[Triumf-seminars] TRIUMF Colloquium today at 14:00

TRIUMF Seminars triumf-seminars at lists.triumf.ca
Thu Apr 18 05:00:00 PDT 2019


Date/Time: Thu 2019-04-18 at 14:00

Location:  Auditorium          

Speaker:   Eric Price (U Saskatoon)

Title:     Synergistic Use of Computational, Spectroscopic, and Radiochemical Methods to Design the Next-Generation of Radiometal Chelators

Abstract: Molecular imaging with positron emission tomography (PET) is a non-invasive technique that provides detailed, quantitative, and clinically power information on cellular and metabolic events. A variety of radiometals with differing nuclear properties have been produced and studied to date, with most of them requiring a different bifunctional chelator (BFCs) to provide optimal radiolabeling and stability properties. We have designed a new family of high-denticity (maximum CN=12) BFCs based on the gold standard for zirconium-89, the bacterial siderophore desferrioxamine (DFO). This new family of chelators includes those we've named DFO2, DFO2glu, DFO2lys, and DFO2', with a synthetic platform that features simple and rapid synthesis of new derivatives with different properties to enable binding to Zr(IV), Ti(IV), Nb(V), and potentially other radiometals. Although several successful new BFCs for zirconium-89 have been published in recent years, we are designing new BFCs with not only enhanced stability, but a focus on easy synthesis and a modular design for fast synthetic iteration. More importantly - we are investigating the use of EXAFS spectroscopy and DFT computations with the goal of validating and then integrating these methods with our rapid synthesis platform and traditional radiochemical stability assays to predict the most promising structures.

We have performed DFT calculations via ComputeCanada (SharcNet, Graham) and compared results obtained from combinations of the functionals B3LYP and PBE - and the basis sets LanL2DZ/6-31G+(d,p), Def2TZVP, and SDD - and used experimentally determined bond-length values from EXAFS spectroscopy as standards to select the most accurate computation method for our application (PCM used to model solvent effects). We have also compared these results to calculations performed on our own local computer system running Materials Studio (DMol3/GGA/PBE). The purpose of this work is to determine the most accurate computation method for predicting the metal-ligand bond lengths of these compounds using the very accurate bond length values determined via EXAFS spectroscopy as references. 

Preliminary zirconium-89 radiolabeling and stability assays have demonstrated that complexes of several of our new chelators are more stable than the "gold standard" chelator desferrioxamine (DFO). We hope to be able to correlate trends between EXAFS/DFT/radiochemical stability results with this first generation of chelators and use this information to more efficiently design new chelators in the future.

To make this seminar more accessible to the multidisciplinary audience, extra time will be dedicated to the introduction of each technique.


Stimulants availabl



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