A non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule. The chemical energy released in the formation of non-covalent interactions is typically on the order of 1-5 kcal/mol (1000–5000 calories per 6.02 x 10^23 molecules). Non-covalent interactions can be classified into different categories, such as electrostatic, π-effects, van der Waals forces, and hydrophobic effects. A non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule. The chemical energy released in the formation of non-covalent interactions is typically on the order of 1-5 kcal/mol (1000–5000 calories per 6.02 x 10^23 molecules). Non-covalent interactions can be classified into different categories, such as electrostatic, π-effects, van der Waals forces, and hydrophobic effects. Non-covalent interactions are critical in maintaining the three-dimensional structure of large molecules, such as proteins and nucleic acids. In addition, they are also involved in many biological processes in which large molecules bind specifically but transiently to one another (see the properties section of the DNA page). These interactions also heavily influence drug design, crystallinity and design of materials, particularly for self-assembly, and, in general, the synthesis of many organic molecules. Intermolecular forces are non-covalent interactions that occur between different molecules, rather than between different atoms of the same molecule For a more detailed introduction to electrostatics, see Coulomb's Law Ionic interactions involve the attraction of ions or molecules with full permanent charges of opposite signs. For example, sodium fluoride involves the attraction of the positive charge on sodium (Na+) with the negative charge on fluoride (F−). However, this particular interaction is easily broken upon addition to water, or other highly polar solvents. In water ion pairing is mostly entropy driven; a single salt bridge usually amounts to an attraction value of about ΔG =5 kJ/mol at an intermediate ion strength I, at I close to zero the value increases to about 8 kJ/mol. The ΔG values are usually additive and largely independent of the nature of the participating ions, except for transition metal ions etc. These interactions can also be seen in molecules with a localized charge on a particular atom. For example, the full negative charge associated with ethoxide, the conjugate base of ethanol, is most commonly accompanied by the positive charge of an alkali metal salt such as the sodium cation (Na+). 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 bonding is a type of non-covalent interaction which does not involve the formation nor breaking of actual bonds, but rather is similar to the dipole-dipole interaction known as hydrogen bonding. In halogen bonding, a halogen atom acts as an electrophile, or electron-seeking species, and forms a weak electrostatic interaction with a nucleophile, or electron-rich species. The nucleophilic agent in these interactions tends to be highly electronegative (such as oxygen, nitrogen, or sulfur), or may be anionic, bearing a negative formal charge. As compared to hydrogen bonding, the halogen atom takes the place of the partially positively charged hydrogen as the electrophile.