Exploring the experiences of male spousal caregivers for their wives with alzheimer disease in their homes : the lived experience and the men's perception of support groups /

This research is qualitative in nature and has explored, by means of interviews, the '^^ experiences of 10 men in their roles in caring for their spouses with Alzheimer Disease (see glossary) in their homes. Additional data were collected by attending 3 formal support group meetings and one informal meeting of a group of men who brought their wives to a support group meeting for their wives with AD. The data retrieved supported the assumption that education about the disease, utilization of formal community support services, and attendance at caregiver support groups or programs can assist healthy male caregivers in caring for their wives with AD in their homes.

Perceptions of some teachers about the similarities and/or differences in teaching online versus in a classroom environment /

The introduction of computer and communications technology, and particularly the internet, into education has opened up some new possibilities for teaching and learning. Courses designed and delivered in an online environment offer the possibility of highly interactive and individually focussed teaching and learning experiences. However, online courses also present new challenges for both teachers and students. A qualitative study was conducted to explore teachers' perceptions about the similarities and differences in teaching in the online and face-to-face (F2F) environments. Focus group discussions were held with 5 teachers; 2 teachers were interviewed in depth. The participants, 3 female and 2 male, were full-time teachers from a large College of Applied Arts & Technology in southern Ontario. Each of them had over 10 years of F2F teaching experience and each had been involved in the development and teaching of at least one online course. i - -; The study focussed on how teaching in the online environment compares with teaching in the F2F environment, what roles teachers and students adopt in each setting, what learning communities mean online and F2F and how they are developed, and how institutional policies, procedures, and infrastructure affect teaching and learning F2F and online. This study was emic in nature, that is the teachers' words determine the themes identified throughout the study. The factors identified as affecting teaching in an online environment included teacher issues such as course design, motivation to teach online, teaching style, role, characteristics or skills, and strategies. Student issues as perceived by the teachers included learning styles, role, and characteristics or skills. As well, technology issues such as a reliable infrastructure, clear role and responsibilities for maintaining the infrastructure, support, and multimedia capability affected teaching online. Finally, administrative policies and procedures, including teacher selection and training, registration and scheduling procedures, intellectual property and workload policies, and the development and communication of a comprehensive strategic plan were found to impact on teaching online. The teachers shared some of the benefits they perceived about teaching online as well as some of the challenges they had faced and challenges they perceived students had faced online. Overall, the teachers feh that there were more similarities than differences in teaching between the two environments, with the main differences being the change from F2F verbal interactions involving body language to online written interactions without body language cues, and the fundamental reliance on technology in the online environment. These findings support previous research in online teaching and learning, and add teachers' perspectives on the factors that stay the same and the factors that change when moving from a F2F environment to an online environment.

The nature experiences of wilderness recreation leaders : throwing a stone

Through this descriptive exploratory study, the ways that wilderness recreation leaders experience nature are illuminated, deconstructing the assumed environmental benefits of and practices used in outdoor recreation (Haluza-Delay, 2001). This study also offers a foundation for advancing an environmental ethic among wilderness recreation leaders, participants, and organizations. With the continued degradation of and threats to natural environments, and the rising popularity of outdoor recreation participation, the outdoor recreation professional can be a leader in promoting human reconnections to the Earth (Henderson, 1999). Leaders of outdoor recreation experiences play an important role in encouraging these revived relationships to natural settings and can contribute to the necessary environmental consciousness shift needed within Western society (Hanna, 1995; Jordan, 1996). The purpose of this research was to describe the lived-experience in nature of wilderness recreation leaders. Specifically, a phenomenological method of inquiry was used to describe the meaning of nature, the connections and relationships to nature, and the behaviours and emotions experienced in nature by a group of wilderness canoe trip leaders employed by a residential summer camp. In addition to the implications of this research, achieving this outcome provides a rich descriptive understanding of wilderness leaders' experiences—a basis from which to extend future research endeavours and programmatic practices that promote effective environmental outcomes of outdoor recreation participation. Each of the five study participants was employed in the summer of 2003 by an Ontario residential summer camp organization that sponsors extended wilderness river canoe trips for youth. Two in-depth and semi-structured interviews were performed with each participant, asking them to reflect on the canoe trip that they led for the summer camp organization during 2003. Phenomenological data was analyzed according to Colaizzi's (1978) thematic analysis process. Consistent with van Manen's (1997) emphasis on phenomenological writing, the final result presents the essence of the nature experiences of wilderness recreation leaders in the format of a narrative description. This narrative piece is the culmination of this research effort. Throughout the journey, however, various foundations within the outdoor recreation field, such as minimum impact principles, environmentally responsible behaviours, anthropocentric and ecocentric worldviews, and effective leadership are deconstructed and discussed.

