Theoretical Studies Of The Self-assemble Property Of Halogen Bonds And Its Application In Biological Systems

The halogen bond(XB), which is analogous to hydrogen bond(HB), has been studied via various experimental and theoretical methods recently. It has became a hot issue in the field of controllable self-assembly research. In2013, IUPAC gave a definition of XB that XB occurs between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity, when there is evidence of a net attractive interaction. The anisotropic distribution of the electron cloud around the covalent halogen atom makes a highly directional HB. The bond angle of XB fall into a very narrow range(approximately180°). Furthermore, The interaction energy varied with substitution groups or atoms of halogen atoms, so the different choice of the substitution groups or atoms is a important way to regulate the XB strength. The bond energy change between5-180kJ/mol. It has been shows that electrostatic effect, polarization effect, dispersion effect and charge transfer interaction all play an important role on the formation of XB. Furthermore, the selectivity of XB is better than that of HB in molecular recognition. It is these characteristics of XB which may provide XB broad applications in molecular recognition, crystal engineering, super molecular chemistry and biological systems. In order to study the function and application of XB in biological macro molecules and macro molecular material, we need a properly force field which can used to describe precisely XB.The development of force field must base on the study of the potential energy surface(PES). The high precision initio method was used to scan the halogen bond PES, which was compared to HB further. By the energy decomposition analyses(EDA) of halogen bond PES, we put forward the formation process of XB has the property of polarization enhancement. Furthermore, We introduced a extra point charge(EP) to represent the α-hole of halogen atom to research the interaction mechanism between small drug molecular and proteins, which has attracted considerable research interest in recent years, and analysis of the pros and cons of this method. Through above analysis, we can conclude what problems should be paid particularly attention to in the development of the XB force field.The research contents and innovations are summarized in the following section:1. By the compare of the PES of XB and HB, we conclude that both HB and XB are angular distortional. The potential well of XB is narrower than that of HB. The SAPT(DFT) results indicate that the linearity of HB or XB is due to exchange-repulsion term. With the elongation of the bond length, the potential energy surfaces are getting flatter. The best fitting functions for angular distortional and the flatting character of angular terms are also been combined into a modified Buckingham potential. These results will shed light on a better understanding on XB and HB and the optimization of XB force fields.2. The EDA result show that the polarization of XB is more powerful than HB. The contribution of polarization to electrostatic interaction was23.9%for the hydrogen bonded dimers, while it varied from2.5to50.5%for the halogen bonded dimers. Secondly, we observed that the dominant term of polarization effects is different for HBs, weak XBs, and strong XBs. It changes from the dispersion component to induction component gradually. Finally, we found that polarization and charge transfers are cooperated mutually. We believe that these findings will be beneficial to designing better halogen bonded materials and accelerate the development of polarizable force fields of XB.3. According to the current situation of XB force field, the extra point (EP) charge model is selected to represent the a-hole of halogen atom and interact with Lewis bases. To explore the possibility and accuracy of this model, the cancer hotspot Y220C mutant of the p53tumor suppressor is selected to act as the XB accepter here. Basing on molecular dynamic simulation, the part of XB in the process of recovering the wild-type function is researched. Through the analysis of the crystal structure of the complexes, we conclude that the halogen atom form simultaneously the XB and HB in the perpendicular direction. Under this condition, the EP will disturb the synergy of XB and HB, so the EP model is destined to bring a large error, even can be used to describe the bonding nature of halogen atom. Therefore, developing the highly quality force field for XB have important implications specially for drug design and development.