1,1-enediamines and β-substituted enamines in heterocyclic synthesis

The work in this thesis mainly deals with l,l-enediamines and ~ -substituted enamines (push-pull olefines) and their reactions, leading to the formation of a number of heterocycles. Various ~-substituted enamines were prepared by a 'one pot synthesis' in which a l,l-enediamine presumably acts as an intermediate. These enamines, various substituted crotonamides and propenamides, were made by using two different orthoesters, various secondary and primary amines and cyanoacetamide. Their structures, mechanism of formation and geometry are discussed. A synthetic route to various unsymmetrically substituted pyridines was examined. Two substituted pyridinones were obtained by using two different ~-substituted enamines and cyanoacetamide. In one case a dihydropyridine was isolated. This dihydropyridine, on heating in acidic conditions, gave a pyridinone, which confirmed this dihydropyridine as an intermediate in this pyridine synthesis. A new synthetic method was used to make highly substituted pyridinones, which involved the reaction of l,l-enediamines with the ~-substituted enamines. A one pot synthesis and an interrupted one pot synthesis were used to make these pyridinones. Two different orthoesters and three different secondary amines were used. Serendipitous formation of a pyrimidinone was observed when pyrrolidine was used as the secondary amine and triethyl orthopropionate was used as the orthoester. In all cases cyanoacetamide was used as the carbon acid. This pyridine synthesis was designed with aI, l-enediamine as the Michael donor and the ~ -substituted enamines as Michael acceptors. Substituted ureas were obtained in two cases, which was a surprise. Some pyrimidines were made by reacting two substituted enamines with two different amidines. When benzamidine was used, the expected pyrimidines were obtained. But, when 2-benzyl-2-thiopseudourea (which is also an amidine) was used, of the two expected pyrimidines, only one was obtained. In the other case, an additional substitution reaction took place in which the S-benzyl group was lost. An approach to quinazolone and benzothiadiazine synthesis is discussed. Two compounds were made from 1, I-dimorpholinoethene

A biochemical predictor of performance during mesophilic anaerobic fermentation of starch wastewater

The aim of this study was to determine the potential of biochemical parameters, such as enzyme activity and adenosine triphosphate (ATP) levels, as monitors of process performance in the Upflow Anaerobic Sludge Blanket (UASB) reactor utilizing a starch wastewater. The acid and alkaline phosphatase activity and the ATP content of the UASB sludge were measured in response to changes in flow rate and nutrient loading. Conventional parameters of process performance, such as gas production, acetic acid production, COD, phosphorus, nitrogen and suspended solids loadings and % COD removal were also monitored. The response of both biochemical and conventional parameters to changing process conditions was then compared. Alkaline phosphatase activity exhibited the highest activity over the entire study perioda A high suspended solids loading was observed to upset the system in terms of gas production, acetic acid production and % COD removala The initial rate of increase in alkaline phosphatase activity following an increase in loading was four times as great during process upset than under conditions of good performance. The change in enzyme actiVity was also more sensitive to process upset than changes in acetic acid production. The change in ATP content of the sludge with time suggested that enzyme actiVity was changing independently of the actual viable biomass present. The bacterial composition of the anaerobic sludge granules was similar to that of other sludge bed systems, at the light and scanning electron microscope level. Isolated serum bottle cultures produced several acids involved in anaerobic carbohydrate metabolism. The overall performance of the UASB system indicated that higher loadings of soluble nutrients could have been tolerated by the system.

A case study of a high functioning autistic female in a games setting

This study detennined whether or not a high functioning autistic girl can develop game structure strategies that may allow her to become an active participant in a game or sport environment. This qualitative case study involved the in-depth observation and description of one high functioning autistic student whose experience in a game setting would be studied. The type of case study carried out was a combination of descriptive and evaluative. This experience was investigated through structured, individual programming. Through on-site observation, journal entries, and hands on instruction, I was able to describe what progress the autistic student made in tenns of skill development. The results of the study demonstrated that a high-functioning autistic female has the potential to develop the necessary motor skills to participate in the chosen sport of basketball. The observation results and field notes contributed to a movement profile which described her habits of body. Teaching strategies and frameworks utilized during the study were described and listed. Insights and commentary are further provided. A thorough examination of autism and games programming is provided in the literature review.

