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Water Soluble and Highly Selective Th(IV) Sequestering Agent

IB-3232

APPLICATIONS OF TECHNOLOGY:

ADVANTAGES:

ABSTRACT:

Berkeley Lab researcher Kenneth N. Raymond and colleagues have developed a Thorium (IV) (Th(IV)) sequestering agent that can be used to bind Th(IV) in water very rapidly at extremely low concentrations. The new agent is a macrocyclic octadentate ligand, 2,3,-Dihydrooxyterephthalamide, called ThL, for short, when bound to Th(IV). Inspired by siderophores, naturally occurring iron-chelating compounds produced by bacteria, the macrocyclic molecule is able to have fast kinetics and extraordinarily strong binding to Th(IV), yet is water soluble. Specifically, dye displacement kinetic studies show that the ligand is a much more rapid chelator of Th(IV) than prevailing ligands (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid and diethylenetriaminepentaacetic acid).

The Berkeley Lab technology can be modified to develop highly specific chelators of lanthanides or other actinides such as plutonium, uranium, or neptunium. The molecules can be tailored to find and sequester radioactive particles, making them soluble for flushing out of the body. Therefore they could be developed into oral chelating agents for radioactive decontamination.

The reverse of this propensity to seek out and bind to actinides makes these sequestering agents, and ThL in particular, attractive for cancer diagnostics or radiotherapy. In fact, the resulting complex was found to have a remarkably high thermodynamic stability, with a formation constant of 1054. These data support potential radiotherapeutic application.

Th(IV) isotope 227 has a relatively short half-life and emits α-radiation, which is highly desirable as a tumor killer due to both its high energy and range of about one human cell width. If paired with tumor-specific antibodies, ThL could transport lethal doses of Th(IV) radiation directly to cancer cells, simultaneously flagging tumor sites while killing tumor cells. The molecule could also be used to sequester zirconium-89, a short half-life isotope that is widely used as a tracer for positron emission tomography (PET) scans.

DEVELOPMENT STAGE:  The thorium complex was structurally characterized by X-ray diffraction and in solution with kinetic studies and spectrophotometric titrations.
 
STATUS:  Patent pending. Available for licensing or collaborative research.

FOR MORE INFORMATION:
Pham, T. A., Xu, J., Raymond, K. N. "A Macrocyclic Chelator with Unprecedented Th4+ Affinity," Journal of the American Chemical Society, May 28, 2014.

SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD:

Two Synergistic Pharmacons for Removing Toxic Radionuclides from the Body, IB-2728

Breast Cancer Therapy and Potential Method for Enhancing Radiation Sensitivity, IB-1965

REFERENCE NUMBER: IB-3232

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