Comparison of Vibrational Coupling and Vibrational Energy Transfer Mechanisms Between Probe Pairs in Different Molecular Scaffolds to Capture Dynamic Structures via 2D IR

With support from the Chemical Structure, Dynamics and Mechanisms-A (CSDM-A) Program in the Division of Chemistry, Matthew Tucker and his group at the University of Nevada-Reno are developing new pairs of vibrational probes for measuring the structural dynamics of biological molecules, including RNA and proteins. The vibrational labels allow the researchers to monitor motions within these molecules with a unique combination of temporal and structural resolution that is relevant to biological activity.

The measurements reveal mechanistic details related to ion transport across cell membranes, a process that has important implications for homeostasis and deviations from normal steady state conditions in human biology. Cellular ion transport often depends on acid levels within the body. Therefore, the researchers use lasers pulses to initiate pH jumps and then track molecular motion using the vibrational probe pairs as labels to produce a step-by-step "molecular movie" of the molecular motions that are responsible for the biological activity.

In addition to the scientific objectives of the project, Dr. Tucker and his research group will work to recruit and train future scientists from diverse and underrepresented backgrounds through participation in programs such as the American Chemical Society SEED program for economically disadvantaged high school students and the Upward Bound Program for first-generation college students.

The Tucker group is also working to develop a seminar series to encourage participation in science, technology, engineering, and mathematics (STEM) education and research. The goal of the seminar series is to show parents and students, especially those from the Native American community, how science and technology affects the world around them.

This research characterizes the interactions between unique IR (Infrared) probe pairs in order to uncover vibrational coupling mechanisms, provide insights into thermal energy flow in molecules, and ultimately capture structural snapshots of molecular motion via 2D IR spectroscopy. Specifically, the research team is using 2D IR measurements to reveal time-resolved structural information about the molecular motions involved in the M2 Influenza proton channel and ion transport through the Kv11.1 K+ channel.

In order to achieve these goals, Tucker and his team are developing novel spectroscopic probe pairs that can be used to simultaneously measure distances and angles within a variety of molecular scaffolds, while also extending the vibrational lifetimes of the probe pairs in order to allow measurements of the molecular dynamics on time scales seldom achieved with 2D IR spectroscopy. The research team is also working to distinguish vibrational coupling and vibrational energy transfer pathways in the probe pairs in order to regulate the coupling mechanisms and expand distance limitations.

Finally, the team is working to combine these new spectroscopic tools with transient pH-jump 2D IR spectroscopy to investigate the reactive pathways of the pH-dependent proton transfer and ion transport mechanisms within model water and ion channels. The approach holds the promise of revealing structural dynamics of key transport events related to ion gating and proton gating within model systems on time scales ranging from single bond rotational periods (fs-ps) to the times required for significant conformational reorganization (ns-ms) by employing both equilibrium and transient 2D IR spectroscopy.

Student training opportunities and educational outreach activities further broaden the impact of the project.

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.