Made available in DSpace on 2015-04-22T22:02:08Z (GMT). No. of bitstreams: 1 Klenicy Yamaguchi.pdf: 4077036 bytes, checksum: cfe6daf81dfaafe618fb478baf8cdfc7 (MD5) Previous issue date: 2011-08-02 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The family Lauraceae is one of the most important families in the Amazon rainforest featuring an significant number of species with different uses due to the quality of products natural.The species this family are Chemically characterized by the presence of alkaloids, neolignans, flavonoids, terpenes and phenylpropanoids. This study contributes to the analysis of the chemical profile of the three genera Endlicheria, Ocotea and Rhodostemonodaphne about directing the investigations on the chemical composition of extracts and essential oils, contributing to the screening of promising genera and species. This work was carried out prospecting phytochemical , alkaloid profile analysis by thin layer chromatography (TLC) and mass spectrometry of the ethanol extracts, identification of the essential oil and analysis of activities: anticholinesterase, antioxidant and cytotoxic of ethanolic extracts of E. citriodora, E. sericea, O. minor, O. ceanothifolia, O. leucoxylon, R. recurva and R. crenaticupula. The species were collected in Reserva Ducke, in Manaus. The material was separated to obtain essential oils and ethanolic extracts. These were analyzed for chemical / biological activities and subjected to acid-base partition to obtain enriched fractions of alkaloids. The alkaloid profile was analyzed by mass spectrometry and TLC with revealing specific. The essential oils were analyzed by GC-FID and GC-MS. It was confirmed the high presence of alkaloids in the genus Ocotea and low in species Endlicheria and Rhodostemonodaphne. In mass spectrometry the peaks m/z 300 and 330 were present in most fractions and may correspond to the type alkaloids Benzylisoquinolines and Aporphines. The yields of essential oils obtained by hydrodistillation in Clevenger modified ranged from 0.02% to 4.29%. The specie Endlicheria citriodora was the highest yield, 2.5% in the branches and 4.3% in the leaves. The Methyl geranate was the major constituent, (above 93%), elucidated by GC-FID, GC-MS RMN1H and RMN 13C. The essential oils from other species showed less than 1% yield and caryophyllene and its oxide were the major constituents. The antioxidant activity was assessed by sequestering ability of the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH ), using quercetin as external standard, expressed as effective concentration values (EC50). The extracts of Ocotea minor presented the best antioxidant potential (EC50 = 7.31 ± 0.32 μg / mL). Qualitative analysis of anticholinesterase activity was performed according to the method of Ellman (modified), with negative results for inhibiting the enzyme acetylcholinesterase. The branches of the three species of Ocotea were positive. The antitumor activity was evaluated against four cell lines (leukemia, breast, colon and glioblastoma) by the method of Mossman. None of the extracts tested showed pronounced cytotoxic activity. / A família Lauraceae é uma das famílias mais importantes na floresta amazônica apresentando um número expressivo de espécies com diversas utilizações devido a qualidade dos seus produtos naturais. Quimicamente as espécies desta família caracterizam-se pela presença de alcalóides, neolignanas, flavonóides, terpenos e fenilpropanóides. Este estudo contribui para a análise do perfil químico dos três gêneros Endlicheria, Ocotea e Rhodostemonodaphne através da varredura dos extratos brutos auxiliando no direcionamento das investigações químicas sobre a composição dos extratos e óleos essenciais, contribuindo para a triagem de gêneros e das espécies promissoras. Neste trabalho foi realizado prospecção fitoquímica, análise do perfil alcaloídico por cromatografia em camada delgada (CCD) e espectrometria de massa (EM) dos extratos etanólicos, identificação dos constituintes do óleo essencial e verificação das atividades anticolinesterásica, antioxidante e citotóxica dos extratos etanólicos das espécies E. citriodora, E. sericea, O. minor, O. ceanothifolia, O. leucoxylon, R. recurva e R. crenaticupula. As espécies foram coletadas na Reserva Ducke, em Manaus e separadas para obtenção de óleos essenciais e extratos etanólicos. Estes foram analisados quanto as atividades química/biológicas e submetidos a partições ácido-base para obtenção de frações enriquecidas de alcalóides. O perfil alcaloídico foi analisado por CCD utilizando reveladores específicos e por EM. Os óleos essenciais foram analisados por CG-DIC e CG-EM. Confirmou-se que a pronunciada presença de alcalóides no gênero Ocotea e em baixas concentrações nas espécies de Endlicheria e Rhodostemonodaphne. Na espectrometria de massa os picos m/z de 300 e 330 estiveram presentes na maioria das frações e podem corresponder