The Elucidation of the involvement of endonuclease DNase y in reducing DNA transfection efficiency in mammalian cells

Gene therapy is predicated upon efficient gene transfer. While viral vectors are the method of choice for transformation efficiency, the immunogenicity and safety concerns remain problematic. Non-viral vectors, on the other hand, have shown high degrees of safety and are mostly non-immunogenic in nature. However, non-viral vectors usually suffer from low levels oftransformation efficiency and transgene expression. Thus, increasing transformation efficiency ofnon-viral vectors, in particular by calcium phosphate co-precipitation technique, is a way of generating a suitable vector for gene therapy and is the aim of this study. It is a long known fact that different cell lines have different transfection efficiencies regardless oftransfection methodology (Lin et a!., 1994). Using commonly available cell lines Madine-Darby Bovine Kidney (MDBK), HeLa and Human Embryonic Kidney (HEK-293), we have shown a decreasing trend ofDNase activity based on a plasmid digestion assay. From densitometry studies, as much as a 40% reduction in DNase activity was observed when comparing HEK-293 (least active) to MDBK (most active). Using various biochemical assays, it was determined that DNase y, in particular, was expressed more highly in MDBK cells than both HeLa and HEK-293. Upon cloning of the bovine DNase y gene, we utilized the sequence information to construct antisense expressing plasmids via both traditional antisense RNA (pASDGneoM) and siRNA (psiRNA-S4, psiRNA-S11 and psiRNA-S16). For the construction ofpASDGneoM, the 3' end of the DNase y was inserted in opposite orientation under a cytomegalovirus (CMV) promoter such that the expression ofRNA complementary to the DNase 2 ymRNA occurred. For siRNA plasmids, the sequence was screened to yield optimal short sequences for siRNA inhibition. The silencing ofbovine DNase y led to an increase in transfection efficiency based on traditional calcium phosphate co-precipitation technique; stable clones of siRNA-producing MDBK cell lines (psiRNA-S4 Bland psiRNA-S4 B4) both demol).strated 4-fold increases in transfection efficiency. Furthermore, serial transfection of antisense DNase y plasmid pASDGneoM and reporter pCMV-~ showed a maximum of 8-fold increase in transfection efficiency when the two separate transfections were carried out 4 hours apart (i.e. transfection ofpASDGneoM, separated by four hours, then transfection ofpCMV-~). Together, these results demonstrate the involvement ofDNase y in reducing transfection efficiency, at least by traditional calcium phosphate technique.

Transforming curriculum leadership: vice principals in independent Christian elementary schools /

The literature on the vice principalship characterizes the position as one filled with clerical record keeping and student discipline and paints a picture of role conflict and general discontent. Research suggests that vice principals desire to take on a more significant role, specifically a role in curriculum leadership. Using open-ended interviews, a focus group interview, document analysis, and my research journal, I have explored the work ofa group of vice principals who have taken on the role of curriculum leader in independent Christian elementary schools in Ontario. When asked to explain their understanding of curriculum, the participants referred to written programs of study. However, their leadership activities reveal a broader understanding of curriculum as something that is in fact dynamic in nature. This leadership is enabled and shaped by their middle position on staff that combines the authority of an administrator and the credibility of a teacher. Although this dual identity creates tension, it also provides opportunities for genuine curriculum leadership. As middle leaders, the participants in this study often pull together or connect elements of the curriculum (teachers, principals, and programs) that have become separated. Such connective leadership is characterized by transformational (Van Brummelen, 2002) tendencies. This research suggests that the further along the continuum one goes from the understanding of curriculum as planned (Eisner, 1994) to acknowledging a lived curriculum (Aoki, 1993), the more transformational one's leadership style becomes.

