were proposed. Aromatic bromination was thought to be induced either by iodane/halide adduct or by BrOH that was formed from iodane/halide adduct. Ester formation and N-nitrosation-dealkylation were believed to be induced either by alkyl nitrite or by nitrous acid, generated from the reaction of iodane/halide adduct with nitromethane.

The focus of this dissertation is the use of aluminum Schiff base compounds, Salen(tBu)AlBr (SAB), in the dealkylation and detection of organophosphates (OPs). Three SAB compounds, Salen(tBu)AlBr (1), Salpen(tBu)AlBr (2), and Salophen(tBu)AlBr (3) were used to dealkylate a variety of trialkyl OPs. These reactions lead to unique organic-soluble aluminum phosphate compounds containing six-coordinate aluminum. Examples include [salen(tBu)AlOP(O)(OCH3)2]n (4), [salen(tBu)AlOP(O)(OCH2CH3)2]n (5), [salen(tBu)AlOP(O)(OPh)2]n (6), [Salophen(tBu)AlOP(O)(OCH3)2 (7), Salpen(tBu)AlOOP(O)(OiPr)2 (8). These compounds are unique examples of polymeric (4, 5, 6 and 7) and dimeric compounds (8) with salenAl units connected by phosphate linkages. The compounds do not decompose in neutral water. This is an advantage in the use of SABs for the deactivation of phosphate esters such as nerve agents. Water-soluble and stable group 13 salen complexes, Salen(SO3Na)MNO3 (M =Al (19), Ga (22)), Salpen(SO3Na)MNO3 (M = Al (20), Ga (23)), and Salophen(SO3Na)M(NO3) (M = Al (21), Ga (24)) were synthesized by using water-soluble Salen(SO3Na) ligand. All the compounds were characterized by various analytical techniques: 1H and 13C NMR, IR, and melting point. One SAB was used to detect the nerve agents (NA). Salen(tBu)Al(Ac), prepared in situ from Salen(tBu)AlBr and NaAc, forms Lewis acid-base adducts with the NAs, GB (sarin) and GD (soman), and the VX hydrolysis product, EMPA, in aqueous solution. The [Salen(tBu)Al(NA)]+ compound is sufficiently stable to allow the identification of the NA with ESI-MS. Molecular ion peak was detected for every compound with little or no fragmentation. The distinctive MS signatures for [Salen(tBu)Al(NA)]+ compounds provide a new technique for identifying NAs in aqueous solution.

Reações de O-desmetilação oxidativa estão entre as várias oxidações realizadas pelas enzimas do citocromo P-450. Entretanto, poucos estudos de O-desmetilação catalisadas por enzimas do citocromo P-450 ou modelos químicos baseados em metaloporfirinas sintéticas têm resultado em dúvidas acerca do mecanismo da O-desmetilação destes compostos orgânicos. Neste trabalho, foi estudada a O-desmetilação oxidativa, com PhIO, do benzil metil éter e alguns de seus derivados para substituídos (com os grupos doadores de elétrons -OCH3 e -CH3 e os grupos retiradores -NO2 e -Cl) catalisada pelas Mn(III)P [Mn(TPP)]Cl, [Mn{T(4-N-MePy)P}](PF6)5, [Mn(TMP)]Cl, [Mn(TDCSPP)]Cl e [Mn(TFPP)]Cl para verificar o efeito destes diferentes catalisadores na conversão e seletividade de produtos da O-desmetilação oxidativa e avaliar o efeito dos diversos substituintes citados no mecanismo de O-desalquilação. Inicialmente, realizou-se o estudo das oxidações catalíticas do metil benzil éter. Todas as reações catalisadas pelas MnP se mostram seletivas, sendo que o benzaldeído foi o produto comum a todas as oxidações. A melhor condição encontrada foi 1:50:1224 (catalisador/oxidante/substrato). Em relação às reações com os substratos contendo os substituintes na posição -para, as reações de oxidações catalíticas do p-metóxibenzil metil éter por PhIO não se mostraram tão seletivas quanto as do metil benzil éter, mostrando claramente que o grupo metóxi alterou a reatividade do aril éter original. Mesmo assim, o p-metoxibenzaldeído ainda foi o produto principal, sendo a conversão ao álcool p-metoxibenzílico observada em escala menor. Já com o substrato p-nitrobenzil metil éter, novamente o efeito provocado pelo