Computational Chemistry, Quinolone Drugs Interact With Biological Macromolecules

The thesis is mainly about interaction between quinolone antibiotics and macrobiomolecular such as protein and nucleic acids, including four parts. The first one, a quantum chemical study of cation-πinteraction of lithium cation–aromatic systems; The second, research on binding mode of pefloxacin mesylate with human serum albumin by fluorescence spectroscopic and molecular modeling; The third, molecular dynamics simulation and thermodynamics analysis of DNA-drug complex, Minor groove binding between aromatic diamidines and DNA duplexes in solution. Detailed illumination as follows:In the first part, a group of 17 lithium cation-aromatic systems have been investigated with MP2 and density functional theory B3LYP at different level. Geometries, charge transfer; binding energies and electrostatic potential have been obtained for all systems both with restricted and unrestricted optimization. For some systems, possible competition of cation-πinteraction with cation-heteroatom interaction has been examined. In order to understand the relationship between binding energy and electrostatic potential in detail, We are engaged in a series of studies by MP2/6-311+G**,B3LYP/6-31G**and HF/6-31G* methods. Particularly, A good correlation between binding energy and electrostatic potential at one point above the center of the aromatic rings was established, which shows that electrostatic potential play an important role in lithium cation-πsystems. It is also demonstrated that for designing or evaluating new larger systems, binding energy can be completely predicted by considering only the aromatic electrostatic potential.In the second part, we carried out research on interaction between quinolone antibiotic and protein, this chapter was designed to explore the binding mode of pefloxacin mesylate(PFLX) with human serum albumin (HSA). Fluorescence spectroscopic results showed that one type of pefloxacin-HSA complex with binding constants of 1.7×105 L·mol-1. The thermodynamics parameters, enthalpy change...