Tag Archives: biomolecules

Pasteur and Chirality

La chance ne sourit qu’aux ésprits bien préparés, Louis Pasteur

The wine industry is and has always been an important part of the French economy. Because wine-making is dependent on chemical processes in which yeast digests the grape sugars and transforms grape juice into wine, French scientists have learned much about chemistry from wine.

In 1847, Louis Pasteur, at age 25, had just received his doctorate in science and was still working in the lab at the French École Normale Supérieure in Paris, when the wine industry presented him with a puzzle.

Tartaric acid is a natural by-product of wine fermentation and was first isolated in 1769. It coated the walls of wine vats and it was also valuable having uses in medicine and manufacturing. Chemists were interested in its properties that could be explored by examination of its crystals. It was known that some crystals were optically active; that is, that some would bend polarized light to the right or to the left.  A French physicist named Biot had done this with tartaric acid crystals and found that the crystals rotated the polarized light clockwise (to the right).

In 1819 an accident resulted in the synthesis of what was believed to be tartaric acid.

However, when a distinguished German chemist and crystallographer named Eihard Mitscherlich compared the natural tartaric acid with the synthetic version he found them to be identical in all respects, except, inexplicably in optical rotation. The synthetic tartaric acid did not cause polarized light to rotate and was therefore distinguished from the natural tartaric acid (TA) with the name of paratartaric acid (PTA).

For Pasteur simply giving the unknown substance a new name didn’t resolve the puzzle.

Why would the synthetic version of tartaric acid have no effect on polarized light when its apparently identical twin caused the light to rotate to the right?

Pasteur grew crystals of the PTA and, using a magnifying glass looked at them very closely.  Each crystal was certainly a mirror image of each other crystal. In a mirror image, one image can be placed over its mate, matching perfectly.  Pasteur later wrote: “Here now is the crystallographic difference between these two types of crystals. They are all hemihedral (that is, having only half the plane surfaces needed for symmetry); but some are hemihedral to the right, others to the left…” The illustration on the left is Pasteur’s drawing of the two types of crystal while the right image marks the right and left facets that make the mirror images non-superposable.

When he tested the crystals with polarized light, he found that “the direction of [optical] rotation depends on this dissymmetry.” (Gal, 2015, p.10)

The puzzle had been solved.  The TA created during the fermentation of grape juice was composed of only “right-handed” (hemihedral to the right) molecules while the PTA, the synthesized tartaric acid was a 1:1 mixture of right-handed and left-handed molecules. The synthetic tartaric acid was optically inactive because the right-left mixture cancelled each other.

Pasteur’s word was that the crystals were “dissymmetric.” Much later, in 1894, Lord Kelvin would name molecules that would form such crystals “chiral” using the Greek word for hand. A chiral molecule will have two versions that are mirror images of one another (like your two hands) but, also like your hands can’t be superposed on one another.

While everyone knows about Pasteur or at least about pasteurization, his discovery of chirality is less well-known but it is one of his most important.

Over time scientists have learned that many molecules, particularly those based on carbon, which means biomolecules, those that compose living organisms are chiral.

And, it turns out, chirality matters, a lot.

In living organisms, chiral compounds are usually present in one form only: amino acids, carbohydrates and nucleic acids as well as enzymes are right-handed or left-handed but never both.

This explains why the natural tartaric acid produced during the fermentation of wine was the right-hand version only. The yeast that changed the grade juice into wine is what is now called “steriospecific;” which means it produces, either the right-hand or left-hand version of molecules but not both. If, on the other hand, chiral molecules are produced by ordinary chemical mixing and reacting, the output will be a mixture of the right and left versions in a 1:1 ratio, as in the paratartaric acid.

More than half of drugs in current use are chiral. And nearly 90% of those are manufactured using ordinary chemical processes which means that half of the molecules (the right-handed or the left-handed) perhaps doing nothing or, perhaps doing harm.

In 1957 thalidomide was introduced as a treatment for morning sickness. However, women who took the drug were likely to bear children who were severely handicapped.  The developers were unaware that the drug contained both the helpful right-handed molecules that eased the morning sickness but also the left-handed molecules that caused severe birth defects.

Modern pharmaceutical science attempts to ensure that the process produces the proper molecule, that is the one that fits the intended receptor.

One way to do this is to make biomolecules by using living organisms. Insulin is now manufactured by a bacterium that has had a gene inserted into its DNA that causes it to create insulin with the proper chirality.

Why did the very young Pasteur make a discovery that was missed by many other, older and more experienced scientists? The adolescent Pasteur wanted to be an artist. He reproduced some of his quite accomplished pictures using lithography in which an image created on limestone is transferred to paper but backwards. “Isn’t this the explanation of how he saw the handedness on the crystals — because he was sensitized to that as an artist.” Klein, 2017).Chappuis

One of Pasteur’s quotations reflects this: “Chance smiles only on those who are well-prepared.”

Resources:

Gal, Joseph (2015). Louis Pasteur, Language, and Molecular Chirality — I. Background and Dissymmetry. PubMed, January 2011, DOI: 10.1002/chir.20866

 

Klein, Joanna (2017). How Pasteur’s Artistic Insight Changed Chemistry. New York Times, June 14, 2017. Retrieved from https://www.nytimes.com/2017/06/14/science/louis-pasteur-chirality-chemistry.html?_r=0

 

Nguyen, Lien Ai, et al. (2006).  Chiral Drugs: An Overview. International Journal of Biomedical Science. 2(2); 85-100. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614593/

 

The images of the paratartaric acid are in the public domain retrieved from http://www.chemistryexplained.com/Ny-Pi/Pasteur-Louis.html

 

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