A classroom-based investigation of reciprocal teaching at the grade seven level

This study assessed the effectiveness of a reciprocal teaching program as a method of teaching reading comprehension, using narrative text material in a t.ypical grade seven classroom. In order to determine the effectiveness of the reciprocal teaching program, this method was compared to two other reading instruction approaches that, unlike rcciprocal teaching, did not include social interaction components. Two intact grade scven classes, and a grade seven teacher, participated in this study. Students were appropriately assigned to three treatment groups by reading achievement level as determined from a norm-referenced test. Training proceeded for a five week intervention period during regularly scheduled English periods. Throughout the program curriculum-based tests were administered. These tests were designed to assess comprehension in two distinct ways; namely, character analysis components as they relate to narrative text, and strategy use components as they contribute to student understanding of narrative and expository text. Pre, post, and maintenance tests were administered to measure overall training effects. Moreover, during intervention, training probes were administered in the last period of each week to evaluate treatment group performance. AU curriculum-based tests were coded and comparisons of pre, post, maintenance tests and training probes were presented in graph form. Results showed that the reciprocal group achieved some improvement in reading comprehension scores in the strategy use component of the tests. No improvements were observed for the character analysis components of the curriculum-based tests and the norm-referenced tests. At pre and post intervention, interviews requiring students to respond to questions that addressed metacomprehension awareness of study strategies were administered. The intelviews were coded and comparisons were made between the two intelVicws. No significant improvements were observed regarding student awareness of ten identified study strategies . This study indicated that reciprocal teaching is a viable approach that can be utilized to help students acquire more effective comprehension strategies. However, the maximum utility of the technique when administered to a population of grade seven students performing at average to above average levels of reading achievement has yet to be determined. In order to explore this issue, the refinement of training materials and curriculum-based measurements need to be explored. As well, this study revealed that reciprocal teaching placed heavier demands on the classroom teacher when compared to other reading instruction methods. This may suggest that innovative and intensive teacher training techniques are required before it is feasible to use this method in the classroom.

A cognitive schematic paradigm for expository essay writing in secondary schools

The methodology outlined in this study for teaching exposit ory writing to advanced (five year phase) grade eleven students is based on the assumption that writing as a problem solving strategy is a high level cognitive skill . In adhering to this assumption, a cognitively based schematic organizer known as a cross-classification chart was tested for its effectiveness a t the planning stage of the writing process . Results were not significant in any of the three components that were evaluated; however , a post- hoc analysis undertaken because of recorded observed data indicated a significant difference in the mean score on the Organization component for the treatment subgroup using the cross- classification organizer . Furthermore, the treatment group's positive response from the attitude survey towards planning writing is encouraging enough that replication and extension of the application of schema theory to wri ting should be pursued in cross-section and longitud i nal studies.

A comparative study of chitin synthase activity in two Mortierella species

An in vitro investigation of some important factors controlling the activity of chitin synthase in cell-free extracts of two Mortierella species has been carried out. Mixed membrane fractions from mycelial homogenates of Mortierella candelabrum and Mortierella pusilla were found to catalyse the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine into an insoluble product characterized as chitin by its insolubility in weak acid and alkali, and the release of glucosamine and diacetylchitobiose on hydrolysis with a strong acid and chitinase, respectively. Apparent Km values for UDP-GlcNAc were 1.8 mM and 2.0 mM for M. pusilla and ~ candelabrum, respectively. Polyoxin D was found to be a very potent competitive inhibitor with values of the constant of inhibition, Ki' for both species about three orders of magnitude lower than theKm for UDP-GlcNAc. A divalent cation, Mg+2 , Mn+2 or Co+2 , was required for activity. N-acetylglucosamine, the monomer of chitin, stimulated the activity of the enzyme. The crude enzyme preparation of ~ candelabrum, unlike that of ~ pusilla, showed an absolute requirement for both Mg+2 and N-acetylglucosamine. Large differences in response to exogenous proteases were noted in the ratio of active to inactive chitin synthase of the two species. A fifteen fold or greater increase was obtained after treatment with acid protease (from Aspergillussaitoi) as compared to a two- to four-fold activation of the M. pusilla membrane preparation treated similarly. During storage at 4°C over 48 hours, an endogenous activation of chitin synthase of ~ pus ilIa was achieved, comparable to that obtained by exogenous protease treatment. The high speed supernatant of both species inhibited the chitin synthase activity of the mixed membrane fractions. The inhibitor of ~ pus ilIa was effective against the pre-activated enzyme whereas that of M. candelabrum inhibited the activated enzyme. Several possibilities are discussed as to the role of the different factors regulating the enzyme activity. The suggestion is made from the properties of chitin synthase in the two species that in vivo a delicate balance exists between the activation and inactivation of the enzyme which is responsible for the pattern of wall growth of each fungus.

