Designer molecules set the trend for advancing science
July 29, 2002--Scientists have long understood that new configurations of molecules--the substance of all things on earth--are the gateway to new advancements in medicine, materials, technologies, energy, and much more. In an address to the annual meeting of the American Association for the Advancement of Science, the President's science advisor Jack Marburger noted that a revolution in science is occurring where we can now design new species from scratch that have unprecedented chemical properties.
The problem with the dream of building the best molecular structure to achieve specific benefits is that the process is vastly complex and has been time consuming and expensive--until now. Scientists at DOE's national user facility, the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL), have developed an automated process that rapidly builds molecular structures on a computer by combining molecular fragments taken from a library of molecular structures.
This new computer software program, called HostDesigner, can generate and evaluate millions of new molecular structures per minute on a desktop personal computer. In contrast, building one new molecular structure by hand takes about 15 minutes employing the graphical user interfaces present in most desktop modeling software.
Decades of DOE research has gone into this process of whittling the time it takes to create new molecular structures, helping to achieve the goal of "materials by design." The result is a less costly and more expedient approach to "ligand" architecture, which holds significant promise for many applications such as new pharmaceuticals, environmental cleanup, and industrial processes.
A ligand is a molecule that attaches to another chemical entity, such as another molecule, an atom, or an ion, to form what is called a complex. For example, in the development of new pharmaceuticals, researchers design ligands that bind to proteins to control certain biological events. For environmental cleanup, ligands can bind to harmful metal ions making it possible to detect and remove metallic contaminants such as radionuclides. Ligands are also essential for new processes important to private industry as well as Federal environmental cleanup operations. Until now the ability to develop new ligands for environmental cleanup applications has been through laborious trial and error research.
"The expediency of the computational approach allows researchers to build molecular structures of interest, then screen the structures to determine if they will behave as predicted before ever synthesizing the new ligand," said Ben Hay, PNNL scientist and creator of HostDesigner. "Our ability to design ligands tailored for specific applications will save time and money by focusing research efforts on the most promising ligand structures. Here, we expect to trim months if not years off of the development of new separation processes because of the increased efficiency in identifying promising ligand architectures," he said.
HostDesigner was created specifically for the discovery of molecules that bind with metal ions--an application that is crucial for environmental cleanup and other industrial processes where the objectives are to detect and recover metals. The software was modeled after similar programs used in the pharmaceutical industry, which concentrate on the design of molecules that bind to proteins.
"The most pressing cleanup tasks at DOE sites involve processing radioactive wastes for long-term storage, as well as performing decontamination and decommissioning activities of nuclear facilities. In both cases, it is necessary to remove the radioactive components--most of which are metals--and concentrate them to minimize the volume of radioactive material for permanent disposal," said Hay.
New separations processes developed from "designer" ligands will feature greater efficiencies in "grabbing" the radionuclides of interest, thus streamlining cleanup activities and allowing work to be accomplished in shorter periods of time, said Hay.
"Designer" ligands also will be beneficial in the development of sensors that will be used to more accurately measure the extent of contamination in the soil or groundwater as well as for homeland security needs. To effectively monitor radioactive contamination, sensors must be able to "recognize" hot metal ions, and new sensors will need to be developed to spot some ions that have previously not been detectable.
Computer-aided design of ligand architecture yields a dramatic enhancement of metal-ion affinity. Comparison of the 3-D structure of a conventional diamide ligand (left) with that of the new computer-designed bicyclic diamide (right). The vectors on each oxygen atom, which indicate the direction required for optimal interaction with a metal ion, diverge in the conventional diamide structure and converge in the computer-designed structure.
Using the concepts embodied in the HostDesigner software, Hay designed a new diamide ligand that targets the f-block metal ions. This group of metal ions, composed of actinides and lanthanides, is present as radioactive contaminants throughout the DOE complex. In addition, the f-block metal ions are of particular interest to operations involving the reprocessing of nuclear fuel, an activity not performed in the United States, but which is conducted in many countries where much of the electrical power is generated through nuclear power plants.
Experimental studies, performed in partnership between Professor Jim Hutchison of the University of Oregon, and PNNL scientists Hay, Brian Rapko, Gregg Lumetta, and Priscilla Garza, have shown that the "designer" diamide molecule is 10 million times more efficient at removing f-block metals from process waste than conventional diamide ligands.
"With the dramatic increase in efficiency, the new diamide ligand promises to reduce the amount of ligand needed and thereby minimize the wastes associated with cleanup," said Hay.
"The knowledge gained from designing the diamide ligand will help in the creation of new ligands tailored for application in sensors and separation processes used in Federal cleanup activities, which is just one of the reasons DOE has been a strong supporter of this research," said Hay.--by Mary Ace
Version 1.0 of the HostDesigner software, developed
by PNNL/EMSL, is available free to the public and can
be downloaded from the HostDesigner website: http://hostdesigner.emsl.pnl.gov
"Deliberate Design of Ligand Architecture Yields Dramatic
Enhancement of Metal Ion Affinity," Lumetta, G. J.,
B. M. Rapko, P. A. Garza, B. P. Hay, R. D. Gilbertson,
T. J. R. Weakley, and J. E. Hutchison, Journal of
the American Chemical Society, Comm. Ed. 124:5644-5645
[Full article - PDF
Designer Bindings," by Phil D. Szuromi, Science
2002 May 10; 296: 985 (in Editors' Choice: Highlights
of the recent literature).
"Designed ligands boost metal binding," Chemical
and Engineering News May 20, 2002; 80(20): 37 (under
the "Science and Technology Concentrates" heading) [Requires
Funding:The U.S. Department of Energy's Office of Science, through its Environmental Management Science Program, has funded research on ligand design and architecture since 1996. The development of the HostDesigner software was funded in part through the Laboratory Directed Research & Development Program of the Fundamental Science Directorate of PNNL and in part through a collaboration between the William R. Wiley Environmental Molecular Sciences Laboratory and the Chemical Separations Group at Oak Ridge National Laboratory funded by the Chemical Sciences division of the Office of Basic Energy Sciences, Office of Science, DOE.
Author: Mary Ace is the Communications Manager for PNNL's Fundamental Science Directorate. She works closely with scientists to help them communicate their accomplishments and implications of their research to many audiences. She has an extensive background in communications and technical journalism, and is a graduate of Oregon State University. For more science news, see PNNL News and Publications.
The Department of Energy's Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time.