AROMATIC INTERACTIONS
Our research interest is to understand how molecules "communicate" in solution through noncovalent interactions. Specifically, we study the noncovalent interactions involving aromatic (π) rings such as π-π, CH-π, cation-π, and NH-π interactions. These interactions are important for many field of science including the chemistry of protein folding, material sciences, and enzyme catalysis. In fact, there is no chemistry without non-covalent interactions! Because of the relatively “weak” interaction energies involved in these types of systems, the experimental measurements of non-covalent interactions in solution are challenging. Our strategy for measuring noncovalent interaction is to use synthetic model compounds such as the "molecular torsion balances" to measure the interaction energies and the physical origins of various noncovalent interactions in solution. The molecular balances are capable of quantifying weak interactions as small as 0.1 kcal/mol in solution. The molecular balances are designed to adopt a “folded” and an “unfolded” conformers in which the interaction between two designated functional groups is only possible in the folded state.
The population of each conformer is subsequently determined by proton NMR spectroscopy, which provides a quantitative measure of the interaction of interest. In addition to chemical synthesis and NMR spectroscopy, we also utilize DFT computational calculations and X-ray solid-state analyses to complement our experimental findings in solution. Our ultimate goals are to be able to measure various types of noncovalent interactions and to provide an explanatory model for predicting their strengths in different media.
CONFORMATIONAL ANALYSIS
Another area of research interest is to understand the changing shapes (conformations) of organic compounds in solution and to understand how external forces, such as weak noncovalent interactions, solvents, and temperature affect these conformations. Conformational studies are important for rationalizing chemical reactions and for the intelligent design of drugs and molecular switches. For example, do you know why 20% of drugs manufactured for clinical trials in recent years contain fluorine (F)? Part of the reason is that fluorine has the ability to change the conformation of molecules, which, in turn, changes the way drug (or ligand) interactions occur within a biological system. Therefore, one of our main interests in this area is to understand why and how fluorine induces conformational changes in molecules and how such effects can be controlled. One method to study fluorine's effect involves the conformational studies of simple models, such as 1,2-disubstituted ethanes of the general form: X-CH2-CH2, -F, where “X” could be any functional group. 1,2-Disubstituted ethane adopts only two low-energy conformations (gauche and trans). In the gauche, the functional group is close to fluorine such that an interaction could occur. In the trans, such interaction is not possible. By using NMR methods, it is possible to determine the position of the conformational equilibrium and the equilibrium constant.