†Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States.
‡Center for Chemical Proteomics, Department of Chemistry, Seoul National University, Seoul 151-747, Korea (South).
Acc Chem Res. 2015 Mar 17;48(3):538-47. doi: 10.1021/ar500370v. Epub 2015 Feb 19.
Owing to its high sensitivity and great applicability, the fluorescence phenomenon has been considered as an inevitable research tool in the modern 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 fluorogenic 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.
由于其高灵敏度和广泛适用性，荧光现象已被视为化学、生物学、材料科学、生物医学科学及其界面等现代科学领域不可或缺的研究工具。人们已经提出了许多策略来理解和操纵荧光材料的光物理性质，但科学界一直专注于重复应用现有的有机荧光团，或者在没有系统研究的情况下，根据试错法来识别独特的荧光性质。此外，最近的研究强调了深入了解有机荧光团的结构-光物理性质关系对于开发更好的荧光探针的必要性。在这里，我们提供了一个新的荧光分子框架 Seoul-Fluor 的概述，该框架可以通过合理的设计，根据光物理性质提供各种荧光团。Seoul-Fluor 建立在基于吲哚嗪的荧光平台上，该平台具有三个不同的位置，可以引入各种取代基：R(1)和 R(2)取代基用于电子扰动；R(3)取代基作为用于生物偶联的功能手柄。在过去的十年中，我们已经证明，Seoul-Fluor 系统具有：（i）可调谐且可预测的发射波长，涵盖整个可见光范围；（ii）通过光致电子转移现象控制量子产率；以及（iii）环境敏感的荧光性质，可以通过分子内电荷转移过程进行修饰。我们通过构建系统的一系列类似物并随后分析其光物理性质，而无需高度复杂的理论支持，令人信服地证明了光物理性质（即发射波长和量子产率）的可预测性。通过可量化的参数，如哈米特取代基常数或分子轨道能级，这种独特的有机荧光团可以作为开发新型荧光可切换生物传感器和荧光生物探针的多功能分子平台。在本报告中，我们将讨论 Seoul-Fluor 的发现和最近的进展、基于 Seoul-Fluor 的生物探针的合理设计以及它们在特定生物学过程中的实际应用，这些应用得益于结构-光物理性质关系的系统研究。
