Publication Date

5-2016

Date of Final Oral Examination (Defense)

3-4-2016

Type of Culminating Activity

Thesis

Degree Title

Master of Science in Chemistry

Department

Chemistry

Supervisory Committee Chair

Eric C. Brown, Ph.D.

Supervisory Committee Member

Don L. Warner, Ph.D.

Supervisory Committee Member

Jeunghoon Lee, Ph.D.

Abstract

The study of bioinorganic chemistry is an important field, as it can provide insight as to why Nature has chosen certain active sites and structures within different kinds of metalloproteins. Ada repair protein, a zinc-containing metalloprotein, is one such topic of interest. Although it is known that Ada RP is able to repair methyl-phosphotriester backbone damage by self-methylation of one of its cysteine groups, the mechanism is not fully understood. Two pathways have been proposed: a dissociative pathway where the Zn-S bond becomes a zinc/sulfur ion pair, and an associative pathway where a four ringed σ-metathesis occurs. Previous research has shown that a sulfur rich environment will increase the probability of thiolate dissociation, and that the probability of dissociation is dependent on the environment of the primary coordination sphere. However, we believe that the secondary coordination sphere (hydrogen bonding) is also able to increase dissociation probability. Two nitrogen-rich complexes, [(TPA)ZnSPh]+and[(BA-TPA)ZnSPh]+, were synthesized (with [(BA-TPA)ZnSPh] + having a hydrogen bond donor). Both the 1H and 13C NMR spectra show broad peaks (a sign of dissociation) within [(BA-TPA)ZnSPh]+ (the hydrogen bonding complex). These broad peaks became sharp when the sample is cooled, giving more plausibility that thiolate dissociation is occurring. Alkylation of the zinc-thiolate complexes showed the [(BA-TPA)ZnSPh]+ complex having alarger rate constant (6.49 x 10-3 M-1s -1) compared to [(TPA)ZnSPh]+ (1.51 x 10-3 M-1s -1). The larger rate constant for [(BA-TPA)ZnSPh]+ is due to the sulfur of [(BA-TPA)ZnSPh]+ being more nucleophilic (another sign of dissociation). These results add credibility to the secondary coordination sphere increasing probability of dissociation, and as a result opens a new opportunity for future research in this field.

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