isosterismthe

Isosterism is a principle in chemistry describing the replacement of atoms or groups with others that have similar electronic structure and size, resulting in similar physical properties and reactivity. The concept, developed in the mid-20th century by Irving Langmuir and colleagues, seeks to explain why different substituents can produce analogous behavior in molecules and crystals. In practice, isosteres are fragments with the same number of valence electrons and similar steric demands, so that the overall shape and electron distribution of the molecule are preserved.

Classical isosteres refer to replacements among elements in the same main group that closely match in size and valence, such as substituting a hydrogen atom with fluorine or a carbonyl carbon with a heteroatom of similar size under certain contexts. Nonclassical isosteres describe more distant substitutions that nevertheless produce similar properties, often through comparable electronic effects or spatial arrangements. Further refinement leads to the concept of bioisosterism, widely used in medicinal chemistry to optimize pharmacokinetic properties and biological activity by replacing functional groups with isosteres while maintaining or improving activity.

Examples include replacing carboxyl groups with tetrazole rings to mimic acidity and charge distribution. Isosterism guides drug design and materials science by helping chemists predict how substitutions will influence binding, metabolism, lipophilicity, and stability. However, isosteric similarity is context-dependent and does not guarantee identical behavior in all environments.