A Semiempirical Transition State Structure for the First Step in the Alkaline Hydrolysis of Cocaine. Comparison between the Transition State Structure, the Phosphonate Monoester Transition State Analog, and a Newly Designed Thiophosphonate Transition State Analog

Semiempirical molecular orbital calculations have been performed for the first step in the alkaline hydrolysis of the neutral benzoylester of cocaine. Successes, failures, and limitations of these calculations are reviewed. A PM3 calculated transition state structure is compared with the PM3 calculated structure for the hapten used to induce catalytic antibodies for the hydrolysis of cocaine. Implications of these calculations for the computer–aided design of transition state analogs for the induction of catalytic antibodies are discussed.

Investigation of the Potential Energy Surface for the First Step in the Alkaline Hydrolysis of Methyl Acetate

The potential energy surface for the first step of the alkaline hydrolysis of methyl acetate was explored by a variety of methods. The conformational search routine within SPARTAN was used to determine the lowest energy am1 and pm3 structures for the anionic tetrahedral intermediate. Ab initio single point and geometry optimization calculations were performed to determine the lowest energy conformer, and the linear synchronous transition (lst) method was used to provide an initial structure for transition state optimization. Transition states were obtained at the am1, pm3, 3-21G, and 3-21 + G levels of theory. These transition states were compared with the anionic tetrahedral intermediates to examine the assumption that the intermediate is a good model for the transition state. In addition, the Cramer/Truhlar sm3 solvation model was used at the semiempirical level to compare gas phase and aqueous alkaline hydrolysis of methyl acetate.

A Computationally Efficient Procedure for Modeling the First Step in the Alkaline Hydrolysis of Esters

A computationally efficient procedure for modeling the alkaline hydrolysis of esters is proposed based on calculations performed on methyl acetate and methyl benzoate systems. Extensive geometry and energy comparisons were performed on the simple ester methyl acetate. The effectiveness of performing high level single point ab initio energy calculations on the geometries obtained from semiempirical and ab initio methods was determined. The AM1 and PM3 semiempirical methods are evaluated for their ability to model the transition states and intermediates for ester hydrolysis. The Cramer/Truhlar SM3 solvation method was used to determine activation energies. The most computationally efficient way to model the transition states of large esters is to use the PM3 method. The PM3 transition structure can then be used as a template for the design of haptens capable of inducing catalytic antibodies.

Synthesis Of Linoleate Analogs With Longer Alkyl Termini To Test For Proposed "Tail-First" Binding In SBLO-1

Lipoxygenases are nonheme-iron proteins that catalyze the oxygenation of polyunsaturated fatty acids to give conjugated diene hydroperoxides. For example, soybean lipoxygenase-1 (SBLO-1) converts linoleate into 13-(S)-hydroperoxy-9(Z),11(E)-octadecadienoate (13(S)-HPOD). Although the crystal structure of SBLO-1 has been determined, it is still unclear how the substrate binds at the active site. This absence of knowledge makes it difficult to understand the role of the enzyme during catalysis of the reaction. We hypothesize that SBLO-1 binds linoleate ¿tail-first¿, so that the methyl terminus is within a hydrophobic pocket deep within the enzyme. It is believed that the hydrophobic residue phenylalanine-557 at this site has stabilizing interactions with the terminal methyl group on linoleate. To test this hypothesis, we have developed a synthetic pathway that will yield linoleate analogs with longer fatty acid chains by 1 and 2 more carbons at the alkyl terminus. These substrates will be analyzed through kinetic assays done in combination with wild type SBLO-1 and mutants in which we have replaced phenylalanine-557 with valine.

Change in First-Year Women's Body Dissatisfaction in Relation to Drive for Thinness and Social Body Comparison

Drive for thinness (DT) and social body comparison (SBC) have been highly correlated with body dissatisfaction, a robust risk factor for eating disorders; however, there is little understanding of how these two variables relate to increases in body dissatisfaction over time. In the present study, I investigated how high initial levels of DT and SBC correlate with changes in body dissatisfaction and ideal body by surveying 110 first-year women at the beginning and end of their first semester. There was no significant relationship between high initial DT and SBC and changes in either body dissatisfaction or ideal body. However, high initial SBC was almost significantly correlated with change in ideal body due to women with low SBC choosing larger bodies at follow-up. In addition, women with high initial DT and SBC had higher body dissatisfaction than women with low initial levels of both variables. Women with high initial SBC chose thinner ideal bodies than women with low initial SBC. Lastly, change in body dissatisfaction was negatively correlated with change in ideal body. If replicated, I would hope these findings could contribute to a better understanding of how women’s perception of their bodies changes over the course of their first semester in college and inform interventions to address this potential risk factor for disordered eating.