substituinte na posição para no anel benzênico pôde ser percebida na distribuição final dos produtos, sendo que houve seletividade total para a formação de p-nitrobenzaldeído em detrimento ao álcool p-nitrobenzóico. Em relação aos dois últimos substratos da série proposta, metil p-metilbenzil éter e metil p-clorobenzil éter, de um modo geral, as reações realizadas com o p-clorobenzil metil éter não se mostraram tão seletivas quanto as do metil p-nitrobenzil éter, mostrando que o grupo cloro aumentou a reatividade do cloroéter em relação ao éter com o substituinte nitro- original. Mesmo assim, o p-clorobenzaldeído foi o produto principal, sendo a conversão ao álcool p-clorobenzílico observada em menor escala. Em relação às reações de oxidação do p-metilbenzil metil éter, observou-se que os resultados experimentais são semelhantes aos encontrados para o metil benzil éter. Esses resultados corroboram o principal mecanismo proposto para os sistemas modelo do citocromo P-450 que envolve abstração inicial do átomo de hidrogênio, o mecanismo por recombinação de oxigênio. / O-dealkylation oxidative reactions are among the several oxidations accomplished by the cytochrome P-450 enzymes. However, few studies on O-dealkylation catalyzed by such enzymes or chemical models based on synthetic metalloporphyrins have resulted in doubts concerning the mechanism of these reactions involving organic compounds. In this work, we studied the oxidative O-dealkylation by PhIO of benzyl methyl ether and some of its para-substituted derivatives (with the electron donor groups -OCH3 and -CH3 and the electronwithdrawing groups -NO2 and -Cl) catalyzed by the following Mn(III)P: [Mn(TPP)]Cl, [Mn{T(4-N-MePy)P}] (PF6)5, [Mn(TMP)]Cl, [Mn(TDCSPP)] Cl, and [Mn(TFPP)]Cl. Our aim was to verify the effect of these different catalysts on the conversion yields and product selectivity, as well as evaluate the effect of the several substituents on the ether on the O-dealkylation mechanism. We initially studied the catalytic oxidation of methyl benzyl ether. All the reactions catalyzed by the various MnPs were selective, and benzaldehyde was the product common to all oxidations. The best reaction condition was catalyst/oxidant/substrate molar ration = 1:50:1224. As for the reactions with the substituted substrates, the catalytic oxidation of p-methoxybenzyl methyl ether by PhIO was not as selective as the ones of methyl benzyl ether, clearly showing that the methoxy group affects the reactivity of the original aryl ether. Nevertheless, p-methoxybenzaldehyde was still the main product, being the conversion to p-methoxybenzylic alcohol observed in minor amount. With the substrate p-nitrobenzyl methyl ether, the effect of the electronwithdrawing substituent in the para- position of the aromatic ring could be observed in the final product distribution once again, and total selectivity toward the formation of p-nitrobenzaldehyde to the detriment of p-nitrobenzoic alcohol was observed. In relation to the two last substrates of the proposed series, the methyl p-methylbenzyl and methyl p-chlorobenzyl ethers, the reactions accomplished with p-chlorobenzyl methyl ether were not as selective as the ones carried out with methyl p-nitrobenzyl ether, showing that the chloro group increased the reactivity of the chloro-ether in relation to the ether with the original nitro- substituent. Even so, p-chlorobenzaldehyde was the main product, being the conversion to the p-chlorobenzylic alcohol observed in smaller amount. Concerning the oxidation reactions of p-methylbenzyl methyl ether, the experimental results were similar to those obtained in the case of methyl benzyl ether. These results corroborate the main mechanism proposed for the cytochrome P-450 model systems, which involves initial hydrogen atom abstraction, followed by oxygen rebound.

