Spectroscopy-guided Design of Biomimetic Fluorescent Probes

通过这个奖项，化学学部的生命过程化学项目资助俄勒冈州立大学的方冲博士使用计算和复杂的光测量方法来指导荧光探针的设计和合成。受到从水母和珊瑚礁珊瑚中获得的“发光”生物分子的启发，新的探针分子的创造可以发出一系列颜色的荧光，这使得许多化学和生物成像取得了进步。虽然化学合成允许对基于这些天然分子的新化学探针发出的荧光灯的颜色和亮度进行一定程度的控制，但目前解决成像应用挑战的瓶颈是缺乏化学信息设计途径。该项目为如何制作适合生物环境成像应用的荧光探针提供了新的信息。本科生、研究生和博士后学者的培训被整合到研究活动中，以实现该项目的目标，即开发强大的“分子电影技术”，这是定制和使用荧光探针的关键。学到的经验是化学和生物物理课程的一部分，以及K-12学生拓展计划的一部分，包括俄勒冈州拉丁裔高中生的年度Juntos化学过夜营。由于荧光本质上是一个超快的过程，目前用于跨学科成像的荧光探针的发展主要是反复试验，缺乏分子洞察力。该项目由俄勒冈州立大学的方冲博士领导，旨在建立一个强大的发现和开发平台，以实现更红、更大的斯托克斯位移和更亮的荧光探针的合理设计原则。通过可调飞秒受激拉曼光谱（FSRS）、瞬态吸收、量子计算以及与化学生物学家的合作，实时跟踪具有各种功能基团的蛋白质衍生合成发色团在战略原子位置的相关电子和振动运动，并通过新提出的“双给体-一受体”策略进行丰富。这样的反馈回路有效地将可概括的机械见解与仿生分子工程联系起来，从而导致了一组具有不同供体-受体支架的多功能荧光探针的出现。该项目是化学、物理和生物的交叉领域，具有广泛的技术应用和科学吸引力，可以吸引各个层次的STEM（科学、技术、工程和数学）学习者。策略包括在物理化学中实施基于证据的教学实践，提高研究生的沟通技巧，以及为俄勒冈州的拉丁裔高中学生开发一个Juntos化学过夜营。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With this award, the Chemistry of Life Processes Program in the Division of Chemistry is funding Dr. Chong Fang at Oregon State University to use calculations and sophisticated light measurement methods to guide the design and synthesis of fluorescent probes. Inspired by "glowing" biomolecules obtained from jellyfish and reef corals, the creation of new probe molecules that emit fluorescent light over a range of colors has enabled numerous chemical and bio-imaging advances. Although chemical synthesis allows for some level of control over the color and brightness of the fluorescent light emitted by new chemical probes based on these natural molecules, the current bottleneck for solving challenges in imaging applications is the lack of chemically-informed design pathways. This project provides new information about how to make fluorescent probes that are appropriate for imaging applications in biological environments. Training of undergraduate and graduate students and postdoctoral scholars is integrated into research activities to reach the project's aims to develop powerful "molecular movie technologies" that are key to the tailor-making and use of fluorescent probes. Lessons learned are made part of chemistry and biophysics courses, as well as K-12 student outreach programs, including an annual Juntos Chemistry Overnight Camp for Latinx high school students in Oregon.The current development of fluorescent probes for imaging across disciplines is largely trial-and-error and lacks molecular insights because fluorescence is intrinsically an ultrafast process. The research in this project led by Dr. Chong Fang at Oregon State University aims to establish a powerful discovery and development platform to achieve rational design principles for redder, larger Stokes-shifted, and brighter fluorescent probes. The real-time tracking of correlated electronic and vibrational motions of protein-derived synthetic chromophores with various functional groups at strategic atomic sites, enriched by the newly proposed "double-donor-one-acceptor" strategy, is facilitated by tunable femtosecond stimulated Raman spectroscopy (FSRS), transient absorption, quantum calculations, and collaborations with chemical biologists. Such a feedback loop effectively bridges generalizable mechanistic insights to biomimetic molecular engineering, which leads to an emerging group of versatile fluorescent probes with diverse donor-acceptor scaffolds. This project at the interface of chemistry, physics, and biology has broad technological applications and science appeal to engage STEM (science, technology, engineering, and mathematics) learners at all levels. Strategies include implementing evidence-based instructional practices in physical chemistry, enhancing graduate student communication skills, and developing a Juntos Chemistry Overnight Camp for Latinx high school students across the state of Oregon.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.