Behavioural characteristics in phylogenetics : a case study using black fly (Diptera: Simuliidae) cocoon spinning behaviour

1-1 is torically, the predominan t method of reconstructing phylogenies has been through the use of morphological characters. There are new techniques now gaining acceptance, including molecular techniques al1d chromosomal information. Altl10ugh the study of behaviour has been used in a comparative framework, these analyses have, historically, been based on intuition. Hennig (1966) devised a neV\' method of reconstructing phylogenies which provided a 110ncircular method for formulating, testing and refining phylogenies. Subsequent s)Tstematists had virtually abandoned ecological and beha\lioural data as primary indicators of phylogenetic relationships (Brooks and McLennan 1991). Therefore, in a modern cladistic framework (sensu Hennig) the analysis of behavioural traits remains underrepresented as a method of reconstructing phylogenies. This thesis will reconstruct the phylogeny for species of black flies (Diptera: Simuliidae), using two steps. The first step is to thoroughl)' understand and explain the cocoon spinning in black fly larvae. There have bee115 previous descriptions of cocoon spinning, but all were incomplete or erroneous. The advances in technology, including video recorders and VCRs, have allowed this behaviour to be analyzed in great detail in 20 different species. A complete description of the cocoon spinning of Simulium \littatum is given. This description will be used as a template for the other species observed. The description and understanding of cococ)n spinning was the first step in undertaking a phylogenetic analysis using this behaviour. The behaviour was then broken down and analyzed, revealing 23 characters, 3 either qualitative and quantitative in nature. These characters were assessed in a cladistic framework (sensu Hennig) and a phylogenetic tree was reconstructed with a e.I of 0.91 and an R.I. of 0.96. This phylogenetic tree closely resembles a previously established pllylogenetic tree produced from morphological and cytological information. The importance of this result is the indication that, contrary to some authors, behavioural characters, if used properly, can add very informative characters to a data set.

Some ecological factors affecting the input and population level of total and faecal coliforms and salmonella in Twelve Mile Creek, Lake Ontario and sewage waters near St. Catharines, Ontario

Some Ecological Factors Affecting the Input and Population Levels of Total and Faecal Coliforms and Salmonella in Twelve Mile Creek, Lake Ontario and Sewage Waters Near St. Catharines, Ontario. Supervisor: Dr. M. Helder. The present study was undertaken to investigate the role of some ecological factors on sewage-Dorne bacteria in waters near St. Catharines, Ontario. Total and faecal coliform levels and the presence of Salmonella were monitored for a period of a year along with determination of temperature, pH, dissolved oxygen, total dissolved solids, nitrate N, total phosphate P and ammonium N. Bacteriological tests for coliform analysis were done according to APHA Standard Methods by the membrane filtration technique. The grab sampling technique was employed for all sampling. Four sample sites were chosen in the Port Dalhousie beach area to determine what bacteriological or physical relationship the sites had to each other. The sample sites chosen were the sewage inflow to and the effluent from the St. Catharines (Port Dalhousie) Pollution Control Plant, Twelve Mile Creek below the sewage outfall and Lake Ontario at the Lakeside Park beach. The sewage outfall was located in Twelve Mile Creek, approximately 80 meters from the creek junction with the beach and piers on Lake Ontario. Twelve Mile Creek normally carried a large volume of water from the WeIland Canal which was diverted through the DeCew Generating Station located on the Niagara Escarpment. An additional sample site, which was thought to be free of industrial wastes, was chosen at Twenty Mile Creek, also in the Niagara Region of Ontarioo 3 There were marked variations in bacterial numbers at each site and between each site, but trends to lower_numbers were noted from the sewage inflow to Lake Ontario. Better correlations were noted between total and faecal coliform population levels and total phosphate P and ammonium N in Twenty Mile Creek. Other correlations were observed for other sample stations, however, these results also appeared to be random in nature. Salmonella isolations occurred more frequently during the winter and spring months when water temperatures were minimal at all sample stations except the sewage inflow. The frequency of Salmonella isolations appeared to be related to increased levels of total and faecal coli forms in the sewage effluent. However, no clear relationships were established in the other sample stations. Due to the presence of Salmonella and high levels of total and faecal coliform indicator organisms, the sanitary quality of Lake Ontario and Twelve Mile Creek at the sample sites seemed to be impaired over the major portion of the study period.

