We perceive ourselves and the world around us in three dimensions, and this same point of view is crucial for understanding the way in which chemicals operate in living systems. Well-established theories predicted how atoms arrange themselves in molecules, but chemists still regarded many complex molecules involved in vital biological processes as if they were rigid. By revealing ways in which these molecules prefer to shape up in real life, the two recipients of the 1969 Nobel Prize in Chemistry transformed the way in which chemists viewed the materials they studied.
Odd Hassel had limited success analysing the structure and properties of simple molecules, until he used a technique that fires electrons at a sample and creates an interference pattern characteristic of the molecule in question. The focus of his attention was cyclohexane, a compound that in two dimensions is represented by a hexagonal ring of carbon atoms, but their electron interference patterns revealed a more complex geometry. The molecule assumes two forms, one chair-shaped and rigid, the other more flexible and boat-shaped. As it turns out, his observations confirmed an unpopular and unproved hypothesis that had been made at the end of the previous century, but what Hassel also observed was how easily these two forms are interchangeable. When the cyclohexane molecule is alone it prefers to assume the chair conformation, but in the presence of other molecules it rapidly adopts the boat formation. The different conformations arise from each atom in a molecule being surrounded by a host of attractive and repulsive forces coming from their charged constituents, and they respond by twisting or bending around the chemical bonds that hold them together, until they each reach a position they find favourable and stable in their environment.
Hassel's view of cyclohexane went largely unnoticed until Derek Barton extended his ideas to more complex compounds. In a modest four-page article published in 1950, Barton proposed the shape of the cholesterol molecule and its chemical relatives, which contain several rings of carbon joined together. More importantly, he proposed that different configurations of these molecules affect fundamental characteristics, such as their stability and the speed in which they react with other molecules. Barton's observations almost immediately solved the problems chemists had in grasping inexplicable details about the behaviour of chemicals. Chemists could now identify the conformation of even the most complex molecules and use this information to understand how they behave and interact with each other, adding a new and crucial dimension to their chemical analyses.
This Speed Read is supported by the Camille and Henry Dreyfus Foundation Special Grant Program in the Chemical Sciences.