Systematic Exploration of Indolizine-Based Small Fluorescent Molecules

This thesis describes an in-depth study of an indolizine-based fluorophore, from understanding of its structure-photophysical property relationship to its application as a useful biological reporter.

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. In this thesis, respective chapters deal with molecular design, organic synthesis, structure-property analysis, and quantum-mechanical interpretation of unexplored family of indolizine-based molecules. This systematic exploration has led to rational development of a new microalgae lipid droplet probe, colorful bioorthogonal fluorogenic probes, and a bright mitochondrial probe, working under live cell conditions.

Harnessing the optical properties of a given fluorophore has been an important topic for a couple of decades, both in industry and in academia. This thesis provides useful insights for the improvement and development of unique small fluorescent materials, or optical materials.

Auteur

Dr. Youngjun Lee is a member of CRI Center for Chemical Proteomics, Department of Chemistry, Seoul National University, Korea. He earned Ph.D. degree in organic chemistry at SNU in February 2018.

Contenu

Abstract

Table of Contents

List of Figures

List of Tables

List of Schemes

List of Abbreviations

Chapter 1. Introduction

1.1 Molecular Fluorescence and Photophysical Parameters

1.2 Organic Fluorophores

1.2.1 BODIPY

1.2.2 Coumarin

1.2.3 Cyanine

1.2.4 Fluorescein

1.2.5 Rhodamine

1.2.6 Seoul-Fluor

1.3 Aims and Scope of the Thesis

1.4 References

Chapter 2. A Comprehensive Studies of an Indolizine-Based Seoul-Fluor System

2.1 Structure and Quantum Yield Relationship Study of Seoul-Fluor

2.1.1 Introduction

2.1.2 Result and discussion

2.1.3 Conclusion

2.2 Optimization of SF-Based Lipid Droplet Bioprobes on the basis of Molecular Lipophilicity

2.2.1 Introduction

2.2.2 Result and discussion

2.2.3 Conclusion

2.3 An Overview of Seoul-Fluor System

2.4 References

2.5 Experimental Section

Chapter 3. Tetrazine-Containing Colorful Bioorthogonal Probes based on the Indolizine Core Skeleton

3.1 Introduction

3.2 Result and Discussion

3.2.1 Initial design and synthesis

3.2.2 Change in absorption property of SFTz0105 upon TCO cycloaddition reaction

3.2.3 Change in fluorescence property of SFTz0105 upon cycloaddition reaction with TCO

3.2.4 Reaction kinetics

3.2.5 Rational expansion of multicolor SFTzs based on a monochromophoric strategy

3.2.6 TD-DFT calculation

3.2.7 Direct comparison of mono- vs bichromophoric SFTzs with long emission wavelength

3.2.8 Bioapplication

3.3 Conclusion

3.4 References

3.5 Experimental Section

Chapter 4. Rational Development of Furoindolizine Core Skeleton Guided by Oscillator Strength

4.1 Introduction

4.2 Result and Discussion

4.2.1 Designing an unexplored fluorophore with high molar absorptivity

4.2.2 Library construction based on a novel furo[3,2-e]indolizine scaffold

4.2.3 Photophysical property analysis

4.2.4 Rational design of novel furoindolizine-based fluorescent compounds and bioapplication

4.3 Conclusion

4.4 References

4.5 Experimental Section