Molecular recognition of DNA by small molecules.

Chemists, like artists, are able to construct new threedimensional objects, molecules and materials that exist only in the mind of a person. I became interested in creating novel molecular shapes with properties different from those found in nature shortly after arriving at Caltech in 1973. One cannot design without the brushes and paint of the craft. Indeed, modern organic chemists, standing on the shoulders of the pioneering achievements of Woodward, Corey, Merrifield, and others are able to apply the power of synthetic chemistry and the logic of incremental change to the field of structure– function. In early 1973, I was inspired by the work of Lehn and Cram in the field of host–guest chemistry where early studies were largely conducted in organic solvents (e.g., cation–crown complexation). I decided that a pivotal path forward would be to understand in a predictive mechanistic sense how to create ensembles of weak bonds between synthetic ligands and biological macromolecules in water, the solvent of life.