Tricationic porphyrins: Synthesis: Characterization and interactions with B -form DNA and photochemical studies of metalloporphyrins with B-form hairpin DNA

Kim Andrews, Purdue University

Abstract

Positively charged N-methylpyridinium-4-yl substituted porphyrins are of significance for their DNA binding, but they can also present steric problems. In Chapter 1, this dissertation begins with the synthetic methodology used to generate the pyridyl porphyrin starting materials, and Chapter 2 describes the syntheses and binding properties of two new ligands: 5,10,15-tri (N-methylpyridinium-4-yl)porphyrin (H2Tri4) and 5-methyl-10,15,20-tri(N-methylpyridinium-4-yl)porphyrin (H2MeTri4). This work shows in Chapter 3 that intercalation is the only detectable binding motif when the trisubstituted porphyrin H2Tri4 combines with [(poly(dA-dT)]2, [(poly(dGdC)]2, or salmon testes DNA. However, parallel studies of H2MeTri4and its Cu(II) derivative reveal that the presence of a fourth meso substituent as small as a methyl group induces external binding when the DNA is rich in adenine-thymine base pairs. At least with the [(poly(dA-dT)]2 hosts, intercalation of H2MeTri4 appears to involve inserting two N-methylpyridinium-4-yl substituents into the major groove. Sterically fit but electrostatically misaligned, the intercalated form of H2MeTri4 is not stable enough to preclude external binding to the [(poly(dA-dT)]2 host. In Chapter 4 a side project is summarized. The project tests whether DNA hairpins with thymine overhangs at the open 5’ and 3’ ends might be useful as mercury(II) sensors. The thought was that forming a thymine-Hg2+-thymine artificial base pair might close the ends of the hairpin and modify the binding motif of a bulky porphyrin. Systems with a 5’-CCCC-3’ loop showed some promise in conjunction with emission studies of Cu(T4). However, uptake of mercury(II) is also facile in the absence of a thymine-thymine mismatch and these results cloudy the possibility of sensor applications.

Degree

Ph.D.

Advisors

McMillin, Purdue University.

Subject Area

Organic chemistry

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