What is the Difference Between Isosteres and Bioisosteres

Isosteres are atoms or molecules that share a similar size and number of valence electrons. These chemicals are used mainly in medicinal chemistry for drug design.

What is the difference between isosteres and bioisosteres? Isosteres are atoms, ions, or molecules with similar size and often electronic properties, whereas bioisosteres are chemical groups or substituents that share similar physical or chemical properties with another group and produce broadly similar biological effects.

Key Areas Covered

1. What are Isosteres  
      – Definition, Features 
2. What are Bioisosteres
      – Definition, Features 
3. Similarities Between Isosteres and Bioisosteres
      – Outline of Common Features
4. Difference Between Isosteres and Bioisosteres
      – Comparison of Key Differences
5. FAQ: Isosteres and Bioisosteres
      – Answers to Frequently Asked Questions

Key Terms

Isosteres, Bioisosteres

What are Isosteres

Isosteres are atoms, ions, or even entire molecules that have a similar size and the same number of valence electrons. Valence electrons are the electrons in the outermost shell. Some examples of isosteres are nitrogen (N₂), carbon monoxide (CO), and cyanide ion (CN-). All three share the same number of valence electrons (6) and a similar linear structure and fluorine ion (F-) and neon (Ne).

Moreover, isosteres have similar van der Waals radii, which is the effective size of an atom when it interacts with other atoms. The number of valence electrons and their arrangement influence the molecule’s shape and geometry. The geometric shapes of isosteres are similar when the electronic configurations are similar.

However, there are limitations associated with isosteres. These factors affect their properties. Some of such factors are core (inner electrons) and the number of atoms.

What are Bioisosteres

Bioisosteres share similar physical or chemical properties with another group, but they also lead to broadly similar biological effects. There are two main types of bioisosteres. They are classical bioisosteres and nom classical bioisosteres. Classical bioisosteres share similar size, shape and electron distribution with the original group. An example of bioisosteres is replacing hydrogen with fluorine. Nonclassical bioisosteres do not necessarily mirror the original fluorine group in every way, but they still lead to similar biological effects. Replacing a carboxylic acid group with a tetrazole ring is an example of this.

Bioisosteres are mostly used by medicinal chemists. Here, the refining of the initial drug candidates without drasticall changing their core strucuture is allowed. Some bioisosteres help the drugs reach its target site efficiently. Sometimes, they fine tune the potency of the drug. There are many benefits of this fine tuning. Swapping in a bioisostere with less harmful properties, the overall drug can become safer. Hence, the toxicity of the drug is reduced.

Similarities Between Isosteres and Bioisosteres

1. Both types have a similar size and shape to the group they are replacing.
2. They often have electron distribution or electronic properties similar to those of the original group.

Difference Between Isosteres and Bioisosteres

Definition

• Isosteres are atoms, ions, or even entire molecules that have a similar size and the same number of valence electrons. Bioisosteres share similar physical or chemical properties with another group, but they also lead to broadly similar biological effects.

Focus

• Isosteres mainly focus on similar size and shape, with less emphasis on biological activity. On the other hand, bioisosteres mainly focus on maintaining or enhancing biological activity while having similar size and shape.

Biological Effect

• Isosteres may or may not have similar biological effects compared to the original group. Bioisosteres are specifically chosen because they are likely to maintain or even improve the biological activity of the molecule.

Predictability

• The impact of isosteric replacement on biological activity can be less predictable. However, bioisosteric replacements are chosen to have a more predictable and desired effect on biological activity.

Conclusion

Isosteres and bioisosteres are both tools used to understand and modify molecules. Isosteres prioritize similar size and shape and may or may not have similar biological effects. Bioisosteres have the ability to maintain or improve a molecule’s biological activity while keeping a similar size and shape. This is the main difference between isosteres and bioisosteres.

FAQ: Isosteres and Bioisosteres

1. What do you mean by isosteres?

Isosteres are atoms, molecules, or ions that share some key similarities such as size, same number of atoms, and same number of valence electrons. For example, nitrogen, carbon monoxide (CO), and the cyanide ion (CN⁻) are all isosteres.

2. What is an example of bioisosterism?

A common example of bioisosterism involves replacing a hydrogen atom (H) with a fluorine atom (F) in a drug molecule. Replacing an H with an F might increase the drug’s resistance to breakdown by the body because the C-F bond is stronger than a C-H bond. This could lead to a longer-lasting drug effect.

3. What is an example of isosterism?

Nitrogen (N₂) and Carbon Monoxide (CO) are isosteres These molecules are isosteres because they share both key characteristics. Both N₂ and CO are small diatomic molecules with similar sizes. They have the same number of valence electrons.

4. How do you identify bioisosteres?

There are several methods of identifying bioisosteres, such as knowledge-based approach, fragment-based methods, and computational methods.

5. What is the importance of bioisosteres?

Bioisosteres are mainly used medicinal chemistry.  It is used in improved drug design, optimising lead compounds, and in the discovery of new drugs.

Reference:

1. Nicholas, A, Meanwell. “Applications of Bioisosteres in the Design of Biologically Active Compounds.” ACS Publications.
2. “Isostere.” Wikipedia. Wikipedia Foundation.

Image Courtesy:

1. “Classical bioisosteres 2” By Iandoxsee – Own work (CC BY-SA 4.0) via Commons Wikimedia