Dr. Brown Research
My research interests fall into the general area of applied quantum chemistry or computational chemistry. Although the majority of these applications involve rigorous quantum chemical methods, I have also applied semi-empirical, QSAR, and molecular mechanics/dynamics methods in areas of drug design and studies on enzyme mechanisms. Another interest is the design of new quantum chemistry experiments for the undergraduate physical chemistry lab and the graduate computational chemistry course offered in this department. These experiments are designed to develop skills in computational chemistry, spectroscopy, and statistical thermodynamics. My research program includes projects applicable to the undergraduate, MS, and PhD levels, and I have directed students at all three levels. Programs generally used in my group include Gaussian-98, GAMESS, HyperChem, and MacroModel. Some areas of current research interest are:
Gas phase acidities of carbon acids: It is often not appreciated that many carbon acids, which have an acidic C-H bond, can be exceptionally strong. In fact, some of these are the strongest acids yet studied such that the anion cannot be protonated even by strong mineral acids such as H2SO4. Systems of interests include the cyano and nitro substituted cyclopentadienes and malanonitriles. The determination of the aqueous phase pKa values of these acids are difficult to determine experimentally since various solvent systems must be used. And there is some interest in identifying new strong carbon acids that can be used for organic synthesis in non-aqueous solutions. Theoretical pKa values can be used to validate trends determined experimentally both in the gas phase and in the solvent phase (using SCRF methods). Of considerable interest are the electronic and structural properties which drive these acidities.
Structure and stability of gas phase complexes: Gas phase clusters are of interest since they offer good models to study solvation effects, nucleation processes, weak van der Waal interactions, interstellar and atmospheric chemistry, and to decipher the identity of unknown plasma complexes. Particular complexes of interest to me are the (HF)n-H2NOH and (HF)n- complexes. For the first case, we have confirmed the experimental prediction of cyclic structures of the HF-H2NOH (HF)2-H2NOH complexes. The anionic complexes for X = HF, H2O, and NH3, (i.e., (X)n- for n=1 to 12) are being studied to decipher the structure and stability of these gas phase anion clusters and to shed light on the nature of the solvated electron.
The Transition State Structure and Stable Conformations of the Myo-Inositol Phosphates: Such studies require the use of much more approximate methods such as the use of force fields in molecular mechanics and molecular dynamics calculations. Of immediate interest is the activity if the phytase family of enzymes to catalyze the conversion of phytic acid, C6(-O-P(OH)2O)6H6, to its various inositol derivatives (where a phosphate group is replaced by a -OH group). Phytic acid and these derivatives (as well as their deprotonated anions) show a high ability and selectivity to complex cations occurring in biological systems. Understanding the nature and energetics of these interactions will be useful in the design and production of phytic acid derivatives which can selectively complex any chosen cation. Phytic acid also plays a critical role in signal transduction processes in living cells. Their conformational flexibility has a major impact on all of their binding interactions with enzymes, receptors and cations. Their structures depend critically on the number, placement, and orientation of the phosphate groups, the pH of the solution and the identity of the counter-ion. This work will use semi-empirical and ab initio methods to look at the important global and local minima of these compounds as well as the transition state for the chair-to-chair interconverison for phytic acid and its various analogues.
The mechanisms for biological activity of Old Yellow Enzyme (OYE) and D-Amino Acid Oxidase (DAAO): OYE and DAAO are perhaps the most studied of the flavin family of enzymes. Both are commonly found in many organisms, however there is no firm opinion on the physiological function of either enzyme, and for each, many questions exits over the mechanism which explains their biological activity. This work will use semi-empirical, ab initio and hybrid calculations to investigate the competition between the various mechanisms that have been proposed for each.
Mechanisms of organic reactions: Reactions such as the mechanisms for the dissociation of substituted hyponitrites and reactions involving iminoxyl radicals have been projects of past interests. Such studies usually involve exploring potential energy surfaces to find the lowest energy pathway and activation energy. Currently, one project of interest is an investigation of the validity of the so-called E2C mechanism for elimination reactions. In this mechanism, the initial attack by the base is at the acarbon rather then at the hydrogen attached to the bcarbon (the E2H mechanism). The E2C and the more commonly accepted E2H mechanism lead to the same products. There is some experimental evidence for the E2C mechanism. This mechanism seems to be favored by weak bases, good leaving groups, polar aprotic solvents, and branched systems. However most of the previous computational work has implied that the E2C mechanism is not valid. These studies have however been in the gas phase and on small systems. This work will involve using systems that are more compatible with the experimental work.