This work explores new catalytic methodologies for the synthesis of N-3 monosubstituted sydnone compounds. Sydnones are widely studied for their chemical behaviour, biological and physical properties, and are the most popular mesoionic compounds. Despite the popularity of sydnones, there are still many unexplored approaches for their synthesis and application. Herein is described a simple, novel, one-pot catalytic procedure for the preparation of sydnones. This method utilizes inexpensive commercially available reagents and mild reaction conditions.

This work outlines the synthesis of three novel silatrane-functionalized lipids and the exploration of their capacity to undergo spontaneous particle formation in aqueous environments. The chemoenzymatic synthesis of the lipids required 1,3-diacylglycerides of octanoyl, lauroyl, and palmitoyl acyl chains to be coupled with 1-(3-aminopropyl)silatrane using 1,1’- carbonyldiimidazole and succinic anhydride. These short, medium, and long-chain models were then subjected to dynamic light scattering analysis after vortexing for 15 minutes in concentrations of 15 mg/mL and 30 mg/mL ultrapure H2O. Previous research has demonstrated that hybrid siloxane phosphocholines that possess a disiloxane moiety appended onto a single tail of many biologically relevant double tail phosphocholines are capable of spontaneously forming vesicles of 100 nm in diameter without the need of extrusion or other forceful techniques at these concentrations. For a direct comparison, the chemoenzymatic synthesis of two medium chain hybrid siloxane phosphocholines and a dynamic light scattering analysis of all six previously studied hybrid siloxane phosphocholines were conducted. At concentrations of 30 mg/mL in ultrapure H2O the six-hybrid siloxane phosphocholines spontaneously formed particles ranging from 97.1 nm to 364.3 nm in diameter, but only the medium chain silatrane derivative formed particles of 200 nm in diameter while the short and long chain silatranyl-lipids required extrusion for particle formation. Attempts were made to further expand the library and synthesize silatranefunctionalized phospholipids using a phosphate to couple the tails to the silatrane rather than succinic anhydride. Despite the various trials, the intermediates were observed to rapidly decompose via 31P NMR, 1H NMR, and TLC, likely due to their hydrolytic instability

Novel bidentate amine – imine, and amido – imine ligands were synthesized. The former species was reacted with ZnMe2 to generate zinc methyl complex. The compound was fully characterized by 1H NMR and X – ray spectroscopy. The zinc methyl complex demonstrated rather limited catalytic activity in hydroboration and hydrosilylation of N – heterocycles. Consequently, a new zinc hydride complex was synthesized using an amido – imine ligand as a precursor. A series of nitrogen heteroaromatics were successfully hydroborated using catalytic amounts of zinc hydride species. Deuterium – labeling experiments, and kinetic studies allowed to get insights into the reaction mechanism. It was proposed that the hydride transfer proceeds via a six – membered transition state orchestrated by the Lewis acidic zinc – hydride complex. Another project was focused on the synthesis of a potentially redox “non – innocent” diimine ligand, using Arduengo’s diketone as the starting point. Attempts to install an imine moiety resulted in a surprising reaction outcome.

The generation of new structural derivatives of narciclasine, an Amaryllidaceae alkaloid, has been explored. The strategy applied to the semi-synthesis of these derivatives involves a key enolization step that produces an enol at the C1 position. This material was converted into a triflate to functionalize the C1 position through cross-coupling. Initial triflation attempts resulted in functionalization at C6 instead, and the C6 triflate was successfully coupled with different functionalities. All the novel C6 derivatives were fully deprotected and subjected to evaluation of their biological activity. Experimental and spectral data are provided for all new compounds

Hydroamidation of carbon–carbon double bonds is an attractive strategy for installing nitrogen functionality into molecular scaffolds and, with it, increasing molecular complexity. To date, metal-based approaches have dominated this area of chemical synthesis despite the drawbacks of air and moisture sensitivity, limited functional group tolerance, toxicity, and/or high cost often associated with using metals. Herein is enclosed an operationally simple, metal-free, one-pot, regioselective, multicomponent synthetic procedure for the hydroamidation of carbon–carbon double bonds. This method features mild reaction conditions and utilizes isocyanides and vinyl ethers for the rapid and modular synthesis of α-oxygenated amide scaffolds. Additional effort was put towards synthesizing reactive natural products as substrates to the developed methodology, and drafting a probable catalytic cycle for the main and side reactions present within this multicomponent procedure.

