A DFT Guided/Experimental Approach to Asymmetric Allylation and Phase-Transfer Catalysis

The Dudding group is interested in the application of Density Functional Theory (DFT) in developing asymmetric methodologies, and thus the focus of this dissertation will be on the integration of these approaches. Several interrelated subsets of computer aided design and implementation in catalysis have been addressed during the course of these studies. The first of the aims rested upon the advancement of methodologies for the synthesis of biological active C(1)-chiral 3-methylene-indan-1-ols, which in practice lead to the use of a sequential asymmetric Yamamoto-Sakurai-Hosomi allylation/Mizoroki Heck reaction sequence. An important aspect of this work was the utilization of ortho-substituted arylaldehyde reagents which are known to be a problematic class of substrates for existing asymmetric allylation approaches. The second phase of my research program lead to the further development of asymmetric allylation methods using o-arylaldehyde substrates for synthesis of chiral C(3)-substituted phthalides. Apart from the de novo design of these chemistries in silico, which notably utilized water-tolerant, inexpensive, and relatively environmental benign indium metal, this work represented the first computational study of a stereoselective indium-mediated process. Following from these discoveries was the advent of a related, yet catalytic, Ag(I)-catalyzed approach for preparing C(3)-substituted phthalides that from a practical standpoint was complementary in many ways. Not only did this new methodology build upon my earlier work with the integrated (experimental/computational) use of the Ag(I)-catalyzed asymmetric methods in synthesis, it provided fundamental insight arrived at through DFT calculations, regarding the Yamamoto-Sakurai-Hosomi allylation. The development of ligands for unprecedented asymmetric Lewis base catalysis, especially asymmetric allylations using silver and indium metals, followed as a natural extension from these earlier discoveries. To this end, forthcoming as well was the advancement of a family of disubstituted (N-cyclopropenium guanidine/N-imidazoliumyl substituted cyclopropenylimine) nitrogen adducts that has provided fundamental insight into chemical bonding and offered an unprecedented class of phase transfer catalysts (PTC) having far-reaching potential. Salient features of these disubstituted nitrogen species is unprecedented finding of a cyclopropenium based C-H•••πaryl interaction, as well, the presence of a highly dissociated anion projected them to serve as a catalyst promoting fluorination reactions. Attracted by the timely development of these disubstituted nitrogen adducts my last studies as a PhD scholar has addressed the utility of one of the synthesized disubstituted nitrogen adducts as a valuable catalyst for benzylation of the Schiff base N-diphenyl methylene glycine ethyl ester. Additionally, the catalyst was applied for benzylic fluorination, emerging from this exploration was successful fluorination of benzyl bromide and its derivatives in high yields. A notable feature of this protocol is column-free purification of the product and recovery of the catalyst to use in a further reaction sequence.

Intraoperative hemodynamic instability during and after separation from cardiopulmonary bypass : importance, mechanism and prevention

Chaque année, environ 1 à 1,25 million d’individus subiront une chirurgie cardiaque. [1] Environ 36 000 chirurgies cardiaques sont effectuées au Canada et 8000 procédures au Québec (http://www.ccs.ca). Le vieillissement de la population aura pour conséquence que la chirurgie cardiaque sera offerte à des patients de plus en plus à risque de complications, principalement en raison d’une co-morbidité plus importante, d’un risque de maladie coronarienne plus élevée, [2] d’une réserve physiologique réduite et par conséquent un risque plus élevé de mortalité à la suite d’une chirurgie cardiaque. L’une des complications significatives à la suite d’une chirurgie cardiaque est le sevrage difficile de la circulation extracorporelle. Ce dernier inclut la période au début du sevrage de la circulation extracorporelle et s’étend jusqu’au départ du patient de la salle d’opération. Lorsque le sevrage de la circulation extracorporelle est associé à une défaillance ventriculaire droite, la mortalité sera de 44 % à 86 %. [3-7] Par conséquent le diagnostic, l’identification des facteurs de risque, la compréhension du mécanisme, la prévention et le traitement du sevrage difficile de la circulation extracorporelle seront d’une importance majeure dans la sélection et la prise en charge des patients devant subir une chirurgie cardiaque. Les hypothèses de cette thèse sont les suivantes : 1) le sevrage difficile de la circulation extracorporelle est un facteur indépendant de mortalité et de morbidité, 2) le mécanisme du sevrage difficile de la circulation extracorporelle peut être approché d’une façon systématique, 3) la milrinone administrée par inhalation représente une alternative préventive et thérapeutique chez le patient à risque d’un sevrage difficile de la circulation extracorporelle après la chirurgie cardiaque.

