Intramolecular Bonds

Chemical bonds are formed when the interaction between two or more atoms requires less energy than maintaining the atoms separately. Chemical bonds are defined by the attractive forces between their nuclei and electrons, and can vary in range from only passing attraction to irreversible binding. Several types of chemical bonds exist, and can be classified based on the atoms involved and the distribution of electrons between the atoms. Intramolecular bonds are the bonds that link together atoms to form compounds. There are 3 types of intramolecular bonds: covalent, ionic, and metallic.

Covalent Bond: a bond in which a pair or pairs of electrons is shared by two atoms.

• Molecular compounds refer to covalently-bonded species, generally of low molecular mass.
• Macromolecular compounds are high molecular mass compounds that are covalently-bonded and linear, branched, or cross linked.
• Network: compounds in which each atom is covalently-bonded to all its nearest neighbors so that the entire crystal is one molecule.

Ionic Bond: a bond that holds atoms together in a compound; the electrostatic attraction between charged ions. Ionic compounds are formed between atoms that differ significantly in electronegativity. The electron(s) involved in bonding is (are) transferred from the less electronegative to the more electronegative atom(s) forming ions. The electron donor (cation) now carries a net positive charge, and the electron acceptor (anion) now carries a net negative charge.

Metallic Bond: a bond resulting from the attraction between positive ions and surrounding mobile electrons.

Intermolecular forces

Intermolecular forces are the forces that attract molecules or particles to like or unlike molecules or particles. Typically, these forcesbetween molecules form much weaker bonds than those bonds that form compounds. Intermolecular forces are described below. They are grouped into 3 subcategories based on the type of intramolecular bonds that form a compound:

• Ionic compounds exhibit electrostatic intermolecular forces that form strong bonds with other ionic species.
• Covalent compounds exhibit van der Waals intermolecular forces that form bonds of various strengths with other covalent compounds. The three types of van der Waals forces include: 1) dispersion (weak), 2) dipole-dipole (medium), and 3) hydrogen (strong).
• Ion-dipole bonds (ionic species to covalent molecules) are formed between ions and polar molecules. These compounds typically form medium to strong bonds.

There are five kinds of intermolecular forces described below; the bond strengths described range from strongest to weakest (the latter 3 are examples of van der Waals forces). Please remember that this comparison is relative to other intermolecular attractions and not to covalent or ionic bond strength; there are numerous exceptions that are not provided here.

• Electrostatic: attractive forces between ions of opposite charge; e.g., NaCl bonded to another NaCl to form a crystal of salt.
• Ion-Dipole: forces of attraction between a cation/anion and the solvent molecules when dissolved in water or other polar molecules; e.g., NaCl dissolving in H2O to form Na+ and Cl- surrounded by water molecules.

Because atoms and molecules are three-dimensional structures, orbiting electrons are seldom evenly distributed around the nucleus. As a consequence, otherwise neutral atoms or molecules experience instantaneous moments of polarity (called instantaneous dipoles). In liquids, nearby molecules may feel the effect of such short lived dipoles and generate instantaneous dipoles of their own. The sum of these changing charge-charge interactions is a weak attraction or bond termed Van der Waals forces.

• Hydrogen Bond: a special type of dipole-dipole interaction between the hydrogen atom in a polar bond like O-H or N-H and the electronegative atoms, N, O, or F. These are much stronger forces of attraction than other dipole-dipole forces. As a result of unequal electron sharing, the hydrogens take on a net positive charge. When H, a very small atom, is bonded to other very small atoms with high electronegativity, they form a strong attraction to other similar atoms. Only N, O, and F form hydrogen bonds. Water molecules also form hydrogen bonds with other water molecules.
• Dipole-Dipole: forces of attraction between polar molecules. For example, one molecule of H2O is attracted to another H2O molecule because H2O is a polar molecule. Water is called the universal solvent because many ionic and covalent compounds will dissolve in it.
• Dispersion (London forces): attractive forces that arise between temporary dipoles and induced dipoles in atoms or molecules; e.g., I2 bonded to I2 to form liquid or solid iodine. The larger the molecule, the stronger the dispersion force.

Chemical Bonds and Drugs

Combinations of covalent, ionic, and hydrogen bonds are required to hold large macromolecules like proteins and nucleic acids in their functional forms. For example, the individual base molecules of each strand of DNA are linked by covalent bonds (phosphodiester) while the two strands are held together by hydrogen bonds. Alternatively, most interactions between drugs and their target receptors are combinations of ionic and Van der Waals forces which allow the reversibility of the drug response. Covalent interactions between a drug and its target are not typically desirable for therapeutic purposes because of the irreversible nature of the covalent bond.