Bonding, binding and isomerism

Abstract

Bonding, binding and isomerism influence the activity and elimination of many drugs. The bonding of drugs by tissues is dependent on their attraction and combination with cellular groups. Four main types of chemical bonds are involved (ionic bonds, dipole-dipole interactions, hydrogen bonds and covalent bonds). Ionic or electrostatic bonds are reversible bonds between ionized compounds and proteins. Hydrogen bonds are a rapidly reversible type of dipole-dipole interaction, and are particularly important in biological reactions. Covalent bonds are stable chemical bonds produced by electron sharing between atoms. The action of most drugs depends on their initial binding by effector proteins (e.g. enzymes, receptors or ion channels). This results in secondary effects (e.g. enzyme activation or inhibition, or the accumulation of intermediate metabolites). In contrast, plasma protein binding plays an essential role in drug distribution, and varies widely (even among closely related drugs). It may be modified in pathological conditions and surgery, and sometimes restricts the hepatic elimination of drugs. Some extensively bound drugs may be displaced from plasma proteins by other agents. Isomers are drugs with the same chemical composition and molecular formula. Structural isomers have different chemical structures due to the different arrangement of their atoms (e.g. enflurane and isoflurane). In contrast, stereoisomers have identical structures but different configurations. Enantiomers are pairs of stereoisomers that are mirror images, due to the presence of a chiral centre. Racemic mixtures are equal mixtures of two enantiomers, which may have a different pharmacodynamic activities and pharmacokinetic properties.