Synthesis and DNA-binding studies with two stericallyfriendly porphyrin frameworks

Ghimire, Srijana. Ph.D., Purdue University, December 2014. Synthesis and DNABinding Studies with two Sterically-Friendly Porphyrin Frameworks. Major Professor: David R. McMillin. 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(Nmethylpyridinium-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-