October 6, 2017 - 3:30 pm to 4:30 pm (already occurred)
Merrill Science Center, Lecture Room 4

Alina Dao, Leonard Yoon, and Gyu-Hee Min will be presenting. Alina is working with Professor Mark Marshall, Leonard is working with Professor Helen Leung, and Gyu-Hee is working with Professor Anthony Bishop.

Alina Dao will discuss "Structure Determination of (E)-1-Chloro-3,3,3-Trifluoropropene Complexed with Hydrogen Fluoride using Microwave Spectroscopy." Microwave spectroscopy has greatly advanced the study of small molecules and their molecular complexes, allowing for a precise determination of their structures and a detailed understanding of intermolecular interactions. This deeper understanding can stand as a basis from which more complicated systems can be investigated. The focus of this research is the experimental structure of the complex formed by (E)-1-chloro-3,3,3-trifluoropropene and the protic acid hydrogen fluoride. It is an extension of prior work by the Marshall and Leung labs on complexes formed by both haloethylenes and, more recently, halopropenes with three different protic acids. To investigate the acid dimer, it is necessary to first characterize the halopropene monomer, (E)-1-chloro-3,3,3-trifluoropropene. To do this, ab initio calculations are performed using the Gaussian09 program at the MP2/6-311++G(2d,2p) level. The theoretical spectroscopic constants given by this program are then used to generate a spectrum, which can be used to assign experimental transitions recorded by a broad-band chirped pulse Fourier transform microwave spectrometer. Spectral assignments have been made for eight isotopologues of the molecule, and will be used to derive an experimental structure. From here, the structure of first the argon complex, and then the complex with hydrogen fluoride, will be characterized.

Leonard Yoon will discuss “Determining the structure of the (Z)-1-chloro-2-fluoroethylene – hydrogen fluoride complex using microwave spectroscopy." Understanding a molecule’s ability to form van der Waals interactions in different electronic environments forms a basis for more complicated (biological) systems. In the case of complexes between hydrogen fluoride and haloethylenes, as researched in the Leung and Marshall labs, a delicate balance between electrostatics and sterics dictates the geometry of the complex. Hydrogen fluoride chooses to interact with the sterically accessible cis H-atom in vinyl fluoride and vinyl chloride as opposed to the electrostatically favorable geminal hydrogen. However, in (Z)-1-chloro-2-fluoroethylene, only electrostatically-inequivalent geminal H-atoms are present. To determine the structure of the (Z)-1-chloro-2-fluoroethylene – hydrogen fluoride complex, ab initio calculations are performed at the MP2/6–311++G(2d,2p) level using GAUSSIAN 09. Holding the geometric parameters of (Z)-1-chloro-2-fluoroethylene fixed at their literature values, the structure corresponding to the minima on the ab initio potential energy surface of the (Z)-1-chloro-2-fluoroethylene – hydrogen fluoride complex suggests a bifurcated hydrogen bond with the two halogen atoms on the haloethylene, and there is no secondary interaction involving the fluorine atom on hydrogen fluoride. This unexpected structure will be corroborated experimentally using microwave spectroscopy in my thesis.

Gyu-Hee Min will discuss “Synthesis of a compound library targeting the allosteric site of Shp-2." Protein tyrosine phosphatases (PTPs) are enzymes that remove a phosphate group from phosphotyrosine from protein substrates. Their role in controlling signal transduction pathways highlights their overall importance; misregulation of PTP activity levels can lead to a variety of pathological effects, including cancer, diabetes, and obesity. Highly selective PTP inhibitors are sought after as drug candidates due to these associations between PTPs and human disease. Unfortunately, PTP-inhibitor discovery is inherently difficult due to two recurring problems observed with many active-site-directed inhibitors: lack of target specificity and poor bioavailability. However, recently a few allosteric regions have been discovered - these have more unique proteins within the group so this makes actively regulating these sites more feasible. In 2014, the Bishop Lab discovered one of these sites in the catalytic domains of Shp-2, a PTP that has been shown to cause both cancer and leukemia when hyperactive, and has been a target for pharmaceutical research. Within the Shp-2 region is an allosteric site with a non-conserved cysteine residue which allows for potential selective inhibition. My project involves the synthesis of a compound series involving vinyl sulphonamides, shown to have yielded highly selective covalent inhibition of the cysteine mutant of our target residue. Beginning with the synthesis of the main structure of the target molecule, this project looks into creating a library of various compounds to test for inhibition by utilizing different functional (R) groups.

Contact Info

Cathy Stillerman
(413) 542-2342
image of e-mail address@amherst.edu