Microkinetic modeling is a powerful approach for studying complex catalytic systems. In microkinetic analysis, all elementary steps comprising the reaction mechanism are considered explicitly, and no assumptions about the rate-determining step are made. The conversion of the reactants and the yields and selectivities of the products are then obtained by coupling the mechanism with appropriate reactor design equations and solving the system of equations. There are two main challenges in putting together microkinetic models: formulating all the reactions and specifying rate constants. We address these challenges using our methodology for computer generation of reaction mechanisms. The chemistry is organized into reaction families and a mathematical operator is specified for each family. The reaction mechanism is then created automatically by applying the operators to all the different reactants and their progeny. Structure/reactivitiy relationships, one for each reaction family, are then used to specify the rate coefficients. Quantum chemical calculations are used extensively to calculate rate coefficients directly for individual elementary steps.

Biomimetic Oxidation Catalysis

In recent decades, much effort has been put forth to find methods to selectively oxidize hydrocarbons. Although it has been proved that synthetic metalloporphyrins can catalyze olefin epoxidation at mild conditions, simple metalloporphyrins are easily destroyed by autoxidation due to m-oxo dimer formation. In natural enzyme systems, the stability and selectivity of metalloporphyrins are improved by a surrounding protein framework that isolates the active site where the reactions are carried out and provides steric and electronic constraints on the reaction. Modifications of the porphyrin have been carried out in the literature to mimic this, but the chemical synthesis is difficult. Recently, Nguyen, Hupp and coworkers have developed an alternate strategy using supramolecular chemistry to construct self-assembling systems that contain regular cavities for porphyrin encapsulation. These structures, known as molecular squares (MS), have rhenium atoms at the corners and zinc porphyrin ligands on the sides forming cavities of ~18Å. By analogy to natural systems, MS were designed to improve the stability of porphyrin catalysts by immobilizing them in tailored environments.

Experiments and microkinetic modeling were used to investigate the kinetics of epoxidation of styrene catalyzed by (porphyrin)Mn using iodosylbenzene. While the kinetics follow the general form of Michaelis-Menten rate expressions as proposed in the literature, these simplified rate forms are not able to capture all the details of the kinetics simultaneously, most notably catalyst deactivation. In contrast, a microkinetic model based on elementary steps, including deactivation via μ-oxo dimer formation and irreversible degradation, is able to capture experimental data over all reaction times and for different (porphyrin)Mn. Experimentally, we show that the encapsulation of the (porphyrin)Mn catalyst in a supramolecular cavity known as a molecular square significantly reduces catalyst deactivation, in agreement with previous experimental studies. Microkinetic modeling was also able to capture the kinetics of this system. Net rate analysis revealed that the production of epoxide was primarily due to encapsulated catalysts, and the model was able to quantify the difference in the concentration of deactivated catalyst with and without encapsulation.

Molecular squares are supramolecular assemblies that can encapsulate active catalytic centers, mimicking biological systems. A Mn-porphyrin is rendered more stable when encapsulated in a molecular square while still retaining activity for oxidation.

Curet-Arana, M.C., Emberger, G.A., Broadbelt, L.J. and Snurr, R.Q., "Quantum Chemical Determination of Stable Intermediates for Alkene Epoxidation with Mn-Porphyrin Catalysts", J. Molecular Catalysis A, 2008, 285, 120-127.

Organocatalysts as Stereoselective Catalysts for C-C and C-N Bond Formation

L-proline is an example of a organocatalyst that is active for C-C and C-N bond formation. The two functional groups, i.e., the carboxylic acid and the amino moieties, work together during the reaction, resulting in cooperative catalysis.

Aldol and aldol-type reactions are the fundamental chemical mechanisms for the formation of carbon-carbon and carbon-nitrogen bonds that are crucial to the creation of complex molecules from small hydrocarbons. In the past thirty years, there has been a growing interest in the scientific community to find diverse catalysts that simultaneously increase the enantioselectivity and yield of the reaction products. L-proline, an amino acid, has been demonstrated to catalyze the direct aldol-type reactions without the need for modification of the carbonyl compounds. Additionally, the strength of L-proline as a catalyst lies in the fact that it is inexpensive, operates at low temperatures, and has been shown to function when attached to heterogeneous support.

The L-proline-mediated α-aminoxylation of aldehydes is a direct aldol-type reaction of particular significance to the organic synthesis of complex molecules. It has been experimentally shown that certain species such as methanol, acetic acid, as well as the final product of the reaction, greatly improve the catalyst activity. At the same time, addition of water to the reaction mixture leads to suppression of the observed kinetic rates. Several hypotheses have been proposed to explain these phenomena. Thus, the purpose of our study is to implement the tools of the density functional theory to investigate the kinetics of the L-proline catalyzed α-aminoxylation of aldehydes at the molecular level. We are currently mapping the reaction pathways, which includes locating all possible intermediates and transition states. Once this step is completed, we will extract thermodynamic information that will allow us to calculate the reaction rate parameters. This data will be used to establish the rate determining steps via microkinetic modeling. Since most of these reactions take place in a variety of solvents, we intend to further investigate the importance of solvolysis on the reaction mechanisms.