Off-campus University of Miami users: To download campus access theses, please use the following link to log into our proxy server with your University of Miami CaneID and Password.

Non-University of Miami users: Please talk to your librarian about requesting this thesis through interlibrary loan.

Publication Date



UM campus only

Embargo Period


Degree Name

Master of Science (MS)


Chemistry (Arts and Sciences)

Date of Defense


First Committee Member

Rajeev Prabhakar

Second Committee Member

Roger M. LeBlanc

Third Committee Member

Burjor Captain

Fourth Committee Member

Stephan C. Schürer


In this study, theoretical and computational approaches have been utilized to investigate the mechanisms of natural and artificial metalloproteases. The active sites of most natural metalloproteases contain a tetrahedral zinc center, coordinated by three amino acid residues combinated from His(N), Cys(S), Glu(O), and Asp(O) with a water molecule as the fourth ligand. However, the roles played by the ligands environment in the catalytic functions of enzyme are not clear. In this study, the effects of different ligand combinations (NS2, N2S, N2O, N3, S3, NO2 and NSO) in the mechanism were investigated energy barriers were compared. The machanism and energetics of the substrate bound artificial metalloproteases Ni(II)cyclen (cyclen: 1,4,7,10-tetraazacyclododecane) and Cd(II)cyclen have been investigated. In addition, the mechanism of hydrolysis of Phe-Phe peptide bond catalyzed by another artificial metalloprotease [Pd(H2O)4]2+ has also been studied.


mechanism; natural and artificial metalloproteases; theoretical insight