Over the recent years, increasing scientific attention has been paid to pharmaceuticals, other drugs and their metabolites. These substances are of particular interest because of their physiological, toxicological and ecotoxicological effects in the human body and respectively in the environment. Cytochrome P450 enzymes (P450s) play a key role in the conversion and detoxification of bioactive compounds including many pharmaceuticals and drugs. Most of these enzymes belong to the monooxygenases; they are intracellular and rather unstable biocatalysts that are difficult to purify and require expensive, complex cofactors, which alltogether hampers their use in isolated form. The investigations carried out here with fungal peroxygenases have shown that this enzyme sub-subclass (EC 1.11.2.x) has a promising potential for oxyfunctionalizations and can catalyze a variety of reactions typical for P450s. Peroxygenases are extracellular, i.e. secreted fungal enzymes with high stability, which merely need peroxide for function. Results obtained with the unspecific/aromatic peroxygenases (APOs) of Agrocybe aegerita, Coprinellus radians and Marasmius rotula have demonstrated that APOs catalyze numerous H2O2-dependent monooxygenations of pharmaceuticals and psychoactive drugs. Among them are i) the monooxygenation of aromatic compounds, ii) the benzylic hydroxylation of toluene derivatives, iii) the O-dealkylation of different ether structures including the scission of benzodioxoles (O-demethylenation) and esters as well as iv) the N-dealkylation of secondary and tertiary amines. The peroxygenases studied considerably differ in their substrate spectrum and the preferred positions of oxidation. This finding opens the possibility to develop in the future an “enzymatic toolbox“ on the basis of fungal peroxygenases for the oxyfunctionalization of pharmaceutically relevant compounds. Mechanistic studies showed that (1) the monooxygenations always proceed via incorporation of one oxygen atom from the peroxide, (2) the demethylation of phenacetind1 established a deuterium isotope effect similar to P450s, (3) the catalytic efficiencies for the studied oxidations are in the same range as those of P450s (though the kcat- and Km values are noticeably higher), (4) the kinetic studies with nitro-1,3-benzodioxole gave parallel double reciprocal plots suggestive of a “ping pong” mechanism, (5) the substrate spectrum and the activity pattern of APOs follows in a wide range those of the human key P450s as well as that (6) the difference spectra obtained in bindings studies are of the phenol type of P450s. Furthermore, APOs were found to be stable and active in long term experiments over two weeks and they oxidized pharmaceuticals at low, environmentally relevant concentration (ppb range). All the above properties strongly indicate that APOs respresent an interesting alternative for the enzymatic conversion of pharmaceuticals as well as for the preparation of human drug metabolites, for example, in medicinal and pharmacological research or the bioremediation sector (removal of pharmaceuticals from environmental media). / In den letzten Jahren sind Pharmazeutika und deren Metabolite mehr und mehr in den Fokus der Wissenschaft gerückt. Diese Substanzen sind aufgrund ihrer physiologischen und toxikologischen sowie ökotoxikologischen Wirkungen im menschlichen Körper bzw. in der Umwelt von besonderem Interesse. Cytochrom-P450-Enzyme (P450s) spielen eine Schlüsselrolle bei der Umsetzung und Detoxifizierung bioaktiver Substanzen, darunter vieler Pharmazeutika und Drogen. Es handelt sich bei diesen Enzymen in erster Linie um Monooxygenasen, die intrazellulär lokalisiert und relativ instabil sind; sie benötigen komplexe, teure Kofaktoren und sind nur unter hohem Aufwand zu reinigen, was ihre Anwendung in isolierter Form insgesamt erschwert. Die hier durchgeführten Untersuchungen zu pilzlichen Peroxygenasen haben gezeigt, dass diese Enzymsubklasse (EC 1.11.2.x) ein hohes Oxyfunktionalisierungspotenzial besitzt und eine Vielzahl