Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.



Degree Program

Chemistry, PhD

Committee Chair

Grapperhaus, Craig

Committee Co-Chair (if applicable)

Buchanan, Robert

Committee Member

Buchanan, Robert

Committee Member

Mueller, Eugene

Committee Member

Bates, Paula

Author's Keywords

copper; ATSM; cancer; hydrogen; nickel


Bis-thiosemicarbazones (BTSC) and their metal chelates have properties that are useful in several different scientific fields. These systems have already received attention in major fields of biology and engineering. Hydrogen evolution reaction (HER) catalysts need to be cheap and operate under minimal overpotentials with a long lifetime. The treatment of cancer requires, novel agents that have potent cytotoxic activity against cancer cells while displaying minimal side effects. In this dissertation the modular synthesis of these bis-thiosemicarbazone systems is utilized to regulate the redox chemistry for employment in the desired sector of chemistry. The ligand and metal chelates synthesized were characterized via cyclic voltammetry, NMR, UV-visible spectroscopy, FT-IR, EPR, and single crystal X-ray crystallography. The first generation replaced the pendent amine functionality of BTSCs with an alkoxy group. This replacement allowed for the structure to retain its physical characteristics that make these systems of interest in biological settings. However the change in functional group allows for tuning of the reduction potential, which is crucial for their activity. The copper diacetyl-bis(4-methylthiosemicarbazonato) (CuATSM) analog lays 250 mV more anodic for its CuII/I couple. Immobilization of NiATSM (2), NiATSDM (28), and NiATSM-F6 (29) on a glassy carbon electrode surface revealed that after reductive cycling, 200-300 cycles, improved the overpotentials of 2 and 28 by 250 mV from 700 mV to 450 mV. The lack of a dramatic effect for 29, is due to solid state interactions between molecules and electrode surface. Raman spectroscopy and SEM reveal that 29, does not remain on the electrode surface, whereas 2 and 28 undergo dynamic rearrangement to improve overall performance. A combination of both the pendant amine and alkoxy functionalities gave rise to the a new BTSC analog which chelated Ni, Cu and Zn. The electrochemical characterization revealed the copper chelates to have reduction potentials around 0.950 V CuII/I . 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed high selectivity and potency with 50% growth inhibitory (GI50) concentrations of 0.09 and 2.0 μM for carcinogenic and healthy cell lines respectively. Further the National Cancer Institute (NCI) 60 profile demonstrates that the copper chelate is effective against a wide variety of cancer types.