Boron Functionalization of BODIPY Dyes, and Their Evaluation as Bioimaging Agents

Abstract

BODIPY, also known as “porphyrin’s little sister,” belongs to a class of fluorescent dyes. It contains a dipyrromethene π-system with a disubstituted boron atom. The basic 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) is known for its numerous useful applications in the fields of biology and materials. Modification of this well-known fluorophore has been shown to change its photophysical and chemical properties. There has been great interest in the modification at the boron center in recent years for synthesizing new dyads and cascade-type dyes. This work focuses on functionalization at the boron center with carbon and oxygen nucleophiles for further investigation as bioimaging agents. Chapter 1 of this dissertation describes an overview of BODIPYs including synthetic development, post-synthetic functionalization strategies, and how BODIPYs can be involved in many biological applications. Chapter 2 discusses the synthesis, characterization, and computational studies of 4,4-dialkoxy BODIPY and its derivatives. Preliminary studies with various Lewis acids and alcohols will be investigated and discussed. In collaboration with Dr. Petia Bobadova-Parvanova of Rockhurst University, the photophysical properties were studied using computational analysis. The structural, spectroscopic and fluorescence properties of all the synthesized BODIPYs will be studied and be compared. Chapter 3 presents the synthesis and characterization of 4,4’-dicyano-BODIPYs. A novel route for preparation of 4,4’-difunctionalized BODIPYs bearing phenyl and various substituents at the boron center was developed. These compounds were synthesized in a three step one-pot reaction between dipyrromethenes and dichlorophenylborane, followed by replacement of chloride with fluoride and various carbon- and oxygen-centered nucleophiles. These BODIPYs’ structural, spectroscopic, and fluorescence properties are reported and discussed. Chapter 4 represents the investigation of six 1,2,3-triazole-BODIPYs under the Cu(I)-catalyzed Huisgen cycloaddition reaction conditions. A novel BODIPY bearing a chiral moiety was synthesized using method C and X-ray crystallography confirmed its identity. Chapter 5 reports the synthesis of chloroalcohol compounds via triphosgene-triethylamine activation. An asymmetric SN1 reaction was investigated through the use of an oxazolidinone.