Towards a just community: an examination of the development of cultural citizenship rights in Canada from a communitarian perspective

The notion of citizenship, while a basic human right, has come under scrutiny. It was once assumed a liberal inspired regime of citizenship rights would reign as the primary ideological perspective in the Western world, however this has not been the case. Numerous competing paradigms have questioned the premise upon which liberal guarantees of citizenship rights are based. In particular, communitarianism has subjected liberal rights discourse to a closer examination. Communitarian theory holds that universalist principles negate any articulation of community and its internal diversity, such as cultural citizenship. It is this understanding of citizenship that has taken hold in Canada. The Canadian political experience illustrates a number of attributes associated with communitarian thought. It is a collectivist society that articulates a notion of the common good, acknowledges the internal diversity of its citizens and possesses a highly developed deliberative democratic process. To this end, Canada can be described as being more communitarian than liberal in nature in the process it has adopted to address citizenship rights. However, the type of commuIiitarianism displayed in Canada differs from the political models examined by such scholars as Michael Sandel, Iris Marion Young or Will Kymlicka. Cultural citizenship rights are fluid and malleable in Canada. While no clear guarantees of citizenship rights exist, there is a common commitment by Canadians to engage in a fair, open and inclusive deliberative process. This model is unique to Canada; it cannot be exported in that it is a product of Canadian political culture. As a result, the contemporary demands of cultural citizenship are dealt with effectively and democratically in Canada in that the proper mechanisms for public deliberation exist.

News in the age of empire : two war scandals

This thesis argues that the motivations underpinning the mainstream news media have fundamentally changed in the 21 sl century. As such, the news is no longer best understood as a tool for propaganda or agenda setting; instead it seems that the news is only motivated by the flow of global network capitalism. The author contrasts the work of Noam Chomsky and Edward S. Herman with that of Gilles Deleuze. Chomsky and Herman's 'Propaganda Model' has been influential within the fields of media studies and popular culture. The 'propaganda model' states that the concentration of ownership of the media has allowed the media elite to exert a disproportionate amount of influence over the mass media. Deleuze, on the other hand, regards the mass media as being yet another cog within the global capitalist mechanism, and is therefore separate from ideology or propaganda. The author proposes that 'propaganda' is no longer a sufficient word to describe the function of the news as terms like 'propaganda' imply some form of national sovereignty or governmental influence. To highlight how the news has 'changed from an instrument of propaganda to an instrument of accumulation, the author compares and contrasts the· coverage of the Abu Ghraib Prison Scandal with that of the Haditha Civilian Massacre. Although similar in nature, the author proposes that the Abu Ghraib Prison Scandal received a disproportionate amount of coverage within the mainstream press because of its exciting and sensational nature.

