Computer-Aided Design of Metal Ion Hosts Benjamin P. Hay, 30 April 2003 Battelle U.S. Department of Energy Pacific Northwest National Laborato
Computer-Aided Design of Metal Ion Hosts Benjamin P. Hay, 30 April 2003 Battelle U.S. Department of Energy Pacific Northwest National Laboratory.
Jan 05, 2016
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Computer-Aided Design of Metal Ion Hosts
Benjamin P. Hay, 30 April 2003
Battelle
U.S. Department of Energy
Pacific Northwest National Laboratory
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The DOE Legacy - Radioactive Waste
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Separations
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
Ion exchange processes also have largescale application at DOE sites. At Hanford, tank waste pretreatment will use ion exchange to remove pertechnetate and cesium prior to vitrification.
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Sensors
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Medical Applications
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Hosts for metal ions
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Host Design
Computer-Aided ?
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Architecture - scaffolds used to connect sets of binding sites
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Structural effects are often difficult to predict
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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How do we approach this problem?
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Electronic structure calculations
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Force field calculations are much, much quicker
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Downside - MM models often require parameterization
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Extending MM3 models for f-element complexes
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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What can we learn by examining host structures?
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Binding site geometry in crowns favors large metals
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Sizematch is not sufficient for a good fit
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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12-crown-4 versus 14-crown-4
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Ligand strain energy
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Binding affinity vs. host strain
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Another example
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Actinide sequestering agents
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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A closer look at the malonamide architecture
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Improved architecture?
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Proof in the pudding . . .
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Structural design criteria
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Structural design is a trialanderror process
Problem: you have to build structures before you can test them.
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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ComputerAided Host Design
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Structure-Based Drug Design
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Structure-based host design?
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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HostDesigner Software
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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LINKER algorithm
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Scoring by geometry
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Linking fragment database
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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CnHm for n = 0 - 6 (excluding alkynes, 3-membered rings, and 4-membered rings)
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Dimethylated 5 and 6membered rings
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Selected fusedrings
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Example of a LINKER run
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Validation
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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How did we do?
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Second generation
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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OVERLAY algorithm
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Tetradentate ether macrocycles
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Applications in progress
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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Further information
Benjamin P. Hay, Pacific Northwest National Laboratory, 30 April 2003
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