Identifier

etd-06112014-202230

Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

Boron dipyrromethene (BODIPY) dyes, have garnered much attention in recent decades due to their enticing photophysical properties and their bioimaging applicability. Despite the progression of this field, the development of BODIPY based anti-cancer agents and radioimaging dyes has seen little progress. The utilization of fluorescent BODIPYs as photosensitizers for photodynamic therapy, and as boron delivery agents for boron neutron capture therapy offers promise as theranostic agents. Additionally, BODIPY derivatives that absorb and emit in the near-IR regions of the electromagnetic spectrum and bear radioisotopes suitable for radioimaging techniques are of great interest. Chapter 1 is a concise overview of the fundamental concepts of the BODIPY fluorophores. The synthetic routes, post-synthetic modification strategies, and several biological applications of BODIPYs are introduced and will be elaborated upon in subsequent chapters. Chapter 2 describes the synthesis, characterization, computational modeling and in vitro biological investigations of a series of meso-aryl tetramethyl BODIPYs and their diiodo derivatives as photodynamic therapy photosensitizers. Variances in the meso-substituent of BODIPY were found to influence the phototoxicity of diiodo-BODIPYs, with some possessing phototoxicity while others were non-toxic. The photophysical properties of these compounds were also explored computationally in collaboration with Dr. Petia Bobadova-Parvanova of Rockhurst University. Chapter 3 reports on the synthesis of several near-IR styrylated diiodo-BODIPYs prepared via the Knoevenagel reaction strategy from one of the most phototoxic BODIPYs described in Chapter 2. The effects of the number and type of styryl substituents on their photophysical properties and in vitro photodynamic activities are discussed. Chapter 4 explores the synthesis, photophysical, and in vitro biological properties of near-IR styryl BODIPYs with applications in near-IR fluorescence, PET, and SPECT imaging. The exploration of radiolabelling highly functionalized long wavelength BODIPYs is detailed herein. Chapter 5 conveys an effective method towards the preparation of carborane-appended BODIPYs for boron neutron capture therapy. The use of highly efficient palladium-catalyzed Suzuki coupling yielded two carboranyl-BODIPYs of varying optical properties in good yield. The photophysical properties and blood brain permeability of these novel-carboranyl BODIPYs was reported.

Date

2014

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Vicente, Maria da Graca

Included in

Chemistry Commons

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