Abstract
A major impediment to introduction of new extractants to practical use is the large cost and long lead times for synthesis and testing of candidate molecules. Toward the goal of reducing this experimental burden, this talk describes a computational approach to the design of molecular receptors that are structurally organized for optimal coordination with ions. With a molecular-level understanding of how host architecture influences ion-binding affinity, it is possible to identify promising potential extractants before they are prepared and tested. Exploiting powerful concepts embodied in structure-based drug design to bear on host design, we have devised novel algorithms for building potential host structures from molecular fragments and rapid methods for comparing the binding-site organization of the resulting candidates. The result is a computer software program, called HostDesigner, which can generate and evaluate millions of new molecular structures per minute on a desktop personal computer. The utility of this software has been illustrated in the structural design of cation receptors such as crown ethers and anion receptors bearing urea groups.