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The Crystals That Founded Stereochemistry

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The Crystals That Founded Stereochemistry

Before germ theory made him famous, Pasteur was a young chemist working on a puzzle in crystallography. Tartaric acid, a byproduct of winemaking, rotates polarized light as it passes through a solution of it, a property called optical activity. A related compound, racemic acid, had the same chemical formula and behaved identically in every respect chemists could test, except that it had no effect on polarized light at all, and no one could explain why two substances that seemed chemically identical behaved so differently.

In 1848, working with crystals of a sodium ammonium salt of racemic acid, Pasteur noticed under a microscope that the crystals came in two subtly different shapes, mirror images of one another, like a left hand and a right hand. Working with tweezers, he sorted thousands of tiny crystals into two piles by hand, one shape in each pile. When he dissolved each pile separately and tested it, one solution rotated polarized light clockwise and the other rotated it counterclockwise by an equal amount, mixed back together, the two solutions canceled out and behaved exactly like racemic acid.

Pasteur had discovered molecular chirality, the fact that some molecules exist in mirror-image forms with identical composition but different three-dimensional structure, without yet having any way to picture what a molecule's three-dimensional shape actually was, the atomic-scale explanation came only decades later, from the chemists Jacobus van 't Hoff and Joseph Le Bel. The finding founded the field of stereochemistry, the study of how the spatial arrangement of atoms within a molecule affects its properties, a field that later proved essential to understanding why one mirror-image form of a drug can be therapeutic while the other is inert or even harmful.

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