Synthesis and Characterization of First Row Transition Metal Polyphosphates

Date of Award

December 2017

Degree Type


Degree Name

Doctor of Philosophy (PhD)




Robert P. Doyle


cobalt, Mycobacterium tuberculosis, pyrophosphate

Subject Categories

Physical Sciences and Mathematics



This thesis focuses on the synthetic challenges inherent in pyrophosphate (PPi) coordination chemistry and the opportunities solving these challenges will have in terms of drug and materials development.

Specifically, the role of hydrolysis in PPi mechanism of action in PPi metallo-complexes against Mycobacteria has not been elucidated.

PPi complexes have been shown to mediate magnetic interaction across paramagnetic metal centers and have the ability to produce ferromagnetic materials, yet only with copper(II), leaving a wealth of unexplored transition metals with greater magnetic moments.

Finally, no iron PPi complexes have been structurally characterized to date, and a fully characterized structure would allow for the development of an iron(II) PPi based pharmaceutical or nutraceutical.

Q1. (Chapter 2) What is the mode of action and mutagenicity of cobalt(II) and copper(II) pyrophosphate complexes?

Goals: Explore the activity of complexes in TB-infected macrophages, determine if cobalt(II) and copper(II) PPi complexes are mutagenic substances, determine if ROS levels are increased and whether such complexes can enter a macrophage and/or are toxic to such.

Q2. (Chapter 3) Does the hydrolysis of PPi play a role in the mechanism of action of PPi bridged metallo complexes?

Goals: Synthesize and characterize a series of cobalt(II) and copper(II) complexes containing a non-hydrolyzable PPi analog, namely, methylene diphosphonic acid (MDP). Screen such complexes against M. tb, assay for ROS generation, and determine cytotoxicity in macrophage cells.

Q3. (Chapter 4) Can multiple bridging PPi units mediate magnetic interactions across two paramagnetic metal centers? Can ferromagnetic cooperativity be observed for PPi complexes beyond those with copper(II)?

Goals: Synthesize and characterize a series of ‘double-bridged’ PPi complexes of Co(II), Ni(II), and Mn(II) and determine the magnetic interaction by measuring magnetic susceptibility.

Q4. (Chapter 5) Can a Fe(II) PPi complex be synthesized and characterized?

Goals: Design, synthesize, and characterize an Fe(II) PPi complex using inert atmosphere, low pH and a pi-acid ligand.


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