A comparative study of in vitro chitin synthase activity in mucoraceous hosts of a mycoparasite

A comparative study of in vitro chitin synthase activity in mucoraceous hosts of a mycoparasite: Chitin synthase, the enzyme responsible for the synthesis of chitin in fungal cell wall was extracted from young hyphae of Choanephora cucurbitarum and Phascolomyces articulosus, susceptible and resistant hosts, respectively, to the mycoparasite, Piptocephalis virginiana. Crude enzyme was identified and characterized by measuring the incorporation of the substrate [14C]-UDP-N-acetylglucosamine, into chitin. Most activity occurred in mixed membrane fraction. Inhibition of activity with Polyoxin D and activation with proteases, N-acetyl-glucosamine and magnesium and other ions was observed. Properties of the crude enzyme preparation such as cofactor requirement, Vmax , apparent Km value for UDP-GlcNAc, inhibition by Polyoxin D, response to pH and to temperature, and stability at 4°C were determined. Enzyme activity from both fungi displayed basically the same features as the corresponding enzymes reported from other mucoraceous fungi. However, the two preparations from P. articulosus and C. cucurbitarum differed from each other in their expressed activity (i.e., the preparations from ~ articulosus exhibited higher latency and higher specific chitin synthase activity than the corresponding preparations from ~ cucurbitarum). Trypsin was effective in activation only over a narrow concentration range. Acid protease was the most effec.tive activator. En.dogenous protease estimation indicated higher protease activity in C. cucurbitarum than in P. articulosus. The suggestion is made that regulation of chitin synthase activities may be related to host resistance in the mycoparasitic system.

A comparative study of protoheme and heme d catalases : role of the heme and the heme pocket in catalysis and ligand binding

Catalase dismutes H20 2 to O2 and H20. In successive twoelectron reactions H20 2 induces both oxidation and reduction at the heme group. In the first step the protoheme prosthetic group of beef liver catalase forms compound I, in which the heme has been oxidized from Fe3+ to Fe4+=0 and a porphyrin radical has been created. Compound II is formed by the oneelectron reduction of comp I. It retains Fe4+=0 but lacks the porphyrin radical and is catalytically inert. Molecular structures are available for Escherichia coli Hydroperoxidase II, Micrococcus Iysodeiktus, Penicillium vitale and beef liver enzymes, which contain different hemes and heme pockets. In the present work, the pockets and substrate access channels of protoheme (beef liver & Micrococcus) and heme d (HPII of E. coli and Penicillium) catalases have been analysed using Quanta™ and CharmMTM molecular modeling packages on the Silicon Graphics Iris Indigo 2 computer. Experimental studies have been carried out with two catalases, HPII (and its mutants) and beef liver. Fluoride and formate' are inhibitors of both enzymes, and their binding is modulated by the heme and by distal residues N201 & H128. Both HPII and beef liver enzymes form compound I with H202 or peracetate. The reduction of beef liver enzyme compound I to II and the decay of compound II are accelerated by fluoride. The decay of compound II is also accelerated by formate, and this reagent acts as a 2-electron donor towards compound I of both enzymes. It is concluded that heme d enzymes (Penicillium and HPII of E. coli) are formed by autocatalytic transformation of protoheme in a modified pocket which contains a characteristic serine residue as well as a partially occluded heme channel. They are less active than protoheme enzymes but also do not form the inactive compound II species. Binding of peroxide as well as fluoride and formate is prevented by mutation of H128 and modulated by mutation of N201.

A comparison between diatom inferred ph changes and diatom populations in brownwater and clearwater lakes