Social neuroendocrinology of competition

The relationship between testosterone concentrations and aggressive behaviour in studies of people has produced very inconsistent findings. However, one consistent fmding that has emerged is that competitive and aggressive interactions potentiate testosterone release in both human and non-human species. It has been argued that socially-induced alterations in testosterone concentrations may function to influence ongoing and/or future social behaviour. Nonetheless, few studies have empirically tested this hypothesis. The current series of experiments was designed to address the extent to which competitioninduced fluctuations in testosterone concentrations were associated with ongoing and/or subsequent social behaviour. In Study 1, men (n = 38) provided saliva samples prior to, and at the conclusion of, the Point Subtraction Aggression Paradigm (PSAP). Although baseline testosterone concentrations were not related to aggressive behaviour, there was a positive correlation between change in testosterone and aggressive behaviour such that men who were most aggressive on the PSAP demonstrated the largest increase in testosterone concentrations. Furthermore, a rise in testosterone during the PSAP predicted willingness to choose a subsequent competitive task. In Study 2, men and women provided saliva samples prior to and after competing against a same-sex opponent on the Number Tracing Task (NTT). The outcome of the competition was rigged such that half of the individuals won most of the races, while the other half lost most of the races, thus experimentally creating a winner and loser in the laboratory. Following the competitive interaction, men and women played the PSAP with their same-sex partner. Results indicated that men selected the aggressive response (but not reward or protection responses), more frequently than women. For men assigned to the loss condition, an increase in testosterone concentrations in response to the NTT predicted subsequent aggressive behaviour. For men assigned to the win condition, an increase in testosterone concentrations in response to the NTT predicted subsequent aggressive behaviour, but only among those men who scored high on trait dominance. Change in testosterone and trait dominance did not predict aggressive behaviour in women. In Study 3, men provided saliva samples prior to, during, and at the end of the PSAP. They were randomly assigned to one of four experimental conditions that differed in the extent to which they were provoked and whether they received reward for behaving aggressively (i.e., stealing points). Results indicated that baseline testosterone concentrations did not correlate with aggression in any of the experimental conditions. Consistent with Study 1, there was a positive correlation between change in testosterone and aggressive behaviour among men who were provoked, but did not receive reward for aggression (i.e., reactive condition). Men who were provoked but did not receive reward for aggression enjoyed the task the most and were more likely to choose the competitive versus non-competitive task relative to men assigned to the other experimental conditions. Also, individual differences in aggressive behaviour among these men were positively correlated with the extent to which they enjoyed the task. Together, these studies indicate that testosterone dynamics within the context of competition influence subsequent competitive and aggressive behaviours in humans and that testosterone may be a marker of the intrinsically rewarding nature of costly aggressive behaviour.

The nesting biology of Ceratina (Hymenoptera: Apidae) in the Niagara Region : new species, nest site selection and parasitism

One of the most common bee genera in the Niagara Region, the genus Ceratina (Hymenoptera: Apidae) is composed of four species, C. dupla, C. calcarata, the very rare C. strenua, and a previously unknown species provisionally named C. near dupla. The primary goal of this thesis was to investigate how these closely related species coexist with one another in the Niagara ~ee community. The first necessary step was to describe and compare the nesting biologies and life histories of the three most common species, C. dupla, C. calcarata and the new C. near dupla, which was conducted in 2008 via nest collections and pan trapping. Ceratina dupla and C. calcarata were common, each comprising 49% of the population, while C. near dupla was rare, comprising only 2% of the population. Ceratina dupla and C. near dupla both nested more commonly in teasel (Dipsacus sp.) in the sun, occasionally in raspberry (Rubus sp.) in the shade, and never in shady sumac (Rhus sp.), while C. calcarata nested most commonly in raspberry and sumac (shaded) and occasionally in teasel (sunny). Ceratina near dupla differed from both C. dupla and C. calcarata in that it appeared to be partially bivoltine, with some females founding nests very early and then again very late in the season. To examine the interactions and possible competition for nests that may be taking place between C. dupla and C. calcarata, a nest choice experiment was conducted in 2009. This experiment allowed both species to choose among twigs from all three substrates in the sun and in the shade. I then compared the results from 2008 (where bees chose from what was available), to where they nested when given all options (2009 experiment). Both C. dupla and C. calcarata had the same preferences for microhabitat and nest substrate in 2009, that being raspberry and sumac twigs in the sun. As that microhabitat and nest substrate combination is extremely rare in nature, both species must make a choice. In nature Ceratina dupla nests more often in the preferred microhabitat (sun), while C. calcarata nests in the preferred substrate (raspberry). Nesting in the shade also leads to smaller clutch sizes, higher parasitism and lower numbers of live brood in C. calcarata, suggesting that C. dupla may be outcompeting C. calcarata for the sunny nesting sites. The development and host preferences of Ceratina parasitoids were also examined. Ceratina species in Niagara were parasitized by no less than eight species of arthropod. Six of these were wasps from the superfamily Chalcidoidea (Hymenoptera), one was a wasp from the family Ichneumonidae (Hymenoptera) and one was a physogastric mite from the family Pyemotidae (Acari). Parasites shared a wide range of developmental strategies, from ichneumonid larvae that needed to consume multiple Ceratina immatures to complete development, to the species from the Eulophidae (Baryscapus) and Encyrtidae (Coelopencyrtus), in which multiple individuals completed development inside a single Ceratina host. Biological data on parasitoids is scarce in the scientific literature, and this Chapter documents these interactions for future research.