The effects of additives and chemical modification on the solution properties of thermo-sensitive polymers

Cette thèse concerne l’étude de phase de séparation de deux polymères thermosensibles connus-poly(N-isopropylacylamide) (PNIPAM) et poly(2-isopropyl-2-oxazoline) (PIPOZ). Parmi des études variées sur ces deux polymères, il y a encore deux parties de leurs propriétés thermiques inexplicites à être étudiées. Une partie concerne l’effet de consolvant de PNIPAM dans l’eau et un autre solvant hydromiscible. L’autre est l’effet de propriétés de groupes terminaux de chaînes sur la séparation de phase de PIPOZ. Pour ce faire, nous avons d’abord étudié l’effet de l’architecture de chaînes sur l’effet de cosolvant de PNIPAMs dans le mélange de méthanol/eau en utilisant un PNIPAM en étoile avec 4 branches et un PNIPAM cyclique comme modèles. Avec PNIPAM en étoile, l’adhérence de branches PNIPAM de à un cœur hydrophobique provoque une réduction de Tc (la température du point de turbidité) et une enthalpie plus faible de la transition de phase. En revanche, la Tc de PNIPAM en étoile dépend de la masse molaire de polymère. La coopérativité de déhydratation diminue pour PNIPAM en étoile et PNIPAM cyclique à cause de la limite topologique. Une étude sur l’influence de concentration en polymère sur l’effet de cosolvant de PNIPAM dans le mélange méthanol/eau a montré qu’une séparation de phase liquide-liquide macroscopique (MLLPS) a lieu pour une solution de PNIPAM dans le mélange méthanol/eau avec la fraction molaire de méthanol entre 0.127 et 0.421 et la concentration en PNIPAM est constante à 10 g.L-1. Après deux jours d’équilibration à température ambiante, la suspension turbide de PNIPAM dans le mélange méthanol/eau se sépare en deux phases dont une phase possède beaucoup plus de PNIPAM que l’autre. Un diagramme de phase qui montre la MLLPS pour le mélange PNIPAM/eau/méthanol a été établi à base de données expérimentales. La taille et la morphologie de gouttelettes dans la phase riche en polymère condensée dépendent de la fraction molaire de méthanol. Parce que la présence de méthanol influence la tension de surface des gouttelettes liquides, un équilibre lent de la séparation de phase pour PNIPAM/eau/méthanol système a été accéléré et une séparation de phase liquide-liquide macroscopique apparait. Afin d’étudier l’effet de groupes terminaux sur les propriétés de solution de PIPOZ, deux PIPOZs téléchéliques avec groupe perfluorodécanyle (FPIPOZ) ou groupe octadécyle (C18PIPOZ) comme extrémités de chaîne ont été synthétisés. Les valeurs de Tc des polymères téléchéliques ont beaucoup diminué par rapport à celle de PIPOZ. Des micelles stables se forment dans des solutions aqueuses de polymères téléchéliques. La micellization et la séparation de phase de ces polymères dans l’eau ont été étudiées. La séparation de phase de PIPOZs téléchéliques suit le mécanisme de MLLPS. Des différences en tailles de gouttelettes formées à l’intérieur de solutions de deux polymères ont été observées. Pour étudier profondément les différences dans le comportement d’association entre deux polymères téléchéliques, les intensités des signaux de polymères correspondants et les temps de relaxation T1, T2 ont été mesurés. Des valeurs de T2 de protons correspondants aux IPOZs sont plus hautes.

Ultrasonic Study Of The Elastic Properties And Phase Transitions In Selected Mixed Sulphate Crystals

The thesis investigated the elastic properties and phase transitions in selected mixed sulphate crystals – Lithium Hydrazinium Sulphate [LiN2H2SO4], Lithium Ammonium Sulphate [LiNH4SO4] and Lithium Potassium Sulphate [LiKSO4] – using ultrasonic technique. The pulse echo overlap technique has been used for measuring ultrasonic velocity and its dependence on temperature along different directions with waves of longitudinal and transverse polarizations. Two major numerical techniques and the corresponding computer programs developed as part of present work are presented in this thesis. All the 9 elastic constants of LHS are determined accurately from ultrasonic measurements and applying misorientation correction refines the constants. Ultrasonic measurements are performed in LAS to determine the elastic constants and to study the low temperature phase transitions. Temperature variation studies of elastic constant of LAS are performed for 6 different modes of propagation for heating and cooling at low temperatures. All the 5 independent elastic constants of LPS is determined using ultrasonic measurements. It is concluded that LPS crystal does not undergo a phase transition near this temperature. A comparison of the three crystals studied shows that LPS has maximum number of phase transitions and LHS has the least number. It is interesting to note that LPS has the simplest formula unit among the three. There is considerable scope for the future work on these crystals and others belonging to the sulphate family.