P450-typischer Reaktionen zu katalysieren vermag. Peroxygenasen sind extrazelluläre, d.h. sekretierte Pilzenzyme, die eine hohe Stabilität aufweisen und lediglich ein Peroxid als Kosubstrat benötigen. Die unter Verwendung der unspezifischen/aromatischen Peroxygenasen (APOs) von Agrocybe aegerita, Coprinellus radians und Marasmius rotula gewonnenen Ergebnisse belegen, dass APOs verschiedene H2O2-abhängige Monooxygenierungen von Pharmazeutika und psychoaktiven Substanzen realisieren. Dazu gehören i) die Monooxygenierung von Aromaten, ii) die benzylische Hydroxylierung von Toluolderivaten, iii) die O-Dealkylierung verschiedener Etherstrukturen einschließlich der Spaltung von Benzodioxolen (O-Demethylenierung) und Estern sowie iv) die N-Dealkylierung von sekundären und tertiären Aminen. Die untersuchten Peroxygenasen wiesen teilweise deutliche Unterschiede im Substratspektrum und den präferierten Oxidationspositionen auf. Dieser Befund eröffnet die Möglichkeit, zukünftig einen „enzymatischen Werkzeugkasten“ auf Basis pilzlicher Peroxygenasen für die Oxyfunktionalisierung von pharmazeutisch relevanten Wirkstoffen zu entwickeln. Mechanistische Experimente zeigten, dass (1) die Monooxygenierungen stets unter Einbau eines aus dem Peroxid stammenden Sauerstoffatoms erfolgen, (2) die Deethylierung von Phenacetin-d1 einen Deuteriumisotopeneffekt ähnlich dem der P450s aufweist, (3) die katalytischen Effizienzen für die untersuchten Oxidationen im gleichen Bereich wie die der P450s liegen (wobei die kcat- und Km-Werte deutlich höher ausfallen), (4) die kinetischen Untersuchungen zur Oxidation von Nitro-1,3-Benzodioxol parallele Verläufe der ermittelten Ausgleichsgeraden in der doppelt reziproken Darstellung ergaben, was für einen “Ping-Pong-Mechanismus“ spricht, (5) sich das Substratspektrum und die Aktivitätsmuster der APOs in einem weiten Bereich mit denen der wichtigsten menschlichen P450s decken sowie dass (6) die in Bindungsstudien gewonnenen Differenzspektren denen des Phenoltyps der P450s entsprechen. Desweiteren erwiesen sich APOs in Langzeitexperimenten über zwei Wochen als stabil und aktiv und sie waren in der Lage, Pharmazeutika in umweltrelevanten Konzentrationen (ppb-Bereich) zu oxidieren. All die genannten Eigenschaften legen nahe, dass APOs eine interessante Alternative zur enzymatischen Umsetzung von Pharmazeutika sowie zur Herstellung von humanen Pharmazeutika-Metaboliten darstellen, die z.B. Einsatz in der medizinischpharmakologischen Forschung oder im Umweltbereich (Entfernung von Pharmazeutika aus Umweltmedien) finden könnten.

Reações de O-desmetilação oxidativa estão entre as várias oxidações realizadas pelas enzimas do citocromo P-450. Entretanto, poucos estudos de O-desmetilação catalisadas por enzimas do citocromo P-450 ou modelos químicos baseados em metaloporfirinas sintéticas têm resultado em dúvidas acerca do mecanismo da O-desmetilação destes compostos orgânicos. Neste trabalho, foi estudada a O-desmetilação oxidativa, com PhIO, do benzil metil éter e alguns de seus derivados para substituídos (com os grupos doadores de elétrons -OCH3 e -CH3 e os grupos retiradores -NO2 e -Cl) catalisada pelas Mn(III)P [Mn(TPP)]Cl, [Mn{T(4-N-MePy)P}](PF6)5, [Mn(TMP)]Cl, [Mn(TDCSPP)]Cl e [Mn(TFPP)]Cl para verificar o efeito destes diferentes catalisadores na conversão e seletividade de produtos da O-desmetilação oxidativa e avaliar o efeito dos diversos substituintes citados no mecanismo de O-desalquilação. Inicialmente, realizou-se o estudo das oxidações catalíticas do metil benzil éter. Todas as reações catalisadas pelas MnP se mostram seletivas, sendo que o benzaldeído foi o produto comum a todas as oxidações. A melhor condição encontrada foi 1:50:1224 (catalisador/oxidante/substrato). Em relação às reações com os substratos contendo os substituintes na posição -para, as reações de oxidações catalíticas do p-metóxibenzil metil éter por PhIO não se mostraram tão seletivas quanto as do metil benzil éter, mostrando claramente que o grupo metóxi alterou a reatividade do aril éter original. Mesmo