Developmental differences in locomotor responsiveness to amphetamine in rats

The developmental remodelling of motivational systems that underlie drug dependence and addiction may account for the greater frequency and severity of drug abuse in adolescence compared to adulthood. Recent advances in animal models have begun to identify the morphological and the molecular factors that are being remodelled, but little is known about the culmination of these factors in altered sensitivity to psycho stimulant drugs, like amphetamine, in adolescence. Amphetamine induces potent locomotor activating effects in rodents through increased dopamine release in the mesocorticolimbic dopamine system, which makes locomotor activity a useful behavioural marker of age differences in amphetamine sensitivity. The aim of the thesis was to investigate the neural basis for age differences in amphetamine sensitivity with a focus on the nucleus accumbens and the medial prefrontal cortex, which initiate and regulate amphetamine-induced locomotor activity, respectively. In study 1, I found pre- and post- pubertal adolescent rats to be less active (i.e., hypoactive) than adults to a first injection of 0.5, but not of 1.5, mg/kg of intraperitonealy (i.p.) administered amphetamine. Although initially hypoactive, only adolescent rats exhibited an increase in activity to a second injection of amphetamine given 24 h later, indicating that adolescents may be more sensitive to the rapid changes in amphetamineinduced plasticity than adults. Given that the locomotor activating effects of amphetamine are initiated in the nucleus accumbens, age differences in response to direct injections of amphetamine into this brain region were investigated in study 2. In contrast to i.p. injections, adolescents were more active than adults when amphetamine was given directly into the nucleus accumbens, indicating that hypo activity may be attributed to the development of regulatory regions outside of the accumbens. The medial prefrontal cortex (mPFC) is a key regulator of the locomotor activating effects of amphetamine that undergoes extensive remodelling in adolescence. In study 3, I found that an i.p. injection of 1.5, and not of 0.5, mg/kg of amphetamine resulted in a high expression of c-fos, a marker of neural activation, in the pre limbic mPFC only in pre-pubertal adolescent rats. This finding suggests that the ability of adolescent rats to overcome hypo activity at the 1.5 mg/kg dose may involve greater activation of the prelimbic mPFC compared to adulthood. In support of this hypothesis, I found that pharmacological inhibition of prelimbic D 1 dopamine receptors disrupted the locomotor activating effects of the 1.5 mg/kg dose of amphetamine to a greater extent in adolescent than in adult rats. In addition, the stimulation of prelimbic D 1 dopamine receptors potentiated locomotor activity at the 0.5 mg/kg dose of amphetamine only in adolescent rats, indicating that the prelimbic D1 dopamine receptors are involved in overcoming locomotor hypoactivity during adolescence. Given my finding that the locomotor activating effects of amphetamine rely on slightly different mechanisms in adolescence than in adulthood, study 4 was designed to determine whether the lasting consequences of drug use would also differ with age. A short period of pre-treatment with 0.5 mg/kg of amphetamine in adolescence, but not in adulthood, resulted in heightened sensitivity to an injection of amphetamine given 30 days after the start of the procedure, when adolescent rats had reached adulthood. The finding of an age-specific increase in amphetamine sensitivity is consistent with evidence for increased risk for addiction when drug use is initiated in adolescence compared to adulthood in people (Merline et aI., 2002), and with the hypothesis that adolescence is a sensitive period of development.

