Undergraduate Research Overview
David R. McMillin

Photodynamic therapy involves the use of visible light to kill diseased cells. Porphyrins are attractive co-factors because they absorb at the long-wavelength end of the visible spectrum and can sensitize the formation of cytotoxic forms of molecular oxygen. Cationic, water-soluble porphyrins prove to be excellent DNA-binding agents, but the mode of uptake depends upon the state of metalation as well as the base content and the sequence of the DNA host. The trade off between the reorganization energy and the DNA- binding energy determines the mode of binding. Recently, we have synthesized and characterized a new, water-soluble, dicationic porphyrin trans-di(N-methylpyridinium-4-yl)porphyrin (H₂D4 in the Scheme). This less sterically demanding porphyrin binds exclusively by intercalation, independent of the DNA base composition or the sequence. Moreover, even the zinc(II) derivative binds by intercalation despite the necessity of losing the axial ligand. Access to less sterically demanding porphyrins, like H₂D4, opens the way to a variety of new and important DNA-binding studies that will allow us to isolate the effects that charge on the porphyrin, substituent orientation, metal content, and DNA composition have on the binding.