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.

Pigment orientation changes detected by low temperature linear dichroism spectroscopy: cold-hardening transition in phycobilisome-containing organisms

Low temperature (77K) linear dichroism spectroscopy was used to characterize pigment orientation changes accompanying the light state transition in the cyanobacterium, Synechococcus sp. pee 6301, and cold-hardening in winter rye (Secale cereale L. cv. Puma). Samples were oriented for spectroscopy using the gel squeezing method (Abdourakhmanov et aI., 1979) and brought to 77K in liquid nitrogen. The linear dichroism (LD) spectra of Synechococcus 6301 phycobilisome/thylakoid membrane fragments cross-linked in light state 1 and light state 2 with glutaraldehyde showed differences in both chlorophyll a and phycobilin orientation. A decrease in the relative amplitude of the 681nm chlorophyll a positive LD peak was observed in membrane fragments in state 2. Reorientation of the phycobilisome (PBS) during the transition to state 2 resulted in an increase in core allophycocyanin absorption parallel to the membrane, and a decrease in rod phycocyanin parallel absorption. This result supports the "spillover" and "PBS detachment" models of the light state transition in PBS-containing organisms, but not the "mobile PBS" model. A model was proposed for PBS reorientation upon transition to state 2, consisting of a tilt in the antenna complex with respect to the membrane plane. Linear dichroism spectra of PBS/thylakoid fragments from the red alga, Porphyridium cruentum, grown in green light (containing relatively more PSI) and red light (containing relatively more PSll) were compared to identify chlorophyll a absorption bands associated with each photosystem. Spectra from red light - grown samples had a larger positive LD signal on the short wavelength side of the 686nm chlorophyll a peak than those from green light - grown fragments. These results support the identification of the difference in linear dichroism seen at 681nm in Synechococcus spectra as a reorientation of PSll chromophores. Linear dichroism spectra were taken of thylakoid membranes isolated from winter rye grown at 20°C (non-hardened) and 5°C (cold-hardened). Differences were seen in the orientation of chlorophyll b relative to chlorophyll a. An increase in parallel absorption was identified at the long-wavelength chlorophyll a absorption peak, along with a decrease in parallel absorption from chlorophyll b chromophores. The same changes in relative pigment orientation were seen in the LD of isolated hardened and non-hardened light-harvesting antenna complexes (LHCII). It was concluded that orientational differences in LHCII pigments were responsible for thylakoid LD differences. Changes in pigment orientation, along with differences observed in long-wavelength absorption and in the overall magnitude of LD in hardened and non-hardened complexes, could be explained by the higher LHCII monomer:oligomer ratio in hardened rye (Huner et ai., 1987) if differences in this ratio affect differential light scattering properties, or fluctuation of chromophore orientation in the isolated LHCII sample.

Structural studies in the Southern Province, South of Sudbury, Ontario

Rocks correlated with the Hough Lake and Quirke Lake Groups of the Huronian Supergroup form part of a northeasterly trending corridor that separates 1750 Ma granitic intrusive rocks of the Chief Lake batholith from the 1850 Ma mafic intrusive rocks of the Sudbury Igneous Complex. This corridor is dissected by two major structural features; the Murray Fault Zone (MFZ) and the Long Lake Fault (LLF). Detailed structural mapping and microstructural analysis indicates that the LLF, which has juxtaposed Huronian rocks of different deformation style and metamorphism grade, was a more significant plane of dislocation than the MFZ. The sense of displacement along the LLF is high angle reverse in which rocks to the southeast have been raised relative to those in the northwest. South of the LLF Huronian rocks underwent ductile defonnation at amphibolite facies conditions. The strain was constrictional, defined by a triaxial strain ellipsoid in which X > Y > z. Calculations of a regional k value were approximately 1.3. Penetrative ductile defonnation resulted in the development of a preferred crystallographic orientation in quartz as well as the elongation of quartz grains to fonn a regional southeast-northwest trending, subvertical lineation. Similar lithologies north of the LLF underwent dominantly brittle deformation under greenschist facies conditions. Deformation north of the LLF is characterized by the thrusting of structural blocks to form angular discordances in bedding orientation which were previously interpreted as folds. Ductile deformation occurred between 1750 and 1238 Ma and is correlated with a regional period of south over north reverse faulting that effected much of the southern Sudbury region. Post dating the reverse faulting event was a period of sedimentation as a conglomerate unit was deposited on vertically bedded Huronian rocks. Rocks in the study area were intruded by both mafic and felsic dykes. The 1238 Ma mafic dykes appear to have been offset during a period of dextral strike slip displacement along the major fault'). Indirect evidence indicates that this event occurred after the thrusting at 950 to 1100 Ma associated with the Grenvillian Orogeny.

