Brooks H. Pate
B.S. University of Virginia, 1987
Ph.D. Princeton University, 1992
NRC Postdoctoral Fellow (NIST, Gaithersburg), 1992-93
Broadband Rotational Spectroscopy for Chemical Analysis
The Pate lab develops instruments for molecular rotational spectroscopy and uses these instruments to solve challenging problems in chemical analysis. Molecular rotational spectroscopy uses low frequency light, typically in the microwave region of the electromagnetic spectrum, to excite transitions between the quantized energy levels that come from the rotational kinetic energy. The energy level patterns for the rotational kinetic energy are determined by the principal moments-of-inertia of the molecule and are, therefore, directly related to the mass distribution relative to the molecular center-of-mass. The fact that the measurement is connected to the mass distribution, and not just the total mass, makes molecular rotational spectroscopy ideally suited for isomer analysis.
Broadband Rotational Spectroscopy
The Pate lab has pioneered the technique of chirped-pulse Fourier transform rotational spectroscopy. The key advantage of this technique over previous instrument designs is the ability to measure a large spectral range in a single spectrum acquisition event. The method has similarities to Fourier transform nuclear magnetic resonance (NMR) spectroscopy: A high-power light pulse (the chirped pulse) creates a macroscopic polarization in the sample by aligning the molecular dipole moments. After the excitation pulse dissipates, the molecular rotational resonances are detected by the light waves coherently emitted by the rotating molecules. This coherent emission eventually decays through Doppler dephasing or collisions. The broadband free-induction decay (FID) from the rotational motion is collected using a high-speed digitizer. Sensitivity is enhanced by acquiring several measurements and co-adding the FIDs. The molecular rotational spectrum is produced by subsequent Fourier transform analysis of the FID. This measurement approach has been extended to low-frequency instruments (2-8 GHz) that are used for analysis of large molecules and to high-frequency instruments (mm-wave range) for smaller molecules such as those important in astrochemistry
Initial Applications of Broadband Rotational Spectroscopy
The first application of chirped-pulse Fourier transform rotational spectroscopy was in the field of intramolecular dynamics. In this application, the instrument is used to acquire the rotational spectrum of a highly vibrationally excited molecule that is prepared by laser excitation. The complex nuclear motion from intramolecular vibrational energy redistribution and conformational isomerization produce dynamic effects in the spectrum. For example, the coalescence of rotational spectra associated with different conformational geometries can be used to measure the energy-resolved unimolecular isomerization rate under collision free conditions.
A second area of application is the structure of molecular clusters. Clusters form in the pulsed jet expansion used to create the cold gas sample used for analysis. The aggregation is driven by non-covalent interactions such as hydrogen bonding and London dispersion forces. A challenge for the analysis of the clusters is that a wide range of cluster sizes are produced and there can be many isomeric structures for each cluster size. Rotational spectroscopy provides the highest spectral resolution of molecular spectroscopy techniques used for chemical analysis. As a result, the technique has no trouble resolving the spectra from all cluster geometries present in the sample. The application of broadband rotational spectroscopy to water clusters has dramatically increased the number of known structures, demonstrated the presence of multiple isomers for a single cluster size, and revealed the dynamics of quantum mechanical tunneling within the water cluster.
Chiral Analysis with Applications to Pharmaceutical Chemistry
The most recent work in the Pate lab is the application of broadband rotational spectroscopy to chiral analysis. The group is developing techniques for quantitative chiral analysis that uses the formation of clusters of an analyte and a small, enantiopure chiral molecule (called the chiral tag) to determine the enantiomeric excess of the sample. Using quantum chemistry modeling of the chiral tag complexes it is also possible to establish the absolute configuration of the dominant enantiomer. A key strength of rotational spectroscopy is that the measurement can simultaneously perform other analyses that are related to the synthesis of chiral molecules. For example, when the analyte has multiple chiral centers there are two types of stereoisomers: the enantiomers (left- and right-handed versions of a molecule) and diastereomers (isomers with different structures and mass distributions that are easily distinguished by molecular rotational spectroscopy). The technique can also be used to quantify regioisomers that are often present due to addition reactions that occur at other activated sites of the reagent in the reaction step. The high-resolution of rotational spectroscopy makes it possible to perform these analyses without extensive sample purification. Furthermore, cavity-enhanced rotational spectroscopy instruments can be used to monitor the synthesis of chiral molecules in real-time by sampling directly out of the reaction flask.
Gordon G. Brown, Brian C. Dian, Kevin O. Douglass, Scott M. Geyer, and Brooks H. Pate, “A Broadband Fourier Transform Microwave Spectrometer Based on Chirped Pulse Excitation” Rev. Sci. Instrum. 79, 053103 (2008).
Brian C. Dian, Gordon G. Brown, Kevin O. Douglass, and Brooks H. Pate, “Measuring Picosecond Isomerization Dynamics via Ultra-broadband Fourier Transform Microwave Spectroscopy”, Science 320, 924-928 (2008).
Cristóbal Pérez, Matt T. Muckle, Daniel P. Zaleski, Nathan A. Seifert, Berhane Temelso, George C. Shields, Zbigniew Kisiel, and Brooks H. Pate, “Structures of Cage, Prism, and Book Isomers of Water Hexamer from Broadband Rotational Spectroscopy”, Science 336, 897-901 (2012).
Jeremy O. Richardson, Cristóbal Pérez, Simon Lobsiger, Adam A. Reid, Berhane Temelso, George C. Shields, Zbigniew Kisiel, David J. Wales, Brooks H. Pate, and Stuart C. Althorpe, “Concerted hydrogen-bond breaking by quantum tunneling in the water hexamer prism”, Science 351, 1310-1313 (2016).
B.H. Pate, L. Evangelisti, W. Caminati, Y. Xu, J. Thomas, D. Patterson, C. Perez, and M. Schnell, “Quantitative Chiral Analysis by Molecular Rotational Spectroscopy”, in Chiral Analysis 2nd Edition Advances in Spectroscopy, Chromatography, and Emerging Methods, P.L. Polavarapu, Editor, Elsevier (2018).
Justin L. Neill, Yuan Yang, Matt T. Muckle, Roger L. Reynolds, Luca Evangelisti, Reilly E. Sonstrom, Brooks H. Pate, and B. Frank Gupton, “Online Stereochemical Process Monitoring by Molecular Rotational Resonance Spectroscopy”, Org. Process Res. Dev. 23, 1046-1051 (2019).