Identifier

etd-11052015-022023

Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

The facile labeling of biomolecules with a radionuclide is a key goal in radiopharmaceutical development. This study explores two different ligand systems for fac-[Re(CO)3L]+ complexes, that could be used in bioconjugation. The first approach uses a tridentate ligand having a sulfonamide linkage and modeled on previously evaluated fac-[Re(CO)3(N(SO2R)dpa)]PF6 complexes. The present goal was to develop new related sulfonamide complexes with more hydrophilic ligands designed to avoid the bioavailability problems that would plague the N(SO2R)dpa ligand system. A series of fac-[Re(CO)3(N(SO2R)dien)]PF6 complexes with different R groups linked to the central nitrogen of a symmetric tridentate sulfonamides were synthesized with the aim of improving the favorable in vivo bioavailability. These compounds are characterized by NMR spectroscopy and by X-ray crystallography. The second approach using monodentate ligands led to the synthesis of several amidine complexes. The challenge of avoiding isomers of amidine complexes was overcome by using C2-symmetrical heterocyclic secondary amines with 6-membered and larger rings to create an amidine substituent bulkier than the amidine CCH3 group. Treatment of fac-[Re(CO)3(Me2bipy)(CH3CN)] BF4 with these amines in organic solvents yielded novel fac-[Re(CO)3(Me2bipy)(HNC(CH3)N(CH2)2Y)]BF4 complexes having only one isomer with the E configuration as established by solid-state and 1H NMR spectroscopic data. The combination of the high steric bulk and the C2-symmetry of the amidine substituents favors the E configuration exclusively. I extended the chemistry to smaller heterocyclic amines with 4- and 5-membered rings and found amidine formation reactions were faster. Moreover, I also showed that the amidine formation reactions were faster when the methyl group of fac-[Re(CO)3(Me2bipy)(CH3CN)]BF4 was replaced by a phenyl group. A series of fac-[Re(CO)3(Me2bipy)(HNC(C6H5)N(CH2)x)]+ complexes were synthesized, characterized and used in the comparison with the analogous fac-[Re(CO)3(Me2bipy)(HNC(CH3)N(CH2)x)]+ complexes in order to understand the properties of amidine complexes and to correlate the structural features with their behavior in solution. Furthermore, a new method employing the fac-[Re(CO)3(H2O)3]+ precursor successfully demonstrated the synthesis of fac-[Re(CO)3(Me2bipy)(amidine)]+ complexes in more aqueous conditions. This new method holds promise for use in biomedical studies.

Date

2015

Document Availability at the Time of Submission

Secure the entire work for patent and/or proprietary purposes for a period of one year. Student has submitted appropriate documentation which states: During this period the copyright owner also agrees not to exercise her/his ownership rights, including public use in works, without prior authorization from LSU. At the end of the one year period, either we or LSU may request an automatic extension for one additional year. At the end of the one year secure period (or its extension, if such is requested), the work will be released for access worldwide.

Committee Chair

Marzilli, Luigi

Included in

Chemistry Commons

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