DC electrical conductivity and phase transitions in (NH4)3H(SO4)2

Four distinct peaks are observed at 140, -26, -132 and -140°C in the sigma x* against T-1 plot between 200 and - 196°C for (NH4)3H(SO4)2, corresponding to four different phase transitions of which the one at -26°C is reported here for the first time. Data on doped samples reveal the charge transport mechanism in the crystal.

Electrical conductivity, dielectric constant and phase transitions in pure and doped diammonium hydrogen phosphate

DC and AC electrical conductivity measurements in single crystals of diammonium hydrogen phosphate along the c axis show anomalous variations at 174, 246 and 416 K. The low-frequency dielectric constant also exhibits peaks exactly at these temperatures with a thermal hysteresis of 13 degrees C for the peak at 416 K. These specific features of the electrical properties are in agreement with earlier NMR second-moment data and can be identified with three distinct phase transitions that occur in the crystal. The electrical conductivity values have been found to increase linearly with impurity concentration in specimens doped with a specific amount of SO42- ions. The mechanisms of the phase transition and of the electrical conduction process are discussed in detail.

Third order nonlinear optical studies in europium naphthalocyanine using degenerate four wave mixing and Z-scan

Third order nonlinear susceptibility χ(3) and second hyperpolarizability (γ) of a bis-naphthalocyanine viz. europium naphthalocyanines, Eu(Nc)2, were measured in dimethyl formamide solution using degenerate four wave mixing at 532 nm under nanosecond pulse excitation. Effective nonlinear absorption coefficient, βeff and imaginary part of nonlinear susceptibility, Im(χ(3)) were obtained using open aperture /Z-scan technique at the same wavelength. Optical limiting property of the sample was also investigated. The role of excited state absorption in deciding the nonlinear properties of this material is discussed.

Photopyroelectric study of thermal properties and phase transitions in selected solids

This thesis presents in detail. the theoretical developments and calculations which are used for the simultaneous determination of thermal parameters, namely thermal diffusivity (a). thermal effusivity (e), thermal conductivity (K) and heat capacity (cr ) employing photopyroelectric technique. In our calculations. we have assumed that the pyroelectric detector is supported on a copper backing. so that there will be sufficient heat exchange between the heated pyroelectric detector and the backing so that the signal fluctuations are reduced to a minimum. Since the PPE signal depends on the properties of the detector that are also temperature dependent. a careful temperature calibration of the system need to be carried out. APPE cell has been fabricated for the measurements that can be used to measure the thermal properties of solid samples from ~ 90 K to ~ 350 K. The cell has been calibrated using standard samples and the accuracy of the technique is found to be of the order of± 1%.In this thesis, we have taken up work n photopyroelectric investigation of thermal parameters of ferroelectric crystals such as Glycine phosphite (NH3CH2COOH3P03), Triglycine sulfate and Thiourea as well as mixed valence perovskites samples such as Lead doped Lanthanum Manganate (Lal_xPb~Mn03) Calcium doped (Lal_xCaxMnOJ) and Nickel doped Lanthanum Stroncium Cobaltate (Lao~Sro5Ni,Col_x03).The three ferroelectric crystals are prepared by the slow evaporation technique and the mixed valence perovskites by solid state reaction technique.Mixed valence perovskites, with the general formula RI_xA~Mn03 (R = La. Nd or Pr and A = Ba, Ca, Sr or Pb) have been materials of intense experimental and theoretical studies over the past few years. These materials show . colossal magneloresis/ance' (CMR) in samples with 0.2 < x < 0.5 in such a doping region, resistivity exhibits a peak at T = T p' the metal - insulator transition temperature. The system exhibits metallic characteristics with d %T > Oabove Tp (wherep is the resistivity) and insulating characteristics with d % T < 0 above T p. Despite intensive investigations on the CMR phenomena and associated electrical properties. not much work has been done on the variation of thermal properties of these samples. We have been quite successful in finding out the nature of anomaly associated with thermal properties when the sample undergoes M-I transition.The ferroelectric crystal showing para-ferroelectric phase transitions - Glycine phosphite. Thiourea and Triglycine sulfate - are studied in detail in order to see how well the PPE technique enables one to measure the thermal parameters during phase transitions. It is seen that the phase transition gets clearly reflected in the variation of thermal parameters. The anisotropy in thermal transport along different crystallographic directions are explained in terms of the elastic anisotropy and lattice contribution to the thermal conductivity. Interesting new results have been obtained on the above samples and are presented in three different chapters of the thesis.In summary. we have carried investigations of the variations of the thermal parameters during phase transitions employing photopyroelectric technique. The results obtained on different systems are important not only in understanding the physics behind the transitions but also in establishing the potentiality of the PPE tool. The full potential of PPE technique for the investigation of optical and thermal properties of materials still remains to be taken advantage of by workers in this field.

