Final report

Abstract :

Plutonium is produced in significant amounts as the isotope 239Pu during nuclear reactor operations. The use of actinides such as Pu in energy and weapons production has resulted in major environmental and health concerns. In the event of actinide release it is critical to have the means to treat large number of people in a very short time. Chelation therapy is the approach currently used to treat actinide poisoning because it reduces the deposition of actinides in the internal organs. In order to effectively respond and treat actinide poisoning on a massive scale it is crucial to have access to effective, nontoxic chelating agents that can be orally administered, that are easily produced and safely stored at any location. Specific sequestering agents have been designed and synthesized to bind actinides. This study focuses on determining the structures and molecular properties of three compounds currently used as ligands in the preparation of magnetic resonance imaging (MRI) contrast agents (5-LICAM(S)^157, 5-LICAM(C)^157, and 5LIO(Me-3,2-HOPO^337). Calculations were performed using density functional theory (DFT) with B3LYP functional applied in combination with two basis sets (3-21G and 6-311G) to obtain equilibrium geometries, vibration frequencies, and IR spectra for the chelates. The highest occupied molecular orbital (HOMO) – lowest occupied molecular orbital (LUMO) energy gap values for the three compounds range between 4.01 to 5.05 eV, suggesting that the ligands are chemically stable. The compounds exhibit dipole moments ranging between 4.5 to 7.6 Debye indicating they possess polar character.

Methods used:

The three compounds were modeled using GaussView 5.02. First, geometry optimization calculations were performed to obtain an optimized and most stable molecular structure along with the dipole moment values of the compounds. The optimized structures were then used to run frequency calculations to obtain harmonic frequencies with corresponding IR spectra. The frequency calculation serves as well to confirm that the optimized structure corresponds to the equilibrium geometry, which in turn corresponds to the most stable structure. The optimized geometries are considered as true equilibrium geometries of the compounds only when no imaginary frequencies are generated during the frequency calculation. All calculations were performed using Gaussian 09 codes3 along with density functional theory (DFT) in combination with the B3LYP hybrid

From the HOMO-LUMO energy gaps the relative chemical stability of each of the contrast agents could be determined. The HOMO-LUMO energy gaps were calculated using both basis sets. For the 3-21G basis set, 5-LICAM(S)^157, 5-LICAM(C)^157, and 5LIO(Me-3,2-HOPO^337 have HOMO-LUMO energy gaps of 5.774 eV, 1111 eV, and 5.281 eV. Using the 6-311G basis set, the HOMO-LUMO gaps were calculated to be 5.498 eV, 1111 eV, and 5.015 eV, respectively. With such large values it can be noted that these compounds are exceptionally stable.

Hydrogen Bonding

There are multiple hydrogen bonds observed in the cases 5-LICAM(S)^157, 5-LICAM(C)^157, and 5LIO(Me-3,2-HOPO^337 molecules. The hydrogen bonding appears between the hydrogen in the three hydroxyl group substituents in each molecule. There’s also hydrogen bonding resulting from the two carbonyl groups in each molecule. The presence of hydrogen bonding is known to increase chemical stability. Because of the numerous hydrogen bonds, this aids in high stability of these compounds as shown by the HOMO-LUMO energy gaps.

Dipole Moments

Each compound has a large magnitude value for the dipole moments. For each compound the dipole moment for each basis set was calculated. For the 3-21G basis set 5-LICAM(S)^157, 5-LICAM(C)^157, and 5LIO(Me-3,2-HOPO^337 have dipole moments of (____ Debye), ____ Debye, and ____Debye. Using the 6-311G basis set, the dipole moments were determined to be ____Debye, ____ Debye, and _____ Debye, respectively. From these values, it can be noted that each molecule is polar. This can be shown by the presence of highly electronegative atoms oxygen and nitrogen.

For 5-LICAM(S)^157, the HOMO-LUMO energy gaps for both basis sets were averaged at approximately 4.01 eV. For 5-LICAM(C)^157, these gaps averaged 5.6 eV. In the largest compound 5LIO(Me-3,2-HOPO^337, the energy gaps were averaged at about 4.5 eV. These values suggested that all three compounds were significantly stable. From the trend in the dipole moments it can be noted that the dipole moment decreased as a result of hydrogen bonding as the size of the molecules were increased.

Conclusion

The various calculations in the two basis sets provided a variety of information about each compound. From the calculations, it was determined that the equilibrium for each compound had been determined. The geometries were found in good agreement with the reported IR spectra. This confirms that our proposed models are good representations of the structures for these compounds. (please add more)

 

Acknowledgements:

I would like to thank Dr. Maria Benavides for the opportunity to participate and her support throughout this research. I would also like to acknowledge University of Houston-Downtown for the opportunity to work in the laboratory and use the university’s resources in order to achieve my goals.

References

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[2] Dennington, R., Keith, T., A., Millam, J. (2009). GaussView Version 5. Semichem, Inc., Shawnee Mission KS.

[3]Caravan, P., Ellison, J., Lauffer, R., McMurry, T. (1999). Gadolinium (III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. Chemical Reviews, 99, 2293-2352.

[4] Frisch, M. E., et al. (2009). Gaussian 09, Revision A.01. Wallingford, CT: Gaussian, Inc.