The objective of this study was to determine whether clearwater and brownwater lakes differed in their rate of acidification as inferred by subfossil diatoms analyzed in recent downcore sediments. Differences between associations of diatom populations in brownwater and clearwater environments were characterized. Sediment cores were taken from four lakes located north and east of Lake Superior, near Wawa, Ontario. Two of these lakes were humicrich, brownwater lakes ( lakes U1 and CB2). The two other lakes were clearwater lakes ( lakes Xl and CF). The regression of Nygaard log index-alpha for surficial diatom sediments on observed pH ( Inferred pH = 6.57 - 0.82 log index-alpha ), was utilized to infer lake pH in recent sediments of these lakes. Upon analyzing the downcore diatoms, it was discovered that no significant change, in downcore diatom inferred pH, could be detected in the two brownwater lakes. In contrast, the two clearwater lakes showed significant shifts in downcore diatom inferred pH. In one of these lakes, pH had dropped from 5.3 to 4.5, in the top 9.0 cm of the core, while in the second lake, pH had dropped from 5.4 to 5.0 in the top 1.5 cm of the core. These findings suggested that humic substances, found in brownwater lakes, imparted a buffering capacity to these lake waters. In the clearwater lakes, the decrease in pH was very probably a consequence of acid precipitation. The Ambrosia rise ( circa 1890 ) occurred at the same depth in both brownwater lakes ( 11.0 - 12.0 cm). In both clearwater lakes, the Ambrosia rise occurred at a depth of 14.0 - 15.0 cm. This suggested a lower sedimentation rate in the brownwater lakes. pH influenced the total percentage composition of diatom pH indicator groups. Greater numbers of alkaliphilous taxa were found in less acidic lakes ( e.g. Lake Ul ), While greater numbers of acidloving forms were found in highly acidic lakes ( e.g. Lake Xl ). There was a greater abundance of indifferent forms in the brownwater lakes, than in the clearwater lakes. A number of diatom genera and species were found to be associated with either clearwater or brownwater conditions. The centric diatom, ~elosira distans, significantly increased in abundance in the recent sediments of both clearwater lakes. This may be indicating a shift toward a more oligotrophic state within these acidic, clearwater lakes. This study suggested that a pH index based on subfossil diatoms may be a sensitive indicator of changing lake pH. This study also indicated that humic substances may playa more important role, than previously acknowledged, in controlling the pH dynamics of lake waters, and in determining diatom populations.

A comparison of cognitive processes and components of neurological maturation in 3-and-11 year-old children

The relationship between the child's cogni tive development and neurological maturation has been of theoretical interest for many year s. Due to diff iculties such as the lack of sophisticated techniques for measur ing neurolog ical changes and a paucity of normative data, few studies exist that have attempted to correlate the two factors. Recent theory on intellectual development has proposed that neurological maturation may be a factor in the increase of short-term memory storage space. Improved technology has allowed reliable recordings of neurolog ical maturation.. In an attempt to correlate cogni tive development and neurological maturation, this study tested 3-and II-year old children. Fine motor and gross motor short-term memory tests were used to index cogni tive development. Somatosensory evoked potentials elici ted by median nerve stimulation were used to measure the time required for the sensation to pass along the nerve to specific points on the somatosensory pathway. Times were recorded for N14, N20, and P22 interpeak latencies. Maturation of the central nervous system (brain and spinal cord) and the peripheral nervous system (outside the brain and spinal cord) was indi~ated by the recorded times. Signif icant developmental di fferences occurred between 3-and ll-year-olds in memory levels, per ipheral conduction velocity and central conduction times. Linear regression analyses showed that as age increased, memory levels increased and central conduction times decreased. Between the ll-year-old groups, there were no significant differences in central or peripheral nervous system maturation between subjects who achieved a 12 plus score on the digit span test of the WISC-R and those who scored 7 or lower on the same test. Levels achieved on the experimental gross and fine motor short-term memory tests differed significantly within the ll-year-old group.

A comparison of life satisfaction, job satisfaction, and happiness using demographic variables

This study examined the interrelationships among life satisfaction, job satisfaction, and happiness and the selected demographic variables of income, age, marital status, education, sex, job tenure, job title, type of school, and location of employment. Survey data were collected from 1,993 elementary, high school, and community college teachers in the southern Ontario area, representing ten public school boards, three Roman Catholic school boards and three community colleges. Several theories were utilized in developing thirteen hypotheses and eleven experimental hypotheses. A thorough review of the literature (to January, 1980) was undertaken and major conclusions noted. Hoppock's (1935) Job Satisfaction Measure, Gurin, Veroff, and Feld's (1960) Happiness Scale, and Converse and Robinson's (1965) Life Satisfaction Scale were used as the instrument. Chi-square analysis was employed as the statistical method. Indicative of the findings: the level of education taught was significantly related to all three organizational variables, sex was unrelated to life satisfaction though positively related to job satisfaction, and income was found not to be related to either happiness or life satisfaction. A minority of findings were contrary to hypothesized relationships. Specifically, age was found to be unrelated to any of the three organizational variables, and educational achievement was not significantly related to happiness. A model was developed to illustrate the interrelationships of the organizational and demographic variables. This model was designed specifically to reflect teacher attitudes, though it may have reasonable application for other relatively homogeneous groups of employees such as nurses, engineers, or social workers.

