The role of halogen bonding in biomolecules

Abstract

This study concerns halogen bonding between small molecules. Except where otherwise stated herein this investigation was performed exclusively using the M06-2X density functional, in conjunction with the 6-31+G* basis set except for iodine and astatine which were treated using the aug-cc-pVDZ-PP basis set with relativistic pseudopotentials. All calculations were performed in the gas phase. The counterpoise procedure was employed for all full geometry optimisations. Statistical analysis of the Cambridge Structural Database, wherein the frequency of structures as a function of halogen bond angle and distance constituted the sole part of this study not to be based on density functional theory. Except in chapter 5, all halogens from fluorine to astatine are investigated. In chapter 3, halogen bonding between halobenzene and a single water molecule is discussed. Competition between R – X•••OH₂ halogen bonding and R – X•••H-O-H hydrogen bonding interactions is described. This system is analogous to the more elaborate microsolvated 1- methyl-5-halouracil system described in chapter 4. In this latter system one 1-methyl-5- halouracil molecule interacts with either one or two water molecules. A central feature of the investigation into this system is competition between R – X•••OH₂ and R=O•••H-O-H hydrogen bonding. In chapter 5, halogen bonding is discussed in the context of the thyroid system. In particular halogen bonding between a thyroxine iodine atom and the protein backbone as well as crystal water molecules is the subject of this chapter. The effect of substitution of the iodine atom with an astatine atom is presented. Chapter 6 is concerned with halogen bonding in halogenated DNA base pairs. Interaction energies are compared with those of the canonical base pairs, and the effect of halogen bonding on geometry is also discussed. For each system, halogen bonding was found to become stronger and more tolerant of non- linear bond angles going down the halogen group.