Atropisomer

Atropisomer

Atropisomerism is a form of stereochemistry that involves the spatial orientation of certain molecules which can lead to the existence of distinct isomers, known as atropisomers. This phenomenon occurs due to hindered rotation around a single bond, typically because of steric effects or the presence of bulky substituents, which makes the rotation around this bond slow on the NMR timescale and thus allows for the isolation of individual isomers. Atropisomerism is a subset of conformational isomerism, where the isomers can interconvert only by overcoming a significant energy barrier.

The concept of atropisomerism is particularly relevant in the field of organic chemistry and has significant implications in medicinal chemistry, as the biological activity of a compound can be highly dependent on its three-dimensional shape. For example, the different atropisomers of a drug might have vastly different pharmacological properties, with one isomer being therapeutically active and another being inactive or even harmful.

The term "atropisomer" was derived from the Greek words a (not) and tropos (turn), referring to the inability of these molecules to freely rotate around certain bonds. This characteristic is crucial for the stability and specific properties of atropisomeric compounds.

Biaryl compounds, where two aromatic rings are connected by a single bond, are common examples of structures that can exhibit atropisomerism. The rotation around the aryl-aryl bond is restricted due to the large size of the aromatic rings, leading to the existence of stable, isolable atropisomers. The physical and chemical properties of these isomers, such as their boiling points, melting points, and reactivity, can differ significantly.

In the pharmaceutical industry, the study of atropisomerism is important for the development of new drugs. It is essential to identify and characterize the different atropisomers of a compound to understand their biological activities fully. This can involve the use of various analytical techniques, such as Nuclear Magnetic Resonance (NMR) spectroscopy, X-ray crystallography, and chiral chromatography, to determine the structure and purity of the isomers.

The concept of atropisomerism also extends to other areas of chemistry and biology, including the study of DNA and proteins, where the spatial arrangement of atoms can affect the function and interaction of these biomolecules.