Synthesis and DNA-binding studies with two stericallyfriendly porphyrin frameworks

<p>Peripheral substituents on cationic porphyrins play a significant role during binding with DNA hosts. Possible applications of these systems in photodynamic therapy as well as in anti-bacterial and anti-cancer therapies motivate the binding studies. For characterizing DNA binding motifs different methods are useful including absorption, emission, and circular dichroism spectroscopies, as well as viscometry and X-ray crystallography. With the classic H₂T₄ porphyrin, or 5,10,15,20-tetra(N-methylpyridinium-4-yl)porphyrin, the mode of binding varies with the base composition of the DNA host. The porphyrin binds adenine-thymine rich sequences externally whereas intercalation occurs in guanine-cytosine rich sequences. The McMillin group has made some dicationic porphyrins which are strictly intercalators but the lower positive charge decreases binding affinity to DNA. One chapter describes competitive binding studies involving a dicatonic porphyrin. Most of the thesis focuses on a new system described here which is H₂TC₃, or (5,10,15,20-tetra[3-(3'-methylimidazolium-1'-yl)]porphyrin). By comparison with the classical H₂T₄ system, H₂TC₃ exhibits a higher molar extinction coefficient but is more prone to self-association. Findings of note include that the copper(II)-containing form Cu(TC3) is adept at internalizing into single-stranded as well as B-form DNA, regardless of the base composition. Surprisingly, however, external binding of H₂TC₃ occurs within domains that are rich in adenine-thymine base pairs. The difference in the deformability of H₂TC₃ vs. Cu(TC3) probably accounts for the reactivity difference. On the other hand, Zn(TC3) binds externally, as the metal center remains five coordinate. Finally, the thesis describes the palladium analogue Pd(TC3). It will be of interest because of the high yield of intersystem crossing and long lifetime of the resulting excited triplet state.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Year

2014

Author dc:creator

• Ghimire, Srijana

Contributors dc:contributor

• David R. McMillin
• Mahdi Abu-Omar
• Christopher Uyeda
• Chengde Mao

• Biochemistry
• Inorganic Chemistry

Repository record dc:identifier

https://docs.lib.purdue.edu/open_access_dissertations/270

OAI identifier oai:identifier

oai:docs.lib.purdue.edu:open_access_dissertations-1319