Publication Date



Open access

Embargo Period


Degree Type


Degree Name

Doctor of Philosophy (PHD)


Chemistry (Arts and Sciences)

Date of Defense


First Committee Member

Rajeev Prabhakar

Second Committee Member

Francisco Raymo

Third Committee Member

Orlando Acevedo

Fourth Committee Member

John Reilly


In this thesis, we have focus on the following three projects: (1) the inhibition of amyloid beta aggregation, (2) structural and mechanical properties of amyloid peptides, and (3) complex biological systems of molecular recognition pertaining to hydrolysis. In the first project, we have looked at the inhibition of early and late forms of Aß peptides using heparin derived disaccharides, small molecules, and a Rhenium centered photoluminescence probe. We have determined and characterized the most relevant binding sites of these complexes to both the monomeric and fibrillar forms of the Aß peptide. Currently, the aggregation of biomolecules has been implicated in a large number of neurological diseases. Furthermore, we have been able to develop models of larger Aß aggregates that clearly represent mature fibril structures based on mechanical property measurements. Our results were compared to experimentally determined values and were found to be in excellent agreement. Lastly, three complex systems of hydrolysis were investigated. Among them, the three transient species associated with the mechanistic cycle of GpdQ were determined as well as the effect of primary and secondary shell residues on the active site conformations. Additionally, binding sites on human serum albumin were identified and characterized based on experimental mass-spec data for ZrK, and the effect of the addition of an ATCUN binding domain on the antimicrobial peptide (Buforin) and its binding to DNA was investigated.


Amyloid beta; Stress-strain; Polyoxometalate; Enzyme; GpdQ; Aggregation