Electronegativity Equalization Principle-based Approach To Accurately Calculate The Atomic Charges In The Molecule

Atomic charges are one of the most important concepts in quantum chemistry and are often used widely to understand and predict the physical and chemical properties. In addition to its application for interpretation of molecular reactivity and charges distribution as a model, atomic charge can also be used as molecular descriptors in QSAR and QSPR studies to predict molecular properties. However, it takes much long time for quantum chemistry to obtain atomic charges, especially for macromolecules. Therefore, the fast and accurate calculation of atomic charges seems to be an urgent task for chemists, instead of simply using the time-consuming ab initio method. In order to obtain accurate atomic charges of large molecules, a new approach based on the electronegativity equalization method (EEM) has been proposed in this work by considering the chemical environment.To validate the hypothesis that the same elemental atoms under different chemical environments own different parameters, we construct a new splitting-combination EEM model and take the n-propanol for example to calculate its atomic charges. The two training sets which contain propyl and hydroxyl group, respectively, are constructed and the particle swarm optimization (PSO) algorithm is used to obtain the effective electronegativity and hardness of each type of atoms in considering. Some other molecules' atomic charges are calculated in the same method. The advantages and disadvantages are also discussed in this part.In order to overcome the defect of the splitting-combination EEM model, an improved EEM model is put forward in the third chapter. Different from the method adopted by the previous model, the same elemental atoms with different hybridization states are considered to own different effective electronegativity and hardness values. A training set of 141 organic molecules is constructed and geometries and atomic charges are calculated at the B3LYP/6-31G* level. The effective electronegativity and hardness values are calibrated using the differential evolution (DE) algorithm. The atomic charges predicted by the optimized parameters for a series of molecules, not contained in the training set, are compared with B3LYP/6-31G~* as well as other theoretical values. It has been shown that the results obtained by our approach are in good agreements with DFT values, and are better than other scales.The drugs molecules of heterocycle and polypeptides are two kinds of important organic molecules in medicinal chemistry. In the last chapter, the atomic charges of these molecules are calculated using the parameters obtained in the improved EEM model and the divided method are further discussed based on the results, with the expectation of improving the model.