Spectroscopy-guided Design of Biomimetic Fluorescent Probes

有了这个奖项，化学系的生命过程化学项目正在资助俄勒冈州州立大学的Chong Fang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中获得的“发光”生物分子的启发，新的探针分子的创造，发射出一系列颜色的荧光，使许多化学和生物成像技术取得了进展。虽然化学合成允许对基于这些天然分子的新化学探针发射的荧光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。该项目提供了有关如何制作适合生物环境中成像应用的荧光探针的新信息。本科生、研究生和博士后学者的培训被纳入研究活动，以实现该项目的目标，即开发强大的“分子电影技术”，这是荧光探针定制和使用的关键。化学和生物物理学课程以及K-12学生拓展计划的一部分，包括每年在俄勒冈州为拉丁裔高中生举办的Juntos化学夏令营。目前，用于跨学科成像的荧光探针的开发主要是试错，缺乏分子见解，因为荧光本质上是一个超快的过程。由俄勒冈州州立大学的Chong Fang博士领导的该项目的研究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。可调谐飞秒受激拉曼光谱（FSRS）、瞬态吸收、量子计算以及与化学生物学家的合作促进了对蛋白质衍生的合成发色团的相关电子和振动运动的实时跟踪，这些发色团具有在战略原子位点处的各种官能团，通过新提出的“双供体-一受体”策略来富集。这样的反馈回路有效地将可推广的机制见解与仿生分子工程联系起来，从而产生了一组具有不同供体-受体支架的多功能荧光探针。这个项目在化学，物理和生物学的接口具有广泛的技术应用和科学吸引力，以吸引各级STEM（科学，技术，工程和数学）学习者。战略包括实施物理化学循证教学实践，提高研究生沟通能力，并为整个俄勒冈州的Latinx高中学生开发一个Juntos化学过夜营。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

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.