Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In contrast, noncovalent interactions are weaker but more selective, requiring a precise fit between the drug and its target. Most drug-receptor interactions occur through electrostatic interactions, ranging from strong ionic linkages to weaker hydrogen bonds and van der Waals forces. The hydrophobic effect occurs when lipophilic drugs interact with hydrophobic pockets within receptors, excluding surrounding water molecules.
The selectivity of drug-receptor interactions must allow drugs to modify the activity of target cells without affecting others. Covalent bonds are highly reactive but lack selectivity, while weaker bonds provide greater selectivity due to the requirement for an exact fit. Designing highly selective drugs involves avoiding highly reactive molecules that form covalent bonds and instead opting for weaker bond formation.
