Ligand Modeling and Design Presenter: Ben Hay, Pacific Northwest National Laboratory1 EM Focus Areas: contaminant plume containment and industry. The initial focus will be to select ether- and remediation; mixed waste treatment and disposal; based ligands that can be applied to the recovery and high-level waste tank remediation. concentration of the alkali and alkaline earth metal ions including cesium, strontium, and radium. Task Description Technology Needs The purpose of this work is to develop and imple- ment a molecular design basis for selecting organic Efficient separation processes are required for the ligands that would be used in applications for the removal of heat emitters (137Cs and 90Sr), long-lived cost-effective removal of specific radionuclides from radionuclides (99Tc), and other metal ions from high- nuclear waste streams. and low-level waste to reduce toxicity and volume at DOE sites. Solvent extraction and ion exchange Organic ligands with metal ion specificity are critical methods are being developed at a number of sites. components in the development of solvent extraction and ion exchange processes that are highly selective The successful performance of these separation for targeted radionuclides. The traditional approach methods largely depends on the properties of the to developing such ligands involves lengthy programs organic ligand (e.g., selectivity, binding affinities, of organic synthesis and testing, which in the absence binding kinetics, and solubility). Therefore, much of reliable methods for screening compounds before effort is spent on the synthesis, characterization, and synthesis, results in wasted research effort. Our testing of many ligands to find those few with the approach breaks down and simplifies this costly desired properties to meet the separations process process by using computer-based molecular model- needs. Current criteria used to select ligands for a ing techniques. specific application are not highly accurate and result in more failures than successes. Commercial software for organic molecular model- ing is being configured to examine the interactions between organic ligands and metal ions, yielding Scientific Background an inexpensive, commercially or readily available This technology is based on adapting the most computational tool that can be used to predict the accurate commercial molecular mechanics modeling structures and energies of ligand-metal complexes. software, MM3, for application to metal-ligand com- Users will be able to correlate the large body of exist- plexes. Historically, molecular mechanics models ing experimental data on structure, solution binding have been developed for exclusive application to affinity, and metal ion selectivity to develop struc- organic molecules; that is, molecules composed of tural design criteria. These criteria will provide a carbon, hydrogen, nitrogen, phosphorus, oxygen, basis for selecting ligands that can be implemented in sulfur, fluorine, chlorine, bromine, and iodine atoms. separations technologies by DOE national laboratories 1 Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy under Contract DE-AC06-76RLQ 1830. Heavy Metals—ESP 59 All commercial molecular mechanics software m packages come with sets of parameters for organic ïcc :o compounds but most do not contain parameters for treating metal-ligand complexes. This is partly because to of the past focus on pure organic systems and partly t^o^J because of the way molecular mechanics models ro, work; that is, a unique set of parameters is required 3 o£ to for each different metal ion and each different type of donor atom. When applying the molecular mechanics 4 aflo technique to metal-ligand complexes, one must focus on a class of metal complexes to limit the number of 4 8 12 16 metal ions and donor atom types and then develop a Ligand Reorganization Energy (kcal/mol) set of parameters before performing the calculations. Figure 1. Plot of experimental complex stability (log Kin methanol In the early stages of this project, we developed an at 25 °C) versus calculated ligand reorganization energy for extended MM3 parameter set that allows accurate potassium complexation by four diastereomers of dicyclohexano- molecular mechanics calculations to be performed 18-crown-6. on metal complexes of the alkali (lithium, sodium, potassium, rubidium, cesium) and alkaline earth based QSARs have been obtained for thermodynamic (magnesium, calcium, strontium, barium, radium) stability constants of sodium, potassium, rubidium, metal ions with ligands that contain aliphatic ether and cesium complexes with aliphatic crown ethers donor atoms (e.g., ligands such as the SREX reagent, (see Figure. 1), and for solvent extraction distribution di-t-butyl-dicyclohexano-18-crown-6). This param- coefficients of lithium by alkyl substituted 14-crown-4 eter set has been completed and validated. A current ligands and strontium by a series of dicyclohexano ' objective is to further extend the MM3 parameter set derivatives of 18-crown-6. to include metal complexes of the alkali and alkaline earth metal ions with ligands bearing benzo ether Generating QSARs requires the availability of refer- donor atoms. This will yield the capability to perform ence experimental data. In the absence of such data, molecular mechanics calculations on a wider range it is possible to use molecular mechanics calculations of ligands (e.g., benzocrown ethers, calixarenes, to predict the relative metal binding affinities for a and spherands). series of ligands and, therefore, to identify ligand structures likely to form the most stable metal ion Molecular mechanics calculations provide structures complexes. The calculated increase in ligand steric and steric energies for organic ligands and their metal energy that accompanies metal ion complexation pro- complexes. These results yield a design basis for vides a yardstick for the measurement of the ligand's ligand selection. This design basis includes quantitative binding site organization, a structural property that structure-activity relationships (QSARs), methods to correlates with the stability of metal-ligand complexes. predict relative complex stability as a function of ligand structure, and criteria for ligand design. Ligand design criteria, or "rules-of-thumb" that can readily be applied by synthetic chemists, are an impor- QSARs are obtained by coupling molecular mechan- tant by-product of this work. For example, to clarify a ics results with experimental data. These QSARs can previously unrecognized preference for trigonal planar be used to predict properties (e.g., thermodynamic geometry at ether oxygen donors established that stability constants) of ligands for which no experi- ethylene-bridged, ether oxygen donor atoms form a mental data exist. To date, molecular mechanics chelate ring that is structurally organized for large 60 Heavy Metals—ESP 60 metal ions. Therefore, the presence of ethylene bridges types and associated metal complexes being in multidentate ethers will promote selectivity for addressed by other DOE programs involving envi- large metal ions. A study of ethylene-bridge alkyla- ronmental cleanup, fate, and transport of environ- tion has yielded a set of simple rules that allows a mental contaminants; development of sensors; and synthetic chemist to predict how the addition of alkyl nuclear medicine. The private sector may also be groups to crown ethers will alter the complex stability. able to apply this technology in the chemical indus- try, medicine and pharmacology, hydrometallurgy, Benefits and geochemistry. This new technology, the design criteria coupled Accomplishments with the computer-based molecular model, will pro- vide a way to assess the reactivity of an organic The inexpensive, off-the-shelf molecular model ligand toward a target metal ion on the basis of MM3 has been configured to handle aliphatic crown molecular structure. This capability can be used to ether ligands and their complexes with the alkali and screen potential ligands before undertaking the time alkaline earth metal ions. The model has been dem- and expense associated with synthesis and testing. onstrated to predict accurately the structure of these ligands and their metal complexes.- Correlations The costs associated with organic synthesis and between calculated structural data and experimental performance testing with radioactive materials are reactivity (complex stability and solvent extraction expected to rise disproportionately to the average distribution coefficients) have been obtained. Design cost of doing business because of increasing regula- criteria for aliphatic crown ethers have been developed. tion regarding the safe handling and disposal of This model is currently being applied to the design chemical reagents. Therefore, this capability will and screening of aliphatic crown ether ligands for the save significant cost in ligand identification, evalua- separation of cesium and radium and the optimization tion, and deployment. of the SREX reagent. The MM3 model is now being This technology will allow the development of ligands extended to treat metal complexes with ligands bear- with improved performance including 1) improved ing benzo ether donor atoms such as benzocrown selectivity and binding affinity for specific aqueous ethers, calixarenes, and spherands. species, 2) improved performance in solvent extrac- tion systems by optimizing the type and placement of the hydrophobic substituents needed for