Relationships between hydrogen bonds and halogen bonds in biological systems

Abstract

The recent recognition that halogen bonding (XB) plays important roles in the recognition and assembly of biological molecules has led to new approaches in medicinal chemistry and biomolecular engineering. When designing XBs into strategies for rational drug design or into a biomolecule to affect its structure and function, we must consider the relationship between this interaction and the more ubiquitous hydrogen bond (HB). In this review, we explore these relationships by asking whether and how XBs can replace, compete against or behave independently of HBs in various biological systems. The complex relationships between the two interactions inform us of the challenges we face in fully utilizing XBs to control the affinity and recognition of inhibitors against their therapeutic targets, and to control the structure and function of proteins, nucleic acids and other biomolecular scaffolds.

Comparison between Hydrogen and Halogen Bonds in Complexes of 6‐OX‐Fulvene with Pnicogen and Chalcogen Electron Donors

“…Due to the extensive applications of non‐covalent interactions, the competition, cooperation and coexistence among them have generated extensive research. It is especially important to study the competition between hydrogen bonds and halogen bonds, as these two types of interactions are directional and relatively strong, and their importance in crystal engineering originates from their shared dependence upon long‐range electrostatic forces] . By combining interactions that do not compete for the same molecular binding sites it is, in principle, possible to avoid or at least minimize “synthon cross‐over” thereby producing architectures of considerable complexity .…”

“…It is especially important to study the competition between hydrogen bonds and halogen bonds, as these two types of interactions are directional and relatively strong, and their importance in crystal engineering originates from their shared dependence upon long-range electrostatic forces]. [26][27][28][29][30] By combining interactions that do not compete for the same molecular binding sites it is, in principle, possible to avoid or at least minimize "synthon cross-over" [31] thereby producing architectures of considerable complexity. [32][33][34][35] Moreover, it is well known that hydrogen bonding plays an important role in the human body; for example, human DNA structure is highly dependent upon hydrogen bonds.…”

Multifacial Recognition in Binary and Ternary Cocrystals from 5-Halouracil and Aminoazine Derivatives

“…[3][4][5][6] Indeed, from one side recently several studies have been focused on the importance of halogen bonding (XB) in directing the conformation of DNA containing halonucleobases. [7][8][9][10] From the other side, the ability of 2-aminosubstituted adenine to form ADA/DAD hydrogen bonding patterns (three-point interactions, TPI) significantly increases the base-pair stability retaining the structural integrity of the nucleic acid nanostructure. 11 Thus, it has been used for chemical fine-tuning of artificial DNA and RNA in synthetic biology.…”

Halogen bonding, chalcogen bonding, pnictogen bonding, tetrel bonding: origins, current status and discussion

“…Although the study of halogen bonding has expanded dramatically over the past 15-20 years, [50][51][52][53][54] analogous interactions involving other main group elements in a Lewis acidic role have seen far less attention over this same period. More recently, with the advent of the s-hole terminology as a framework for describing such interactions, 13 there has been a growing interest in the study of such interactions, which like halogen bonding have the potential to lead to a variety of applications in supramolecular chemistry, crystal engineering, materials chemistry and in medical/biological areas.…”