This thesis describes the synthesis and use of an N– based proline–derived directing group towards the Birch reduction, diastereoselective alkylation, and the synthesis of NHC–iridium complexes that are precursors for the study of intramolecular aryl C–H activation. A pair of ortho–benzoate esters containing epimeric pyrroloimidazolone chiral auxiliaries underwent sequential Birch reduction and diastereoselective alkylation to provide products ranging from a 50:50 to 95:5 dr for the anti– epimer, and 88:12 to >95:5 diastereomeric ratio (dr) for the syn– epimer. Single crystal X–ray analysis of key anti–epimer–derived products, along with the comparison of the optical rotation measurements of enantiomers that were prepared from the syn–or anti– starting materials to its known enantiomer confirmed the stereoselectivity of the products. This work includes related Schultz stereoselective Birch reduction alkylation of anisole with a chiral benzamide except that the pyrroloimidazolone replaces the achiral methoxy group and serves as the stereodetermining element. In addition, the synthesis and evaluation of the N–phenyl iridium complex derived from the annulated aminal with syn–stereochemistry in the backbone was achieved. Exposure of the neutral Ir–complexes to anionic nucleophiles such as MeLi resulted in an increase of electron density at the Ir atom that initiated C–H bond activation. Lastly, a N–heterocyclic carbene ligand derived from the N–benzyl analogue of the auxiliary was also investigated. Attempts to design a monodentate ligand as well as a bidentate ligand bearing an alcohol side chain were both shown to be unsuccessful at this time.

The following research regarding heteroleptic redox-active complexes with the potential for spin-crossover is synthetic in nature. The intent behind incorporating the Schiff base ligand N-(8-quinolyl)salicylaldimine with some redox-active species into a mixed ligand complex featuring a d4-d7 metal ion center was to prime the material for spin-crossover based on strong intermolecular interactions that would enhance cooperativity of the system. Single component systems that display spin-crossover behaviour paired with other physical properties like electrical conductivity hold significance in the field of multifunctional materials, of which there are few examples that feature mixed ligand systems. Information describing this type of chemistry and the magnetic interactions that govern these characteristics is introduced in the first chapter of this work. The synthetic strategies toward mixed ligand complexes in the form of [(Qsal)Fe(RAL)]+X- and [(Qsal)Co(RAL)]+X- have been realized from the use of mononuclear [(Qsal)FeCl2(CH3OH)] and [(Qsal)Co(OAc)]+OAc- species, respectively. The redox-active ligand (RAL) component is an arylazo ligand like 10-(8-quinolylazo)-9-phenanthrol (Qapl) or 1-(2-Pyridylazo)-2-phenanthrol (Papl), which possess a low-lying π* MO that makes them susceptible to multi-step reductions that give rise to radical intermediates. Heteroleptic complexes that were synthesized and isolated like [(Qsal)Fe(Qapl)]+BPh4-, [(Cl-Qsal)Fe(Qapl)]+BPh4-- and homoleptic [Fe(Qapl)2]+BPh4- were diffracted and measured several intermolecular π-π contacts of distances typically between 3.5-3.7 Å, often between the phenanthrene rings of adjacent Qapl ligands. Complexes In the form of [(Qsal)Fe(Qapl)]+X (X= BPh4- or SCN-) showed early onset of spin transition in solution usually beyond 298 K. These complexes were overly reduced in the glovebox which resulted in their deterioration, presumably from the cleavage of the RAL azo bond. The framework developed for the heteroleptic Fe3+ coordination chemistry was applied to cobalt, with some amendments, and afforded several heterleoptic Co3+ complexes using Qsal with the arylazo ligands Qapl and Papl. The heteroleptic cobalt complexes presented here were found to be LS Co3+ which is diamagnetic. However, there is potential under inert atmosphere to produce Co2+ and possibly a phenoxyl radical species with redox-active valence tautomers.

