Collision Cross Section Measurements Using Fourier Transform Ion Cyclotron Resonance Techniques

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With support from the Chemical Measurement and Imaging program in the Chemistry Division, Professors David Dearden and Matthew Asplund of Brigham Young University and their students are devising a new approach to measuring the shapes of molecules, including the way that biological molecules like proteins are folded. While superb techniques exist for such measurements, those techniques require specialized instrumentation. This team is developing new techniques to extend these capabilities to an additional class of existing instrumentation with only minimal modification, making these measurements more widely available. Their approach may also offer enhanced performance for some applications. These measurements are important because just as a misshapen, misfolded parachute may not unfurl correctly, misfolded protein molecules (for example) do not function properly and are believed to be among the root causes of debilitating conditions like Alzheimer?s or Parkinson?s diseases. Sensitive detection of the shape is essential to understanding how molecules fit together and function, and what can go wrong at the molecular level. Students carrying out this work are trained in skills essential to the 21st century science that is the foundation of the U.S. economy.In this project, graduate and undergraduate students are developing techniques designed to measure the collision cross sections of gas phase ions, without requiring a dedicated ion mobility instrument. Two independent approaches to these measurements are taken. The first examines signal decay as ions are scattered out of a coherently-orbiting ensemble in a Fourier transform ion cyclotron resonance mass spectrometer (FTICR/MS). The decay rate (and the corresponding FTICR linewidth) depends on the collision cross section. The second approach measures the phase lag between the radiofrequency electric field used to excite the ions and the ion motion in the presence of a damping buffer gas. This approach overcomes mass-to-charge and energy limits that are inherent in the linewidth method. The utility of these techniques is demonstrated by examining problems in supramolecular chemistry and structural biochemistry. In the course of this work, graduate students are trained in advanced techniques for high performance mass spectrometry that are vital for the biotechnology industry and the emerging field of proteomics. Many of the talented undergraduate students engaged in this research subsequently pursue graduate studies. The instrumentation used in this study is also made available for undergraduate courses in general, analytical and physical chemistry at BYU, which is a significant supplier of B.S. chemistry and biochemistry students to U.S. graduate programs.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.