Session: Undergraduate Research Posters: Biochemistry:

Metalloenzymes are vital in biochemical processes. A subset of them catalytically hydrolyze substrates in cells. Enzyme mimics are minimalist synthetic molecules that resemble the structural and functional properties of these enzymes’ active site. They are commonly used as models due to their tolerance to experimental conditions and ultimately, they could be used as more efficient in vitro mimics for drug discovery. The coordination sphere of Zn(II) in the carboxypeptidase-A metalloenzyme active site was mimicked using a macrocyclic polyamine, namely, 1,5,9 - Triazacyclododecane (TACD). In this paper we present the synthesis of 1,5,9- triazacyclododecane (TACD) that is postulated to present three nitrogen donor ligands to coordinate with Zn (II) ions in an attempt to reproduce the coordination geometry in the active site of metalloenzymes. The synthesis was performed in two steps. In the first step, Hexahydropyrimidopyrimidine underwent a substitution nucleophilic bimolecular reaction (SN2) with 1,3-propane ditosylate reagent at room temperature resulting in a tricyclic salt of a carbocation intermediate at the most centered carbon in the molecule. This intermediate was subsequently reduced in situ by a mild reducing agent, sodium borohydride to form an orthoamide. In the second step, the orthoamide was hydrolyzed to form TACD. The product was confirmed using nuclear magnetic resonance spectroscopy (¹H NMR and ¹³C NMR) and infra-red spectroscopy (IR). Significant modifications to the published reactions resulted in increasing the yield of the final product by two-fold.¹ The TACD ligand will be used as a scaffold to add pendant groups for binding substrates to study their hydrolysis in presence of Zn (II) ions.²

Ajay Lajmi

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