This thesis describes the attempted synthesis of phosphatidylinositol bolalipids to be used in the investigation of the mechanism of the phosphatidyl inositol transfer protein, Sec14, and the PI(4)-kinase, Pik1. The synthesis of two unique bolalipids was the goal of this thesis. The esterification of the sn1 position of a protected glycerol unit to stearic acid as well as esterification at the sn2 position to either the C20 or C36 diacid gave the framework of the desired bolalipid. Further success was seen in the coupling of benzyloxybis(diisopropylamino) phosphine to the sn3 position of the deprotected glycerol unit in the generation of a phosphoramidite. However, efforts in the final step of the synthetic method were unsuccessful and did not lead to the complete synthesis of the bola-PI. Though it was possible to couple the 2,3,4,5,6-benzyl protected myo- inositol to the phosphoramidite, the most significant issues in the synthesis of the bola-PI is the oxidation of the phosphite to the phosphonate. Despite multiple attempts with varying oxidizing agents, no oxidation was observed by TLC, P NMR or mass spectrometry data. Two phosphoramidites, precursors to the desired bola-PI molecules, have been synthesized to date. The two phosphoramidites were characterized by H NMR, C NMR, P NMR, mass spectrometry, and optical activity. They are both air and water sensitive and have been observed to decompose with storage, even when placed under nitrogen at -4 oC. Spectral and experimental data are provided for all new compounds.

This thesis focuses on the synthesis of recyclable and self-healing polysiloxane elastomer networks. These features were achieved through the use of thermally reversible Diels-Alder (DA) and retro-Diels-Alder (rDA) reactions. In this work, for the model system, two different dienes (3 and 8) and six dienophile were explored, of which five of the dienophiles are commercially available and one of them was synthesized in the lab (13) to produce a series of model DA adduct. Model systems consisting of diene-functionalized trisiloxanes and bismaleimides as dienophiles were utilized to develop a fundamental understanding of how the electronic differences in the coupling systems would influence the efficiency of the overall reaction. Then for the elastomers, three different methylhydrosiloxane-dimethylsiloxane copolymer, trimethylsiloxane terminated (PDMS) with different molecular weights and Si-H group mole percentages [32 a = 3-4% Si-H and 13000 g/mol; 32 b = 7-9% Si-H and 5500-6500 g/mol; 32 c = 25-30% Si-H and 2000-2600 g/mol] were used and functionalized with two different dienes (3 and 8) to produce six polymeric diene systems (33 a, 33 b, 33 c, 34 a, 34 b and 34 c). After analyzing the model systems, the optimal temperature for adduct formation was determined to be between 60 °C – 70 °C, while the rDA reactions occur were found to occur between 90 °C and 110 °C , depending on the system. The tensile strengths of the elastomer systems correlated well with the cross-link densities of individual elastomers (elastomers were elongated between 0.3 cm and 2.54 cm). Furthermore, the hardness of the elastomers also correlated with the cross-link density of the elastomer (Shore 00 values ranged from 32 to 8 ). However, all of the elastomers displayed a decrease in their Shore 00 values after being damaged and healed. Of particular note in this study are elastomers 35 b and 35 c. Not only were these the only examples of translucent and colourless materials, the elastomers fully cured at room temperature in only 5 h. After mechanical damage the elastomers were heated to 80 °C to induce mobility in the polymer chains, complete healing of the mechanical damage was observed to occur in approximately 3 min and upon cooling to room temperature it cured and got solid again.

This thesis is focused on the development of field-deployable nucleic acid testing platforms to allowed rapid detection and quantification of nucleic acids. Two distinct platforms suitable for nucleic acid testing in resource-limited settings were developed. First, a paper-based diagnostic device was developed. The principle of this paper-based device was based on the unique interfacial interaction of DNA and the DNA intercalating dye with cellulose on chromatographic paper. Second, a colorimetric reader was developed. The principle of the reader was based on measuring the absorbance change of a chromogenic substrate which is triggered by DNA and DNA intercalating dyes under light illumination. The performance of both devices was tested using synthetic DNA, nucleic acid amplicons, and actual parasites nucleic acid samples collected from school-age children in rural areas of Honduras.