Electrical properties and phase transitions in ethylenediammonium dinitrate

dc and ac electrical conductivities, dielectric constant and dielectric loss factor in single crystals of ethylenediammonium dinitrate (EDN) have been measured axiswise as a function of temperature. All the above properties exhibit anomalous variations at 404 K thereby confirming the occurence of a phase transition in EDN at this temperature. Electrical conductivity parameters have been evaluated and possible conduction mechanisms are discussed. The role of protons in electrical trasport phenomenon is established by chemical analysis.

Effect of deuteration on the electrical conductivity, dielectric constant and phase transitions in LiNH4SO4

Measurements of dc conductivity and dielectric constant show that deuteration causes an upward shift of the high temperature phase transition point from 186.5 to 191°C and a downward shift of the low temperature transition point from 10 to -1.5°C in LiNH4SO4. Mechanisms of phase transitions and of electrical transport in the crystal are discussed.

Electrical conductivity, dielectric properties and phase transition in ethylenediammonium sulphate single crystals

D.C. and a.c. electrical conductivities, dielectric constant and dielectric loss factor in single crystals of ethylenediammonium sulphate, (H3NCH2CH2NH3)(SO4), have been measured axiswise as a function of temperature. Anomalous variations in all the above properties at 480 K indicate the occurrence of a phase transition in the above material at this temperature. The existence of such a phase transition is also confirmed by DSC measurements. Electrical conductivity results are analysed and the activation energies of conduction at different temperature regions have been evaluated from the logσ vs 103T−1 plot. Possible mechanisms for the electrical conduction process are discussed, the available results being in favour of a proton transport model.

Electrical properties and phase transitions insome ammonium containing ferroelectrics

The thesis aims to present the results of the experimental investigations on the electrical properties like electrical conductivity, dielectric constant and ionic thermo~ currents in certain ammonium containing ferroelectric crystals viz. LiNH4SO4, (NH4)2SO4 and (NH4)5H(SO4)2. Special attention has been paid in revealing the mechanisms of electrical conduction in the various phases of these crystals and those asso~ ciated with the different phase transitions occurring in them, by making studies on doped, quenched and deuterated crystals. The report on the observation of two new phase transitions in (NH4) S O2 and of a similar one in ( NH4 ) H (2SO4 ) are included. The relaxation mechanisms of the impurity-vacancy complexes and the space charge phenomena in pure and doped crystals of LiNH4SO4 and (NH4)2SO4 and the observation of a new type of ionic thermo-current viz. Protonic Thermo-Current (PTC) in these crystals are also presented here.

Molecular computations for reactions and phase transitions: applications to protein stabilization, hydrates and catalysis

In this work we have made significant contributions in three different areas of interest: therapeutic protein stabilization, thermodynamics of natural gas clathrate-hydrates, and zeolite catalysis. In all three fields, using our various computational techniques, we have been able to elucidate phenomena that are difficult or impossible to explain experimentally. More specifically, in mixed solvent systems for proteins we developed a statistical-mechanical method to model the thermodynamic effects of additives in molecular-level detail. It was the first method demonstrated to have truly predictive (no adjustable parameters) capability for real protein systems. We also describe a novel mechanism that slows protein association reactions, called the “gap effect.” We developed a comprehensive picture of methioine oxidation by hydrogen peroxide that allows for accurate prediction of protein oxidation and provides a rationale for developing strategies to control oxidation. The method of solvent accessible area (SAA) was shown not to correlate well with oxidation rates. A new property, averaged two-shell water coordination number (2SWCN) was identified and shown to correlate well with oxidation rates. Reference parameters for the van der Waals Platteeuw model of clathrate-hydrates were found for structure I and structure II. These reference parameters are independent of the potential form (unlike the commonly used parameters) and have been validated by calculating phase behavior and structural transitions for mixed hydrate systems. These calculations are validated with experimental data for both structures and for systems that undergo transitions from one structure to another. This is the first method of calculating hydrate thermodynamics to demonstrate predictive capability for phase equilibria, structural changes, and occupancy in pure and mixed hydrate systems. We have computed a new mechanism for the methanol coupling reaction to form ethanol and water in the zeolite chabazite. The mechanism at 400°C proceeds via stable intermediates of water, methane, and protonated formaldehyde.