a alcalóides do tipo benzilisoquinolínicos e aporfínicos. Os rendimentos dos óleos essenciais obtidos por hidrodestilação em clevenger modificado variaram de 0,02% a 4,29%, sendo Endlicheria citriodora a espécie que apresentou maior rendimento, 2,5% nos galhos e 4,3% nas folhas, tendo como constituinte majoritário, o geranato de metila (acima de 93%), elucidado por CG-DIC, CG-EM, RMN1H e RMN 13C. Os óleos essenciais das outras espécies apresentaram rendimento inferior a 1% e como constituinte majoritário o cariofileno e seu óxido. A atividade antioxidante foi avaliada através da capacidade seqüestrante do radical estável 2,2-difenil-1-picrilhidrazil (DPPH ), utilizando quercetina como padrão externo, expressos como valores de concentração eficiente (CE50).Os extratos de Ocotea minor foram os que apresentaram maior potencial antioxidante (CE50=7,31 ± 0,32 μg/mL). A análise qualitativa da atividade anticolinesterase foi realizada de acordo com o método de Ellman (modificado), com resultados negativos para inibição da enzima acetilcolinesterase. Os galhos das três espécies de Ocotea apresentaram resultado positivo. A atividade antitumoral foi avaliada contra quatro linhagens de células (leucemia, mama, cólon e glioblastoma) segundo o método de Mossman.Nenhum dos extratos testados apresentou atividade citotóxica pronunciada.

The first goal of the current research was to determine whether gene expression profiles differed between whole pituitaries of growing beef steers grazing pastures containing high (HE) or low (LE) amounts of toxic endophyte-infected tall fescue. The global (microarray analysis) and selected targeted (RT-PCR) mRNA expression patterns of pituitaries collected from beef steers (BW = 266 ± 15.5 kg) that had been randomly assigned to undergo summer-long grazing (89 to 105 d) of either HE (0.52 ppm ergot alkaloids) or LE (< 0.03 ppm ergot alkaloids) pastures were compared. Gene expression data were subjected to one-way ANOVA. The pituitaries of HE steers had 542 differentially expressed genes, and the pattern of altered gene expression was dependent on treatment. Targeted RT-PCR analysis corroborated these findings, including decreased expression of DRD2, PRL, POU1F1, GAL, and VIP and that of POMC and PCSK1, respectively. Canonical pathway analysis (Integrated Pathway Analysis, IPA) identified HE-dependent alteration in signaling of additional pituitary-derived hormones, including growth hormone and GnRH. In conclusion, consumption of endophyte-infected tall fescue alters the pituitary transcriptome profiles of steers in a manner consistent with their negatively affected physiological parameters. The second goal of this project was to test the hypothesis that sodium selenite (ISe), SEL-PLEX (OSe), vs. a 1:1 blend (MIX) of ISe and OSe in a basal vitamin-mineral (VM) mix would differentially alter pituitary transcriptome profiles in growing beef steers (BW = 183 ± 34 kg) commonly grazing an endophyte-infected tall fescue (HE) pasture. Steers were randomly selected from herds of fall-calving cows grazing HE pasture and consuming VM mixes that contained 35 ppm Se as either ISe, OSe, or MIX forms. Steers were weaned, depleted of Se for 98 d, and subjected to summer-long common grazing of a 10.1 ha HE pasture containing 0.51 ppm ergot alkaloids. Steers were assigned (n = 8) to the same Se-form treatments on which they were raised. Selenium treatments were administered by daily top-dressing 85 g of VM mix onto 0.23 kg soyhulls, using in-pasture Calan gates. Pituitaries were collected at slaughter and changes in global (microarray) and selected (RT-PCR) mRNA expression patterns determined. The effects of Se treatment on relative gene expression were subjected to one-way ANOVA. The form of Se affected the expression of 542 annotated genes. Integrated Pathway Analysis found a canonical pathway network between prolactin and POMC/ACTH/ α-MSH synthesis-related proteins, and that mitochondrial dysfunction was a top-affected canonical pathway. Targeted RT-PCR analysis found that the relative abundance of mRNA encoding prolactin and POMC/ACTH/ α-MSH synthesis-related proteins was affected by the form of Se, as were mitochondrial dysfunction-related proteins OSe steers appeared to have a greater prolactin synthesis capacity vs. ISe steers through decreased dopamine receptor D2 signaling, whereas MIX steers had a greater prolactin synthesis capacity and release potential by increasing TRH concentrations than ISe steers. OSe steers also had a greater ACTH and α-MSH synthesis potential than ISe steers. We conclude that form of Se in VM mixes affected genes responsible for prolactin and POMC/ACTH/α-MSH synthesis, and mitochondrial function in pituitaries of growing beef steers commonly grazing an HE pasture. The third goal was to test the hypothesis that sodium selenite (ISe), SEL-PLEX (OSe), vs. a 1:1 blend (MIX) of ISe and OSe in a basal vitamin-mineral (VM) mix would differentially alter selenoprotein profiles in pituitaries and livers of growing beef steers commonly grazing an endophyte-infected tall fescue (HE) pasture (i.e., the same steers used in Goal 2). The effects of Se treatment on relative gene expression were subjected to one-way ANOVA. The mRNA content of 6 selenoproteins in the pituitary was affected by Se treatments, along with two selenoprotein P receptors, whereas the expression of two selenoproteins was altered in the liver. We conclude that the change in selenoprotein gene expression in pituitaries indicates that OSe steers have a greater potential capacity to manage against oxidative damage, maintain cellular redox balance, and have a better quality control of protein-folding in their pituitaries than ISe steers. The change in selenoprotein gene expression by the liver indicates that MIX steers have a greater redox signaling capacity and capacity to manage oxidative damage than ISe steers.

Consumption of endophyte-infected (E+) grasses has long been associated with health problems in animals. In cattle E+ tall fescue consumption leads to fescue toxicosis, and in horses it leads reproductive problems. The health-related issues associated with endophyte consumption have been attributed to the effects caused by the ergot alkaloids produced by the fungus. These ergot alkaloids are considered D2-like receptor agonists, and 5-HT2 serotonin and α-adrenergic receptor partial agonists. Many studies in humans, swine, cattle, and horses have identified that ergopeptines cause a decrease in prolactin production due to their dopaminergic activities. Additionally, these molecules have been found to cause vasoconstriction in cattle and horses through their other agonistic activities. Furthermore, dopamine agonists are currently being used to treat pituitary pars intermedia dysfunction (PPID) in horses, a condition in which the horse lacks sufficient dopamine. However, the ergot alkaloids found in E+ tall fescue had not previously been investigated for their potential benefits in treating PPID horses. Moreover, little research has investigated the effects of ergot alkaloids and dopamine agonists on the immune system of horses, even though many health problems associated with E+ tall fescue consumption suggest there to be an elicited inflammatory response. Thus, the primary objective of this study was to establish an understanding of immune and hormone responses to ergot alkaloids and dopamine agonists in the horse. The hypothesis of this body of research was that ergot alkaloids and bromocriptine both would elicit inflammatory and hormone responses in the horse. Specifically, this research was conducted to determine the effects of E+ tall fescue seed consumption on immune, hormone, and vasoconstrictive responses, in both non-PPID and PPID horses. In addition, both the in vitro and in vivo effects of bromocriptine on cytokine production from equine peripheral blood mononuclear cells (PBMCs) were investigated. In the first study, there were no significant changes in body morphometrics, vasoconstriction, hormone responses or cytokine expression due to the consumption of ergot alkaloids in non-PPID and PPID horses. The second study was an in vitrostudy in which PBMCs were exposed to varying concentrations of either bromocriptine, a D2-like receptor agonist that is used as a model for ergot alkaloid consumption, or dopamine. This experiment demonstrated that exposure to dopamine or a dopamine agonist at a concentration greater than 10-5M is toxic to PBMCs, and that bromocriptine elicits an anti-inflammatory effect at concentrations less than 10-5M. Concentrations of dopamine less than 10-5M, on the other hand, did not cause any significant changes in cytokine expression. A third study was conducted that evaluated the effects of an intravenous injection of bromocriptine on hormone and immune responses in the aged mare. This study identified that bromocriptine maximally reduced prolactin levels 12 hours post-injection and prolactin returned to baseline levels approximately 56 hours post-injection. Additionally, only a significant increase in IL-1β was detected 12 hours post-injection, which suggests bromocriptine was activating an innate immune response. Overall, the body weights and rectal temperatures of horses did not significantly change in any of the experiments, which indicated that aged non-pregnant horses are able to tolerate E+ tall fescue. In addition, this body of research identified that intravenous delivery of a semi-synthetic dopamine agonist, bromocriptine, and not an oral delivery of an E+ tall fescue seed derived dopamine agonist, caused a decrease in prolactin concentrations, but revealed conflicting results regarding inflammatory responses. In summary, further research is warranted to determine the mechanism of action that dopamine agonists have on the immune system of horses.

