| Research laid out in this work describes the development of chemical mechanistic insight and synthesis of molecular building blocks in medicinal and diagnostic fields. The aerobic oxidation of azolines to azoles is of utmost significance in medicinal chemistry. The azole core is a ubiquitous structural component in biologically active natural products. Therefore, the necessity to efficiently and inexpensively synthesize these azole targets is of interest to chemists and clinicians alike. This work describes a copper-catalyzed aerobic oxidation of azolines to azoles that is high yielding and cost efficient.;Along with copper-catalyzed conditions, a second set of copper-free, stoichiometric base-mediated conditions were developed for the entire substrate scope of the azoline to azole transformation. Both catalytic and stoichiometric base-mediated conditions demonstrate good yields with a substrate scope of thiazolines with aryl substituents in the 2-position with a range of electron withdrawing and electron donating groups. Catalytic conditions proved necessary for the transformation in the presence of labile protons such as the N-H proton of indole. The oxidation of azolines to azoles with both conditions were scaled to 1 g without a significant change in yield.;Additionally, this work describes the development and characterization of the first ultrasound activated MRI contrast agent. The premise of an activatable MRI contrast agent can be applied to many different therapeutic and diagnostics systems. A two-component system has been developed in which contrast from a MRI contrast agent, Gd--DOTA, is masked by a proprietary shell formulated to be water impenetrable yet water-soluble. The hydrogen bonding interaction holding the shell to the contrast agent prevents water exchange with the paramagnetic gadolinium core, thus attenuating contrast. At the desired time and location, the contrast agent-shell interaction can be selectively disrupted externally with sonication to reveal the contrast. |