assim, o p-metoxibenzaldeído ainda foi o produto principal, sendo a conversão ao álcool p-metoxibenzílico observada em escala menor. Já com o substrato p-nitrobenzil metil éter, novamente o efeito provocado pelo substituinte na posição para no anel benzênico pôde ser percebida na distribuição final dos produtos, sendo que houve seletividade total para a formação de p-nitrobenzaldeído em detrimento ao álcool p-nitrobenzóico. Em relação aos dois últimos substratos da série proposta, metil p-metilbenzil éter e metil p-clorobenzil éter, de um modo geral, as reações realizadas com o p-clorobenzil metil éter não se mostraram tão seletivas quanto as do metil p-nitrobenzil éter, mostrando que o grupo cloro aumentou a reatividade do cloroéter em relação ao éter com o substituinte nitro- original. Mesmo assim, o p-clorobenzaldeído foi o produto principal, sendo a conversão ao álcool p-clorobenzílico observada em menor escala. Em relação às reações de oxidação do p-metilbenzil metil éter, observou-se que os resultados experimentais são semelhantes aos encontrados para o metil benzil éter. Esses resultados corroboram o principal mecanismo proposto para os sistemas modelo do citocromo P-450 que envolve abstração inicial do átomo de hidrogênio, o mecanismo por recombinação de oxigênio. / O-dealkylation oxidative reactions are among the several oxidations accomplished by the cytochrome P-450 enzymes. However, few studies on O-dealkylation catalyzed by such enzymes or chemical models based on synthetic metalloporphyrins have resulted in doubts concerning the mechanism of these reactions involving organic compounds. In this work, we studied the oxidative O-dealkylation by PhIO of benzyl methyl ether and some of its para-substituted derivatives (with the electron donor groups -OCH3 and -CH3 and the electronwithdrawing groups -NO2 and -Cl) catalyzed by the following Mn(III)P: [Mn(TPP)]Cl, [Mn{T(4-N-MePy)P}] (PF6)5, [Mn(TMP)]Cl, [Mn(TDCSPP)] Cl, and [Mn(TFPP)]Cl. Our aim was to verify the effect of these different catalysts on the conversion yields and product selectivity, as well as evaluate the effect of the several substituents on the ether on the O-dealkylation mechanism. We initially studied the catalytic oxidation of methyl benzyl ether. All the reactions catalyzed by the various MnPs were selective, and benzaldehyde was the product common to all oxidations. The best reaction condition was catalyst/oxidant/substrate molar ration = 1:50:1224. As for the reactions with the substituted substrates, the catalytic oxidation of p-methoxybenzyl methyl ether by PhIO was not as selective as the ones of methyl benzyl ether, clearly showing that the methoxy group affects the reactivity of the original aryl ether. Nevertheless, p-methoxybenzaldehyde was still the main product, being the conversion to p-methoxybenzylic alcohol observed in minor amount. With the substrate p-nitrobenzyl methyl ether, the effect of the electronwithdrawing substituent in the para- position of the aromatic ring could be observed in the final product distribution once again, and total selectivity toward the formation of p-nitrobenzaldehyde to the detriment of p-nitrobenzoic alcohol was observed. In relation to the two last substrates of the proposed series, the methyl p-methylbenzyl and methyl p-chlorobenzyl ethers, the reactions accomplished with p-chlorobenzyl methyl ether were not as selective as the ones carried out with methyl p-nitrobenzyl ether, showing that the chloro group increased the reactivity of the chloro-ether in relation to the ether with the original nitro- substituent. Even so, p-chlorobenzaldehyde was the main product, being the conversion to the p-chlorobenzylic alcohol observed in smaller amount. Concerning the oxidation reactions of p-methylbenzyl methyl ether, the experimental results were similar to those obtained in the case of methyl benzyl ether. These results corroborate the main mechanism proposed for the cytochrome P-450 model systems, which involves initial hydrogen atom abstraction, followed by oxygen rebound.