Doctor of Philosophy (PhD)



Document Type



Chapter 1 contains a brief overview of the history, synthesis, and properties of BODIPY dyes as well as that of the biomedical applications of bio-imaging and photodynamic therapy. Additionally, an overview of the theoretical framework of density functional theory and its time-dependent variant are provided. In Chapter 2, the effects of structural modification on the electronic structure and electron dynamics of cationic meso-(4-pyridyl)-BODIPYs were investigated. A library of 2,6-difunctionalized meso-(4-pyridyl)-BODIPYs bearing various electron-withdrawing substituents was designed and DFT calculations were used to model the redox properties, while TDDFT was used to determine the effects of functionalization on the excited states. Structural modification was able to restructure the low lying molecular orbitals to effectively inhibit d-PeT. A new meso-(4-pyridyl) BODIPY bearing 2,6-dichloro groups was synthesized and shown to exhibit enhanced charge recombination fluorescence. The fluorescence enhancement was determined to be the result of functionalization modulating the kinetics of the excited state dynamics. The syntheses employed in the preparation of several additional derivatives from the previously designed meso-(4-pyridyl)-BODIPY library are reported in Chapter 3. The dyes were then characterized photophysically and biologically. The photophysical properties were found to follow the expected trend. The ionic derivatives all displayed decreased cellular uptake and the only derivatives exhibiting high phototoxicity were the neutral dyes containing heavy atoms. Chapter 4 presents a comparative study of the differences in the photophysical and biological properties of the series of meso-pyridinium BODIPY isomers through an experimental and computational investigation. The three structural isomers were synthesized and photophysically characterized revealing differences in both absorption and emission wavelengths as well as fluorescence quantum yields. TDDFT calculations were used to model the dyes’ electronic structure and excited states to evaluate the impact of pyridine orientation on the optical properties. The dyes’ biological activity was evaluated in human epithelial type-2 (HEp-2) cancer cells. Decreasing cellular uptake from 4-Py > 2-Py > 3-Py was observed for both neutral and ionic derivatives. All three derivatives, both neutral and ionic, displayed equivalent phototoxicity (IC95 = 100 μM) with the exception of 4-Py+ (IC90 = 100 μM).



Committee Chair

Vicente, Graca