Synthesis, Properties and Dynamics of BODIPY-based Fluorophores

在这个由化学系化学结构、动态和机理B计划资助的项目中，路易斯安那州立大学化学系的Maria da Graça H.Vicente教授与阿巴拉契亚州立大学化学和发酵科学系的Petia Bobadova教授将开发用于生物和材料应用的新型荧光染料，包括生物成像和化学传感。本论文的主要目标是设计和合成新型的硼二吡咯亚甲基(BODIPY)染料，并研究它们的光物理、电化学性质和电池性质。这项研究旨在开发能够与蛋白质和其他生物分子偶联的近红外吸收和发射荧光团。将利用计算和实验方法来设计、合成和评价新的荧光染料及其偶联物，以期为实际应用寻求更好的稳定性、生物相容性和性能。该项目涵盖有机化学和无机化学、光谱学、化学动力学、计算建模、细胞和分子生物学、分子识别和生物医学成像，因此非常适合于各级科学家的教育。这一群体也处于有利地位，可以为科学方面代表性不足的学生提供最高水平的教育和培训。Vicente博士在路易斯安那州立大学领导的项目将提高学生的学习和专业技能，丰富他们的教育经验，并鼓励他们追求研究事业。涉及K-12学生的外展活动也将是该资助项目的一部分。二吡咯亚硼(BODIPY)染料表现出丰富的光物理和光电性质，包括强烈的吸收和发射轮廓、高的摩尔消光系数、高的荧光量子产率和长的荧光寿命。BODIPY核心的化学修饰可用于调节吸收和发射波长、斯托克斯位移、稳定性、量子产率、水溶性，以及引入适合于共轭的官能团。本项目旨在为生物成像和生物传感领域的实际应用提供具有增强的稳定性、溶解性和光物理性质的新型BODIPY体系。主要的策略是：1)通过有效的分子内环合反应，利用苯并芳化反应合成具有更高刚性和近红外吸收/发射的[a]-稠合BODIPY体系。2)区域选择性官能化，以创建具有增强的摩尔消光系数、荧光发射和斯托克斯位移、以及具有更高的氧化电位和溶解度的推拉式BODIPY体系和BODIPY二聚体。3)使用多氟化来增强细胞的通透性、稳定性和生物相容性。将使用计算方法通过模拟BODIPY的性质和机制来协助目标设计，从而促进开发合成BODIPY和功能化BODIPY的新方法。该项目涵盖了广泛的科学和技术，将为科学领域中代表性不足的学生提供最高水平的教育和培训。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

In this project, funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Maria da Graça H. Vicente of the Department of Chemistry at Louisiana State University, in collaboration with Professor Petia Bobadova of the Department of Chemistry and Fermentation Sciences at Appalachian State University, will develop new fluorescent dyes for use in biological and materials applications, including bioimaging and chemosensing. The main goals are to design and synthesize new boron dipyrromethene (BODIPY) dyes, followed by investigation of their photophysical, electrochemical and cellular properties. This research is directed toward the development of near-infrared absorbing and emitting fluorophores that can be conjugated with proteins and other biomolecules. Computational and experimental methods will be used to design, synthesize and evaluate new fluorescent dyes and their conjugates, seeking enhanced stability, biocompatibility and performance for practical applications. This project encompasses organic and inorganic chemistry, spectroscopy, chemical kinetics, computational modeling, cell and molecular biology, molecular recognition, and biomedical imaging, and is therefore well suited to the education of scientists at all levels. This group is also well-positioned to provide the highest level of education and training for students underrepresented in science. Dr. Vicente leads programs at LSU that will enhance student learning and professional skills, enrich their educational experiences, and encourage them to pursue research careers. Outreach activities involving K-12 students will also be part of the funded project. Boron dipyrromethene (BODIPY) dyes display a rich array of photophysical and optoelectronic properties, including intense absorption and emission profiles, high molar extinction coefficients, high fluorescence quantum yields and long fluorescence lifetimes. Chemical modifications of the BODIPY core can be used to tune the absorption and emission wavelengths, Stokes shifts, stability, quantum yields, water-solubility, and to introduce functionality suitable for conjugation. This project aims to provide new BODIPY-based systems with enhanced stability, solubility, and photophysical properties for practical applications in bioimaging and biosensing. The main strategies are: 1) Use of benzo-annelation via efficient intramolecular cyclizations to produce [a]-fused BODIPY systems with enhanced rigidity, and near-infrared absorptions/emissions. 2) Regioselective functionalizations to create push-pull BODIPY systems and BODIPY dyads with enhanced molar extinction coefficients, fluorescence emission and Stokes shifts, as well as with increased oxidation potentials and solubility. 3) Use of polyfluorination for enhancement of cellular permeability, stability, and biocompatibility. Computational methods will be used to assist the target design by modeling BODIPY properties and mechanisms, thus facilitating the development of new methodologies for the synthesis and functionalization of BODIPYs. This project encompasses a broad range of science and techniques, which will provide the highest level of education and training for students underrepresented in science.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.