Theoretical Study On Stability Constants Of Iron And Zinc Complexes And On The Hydrolysis Energy Of Phosphorate Diester

In this work, a series of theoretical methods were employed to investigate the stability constants of the complation reaction and the hydrolysis energy of the phosphate diester. The thesis consists of three chapters, including (1) basic theory and computational methods. (2) Theoretical study on stability constants of iron and zinc complexes. (3) Quantum mechanical and molecular dynamics calculations on hydrolysis energy of phosphate diesters.In the first chapter, Molecular mechanics methods, Molecular dynamics methods and quantum chemical methods were briefly introduced.For the studies described in the second chapter, a new method was introduced to predict the stability constants of the complexes theoreticaly. We take iron and zinc complexes as example, the Gibbs free energy of the complation reaction were calculated and were fitted with the experimental stability constants. The predicted stability constants are all in good agreement with available experimental data, providing a rational basis for future prediction of stability constants of unknown chelators.In the third chapter, molecular dynamics and first-priciple electronic theoretical method were employed to study the hydrolysis reactions of the phosphate diesters. By comparing the contributions of different conformation and functional group to reaction enthalpies and free energies, we further explored the possible factor that lead to the high reaction free energies of cAMP and cGMP. We examined the different conformation of cAMP and cGMP and their hydrolysis product, it is suggested that the the difference of conformation and relative positon of base, ribofuse cylcle and phosphorate cycle may produce large energy discrepancy. It is concluded from the contrast of the most stable conformation of cAMP and cGMP that the higher hrdrolysis energy of cAMP than cGMP is caused by reversing the conformation of the base.