This grant supported an experimental physical chemistry effort at Yale University. The specific aim of our project was to exploit the capabilities of a new type of instrumentation, largely developed by our team over the past decade, that can determine the structures of very fragile molecular assemblies at low temperature by combining the precision of laser spectroscopy with the extreme sensitivity of mass spectrometry.  In our approach, species in solution are isolated in the gas phase, cooled close to absolute zero using cryogenic ion trapping techniques, separated according to mass-to-charge ratio, and subjected to structure determination using vibrational spectroscopy carried out using two infrared lasers. This hybrid capability is a new and powerful type of chemical analysis that can isolate the molecular-level rearrangements that define the pathways controlled at the macroscopic scale in the course of chemical synthesis.  One example central to this grant has been the capture and identification of key reaction intermediates in the alkali metal ion (potassium in this case)-mediated transformation of the very stable N₂ molecule into compounds that feature NH chemical bonds. That application was carried out in close collaboration with Yale synthetic chemist Patrick Holland, who designed the reaction strategy. Together, we demonstrated the utility of our hybrid instrument to elucidate individual NH bond formation events that ultimately lead to the formation of stable products. This success illustrated how the new instrument can reveal structural details of chemical transformations that are inaccessible to traditional methods of chemical analysis.  We leveraged that feature in another collaborative study, this time with synthetic chemist Scott Miller at Yale, in which we captured and characterized metabolites, species that are generated in very low abundance when the body digests drugs. Characterization of these species is a critically important step that must be overcome before a drug can be cleared for general use, and is very expensive because the metabolite yields are so small. In this case, we demonstrated that the structures and chemical identities of the metabolites formed by digestion of the commonly used drug, Diovan^(R)  (Valsartan), used to control blood pressure, could be readily determined using advanced capabilities of our instrument that can efficiently sort out the structures of individual species, including those that are embedded in complex mixtures and have the same mass-to-charge ratio (isomers).  

The work outlined above addresses the broader impact of our custom instrumentation in the chemical sciences. As physical chemists, however, we are also exploring fundamental questions about the structure of water and the special nature of water at the air-water interface. Because water is pervasive across all branches of chemistry and biology, there is an extensive, world-wide effort to simulate its properties in extreme environments from first principles. Our new instrument provides an unprecedented way to monitor how individual water molecules, and even single OH oscillators within a water molecule, contribute to the behavior of bulk water at the interface. This information is critically important for the simulation of spectral patterns obtained using surface-selective spectroscopic schemes, which in turn are the benchmarks most commonly used to test the accuracy of theoretical methods. However, because the spectra of interfacial water at room temperature are broad and largely unstructured, they often do not challenge fundamental theoretical assumptions. By isolating the spectral behavior of interfacial water at the molecular level, we have provided detailed benchmarks upon which to build secure theoretical frameworks. We developed a methodology by which small, cage-like structures of water molecules enclosing a metal ion are isolated. These structures naturally form when a sheet of 20 water molecules, only one water molecule thick, wraps around a metal ion. We then used isotopes to block out 19 of the 20 waters in the sheet, and monitored the behavior of the single remaining H₂O molecule embedded in the surface. The results are the first of their kind, and were reported in a 2019 article in Science. This effort was carried out in collaboration with theoretical chemist Anne McCoy (U. Washington), and established how the various spectroscopically distinct ways that a water molecule can lock into the web of hydrogen bonds are encoded in the correlated frequencies between the two OH oscillators. The results also describe a new feature that appears in the spectrum when the OH stretching vibration interacts with the bending motion of the molecule. This work is on-going under current NSF support, where we are extending the measurements to completely deconstruct the molecular-level motions underlying the vibrational spectrum of interfacial water.

Last Modified: 12/17/2019
Modified by: Mark A Johnson