Non-covalent interactions
A hydrogen bond (H-bond), is a specific type of interaction that involves dipole-dipole attraction between a partially positive hydrogen atom and a highly electronegative, partially negative oxygen, nitrogen, sulfur, or fluorine atom (not covalently bound to said hydrogen atom). It is not a covalent bond, but instead is classified as a strong non-covalent interaction. It is responsible for why water is a liquid at room temperature and not a gas (given water's low molecular weight). Most commonly, the strength of hydrogen bonds lies between 0 - 4 kcal/mol, but can sometimes be as strong as 40 kcal/mol In solvents such as chloroform or carbontetrachloride one observes e.g. for the interaction between amides additive values of about 5 kJ/mol. According to L. Pauling the strength of a hydrogen bond is essentially determined by the electrostatic charges. Measurements of thousands complexes in chloroform or carbontetrachloride have led to additive free energy increments for all kind of donor-acceptor combinations.
Halogen bond
On the bio-molecular level, halogen bonding is important for substrate specificity, binding and molecular folding. In the case of protein-ligand interactions, the most common charge-transfer bonds with polarizable halogens involve backbone carbonyls and/or hydroxyl and carboxylate groups of amino acid residues. Typically in DNA and protein-ligand complexes, the bond distance between Lewis base donor atoms (e.g. O, S, N) and Lewis acid (halogen) is shorter than the sum of their Van der Waals radius. Depending on the structural and chemical environment, halogen bonding interactions can be weak or strong. In the case of some protein-ligand complexes, halogen bonds are energetically and geometrically comparable to that of hydrogen bonding if the donor-acceptor directionality remains consistent. This intermolecular interaction has been shown to be stabilizing and a conformational determinant in protein-ligand and DNA structures.