A comparison of two computer-assisted remedial reading programs for adolescent unskilled readers : component reading skills and repeated reading

This study compared the relative effectiveness of two computerized remedial reading programs in improving the reading word recognition, rate, and comprehension of adolescent readers demonstrating significant and longstanding reading difficulties. One of the programs involved was Autoskill Component Reading Subskills Program, which provides instruction in isolated letters, syllables, and words, to a point of rapid automatic responding. This program also incorporates reading disability subtypes in its approach. The second program, Read It Again. Sam, delivers a repeated reading strategy. The study also examined the feasibility of using peer tutors in association with these two programs. Grade 9 students at a secondary vocational school who satisfied specific criteria with respect to cognitive and reading ability participated. Eighteen students were randomly assigned to three matched groups, based on prior screening on a battery of reading achievement tests. Two I I groups received training with one of the computer programs; the third group acted as a control and received the remedial reading program offered within the regular classroom. The groups met daily with a trained tutor for approximately 35 minutes, and were required to accumulate twenty hours of instruction. At the conclusion of the program, the pretest battery was repeated. No significant differences were found in the treatment effects of the two computer groups. Each of the two treatment groups was able to effect significantly improved reading word recognition and rate, relative to the control group. Comprehension gains were modest. The treatment groups demonstrated a significant gain, relative to the control group, on one of the three comprehension measures; only trends toward a gain were noted on the remaining two measures. The tutoring partnership appeared to be a viable alternative for the teacher seeking to provide individualized computerized remedial programs for adolescent unskilled readers. Both programs took advantage of computer technology in providing individualized drill and practice, instant feedback, and ongoing recordkeeping. With limited cautions, each of these programs was considered effective and practical for use with adolescent unskilled readers.

A cytophylogenetic study of Pacific black flies (Diptera: Simuliidae)

The sequential banding patterns of the larval salivary gland polytene chromosomes of seven species of Inseliellum (Diptera: Simuliidae) were mapped. This was completed through the comparison with the standard maps of an eighth species of Inseliellum, Simulium cataractarum. During chromosomal analysis, both fixed and floating inversions were identified. A floating inversion (IIL-l ex,2ex) revealed a cytotype within Simulium exasperans that is distributed between two islands, Moorea and Tahiti. Inversion data revealed three shared fixed inversions that could be used as phylogenetic characters. In addition, the placement of a chromosomal landmark (the nucleolar organizer, or NO) was used as a phylogenetic character. The result of a cytophylogenetic (transformational) analysis showed two groups: the NO-IL group, and the NO-IS group. A combined phylogeny was created using the published morphological data and the cytological data of the eight species. The combined tree did not differ from the morphological data only tree. Possible routes of dispersal are hypothesized using geological, chromosomal, and phylogenetic data. These data showed a general pattern of dispersal and colonization from older islands to younger islands, with one possible instance of dispersal from younger to older islands. It is postulated that inter-island speciation has allowed this dispersal and colonization, but intra-island speciation has created the diversity seen in Inseliellum.

A dimensional analysis of the benzylic hydroxylase active site in mortierella isabellina

The spatial limits of the active site in the benzylic hydroxylase enzyme of the fungus Mortierella isabellina were investigated. Several molecular probes were used in incubation experiments to determine the acceptability of each compound by this enzyme. The yields of benzylic alcohols provided information on the acceptability of the particular compound into the active site, and the enantiomeric excess values provided information on the "fit" of acceptable substrates. Measurements of the molecular models were made using Cambridge Scientific Computing Inc. CSC Chem 3D Plus modeling program. i The dimensional limits of the aromatic binding pocket of the benzylic hydroxylase were tested using suitably substituted ethyl benzenes. Both the depth (para substituted substrates) and width (ortho and meta substituted substrates) of this region were investigated, with results demonstrating absolute spatial limits in both directions in the plane of the aromatic ring of 7.3 Angstroms for the depth and 7.1 Angstroms for the width. A minimum requirement for the height of this region has also been established at 6.2 Angstroms. The region containing the active oxygen species was also investigated, using a series of alkylphenylmethanes and fused ring systems in indan, 1,2,3,4-tetrahydronaphthalene and benzocycloheptene substrates. A maximum distance of 6.9 Angstroms (including the 1.5 Angstroms from the phenyl substituent to the active center of the heme prosthetic group of the enzyme) has been established extending directly in ii front of the aromatic binding pocket. The other dimensions in this region of the benzylic hydroxylase active site will require further investigation to establish maximum allowable values. An explanation of the stereochemical distributions in the obtained products has also been put forth that correlates well with the experimental observations.