Novel Hydroporphyrin Arrays and Metal Complexes For Improved Photodynamic Therapy.

Abstract

Since ancient times, humans have always had a fascination for light-emitting substances. This phenomenon, termed fluorescence by Stokes in 1852, has since become ubiquitous to the human experience. Today fluorescence enables us to keep our streets and homes lit, allows for rapid analytic and biochemical detection, or simply allows the appreciation of arts in the form of fluorescent paintings. Simply put, fluorescence has had and continues to have a deep impact on our way of life. Of particular interest is the impact fluorescence has in the field of medicine. The introduction of fluorophores dramatically improved diagnostic capabilities, and when combined with an ability to photosensitize reactive oxygen species, has led to significant improvements in therapeutic outcomes in the treatment of several neoplastic conditions. The driver for this advancement is a systemic approach to understanding the structure-property relationship in these fluorophores, which elicit desirable properties in the engineered compounds. In this work, we utilize a systemic approach to understand structure-property relationships in a series of newly developed weak and strongly conjugated hydroporphyrin dyads and a new family of peripherally metalated hydroporphyrin metal complexes. Hydroporphyrins are an excellent template for studies because of their long wavelength of absorption and emission, good fluorescence quantum yields (?f), good photostability, high intersystem crossing yields (?ISC), and the ability to photosensitize singlet oxygen (??). First, we developed symmetrical and non-symmetrical directly linked dyads to understand the impact of asymmetrical architecture on the photophysics of these compounds. In the next chapter, we varied the strength of the electronic interactions between macrocycles in the dyads and established a solvent polarity-dependent relationship in the properties of these dyads. In the following chapter, we focused on strongly conjugated dyads as a model to accurately gauge fluorescence and photosensitization response as a function of the local microenvironment. Finally, we developed a new set of metal complexes and organometallic hydroporphyrin with improved singlet oxygen quantum yields and evaluated their ability to ablate neoplastic lesions.