This research is supported by a Marie Curie Action

This research is supported by a Marie Curie Action
This research has received funding from the People Programme (Marie Curie Actions) of the EU (FP7/2007-2013) under REA grant agreement nº PIEF-GA-2013-622413

Saturday, 15 November 2014

Chiral molecules in everyday life: from natural compounds to pharmaceuticals.

Nature is chiral exemplified by the fact that molecules of living organisms (both plants and animals) such as amino acids, peptides, proteins, enzymes, carbohydrates and nucleic acids are chiral. However, not only these biomolecules are chiral but also many other molecules we find on a daily basis are chiral. Most of these molecules are artificial coming from the human activity who synthesized these compounds in order to be used as agrochemicals, or pharmaceuticals just only to cite two relevant applications.



Independently of its origin (natural or artificial) these chiral molecules (namely, their enantiomers) may have different biological activity. This can be illustrated by means of the following examples:

The enantiomers of limonene, both formed naturally, smell differently. One of the enantiomers (S)-limonene smells of lemon while its mirror image compound (R)-limonene smells of oranges. We distinguish between these two enantiomers because our nasal receptors are also made up of chiral molecules that recognise the difference.




Chirality also plays a role on odorants such as (4S)-(+)-carvone, which has a distinct caraway odour, as compared to (4R)-(-)-carvone which has a characteristically sweet spearmint odour. Again our nasal receptors let us to allow us to distinguish the difference in smell.

   
These two odorants possess different odours due to the role of chirality on bioactivity, in this case a different 3-D fit on an odour receptor and/or on different odour receptors. Although the role of chirality in odour perception is still a rather modern area of interest, it should be noted that more than 285 enantiomeric pairs (570 enantiomers) are known to exhibit either differing odours or odour intensities.

Insects use chiral chemical messengers (called pheromones) as sex attractants. Similarly to odorants, in the case of insect pheromones chirality can influence the degree of attractiveness of the insect. (S)-Olean is the female-attracting sex pheromone of the olive fruit fly (Bactrocera oleae Gmelin). On the other hand, the (R)-enantiomer attracts males of the species.



The same principals are important for herbicides and pesticides containing chiral molecules. For example, the (R)-(+)-enantiomer of the herbicide dichlorprop is the active enantiomer in killing the weeds, while the (S)-(-)-enantiomer is inactive as an herbicide.



Thus, biology is very sensitive to chirality and the activity of pharmaceuticals depends on which enantiomer is used. Most drugs consist of chiral molecules. And since a drug must match the receptor in the cell, it is often only one of the enantiomers that is of interest.
One of the earliest known uses of a chiral compound to cure a disease is the case of Quinine (and other Cinchona alkaloids). These compounds possess anti-malarial properties and were used as a medicine since the XVII century. Cinchona extracts and quinine are also used in tonic waters, which were popularized in the British colonies as both a malaria prophylactic and for enjoyment in the form of a “Gin & Tonic”. Tonic water is now one of the largest industrial uses of quinine.



Another early use of a chiral compound to cure a disease is the case of Vitamin C (albeit from foodstuffs). Natural Vitamin C (chemically named (+)-ascorbic acid) has anti-scurvy activity and shows strong anti-oxidant properties.




In certain cases, one of the enantiomers may even be harmful. This was the case, for example, with the drug thalidomide, which was sold in the 1960s to pregnant women. One of the enantiomers of thalidomide helped against nausea, while the other one could cause fetal damage.




Since the two enantiomers of a chiral molecule often have very different effects on cells, it is important to be able to produce each of the two forms pure. These are key processes in modern chemistry and is particularly important in the field of pharmaceuticals.

Saturday, 1 November 2014

What is chirality? Importance in Nature.

It is all about symmetry!

Chirality is a property of asymmetry of objects. The word chirality is derived from the Greek word  χειρ (kheir), which means "hand".
An object (or a system) is chiral if it is not identical to its mirror image, that is, it cannot be superposed onto it. A chiral object and its mirror image are called enantiomorphs (Greek opposite forms) or, when referring to molecules, enantiomers. A non-chiral object is called achiral and can be superposed on its mirror image.

Human hands are perhaps the most universally recognized example of chirality in the real world. The left hand is a non-superimposable mirror image of the right hand; no matter how the two hands are oriented, it is impossible for all the major features of both hands to coincide.
In chemistry, chirality usually refers to molecules. A chiral molecule is a type of molecule that has a non-superposable mirror image. Achiral molecules are symmetrical, identical to their mirror image. These two mirror images of a chiral molecule are called enantiomers or optical isomers. Pairs of enantiomers are often designated as "right-" and "left-handed".



Nature is chiral

One may well think that both forms of chiral molecules ought to be equally common in nature. But when we study the molecules of the cells in close-up, it is evident that nature mainly uses one of the two enantiomers. That is why we have – and this applies to all living material, both vegetable and animal – amino acids, and therefore peptides, enzymes and other proteins, only of one of the mirror image forms. Carbohydrates and nucleic acids like DNA and RNA are other examples.
Thus the enzymes in our cells are chiral, as are other receptors that play an important part in cell machinery. This means that they prefer to bind to one of the enantiomers. In other words, the receptors are extremely selective; only one of the enantiomers fits the receptor's site like a key that fits a lock.
Since the two enantiomers of a chiral molecule often have totally different effects on cells, it is important to be able to produce each of the two forms pure. Chemistry brings us solutions to achieve this goal.

For more info, see also an interesting video "What is chirality and how did it get in my molecules?" at http://ed.ted.com/lessons/michael-evans-what-is-chirality-and-how-did-it-get-in-my-molecules

Aarhus University

Aarhus University
Aarhus University website

Center for Catalysis, AU

Center for Catalysis, AU
Center for Catalysis, AU website

Marie Curie Actions

Marie Curie Actions
Marie Curie Actions website