In chemistry, shape matters. For chemicals to function properly in the body it is not only important that the molecular components are connected in their correct order but also that these components occupy their correct three-dimensional positions in space. A wrongly positioned atom or structural element creates either an ineffective chemical, much like using the wrong key to open a lock, or a chemical that can have unintended effects.
How the shape of a molecule, or its stereochemistry, is created, and how this affects its behaviour, is the focus of the 1975 Nobel Prize in Chemistry. John Cornforth investigated the role of enzymes, the biological catalysts that control important chemical reactions, by detailing how they construct the essential precursor for cholesterol, squalene, in the cell. Creating squalene from its chemical building blocks involves a complicated 14-step procedure, and at each step the enzyme must select which one of two hydrogen atoms it needs to remove. By substituting these atoms with deuterium atoms, which are heavier versions of hydrogen, Conforth could track which choice the enzyme makes at each stage to create the correct product. Using variations of this technique, Cornforth revealed the chemical sculpting processes that occur in several other biologically important reactions.
Vladimir Prelog’s interest in shape focused on the ways in which the three-dimensional arrangement of atoms in a molecule influences the course of chemical reactions. Amongst his many achievements, Prelog looked at ring-shaped molecules containing 8–12 carbon atoms, which behave in a limp rather than rigid manner. By replacing ring atoms with carbon atoms that have a different mass, he tracked how the flexibility allows distant parts of the ring to come into close contact, resulting in unexpected reactions. He also helped to classify chirality, a peculiar quality that many biologically important molecules share. Such molecules can exist as two versions, which contain the same atoms but are mirror images of each other, like right and left hands. Prelog, together with Robert Cahn and Christopher Ingold, formulated the rules for describing the two mirror images of any position or shape of the molecule which contribute to the chirality of the molecule.
Their work and discoveries range from paleogenomics and click chemistry to documenting war crimes.
See them all presented here.