Synthesis, Properties and Dynamics of BODIPY-based Fluorophores

本课题由化学系化学结构、动力学机制B项目资助，Maria da Graça H.路易斯安那州立大学化学系的Vicente与阿巴拉契亚州立大学化学和发酵科学系的Petia Bobadova教授合作，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，并对其物理、电化学和细胞性能进行研究。 本研究旨在开发可与蛋白质和其他生物分子结合的近红外吸收和发射荧光团。计算和实验方法将用于设计，合成和评估新的荧光染料及其共轭物，寻求增强的稳定性，生物相容性和实际应用的性能。该项目包括有机和无机化学，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，因此非常适合各级科学家的教育。 该小组也有能力为科学领域代表性不足的学生提供最高水平的教育和培训。 Vicente领导LSU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学生的外联活动也将是资助项目的一部分。 硼二吡咯亚甲基（BODIPY）染料显示出丰富的物理和光电性质，包括强的吸收和发射曲线、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，并引入适合于缀合的官能度。该项目旨在提供新的基于BODIPY的系统，具有增强的稳定性，溶解性和生物物理特性，用于生物成像和生物传感的实际应用。 主要战略是：1）使用苯并-环己基化合物通过有效的分子内环化来产生具有增强的刚性和近红外吸收/发射的[a]-稠合BODIPY系统。2)区域选择性官能化以产生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增加的氧化电位和溶解度的推拉BODIPY系统和BODIPY二联体。 3)聚乙烯用于增强细胞渗透性、稳定性和生物相容性的用途。计算方法将被用来帮助目标设计建模BODIPY的属性和机制，从而促进新的方法的发展，BODIPY的合成和功能化。该项目涵盖广泛的科学和技术，将为科学领域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价值和更广泛的影响进行评估，被认为值得支持。审查标准。

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.