Thesis Title

A Computational Investigation Of The Addition Of Water To (24E)3A, 7A, 12A,-Tri Hydroxy-5B-Cholest-24-Enoyl-Coenzyme A

Date of Graduation

Summer 2003


Master of Science in Chemistry



Committee Chair

Shujun Su

Subject Categories



The addition of water, catalyzed by hydratases, to a,ß unsaturated thioesters has been found experimentally to proceed via a syn addition mechanism. However, the catalyzed addition of water to a,ß unsaturated carboxylates has been found to proceed via an anti addition pathway. Under non-enzymatic conditions, a,ß unsaturated thioesters have been reported as preferring an anti addition mechanism. A computational study was designed in effort to further characterize a,ß unsaturated thioesters and carboxylates in terms of their addition preference. In particular, the geometric structures of isolated and solvated modeling molecules were optimized and verified to be at a minimum on the potential energy surface. The isolated optimizations were done at the HF/6-31G(d,p), HF/6-311G(d,p), B3LYP/6-31G(d,p) and B3LYP/6-311G(d,p) theory levels using Gaussian98 software. The solvated optimizations were performed at the HF/6-31G(d,p) theory level. A characterization of the thermochemistry (an energetic analysis) was performed for both syn and anti addition products. Electronic data was also evaluated for all modeling molecules studied. Geometric data obtained suggests an optimized geometric structure for the a,ß unsaturated thioester models that was different from other models. The orientation provided in these thioester models supported a bottom-side syn addition. Thermochemical results show that both the syn and anti addition of water to the majority of the models studied are exothermic reactions. The data presented a general favoring of the anti addition for modeling molecules by a mere 6.0 kcal/mole. The results of the study were inconclusive. Precise reasons for the syn preference exhibited by a,ß unsaturated thioesters were not determined. Additional computational work is necessary to fully characterize the addition pathways of both a,ß unsaturated thioesters and carboxylates.


© Danielle R. Smith