Research Interests
• Properties of Ionic Liquids: The use of ionic liquids as
solvents for a variety of chemical processes is one of the most
significant developments in chemical and material sciences. Ionic
liquids are thermally stable over a wide temperature range, have
no detectable vapor pressure, incombustible and most are unaffected
by moisture. Due to this combination of properties, ionic liquids
are candidates for use as recyclable solvents in "green"
chemistry. Results from preliminary experiments show that ionic
liquids can be used to influence the outcomes of asymmetric reactions.
Asymmetric synthesis is widely used in organic, medicinal and biological
chemistry, and the use of ionic liquids as solvents for these reactions
is limit. In this project, a series of novel chiral ionic liquids
will be designed, synthesized and used to optimize the outcomes
of asymmetric reactions, including asymmetric halo Aldol reaction
and the Baylis-Hillman-type couplings. In addition, the effects
that structurally different chiral ionic liquids have on asymmetric
outcomes will be evaluated from structure-property relationships
(QSPR). The information gained from this project will provide fundamental
insights into how chiral ionic liquids induce asymmetric control
for many asymmetric reactions.
Quantitative Structure-Activity-Relationships Involving Biological Molecules: Certain formyl peptides are powerful chemoattractants towards neutrophils. In this study, a series of tripeptides were synthesized and used to investigate the effect of different amino acid residues in position 1, on their ability to stimulate neutrophil chemotaxis. Pig neutrophil chemotaxis towards the formyl tripeptide, HCO-Ac3C-Leu-Phe-OMe 1, where Ac3C represents 1-amino-1-cyclopropane carboxylic acid, was observed. Pig neutrophil chemotaxis towards a very similar formyl tripeptide, HCO-Aib-Leu-Phe-OMe 2, where Aib represents ?-amino isobutyric acid, was not observed. Compared to the isopropyl group, it was shown that the cyclopropyl group induces a greater percentage of the E conformation about the formamide functionality in these peptides. For 1 and 2, the E isomer distributions in CDCl3 are 36% and 9%, respectively. Since a major difference between these two peptides is the Z/E isomeric distribution, one implication is that the peptide-receptor site interactions involving the E conformer are more effective than those of the Z conformer. No pig neutrophil chemotaxis towards the formyl tripeptides, HCO-Ala-Leu-Phe-OMe 3 and HCO-Gly-Leu-Phe-OMe 4 was observed. These formyl tripeptides exhibit a low percentage of the E isomer, similar to that of peptide 2.
Conformational Analysis of Amino Acids and Peptides using Ab Initio Calculations: Optimized conformations of trifluoroalanine (NH2CH(CF3)COOH) have been obtained from high-level ab initio calculations (MP2/6-31+G*). Several conformers are exceptionally stable compared to the analogous conformers of alanine (NH2CH(CH3)COOH). Anomeric effect, which plays a role in the stabilization of the hypothetical ?-fluoroglycine, does not appear to play a role in the stability of trifluoroalanine conformers. Compared to fluorine, anomeric effect exhibited for the CF3 group is highly attenuated. The unusual stability of some ?-trifluoroalanine conformers (relative to alanine) arises from differences in dipole moments caused by the very inductive trifluoromethyl substituent and from favorable hydrogen bonds. The results of this study also indicate that the trifluoromethyl substituent participates in intramolecular hydrogen bond interactions (F---H-O). This type interaction results in conformers that are more stable than those of alanine, which cannot exhibit such interactions.