The cultured tissues and organs of Duboisia myoporoides, an endemic medicinal plant of Australia, were investigated with the aim of establishing a relationship between organogenesis, differentiation and alkaloid localization. Histological analyses explained the relationship between cell arrangement in the cultured tissues and organs and the cytokinin/auxin combinations used at the callus induction stage. The cultured tissues and organs were analysed histochemically to localize alkaloids in different types of cells by using selected alkaloid colour reagents i.e., platinic chloride (5%) and iodoplatinate. The presence or absence of nicotine, hyoscyamine and scopolamine in the cultured tissues and organs was then confirmed by GC-MS analysis. This is the first work to show that tropane alkaloid formation in the separated cultured organs is related to xylem differentiation and tropane alkaloid formation in the calli cultured in suspension may allow commercial tropane alkaloid production without regenerating the organs. The roots of the D. myoporoides field-grown trees were colonized by the AM fungi and the mycorrhizal infection was ranged from 0-30% which indicates that the secondary metabolite atropine and scopolamine did not prevent AM fungal colonization. / Doctor of Philosophy (PhD)

<p>The development of resistance by tumour cells to chemotherapeutic agents is a major problem in cancer treatments. One way to counter this is to find compounds with cytotoxic mechanisms other than those of drugs in clinical use today. The biological and chemical diversity encountered in Nature provide opportunities to discover completely new chemical classes of compounds. Some of these may represent previously unknown anticancer agents, and in some cases, novel, potentially relevant cytotoxic mechanisms. </p><p>The selection of plants for the cytotoxic investigation in this project was designed to cover large parts of the angiosperm system, providing a broad representation of species. Extracts of the plants were subjected to a polypeptide fractionation protocol, followed by bioassay-guided isolation, yielding series of fractions with increasing purity and cytotoxicity. The cytotoxicity assay included tumour cells from patients and a cell-line panel including ten different cell lines representing several types of resistant and non-resistant tumours. This screening strategy allowed fractions and compounds acting with novel mechanisms to be detected at an early stage. </p><p>The compounds isolated represent substantial chemical diversity and originate from diverse parts of the phylogenetic spectrum examined. They include the highly potent cytotoxic alkaloid, thiobinupharidine, the structure of which was determined by NMR techniques. Furthermore, two types of compound were shown to have previously unreported cytoxic activity: cyclotides (small macrocyclic polypeptides, in this case from violets) and polypeptides, possibly of thionine type, of loranthaceaeous mistletoes (collected in Panama). The well known cardiac glycosides from the foxglove, Digitalis, were identified as being responsible for the anti-tumour activity of this species.</p><p>In conclusion, the results obtained in this project show that selection based on phylogenetic information, together with a robust and reliable method to detect cytotoxicity, can be a useful approach for exploring the plant kingdom for cytotoxic substances.</p>

The development of resistance by tumour cells to chemotherapeutic agents is a major problem in cancer treatments. One way to counter this is to find compounds with cytotoxic mechanisms other than those of drugs in clinical use today. The biological and chemical diversity encountered in Nature provide opportunities to discover completely new chemical classes of compounds. Some of these may represent previously unknown anticancer agents, and in some cases, novel, potentially relevant cytotoxic mechanisms. The selection of plants for the cytotoxic investigation in this project was designed to cover large parts of the angiosperm system, providing a broad representation of species. Extracts of the plants were subjected to a polypeptide fractionation protocol, followed by bioassay-guided isolation, yielding series of fractions with increasing purity and cytotoxicity. The cytotoxicity assay included tumour cells from patients and a cell-line panel including ten different cell lines representing several types of resistant and non-resistant tumours. This screening strategy allowed fractions and compounds acting with novel mechanisms to be detected at an early stage. The compounds isolated represent substantial chemical diversity and originate from diverse parts of the phylogenetic spectrum examined. They include the highly potent cytotoxic alkaloid, thiobinupharidine, the structure of which was determined by NMR techniques. Furthermore, two types of compound were shown to have previously unreported cytoxic activity: cyclotides (small macrocyclic polypeptides, in this case from violets) and polypeptides, possibly of thionine type, of loranthaceaeous mistletoes (collected in Panama). The well known cardiac glycosides from the foxglove, Digitalis, were identified as being responsible for the anti-tumour activity of this species. In conclusion, the results obtained in this project show that selection based on phylogenetic information, together with a robust and reliable method to detect cytotoxicity, can be a useful approach for exploring the plant kingdom for cytotoxic substances.