Exploring Reciprocity in International Service Learning Programs

Using aspects of grounded theory methodology, this study explored the perceptions and practical implementation of reciprocity in International Service Learning (ISL) Programs. Data were collected through interviews with nine ISL practitioners representing a variety of organizations offering international service learning programs. Findings suggest that multiple conceptualizations of ISL programs exist. ISL programs are interdisciplinary in nature and that using reciprocity as a guiding framework is problematic. Further attention is needed in relation to shifting the guiding framework of ISL programs from reciprocity to interdependence.

Singing Nature, Dancing Buddha: Zen, Language, and the Groundlessness of Silence

This thesis presents Zen experience as aesthetic in nature. This is done through an analysis of language, a central concern for Zen Buddhism. The thesis develops two modes of language at work in Zen: representational and indexical. What these modes of language entail, the kind of relations that are developed through their use, are explored with recourse to a variety of Zen platforms: poetry, the koan, zazen, music, and suizen. In doing so, a primacy of listening is found in Zen - a listening without a listener. Given this primacy of listening, silence comes to the forefront of the investigation. An analysis of John Cage's 4'33" provides this thesis with justification of the groundlessness of silence, and the groundlessness of subjectivity. Listening allows for the abyssal subject to emerges, which in tum allows for reality to present itself outside of the constitutive function of language.

Mirroring Enzymes: The Role of H-Bonding In HQuin-BAM Catalyzed Asymmetric Aza-Henry Reactions: A DFT Study into the Reactivity, Mechanism, and Origins of Selectivity

The exact mechanistic understanding of various organocatalytic systems in asymmetric reactions such as Henry and aza-Henry transformations is important for developing and designing new synthetic organocatalysts. The focus of this dissertation will be on the use of density functional theory (DFT) for studying the asymmetric aza-Henry reaction. The first part of the thesis is a detailed mechanistic investigation of a poorly understood chiral bis(amidine) (BAM) Brønsted acid catalyzed aza-Henry reaction between nitromethane and N-Boc phenylaldimine. The catalyst, in addition to acting as a Brønsted base, serves to simultaneously activate both the electrophile and the nucleophile through dual H-bonding during C-C bond formation and is thus essential for both reaction rate and selectivity. Analysis of the H-bonding interactions revealed that there was a strong preference for the formation of a homonuclear positive charge-assisted H-bond, which in turn governed the relative orientation of substrate binding. Attracted by this well-defined mechanistic investigation, the other important aspect of my PhD research addressed a detailed theoretical analysis accounting for the observed selectivity in diastereoselective versions of this reaction. A detailed inspection of the stereodetermining C-C bond forming transition states for monoalkylated nitronate addition to a range of electronically different aldimines, revealed that the origins of stereoselectivity were controlled by a delicate balance of different factors such as steric, orbital interactions, and the extent of distortion in the catalyst and substrates. The structural analysis of different substituted transition states established an interesting dependency on matching the shape and size of the catalyst (host molecule) and substrates (guest molecules) upon binding, both being key factors governing selectivity, in essence, offering an analogy to positive cooperative binding effect of catalytic enzymes and substrates in Nature. In addition, both intra-molecular (intra-host) and inter-molecular (host-guest, guest-guest) stabilizing interactions play a key role to the high π-facial selectivity. The application of dispersion-corrected functionals (i.e., ωB97X-D and B3LYP-D3) was essential for accurately modeling these stabilizing interactions, indicating the importance of dispersion effects in enantioselectivity. As a brief prelude to more extensive future studies, the influence of a triflate counterion on both reactivity and selectivity in this reaction was also addressed.