Spectroscopy-guided Design of Biomimetic Fluorescent Probes

点击翻译按钮获取中文摘要

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.