A number of 3,3'-disubstituted binaphthol-modified allylboronates (<strong>2. 42a-m</strong>) were prepared from the reaction between triallylborane and the corresponding 3,3'-disubstituted binaphthols. These chiral allylboronates could allylate carbonyl compounds to produce chiral homoallylic alcohols in high chemical and optical yields. Chiral ligands were readily recycled through simple acid-base extraction. Among all allylboronates tested, 3,3'-(CF₃)₂-BINOL-modified allylboronate (<strong>2. 42b</strong>) is an especially effective reagent that allows for allylborations of both aldehydes and ketones in high enantioselectivities (up to 98% yield and >99% <em>ee</em>). Reagent <strong>2. 42b</strong> represents one of the best allylation reagents for carbonyl compounds developed thus far. <br /><br /> Allylations of cyclic imines using 3,3'-disubstituted binaphthol-modified allylboronates (<strong>2. 42a-j</strong>) were carried out at low temperature. 3,3'-Bis[3,5-(CF₃)₂-C₆H₃]-binaphthol-modified allylboronate (<strong>2. 42j</strong>) gave the best enantioselectivities (91% <em>ee</em> to >99% <em>ee</em>) in the allylation of a variety of cyclic imines. This methodology represents the first successful enantioselective allylboration of cyclic imines. The versatility of the allylation products (chiral a-allyl cyclic amines) was demonstrated through efficient total syntheses of several naturally occurring alkaloids such as coniine, crispine A and corynantheidol. <br /><br /> 3,3'-Disubstituted binaphthol-modified alkynylboronates (<strong>4. 47a-g</strong>) were synthesized according to a reported procedure. It was found that these chiral alkynylboronates add to <em>N</em>-acylaldimines in an enantioselective manner to produce chiral propargylamides in excellent yields and enantioselectivities. Up to >99% <em>ee</em> could be obtained with 3,3'-diphenyl binaphthol-modified alkynylboronates (<strong>4. 47f</strong>). This represents the first direct asymmetric synthesis of chiral propargylamides. Using this methodology, an antitubulin agent (-)-<em>N</em>-acetylcolchinol (AstraZeneca® ZD6126 phenol) was synthesized in 4 steps from commercially available 3-hydroxybenzaldehyde. <br /><br /> During a study of the asymmetric conjugate alkynylation of enones via chiral alkynylboronates, it was found that achiral dialkyl alkynylboronates could add to enones enantioselectively in the presence of catalytic amounts of chiral bidentate ligands (such as 3,3'-disubstituted binaphthols, diisopropyl tartrate and activated chiral amino acids). A catalytic cycle driven by "ligand-exchange" processes was proposed to rationalize this asymmetric induction. This is the first reported example of an asymmetric reaction that is promoted by a catalytic amount of an exchangeable chiral ligand on the boron reagent. More importantly, we have demonstrated a proof of principle that ligand exchange with boronates can be sufficiently fast that catalytic amounts of chiral ligands can be used to effect high levels of stereoselectivity. This catalytic protocol can potentially be applied to other asymmetric reactions providing the following three requirements are met: (1) the starting achiral boronate does not react with the electrophile (no background reaction); (2) the chiral boronate reacts with the electrophile and (3) ligand exchange or transesterification occurs under the reaction conditions. Potential applications of this principle include asymmetric allylboration, hydroboration, aldol reaction and reduction, just to name a few.

