| Summary: | <p> Solvation and solvent effects play an important role in diverse chemical processes ranging from reaction kinetics to molecular recognition, solubility, solvato-chromism and phase separations. Despite enormous activities in this field, quantitative solvation calculations remain an enormous intellectual challenge. </p><p> My thesis is focused on development and application of molecular density functional theory (MDFT) and molecular dynamics (MD) simulation to predicting solvation properties. Accomplishments include 1) improved the average unsigned error of MDFT predictions for the room-temperature solvation free energies (SFE) of 504 pharmaceutical molecules in water from 1.04 kcal/mol to 0.66 kcal/mol; 2) established a more reliable numerical procedure to calculate the direct correlation functions (DCF) of solvent from MD simulations; 3) extended MDFT prediction of SFE to different temperatures and calibrated the theoretical results with experimental data for the hydration free energies of 5 nitrotolunenes and a library of 197 solutes at 277 K, 298 K and 313 K. In addition, I investigated the 3-dimensional (3D) solvation structure of amine-grafted silica gel in liquid water by applying a spherical harmonics expansion method to the MD trajectories. The simulation results provide evidence on the strong influence of the silica surface on hydration structure, which is often ignored in the theoretical analysis of surface reactions. Furthermore, I developed a hybrid method for predicting the SFE of spherical ions by combining MDFT with MD simulations. The numerical analysis justifies the universality of the bridge functional that can be reasonably approximated by the modified fundamental measure theory (MFMT) for hard-sphere systems. </p><p> Results from this thesis demonstrate that the DCFs are important in application of MDFT to SFE predictions. Based DCF from on integral-equation methods, MDFT can also capture the temperature effect on SFE in good agreement with experiment. In addition, the hybrid MDFT-MD method provides accurate predictions of hydration free energies for charged solutes and the numerical analysis sheds light on future theoretical development. The efficient sampling method for generating 3D density profiles from MD may open up opportunities for application of MDFT to more complex systems, for example, protein solvation and enzyme kinetics. By studying the solvation structure of amine-grafted silica shell, I found that the silica surface affects not only the distribution of surrounding water but also the hydrogen-bonding network. This surface effect is long-ranged and can be reduced with longer grafted amine chains.</p><p>
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