Systematic Exploration of Indolizine-Based Small Fluorescent Molecules - Synthesis, Analysis, and Application -

Abstract

Organic fluorophores have been extensively used in the field of molecular biology owing to their excellent photophysical property, suitable cell permeability, and synthetic flexibility. Understanding of the structure-photophysical property relationship of a given fluorophore often paves the road to the development of valuable molecular probes to visualize and transcribe biological networks. This thesis describes in-depth study of an indolizine-based fluorophore, including molecular design, organic synthesis, structure-property analysis, and quantum mechanical interpretation. Chapter 1 explains fundamental aspects of molecular fluorescence and photophysical parameters, together with a brief illustration of synthesis, general property, structure-photophysical property relationship, and bioapplication of representative organic fluorophores. Chapter 2 deals with fluorescent quantum yield and molecular lipophilicity of indolizine-based Seoul-Fluor system, by analyzing a series of relevant derivatives. Chapter 3 depicts a comprehensive study of tetrazine-embedded bioorthogonal probes, on the basis of well-studied indolizine fluorophore platform. By constructing a systematic series of tetrazine-indolizine conjugates, the usefulness of a newly suggested design strategy for fluorogenic bioorthogonal probes has been demonstrated, compared with conventional FRET- or TBET- based strategies. Chapter 4 discusses a rational approach to enhance molar absorptivity of a given fluorophore, with the guidance of calculated oscillator strength values. An unprecedented fluorophore is logically designed and synthesized, and structure-property relationship study of the novel fluorophore has been also dealt with in detail. Overall, systematic exploration of an indolizine-based fluorophore has led to development of a new microalgae lipid droplet probe (in chapter 2), colorful bioorthogonal fluorogenic probes (in chapter 3), and a bright mitochondrial probe (in chapter 4), working under live cell conditions.