A number of 3,3'-disubstituted binaphthol-modified allylboronates (<strong>2. 42a-m</strong>) were prepared from the reaction between triallylborane and the corresponding 3,3'-disubstituted binaphthols. These chiral allylboronates could allylate carbonyl compounds to produce chiral homoallylic alcohols in high chemical and optical yields. Chiral ligands were readily recycled through simple acid-base extraction. Among all allylboronates tested, 3,3'-(CF₃)₂-BINOL-modified allylboronate (<strong>2. 42b</strong>) is an especially effective reagent that allows for allylborations of both aldehydes and ketones in high enantioselectivities (up to 98% yield and >99% <em>ee</em>). Reagent <strong>2. 42b</strong> represents one of the best allylation reagents for carbonyl compounds developed thus far. <br /><br /> Allylations of cyclic imines using 3,3'-disubstituted binaphthol-modified allylboronates (<strong>2. 42a-j</strong>) were carried out at low temperature. 3,3'-Bis[3,5-(CF₃)₂-C₆H₃]-binaphthol-modified allylboronate (<strong>2. 42j</strong>) gave the best enantioselectivities (91% <em>ee</em> to >99% <em>ee</em>) in the allylation of a variety of cyclic imines. This methodology represents the first successful enantioselective allylboration of cyclic imines. The versatility of the allylation products (chiral a-allyl cyclic amines) was demonstrated through efficient total syntheses of several naturally occurring alkaloids such as coniine, crispine A and corynantheidol. <br /><br /> 3,3'-Disubstituted binaphthol-modified alkynylboronates (<strong>4. 47a-g</strong>) were synthesized according to a reported procedure. It was found that these chiral alkynylboronates add to <em>N</em>-acylaldimines in an enantioselective manner to produce chiral propargylamides in excellent yields and enantioselectivities. Up to >99% <em>ee</em> could be obtained with 3,3'-diphenyl binaphthol-modified alkynylboronates (<strong>4. 47f</strong>). This represents the first direct asymmetric synthesis of chiral propargylamides. Using this methodology, an antitubulin agent (-)-<em>N</em>-acetylcolchinol (AstraZeneca® ZD6126 phenol) was synthesized in 4 steps from commercially available 3-hydroxybenzaldehyde. <br /><br /> During a study of the asymmetric conjugate alkynylation of enones via chiral alkynylboronates, it was found that achiral dialkyl alkynylboronates could add to enones enantioselectively in the presence of catalytic amounts of chiral bidentate ligands (such as 3,3'-disubstituted binaphthols, diisopropyl tartrate and activated chiral amino acids). A catalytic cycle driven by "ligand-exchange" processes was proposed to rationalize this asymmetric induction. This is the first reported example of an asymmetric reaction that is promoted by a catalytic amount of an exchangeable chiral ligand on the boron reagent. More importantly, we have demonstrated a proof of principle that ligand exchange with boronates can be sufficiently fast that catalytic amounts of chiral ligands can be used to effect high levels of stereoselectivity. This catalytic protocol can potentially be applied to other asymmetric reactions providing the following three requirements are met: (1) the starting achiral boronate does not react with the electrophile (no background reaction); (2) the chiral boronate reacts with the electrophile and (3) ligand exchange or transesterification occurs under the reaction conditions. Potential applications of this principle include asymmetric allylboration, hydroboration, aldol reaction and reduction, just to name a few.

Chapter 1: Reaction of benzoaldehyde with wittig agents or isophone to build up conjugate carbon chain, then combined with electron acceptor to furnished the chromophores. The charge-transfer chromophores, which have the first molecular hyperpolarizability

In this study, aerobic biological treatment of opium alkaloid wastewater and the effect of gamma preirradiation and fenton&amp / #8217 / s oxidation were investigated. First, the biodegradability of alkaloid wastewater was investigated by batch reactors and wastewater was found to be highly biodegradable providing 83 &amp / #8211 / 90 % COD degradation. In order to evaluate the effect of irradiation, original wastewater and irradiated wastewaters (40 &amp / 140 kGy) were compared by means of BOD5/COD values and through aerobic batch experiments. Results indicated that irradiation imparted no further enhancement in biodegradability. Sequencing batch reactor (SBR) studies revealed that the treatment operation was not possible due to sludge settleability problem observed beyond an influent COD value of 2 g/L. Possible reasons for problem were investigated, and the high molecular weight, larger size and aromatic structure of the organic matters present in wastewater was thought to contribute to poor settleability characteristics. Some operational modifications including phosphate buffer addition cured the settleability problem. Influent COD was then increased to 5,000 mg/L. Significant COD removal efficiencies (&gt / 70 %) were obtained in SBRs fed with both original and irradiated wastewaters. Preirradiated wastewater provided a better settling sludge in comparison to original wastewater. Degradation of the complex structure was followed by GC/MS analyses, particle size measurements and enhancement in filterability. Pre-irradiation enhanced the filterability of wastewater more than Fenton&amp / #8217 / s treatment and degradation by irradiation was proved by GC/MS analyses.