Isosterically

Isosterically refers to the concept of isosterism, a principle in chemistry and pharmacology that describes molecules or ions that have the same number of atoms, the same number of valence electrons, and similar spatial arrangements. These similarities often lead to comparable physical and chemical properties, as well as biological activity. The term "isosteric" is derived from the Greek words "isos" meaning equal and "stereos" meaning solid or three-dimensional.

The concept of isosterism was first introduced by the Swedish chemist Irving Langmuir in 1919. He observed that certain molecules with the same number of electrons exhibited similar physical properties. Later, the definition was expanded to include molecules with the same number of atoms and similar shapes, even if the electron count differed slightly. For example, carbon monoxide (CO) and nitrogen (N2) are considered isosteres because they both have two atoms and a total of 14 valence electrons, and their bond lengths and molecular geometries are very similar.

In medicinal chemistry, isosterism is a valuable tool for drug design. By replacing one atom or group in a molecule with an isosteric equivalent, chemists can modify a drug's properties such as solubility, metabolism, or binding affinity to a target receptor, while potentially retaining or improving its therapeutic effect. This strategy can help optimize drug efficacy, reduce toxicity, or overcome resistance mechanisms. Examples include replacing a carboxylic acid group with a tetrazole ring, which is structurally similar and has a similar pKa.

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