Publication Date

Spring 2020

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

Advisor

David Brook

Subject Areas

Organic chemistry

Abstract

The use of probe molecules has been integral to the understanding of protein structure and dynamics. Spin labels are commonly used as probes on molecules, such as phospholipids, peptides, proteins, or drugs in vivo. The probes enable the precise and quantitative measuring of the movements of these molecules which has led to the elucidation of function. Nitroxides are the most widely studied and employed spin probes, despite being reduced to hydroxylamines by ascorbic acid in vivo in a matter of minutes. Verdazyls provide comparable applications to nitroxide radicals, with the added benefits of having tunable conformation and hydrophobicity by altering the R1/R5 ligand groups. Verdazyls are defined by their 6-membered ring containing four nitrogen atoms, and are notable for their exceptional stability and high variability in substitution. The radicals are stable in solutions over a wide range of pH, resistant to reduction by ascorbic acid, and can quench the fluorescence of organic dyes. We have synthesized a chloromethyl verdazyl as a possible spin probe for biological molecules, as well as a fluorescence quenching agent. The precursor tetrazane species was definitively identified by NMR spectroscopy, and the novel verdazyl by EPR, UV, and IR spectroscopy. Replacement of chlorine with iodide in the chloromethyl verdazyl demonstrated its ability to undergo SN2 nucleophilic substitution. The chloromethyl verdazyl can be incorporated onto a peptide as a side chain attached label via an SN2 nucleophilic substitution reaction.

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