Discovery, Understanding, and Bioapplication of Organic Fluorophore: A Case Study with an Indolizine-Based Novel Fluorophore, Seoul-Fluor

CONSPECTUS: Owing to its high sensitivity and great applicability, the fluorescence phenomenon has been considered as an inevitable research tool in the modem scientific fields of chemistry, biology, materials science, biomedical science, and their interfaces. Many strategies have been pursued to understand and manipulate the photophysical properties of fluorescent materials, but the scientific community has been focused on the repeated application of existing organic fluorophores or the identification of unique fluorescence properties in a trial-and-error basis without systematic studies. Moreover, recent studies are emphasizing the necessity of deeper understanding about the structure photophysical property relationship of organic fluorophores for the development of better fluorescent probes. Herein, we provide an overview of a novel fluorescent molecular framework, Seoul-Fluor, which can be rationally engineered to furnish a wide variety of fluorophores in terms of the photophysical properties. Seoul-Fluor is built on an indolizine-based fluorescent platform with three different positions to introduce various substituents: R-1 and R-2 substituents for electronic perturbation; R-3 substituent as a functional handle for bioconjugation. Over the past decade, we have demonstrated that the Seoul-Fluor system has (i) tunable and predictable emission wavelength covering a full visible-color range; (ii) controllable quantum yield via photoinduced electron transfer phenomenon; and (iii) environment-sensitive fluorogenic properties that can be modified through intramolecular charge transfer processes. We convincingly demonstrated the prediction of photophysical properties, that is, emission wavelength and quantum yield, through the construction of a systematic set of analogues and the subsequent analysis of their photophysical properties without the highly sophisticated theoretical support. Guided, by quantifiable parameters such as the Hammett substituent constants or energy levels of the molecular orbitals, this unique organic fluorophore can serve as a versatile molecular platform for the development of novel fluorescent switchable biosensors and filuorogenic bioprobes. In this Account,;we will discuss the discovery and recent progress made on Seoul-Fluor, the rational design of Seoul-Fluor-based bioprobes, and their practical applications to specific biological processes that are facilitated by systematic studies of the structure photophysical property relationships.