Correspondence between the American and British Plentipotentiaries relative to the commercial convention concluded on the 3rd of July, 1815.--

January 16, 1816.

Letter from the acting Secretary of War, transmitting information relative to the claims of the State of Massachusetts for payment of the expenses of the militia ordered out by the executive authority of the state, during the late war. --

15th Congress, 1st session, 1817-1818, House. Doc. 81.

Letter from the Secretary of War, transmitting documents containing the information required by the resolution of Mr. Wright, on the 22d inst. relative to the execution of the act fixing the military peace establishment. --

14th Congress, 1st session, 1815-1816. House. Document no. 33.

Message from the President of the United States, transmitting documents relative to the commencement and progress of any acts or system of retaliation upon prisoners of war, by the Governments of Great Britain and the United States. --

13th Congress, 3d session. House. Doc. no. 13.

Message from the President of the United States, transmitting a report of the Secretary of State, in obedience to a resolution of the thirteenth inst. "requesting the President to lay before this House such documents relative to the Russian mediation as in his opinion it may not be improper to communicate." --

United States,13th Congress, 2d session, 1813-1814. House. Doc. no. 35.

Report of the Committee on Military Affairs, on the differences that exist, between the United States and some of the individual States, respecting the relative powers of the general and state governments over the militia.--

February 28, 1815. Printed by order of the Senate of the United States.

Report of the Committee to whom was Referred the Correspondence between Mr. Monroe and Mr. Canning, and between Mr. Madison and Mr. Rose, relative to the attacked of Chesapeake : and also a communication from the President of the United States of the 30 March last, with a letter from Mr. Erskine to the Secretary of State, and a letter from M. Champagny to Gen. Armstrong.--

April 16, 1808. Printed by Order of the Senate.

Orientation of Non-Native 2-Monosubstituted and 2,3-Disubstituted 1,4-Naphthoquinones in the A1 binding site of PSI and the effect on the rate of electron transfer : an electron paramagnetic resonance spectroscopy study

The proce-ss ofoxygenic photosynthesis is vital to life on Earth. the central event in photosynthesis is light induced electron transfer that converts light into energy for growth. Ofparticular significance is the membrane bound multisubunit protein known as Photosystem I (PSI). PSI is a reaction centre that is responsible for the transfer of electrons across the membrane to reduce NADP+ to NADPH. The recent publication ofa high resolution X-ray structure of PSI has shown new information about the structure, in particular the electron transfer cofactors, which allows us to study it in more detail. In PSI, the secondary acceptor is crucial for forward electron transfer. In this thesis, the effect of removing the native acceptor phylloquinone and replacing it with a series of structurally related quinones was investigated via transient electron paramagnetic resonance (EPR) experiments. The orientation of non native quinones in the binding site and their ability to function in the electron transfer process was determined. It was found that PSI will readily accept alkyl naphthoquinones and anthraquinone. Q band EPR experiments revealed that the non-native quinones are incorporated into the binding site with the same orientation of the headgroup as in the native system. X band EPR spectra and deuteration experiments indicate that monosubstituted naphthoquinones are bound to the Al site with their side group in the position occupied by the methyl group in native PSI (meta to the hydrogen bonded carbonyl oxygen). X band EPR experiments show that 2, 3- disubstituted methyl naphthoquinones are also incorporated into the Al site in the same orientation as phylloquinone, even with the presence of a halogen- or sulfur-containing side chain in the position normally occupied by the phytyl tail ofphylloquinone. The exception to this is 2-bromo-3-methyl --.- _. -. - -- - - 4 _._ _ _ - _ _ naphthoquinone which has a poorly resolved spectrum, making determination of the orientation difficuh. All of the non-native quinones studied act as efficient electron acceptors. However, forward electron transfer past the quinone could only be demonstrated for anthraquinone, which has a more negative midpoint potential than phylloquinone. In the case of anthraquinone, an increased rate of forward electron transfer compared to native PSI was found. From these results we can conclude that the rate ofelectron transfer from Al to Fx in native PSI lies in the normal region ofthe Marcus Curve.

Relative importance of body composition, osteoporosis- related behaviours and socioeconomic status on bone SOS in adolescent females

The purpose of this study was to examine the associations between bone speed of sound (SOS) and body composition, osteoporosis-related health behaviours, and socioeconomic status (SES) in adolescent females. A total of 442 adolescent females in grades 9-11 participated. Anthropometric measures of height, body mass, and percent body fat were taken, and osteo-protective behaviours such as oral contraceptive use (OC), physical activity and daily calcium intake were evaluated using self-report questionnaires. Bone SOS was measured by transaxial quantitative ultrasound (QUS) at the distal radius and mid-tibia. The results suggest that fat mass is a significant negative predictor of tibial SOS, while lean mass is positively associated with radial SOS scores and calcium intake was positively associated with tibial SOS scores (p