Chiral Environments: Sometimes, the environment shapes you

In previous entries, we have discussed about enantiomers and how they have different arrangements in space. These different enantiomers can only be distinguished when we are looking at a chiral environment. In an achiral environment, we will not be able to see a difference in the various enantiomers. 

An analogy for this would be to think about a left- and right- handed glove [1]. When we place these gloves on a table-top, the glove will interact in the same way with the table. However, when we use our left hand to interact with these gloves, we are able to distinguish between the glove meant for the left hand and the glove meant for the right hand. In this case, the table-top is the achiral environment while the left hand is the chiral environment [1].  

As such, in a chiral environment, the different enantiomers will interact differently with the environment due to their different arrangements in space and this will lead to differences in reactions. A common chiral environment would be that of enzymes. Enzymes are able to differentiate between enantiomers because the different groups of atoms occupy different regions in a three-dimensional space [2].  

Different enantiomers can have different reactions and properties in a chiral environment. Besides this, prochirality is also an important factor to consider in chiral environments. This leads into an important concept of prochirality. A prochiral molecule refers to one that has no chiral centre prior to the reaction but will have a chiral centre after the reaction [3].  

An example of this is shown in Figure 1. In the original compound on the left, the molecule is achiral as there is no chiral centre. When one of the hydrogen atoms is changed to deuterium, this causes the carbon to become a chiral centre. We call this carbon a prochiral carbon. In the same way, the two hydrogens attached to the prochiral carbon is also known as prochiral hydrogens [3].  

The prochiral hydrogens can be named pro-R of pro-S based on the resultant stereochemistry of the the product formed after changing the hydrogen atom into something else [1]. For example, in the case of Figure 1, the red hydrogen atom is said to be pro R as the resultant enantiomer formed has the R-configuration. On the other hand, if the blue hydrogen is being changed to deuterium instead, the resultant enantiomer will have the S-configuration, so it the blue hydrogen is said to be pro S.  

Prochirality is an important concept to deal with when looking at chiral environments. It is especially important in reactions which involve the use of enzymes. This is because, even with prochiral molecules that are symmetrical, the enzymes can function in an asymmetrical way. In other words, enzymes can distinguish between two of the same substituents that are bound to a prochiral centre [3].  

An example of this is the reaction in Figure 2, which is an important step in the oxidation of fatty acids. In the case of this reaction, only the HD and HA which are pro-R will be lost in the reaction [2]. The pro-S HC and HB will always remain attached to the prochiral carbons [2]. This shows that the enzymes involved in this reaction are specific to the pro-R hydrogens and are able to differentiate between the two prochiral hydrogens even though they are identical to each other due to differences in their pro-chirality.  

Classification of Prochiral Hydrogens

Prochiral hydrogens can be further classified into enantiotopic and diastereotopic hydrogens.  

 1. Enantiotopic Hydrogens
For enantiotopic hydrogens, when the pro-R and pro-S hydrogens are separately replaced, the products would be enantiomers because there is only one resultant chiral centre [2].  

 2. Diastereotopic Hydrogens
In the case of diastereotopic hydrogens, when the pro-R and pro-S hydrogens are separately replaced, the resultant products would be diastereomers because there are more than one chiral centres in the product [2]. This will be an important when we are concerned about Nuclear Magnetic Resonance.  

 3. Homotopic Hydrogens
Lastly, if hydrogens cannot be considered enantiotopic or diastereotopic, it is because when they are replaced, they do not result in a chiral centre being formed [2]. As such, they are not considered prochiral and an enzyme will not be able to differentiate between these hydrogens. 


References

  1. Chirality. Available from: http://www.chemistryexplained.com/Ce-Co/Chirality.html
  2. Soderberg, T. Prochirality. 2017; Available from: https://courses.lumenlearning.com/suny-mcc-organicchemistry/chapter/prochirality/
  3. P, B.C.. Chirality. Available from: https://chem.libretexts.org/Textbook_Maps/Organic_Chem istry/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg) /Chapter_03%3A_Conformations_and_Stereochemistry /3.11%3A_Prochirality

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