Asymmetry and enzyme action.

It must, I think, be rare to be rewarded so generously for work that was so purely a pleasure in planning and execution. I shall try, in return, to impart some of that pleasure today. In 1948, a short but historic note by Alexander Ogston appeared in the scientific magazine Nature, demonstrating the importance of a particular type of stereochemical thinking in relation to biochemical processes catalysed by enzymes. Up to that time I had, as an organic chemist interested in the synthesis of natural products, the same kind of feeling for stereochemistry that a motorist might have for a system of one-way streets a set of rules forming one more obstacle on the way to a destination. But 1948 was a year in which as well as continuing collaboration with Robert Robinson on the total synthesis of sterols, I had begun to co-operate with biological scientists at the National Institute for Medical Research; so that Ogston’s note was a seed that germinated the more readily in my mind. The essential principles of the three-dimensional structure of organic molecules had been correctly formulated by the first Nobel laureate in Chemistry, Jacobus van’t Hoff, as early as 1874. In particular he (and independently Le Bel) gave a structural basis to Louis Pasteur’s discovery that certain molecules can exist in two optically active forms that differ from each other in their effect on a beam of plane polarized light; the plane of polarization is rotated to the right when the beam passes through a solution of one form, and to the left when the other form is substituted. van’t Hoff theorized that when a carbon atom in a molecule is attached to its maximum number of four other atoms, these occupy the four apices of a tetrahedron, with the carbon atom in the middle. Another way of saying the same thing is that the four atoms keep as far away from each other as they can, given that they are bound at fixed distances from the central atom. If these four atoms are all different, or at any rate if each forms part of a different group of atoms, they can occupy two distinct spatial arrangements that are chiral: their relationship is that of a right hand with a left hand and they are mirror images of one another (I, II).