Chemical Reaction: The Chirality of Life

Oct 14th, 2008

Steve Herman

The universe is asymmetric and I am persuaded that life, as it is known to us, is a direct result of the asymmetry of the universe or of its indirect consequences. The universe is asymmetric. —Louis Pasteur

We all know that cosmetics contain chemicals and pH. To make matters worse, we now talk about “chirals”:

… even labels that appear to have “good” ingredients—vitamins, enzymes, alpha hydroxy and beta hydroxy acids—can be deceiving, because of something called a “chiral.” Chemical molecules, such as vitamin C, for instance, are composed of mirror-image components, which are exact opposites of each other. Oversimplified, one part of the molecule does good work in the body, while the other—the evil twin, or chiral—wreaks harm. “Everything in nature appears in opposition to each other,” the doctor explains. “It’s the same with every chemical compound. You have to purify out the bad chemicals that cause harm, and keep the good ones. People need to look for chiral-free products.”1

Ah, if only we could remove the chirals from our products.

In all fairness, there is science behind this, very significant science. Life on earth is left-handed. Specifically, the 18 optically active amino acids of life are all l-enatiomers. This chemistry comes out of the plane of the paper when we draw pictures of it.

Figure 1 has a simple organic molecule, with all the covalent bonds pointed to the corners of a tetrahedron. If all the colored balls were hydrogen it would be methane. If all the balls are different colors, the mirror image becomes a different molecule, and the two images cannot be superimposed. If you don’t have a molecular model kit handy to test this idea, try putting a left-handed glove on your right hand.

Figure 2 illustrates the “handedness” of an amino acid. These amino acids are the building blocks of protein. Thus skin and hair, at the molecular level, are stereospecific and left-handed. By contrast, the DNA double helix has right-handed chemistry in its turns.

Louis Pasteur discovered chemical asymmetry in 1840. He noticed that a sample of sodium ammonium tartrate, a salt of tartaric acid used in wine making, contained two crystalline forms. Pasteur separated them using a pair of tweezers. One form was the mirror image of the other, and each was optically active in an equal but opposite way. Mixtures were optically inactive. This was the birth of stereochemistry. Lord Kelvin is credited with introducing the word “chirality” (from the Latin chiro, meaning hand) into science.

How important is chirality? Thalidamide is the classic, and tragic, example. In the early 1960s when the synthetic tranquilizer thalidomide was widely prescribed as a sedative, some pregnant women used it for morning sickness. They later gave birth to deformed children. The drug had been administered as a racemic mixture. Later, it was found that one isomer was teratogenic and interfered with DNA metabolism, while the other isomer was safe: the l-isomer produced the severe fetal abnormalities Life does not have to be left-handed. Some factor operating when life started here preferred l-enantiomers, or it just happened by chance. Another significant natural event that was not symmetrical was the Big Bang. Matter and antimatter should have been created in equal amounts, and it would have self-annihilated. Thus life on earth, and the entire universe, would not exist except for some imbalance at the moment of creation.

The proteins produced by nature are made from polymeric chains of 20 amino acids. What if there are more amino acids available? Then new proteins can be constructed with novel properties. Non-natural amino acids already are being made, and the first microorganism that both produces a non-natural amino acid and incorporates it into proteins has been created.

Customized Proteins

The cosmetic industry has been customizing proteins for many years. Hydrolyzed proteins, quaternized proteins, protein fragments and proteins with pendant groups added to the reactive sites of amino acids are common. These products usually are modified for solubility or substantivity, not biological activity. The main exception is the short peptide chains used in skin care. New proteins using genetic engineering, and incorporating the proper chiral forms would, potentially, be a giant evolutionary step in raw material construction.

Making designer proteins from scratch is well beyond current technology, and even predicting the behavior of a completely new molecule would overwhelm available computational methods. New proteins are being made from existing structures, retaining the desirable traits of the original in addition to the properties contributed by the specially engineered amino acid.

Pharmaceuticals are 70% of a $15 billion chiral chemical market.2 It surely will become an increasingly important factor in skin care. Using naturally derived materials will usually provide the right stereochemistry, but as technology advances, there will be increased likelihood of chiral factors impacting either raw material synthesis or biological activity.

Companies that commercialize chiral chemicals have specific challenges relating to synthesis, catalysis and separation by methods such as chiral liquid chromatography. Technology ranges from the newest biocatalytic transformations to the protecting groups that aid asymmetric synthesis. To create new enantioselective technology, researchers use the chiral pool, resolution of racemates, and asymmetric synthesis. The chiral pool consists of all the carbohydrates, amino acids, lipids, terpenes and alkaloids from plant and animal sources. Either chemical or biocatalytic methods are used.

A highly unscientific survey at a recent meeting of the New York Society of Cosmetic Chemists revealed little awareness of the potential for developing a new generation of cosmetic actives based on chiral properties. Yet, in the past, the cosmetic industry has taken many concepts from pharmaceuticals. If history repeats itself, and it often does, chirality will someday be one more tool in the quest for the perfect cosmetic.

Life on earth is asymmetrical, and we end with another significant example of asymmetry. As stated earlier, the Big Bang should have produced equal amounts of matter and antimatter, which would have immediately self-annihilated. That clearly did not happen—we are here! We owe our existence to a very small asymmetry between matter and antimatter. Life, the Universe, and Everything is not just a book by Douglas Adams—it is part of the chemistry of every bit of protein in our body.

General reference:

RM Hazen, “Life’s Rocky Start,” Scientific America, April 2001

References